Archive for the ‘Male Genetics’ Category

The headline of a recent article by Dani Blum, a News Assistant in the Well section of the New York Times, forced me to ask myself, Are we really this misinformed about what contributes to good health and wellness, and the basic actions we can take to improve our chances of aging well and avoiding disease and chronic pain? Blums piece, entitled, You Wont Live Longer by Diet or Exercise Alone, Study Says, began by stating Sprawling new research showed that healthy eating and regular workouts do not, in isolation, stave off later health issues. They need to be done together.

Really? You mean it took Sprawling new research to verify that walking Fido vigorously each morning, then taking him with me for a pancake and whipped cream breakfast seven days a week might not be the best preparation for my senior years? That three-times-a-week to the gym followed by a mocha cookie crumble frappuccino and double-smoked bacon, cheddar and egg croissant sandwich wont necessarily qualify me for the Canada Summer Games next time they swing into Niagara?

Assume my diet is a perfect combination of organic leafy greens, black beans, lentils and gluten-free, hearth-baked bread with natural honey on seaweed crackers for dessert. Does this mean I can sit in an ergonomic chair at work or in front of my home computer all day, then watch four hours of Netflix every evening without risking my long-term health? Of course not. Next up was an article in The Guardian by Linda Geddes, Science Correspondent, entitled, Sunlight may trigger hormone that makes men hungrier, study suggests.

The piece was based on a study by Carmit Levy, a Professor of Human Molecular Genetics and Biochemistry, at Tel Aviv University, examining the effect of sunlight on appetite in male and female people and similar genders of mice.

The substance of the article was that his team had discovered ghrelin levels (a gut hormone which stimulates food intake, fat deposition and growth hormone release in our bodies) rise in males blood after sun exposure, but estrogen appears to block a similar increase in females. The article stated, Analysis of 3,000 people revealed that men, but not women, increased their food intake during the summer months. Okay, but could there possibly be any other reasons than exposure to sunlight?

I dont recall many of my male buds worrying about losing a few pounds to fit into a new bathing suit before hitting the beach and going on a summer crash diet, or blaming sunshine for the need to have a beer or three and plate of fries after playing a round of golf, which is most-often done in the summer. Seems backyard steak and sausage BBQs are more prevalent in the summer than winter too. Could any of these be a factor?

As I completed reading Geddes article, my skepticism was rewarded by a review notation in the second to last paragraph. It read, Dr. Duane Mellor, a dietitian and senior teaching fellow at Aston University (Birmingham, England) was more cautious. What it does show is the potential mechanism of how UVB can influence hormone metabolism, and how this may be associated with an increase in the appetite hormone ghrelin, at least in mice, he said.

The need to evaluate wellness and health advice, as this column generally cautions when it ventures into these topics, through additional corroborating evidence mixed with our own best common sense is clear. Indiscriminately accepting what fits into our preconceived ideas is seldom useful, and understanding the motivation behind conflicting health information is helpful. Those of us born in the two decades immediately following the Second World War remember our mothers constantly telling us to eat carrots by the bunch to improve our vision. Dear mom was aided in this unabashed conspiracy of forced carrot consumption by Bugs Bunny, Warner Bros sassy carrot-chomping wild hare in cartoon after cartoon.

Science later proved that the beta-carotene in carrots does indeed help our bodies produce vitamin A, which increases the ability of our eyes to convert light into signals the brain understands, and reduces cornea degeneration as we age.

Problem is, this carrot and eyesight health link wasnt founded on solid health science in the early 1940s. It seems that the British Royal Air Force had developed radar technology late in the war, suddenly increasing the success of their bombing raids on Germany. In an effort to hide their discovery, the British promoted the myth that their airmen had suddenly become more capable of night vision by eating volumes of carrots. The science came much later than the headlines.

Remember the MSG (monosodium glutamate, a common amino acid with one sodium atom added) scare which began in the late 1960s? Im still afraid of this food additive, or at least I was until I read that MSGs bad rap began in 1968, when an American doctor named Robert Ho Man Kwok wrote a letter to the New England Journal Medicine, calling a medical condition of general numbness and weakness the Chinese restaurant syndrome, citing the MSG used to flavour Chinese food as the culprit. The American Chemical Society, a potentially unbiased stakeholder if ever there was one, swiftly responded with the vague non-statement that MSG can temporarily affect a select few when consumed in huge quantities on an empty stomach, but its perfectly safe for the vast majority of people.

Confused by this conundrum between natural salt and MSG, I personally chose to switch to pink Himalayan salt. Its reputed to contain healthy trace minerals, which worked for me until my son pointed out that the dispenser I was using to grind it had hardened plastic cutting teeth rather than metallic ones. I was in fact ingesting more trace plastic than healthy trace minerals. Now its Pass the sea salt please at our house.

Then theres the five-second rule, the idea that if a piece of food drops on the floor you can safely pick it up and eat it as long as it doesnt sit there for more than five seconds. Apparently Julia Child gets the blame for this one. During one of her TV shows she dropped a potato pancake, promptly returned it to the pan, and continued with her cooking demonstration as if nothing had happened.

The crazy part is that the five-second rule has since been the subject of countless studies which have determined that food on the floor can pick up bacteria quickly, that sticky wet food will collect more potential pathogens than dry morsels, that some floor bacteria are more harmful than others, and that dirty floors are more likely to be unsafe for five second food drops than clean ones. Sure hope our taxes werent funding Health Canada to participate in this research. My personal interpretation of the five-second rule doesnt need scientific guidance. If the food dropped is a cookie or ripe sweet cherry, it will be picked up and eaten. Dropped soggy cooked brussels sprouts go straight to the compost bucket. Pizza is situational. When I bought the last slice of warm pizza at 5:59 PM from the only gas station still open along some desolate road in northern Ontario, after cycling 120 kilometres, then promptly dropped it face-down on the sidewalk, a five-second or five-minute rule wouldnt have saved that pizza slice and a few fresh tiny specs of gravel from being eaten.

Are the natural sugars in honey better for you than processed sugar? Will an apple a day keep the doctor away? Is herbal tea or juice better for detoxing? The list goes on.

As Dani Blum suggested at the beginning of this column, Ill stick with balancing diet and exercise, and do my best research before I intentionally change a wellness habit. In the meantime, I just viewed the beginning of a podcast, and now I really need to find out why Dr. Steven Gundry, MD and best-selling author of nutrition and cookbooks, claims that, Beans are so lethal that five raw kidney beans will kill a human being in five minutes by coagulating their blood.

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THE BALANCED LIFE | Use common sense when digesting wellness advice | - The Voice of Pelham

Before its 75th Independence Day, India will have brought back cheetahs to semi-wild conditions in Madhya Pradesh, where cheetah roamed more than 100 years ago.

It will surely be a moment of rejoice but one should remember that these animals may be more of a tourist attraction than add ecological value. It is the worlds first species re-introduction programme and comes at the time when less than 7,000 cheetahs are remaining in the world with their population on decline.

Last Wednesday, India and Namibia signed a historic memorandum of understanding (MoU) on translocation of cheetahs to India for a period of 5 years, which can be renewed for successive 5-year periods, unless either party terminates the agreement. Namibia has promised to provide India eight cheetahs in two batches of four each.

The agreement speaks about biodiversity conservation with specific focus on restoration of the cheetah in its former range areas; sharing expertise and capacities for cheetah conservation in the two countries, wildlife conservation and sustainable biodiversity utilisation and mechanisms of livelihood generation for local communities living in wildlife habitats.

On the face of it, the agreement looks good but wildlife experts point out that the provision on sustainable conservation of biodiversity actually means supporting Namibia at the meetings of Convention on International Trade in Endangered Specials of Wild Flora and Fauna (CITES) to allow trade of wildlife and its body parts. Namibia and several other African countries, which have a huge stockpile of wildlife body parts, have been trying for long to negotiate the trade at CITES, the international wildlife regulator, for their sale in high demand western and West Asian countries.

This is a historic event. After a 75-year gap we will see cheetahs back in India. This will be the first inter-continental wild to wild transfer of cheetahs in the world. Some concerns regarding the agreement were there but those have been resolved now. Negotiations on modalities of translocation are underway. Initially, we may get 8 cheetahs by August, said SP Yadav, head of National Tiger Conservation Authority (NTCA), the national big cat regulatory body.

The Cheetah project

The Supreme Court appointed panel had surveyed 10 sites between 2010 and 2012 to select where the cheetah could be introduced. Based on the International Union for Conservation of Nature (IUCN) guidelines for reintroductions that consider species viability according to demography, genetics and socio-economics of conflict and livelihoods, Kuno Palpur National Park in Shivpuri district of Madhya Pradesh was considered ready for receiving the cheetah. This was because there had been already been a lot of investments in this protected area for introducing Asiatic lions from Gir National Park in Gujarat.

The current carrying capacity for Kuno (748 sq km) is a maximum of 21 cheetahs and it could be enhanced for another 20 by including the remaining part of the Kuno Wildlife Division (1,280 sq km) through prey restoration, the ministry said. It has also provided R10 crore for the project and is sourcing money from private funders. The Wildlife Institute of India (WII) with national and international cheetah experts is providing technical and knowledge support, the ministry said.

According to an environment ministry report on Cheetah Translocation Project, the aim of bringing cheetahs to India is to establish a viable cheetah meta-population in India that allows the cheetah to perform its functional role as a top predator and provide space for the expansion of the cheetah within its historical range.

According to a Ravi Chellam, biodiversity expert and CEO, Metastring Foundation & Coordinator, Biodiversity Collaborative, in March 2022, published a report saying that range of cheetahs extended from Punjab in north to Bihar in the east to Gujarat and Rajasthan in the west and till Western Ghats in south. The last cheetah spotted in India was in Western Ghats and northern Bihar in 1967. Madhya Pradesh where the cheetahs are being brought lost their last this big cat in 1912 and 1932, as per the study.

There are authentic reports of their occurrence from as far north as Punjab to the Tirunelveli district in Tamil Nadu. The cheetahs habitat was also diverse, favouring the more open habitats, scrub forest, dry grasslands, savannas and other arid and semi-arid open habitats, he said in the report.

The consistent and widespread capture of cheetahs from the wild over centuries, its reduced levels of genetic heterogeneity due to a historical genetic bottleneck resulting in reduced fecundity and high infant mortality in the wild, its inability to breed in captivity, sport hunting and bounty killings are the major reasons for the extinction of the Asiatic cheetah in India, Chellam had said.

On the ministry statement that it wants cheetah to perform its functional role as a top predator, Chellam said the role is being done by Asiatic lion and leopards in the country. Moreover, data from African countries show that farm bred cheetahs (which India is getting) are very vulnerable to leopard. In Kuno, where they would be habituated for wild, top predator is leopards with officials estimate their number to be more than 50.

The translocation process

The ministry said cheetahs from Namibia will be first to arrive by August 15 and the animals have been identified there.

According to a University of Pretoria statement, 12 animals are being prepared in South Africa for their new home in Madhya Pradesh. Of them, at least six are expected to be in Kuno by end of 2022, which would by then have four cheetahs from Namibia.

The ministry has made Kuno National Park management responsible for monitoring and protection of cheetahs with the help of Wildlife Institute scientists and international experts from South Africa and Namibia. For people living in and around Kuno, an awareness campaigns is underway with a local mascot named Chintu Cheetah, ministry said.

Cheetahs brought in from Namibia would be soft released (providing wild animals with a gradual transition to the wild during translocation) into a 10 sq km enclosure in Kuno to reduce their tendency to disperse long distances from their site of release, officials said, adding they would be housed in the predator proof fenced enclosures.

Initially, male and female cheetahs would be kept separately in five square kilometre enclosure but adjoining compartments and will be allowed to co-habit as and when indications would be there. The location of the enclosure will be such that the cheetahs can sense the presence of prey and predators before release.

A new study by a United Nations affiliated global wildlife regulator in July 2022 said that cheetahs are notoriously difficult to breed in captivity based on long-time research on cheetah breeding in captive facilities in Africa. Cheetahs are notoriously difficult to breed in captivity for example, North American cheetahs have excellent genetic variation as well as housing and veterinary care, yet only 23 out of 111 females have had offspring, the study said.

The concerns

Experts point out that apart from breeding in captivity concerns, there are also questions over whether Kuno, a Vindhya forest with limited grassland, is a perfect habitat for cheetah, which like vast open spaces for their biological and physical needs. Studies in Africa have shown that female cheetah are solitary and roam vast distances whereas male defends smaller territories and mate when female pass through, creating breeding issues.

Even the national action plan for cheetah translocation released in January 2022 hinted at the animals low reproduction issues saying Kuno has current capacity to sustain 21 cheetahs in 15 years and 36 after 30-40 years.

Wildlife experts also point out to the presence of leopards in Kuno which would make release of the animals in the wild difficult. Studies have shown that in Africa, the leopards have hunted down cheetah as prey, and similar fears are being expressed for Kuno also, which has about 50 leopards in and around the core area, where cheetahs will be housed.

Another pivotal issue is whether a cheetah living in an enclosure and being fed with a prey will be able to hunt in wild on its own. In the past decade or so, not even a single wild big cat such as tiger and lion treated or bred in enclosure have been able to return to life in wild. Sundari, the tigress which returned from Satkosia in Odisha after failed relocation attempt, was finally kept captive for life in Bhopal Zoo. Close to 30 lions kept in an enclosure after CDV outbreak in Gir National Park would go to different zoos in the country.

Anish Andheria, President of Wildlife Conservation Trust, however, rebuffed some concerns. In Africa, cheetahs live alongside other felids like lions and leopards. Cheetah is an intermediate size cat. Male tigers do migrate to Kuno from Ranthambore off and on, but they haven't bred due to the absence of tigresses. So, conflict with tigers is not a major concern. We will have to see how cheetahs cope with leopards, he said.

He also pointed out cheetahs survived in wooded habitats in Africa also and therefore, forest of Kuno should not be a major concern. I agree it is not the best habitat for cheetah. I think the ministry should start exploring other larger, more open habitats in Gujarat and Rajasthan and prepare them for cheetah introduction in 10 years he said.

More than 117 years after the project to rehabilitate lions from Africa failed, the government has readied an enclosure for cheetahs in the dry deciduous forest landscape of Kuno Palpur. In 1905, 10 lions were brought from Africa and of them, seven reached, who were killed by local villagers. Kuno had lost all its lions till 1872 and cheetahs by early 1920s. Getting back cheetah is a milestone in Indias wildlife management history that started in 1973 with declaration of first tiger reserve. The Cheetah project is an experiment worth pursuing to improve forest and wildlife management. Whether it succeeds or fails, the future will tell.

The views expressed are personal

Chetan Chauhan heads regional editions as Deputy National Affairs Editor. A journalist for over 20 years, he has written extensively on social sector with special focus on environment and political economy. ...view detail

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Ecostani | Despite concerns, the Cheetah project is worth pursuing - Hindustan Times

IntroductionThis essay explores why people should not be held fully morally responsible for their choices. It first draws from theories developed by scholars in psychology and sociology, then refers to case studies in criminality to explore these ideas. The first part explores the 'just world' fallacy, which explains that people wish to believe the world is just, thus most have a desire for others to be held responsible for their choices. Whilst that may be the case, people's choices are undoubtedly influenced by their environmental and genetic conditions. This suggests that social circumstances and innate factors are the main influencers on our behaviour, which means that people are not fully responsible for their choices. The second and third sections use academic research and case studies in criminogenic literature to explore the extent to which social environment and innate factors influence people's choices and lead some individuals or groups to criminality. Finally, in conjunction with Jung's complex theory, I conclude that poor social conditions and congenital deficiencies can make people more susceptible to mental illness and be more prone to irrational, criminal acts, especially when violence is concerned. This leads me to argue that prisons should rehabilitate criminals rather than punish them. As criminals cant possibly take full moral responsibility for their choices, empathy rather than retribution should be societys focus.Main bodyMelvin J Lerner developed the just world fallacy in the 1960s. This theory puts forth the case that people often think the world is fair only to understand or cope with various injustices.[1]It thus explains why people are keen to attribute the mistakes of others or to their own personal behaviour for a misfortune, as opposed to pointing to the circumstances and other factors beyond their control.[2] Conversely, if one has a positive or beneficial outcome, they often attribute its cause to their own efforts. The key thesis of this concept is that humans need a sense of just deserts in order to make sense of reality. In one study, for instance, Melvin J Lerner asked a group of students to observe a girl receive electric shocks as a punishment for making a mistake on a faux mission.[3] Following the observation, the students disparaged the victim and behaved as if she deserved the harsh punishment she received. At the same time, however, they also recognised that they felt powerless to help the girl. This observation demonstrates that a punishment, especially one carried out by an authority figure, can play in to the just world fallacy and suspend critical thought. The Just World fallacy may also compliment Jung's view that human begins are in state of moral conflict. This is due to our innate awareness that we are imperfect, a realisation that triggers a type of trauma-complex."[4] This forces people to behave irrationally in ways that are not otherwise acceptable to the self, as the confrontation between their ego and this complex disturbs them.[5] Jung, however, believed that everyone was more or less prone to multiple personalities as everyone had complexes.[6] This means that with the right amount of psychological help and understanding of people's 'attitudes' (introversion and extroversion), people are largely able to maintain a healthy state of mind and are less likely to behave in extreme ways. As such, Jung can grant us insights about the issue of moral responsibility as he views our consciousness as far from a singular entity with one narrative. He is, therefore, still of great influence in how we can understand the complexities of personality.Modern psychology, however, now demands more scientifically rigorous studies that explore the complexities of consciousness. Firstly, genes may play a role in determining human behaviour. This is because genes can not only determine ones sex or biological structure of the human body in general, but may also may influence ones psychological characteristics.[7] According to Laura A. Baker, the genes of ones parents can influence an individuals behaviour (including the way they raise their children), and children's genes influence their behaviour in return (including the way they react to their parents).[8] For example, in one controversial study, working-class families and their descendants are more likely to possess genes that predispose individuals to aggressive behaviour. This is because, the study argues, their ancestors were more likely to drink or used drugs which can cause genetic defects. These defected genes then pass on to their offspring, depriving them of what could have been their expected learning abilities and physiological systems. This is called epigenetics, which means people's diseases, behaviours, and other health indicators are inherited from family members a generation or even several generations prior.[9]Notwithstanding, although genes are essential to understanding ones predisposition to certain behaviours, factors such as the political environment and ones socialisation directly also influence thoughts and behaviour. As mile Durkheim famously argued, individuals or social groups who do not follow what is deemed the acceptable rules of the society are deviants.[10] Whilst Durkheim viewed deviants as necessary elements of the social structure, most people arguably suppress their true thoughts and actions in order to conform to the moral maxims that are generally expected of them. This is the case even if it results in them not achieving their personal goals. Jung, once again, is useful to draw from here, as he uses the term "persona" to describe the phenomenon where people choose to hide their true selves in order to form functional relations with society.[11] For example, in Solomon Aschs conformity experiments, fifty students were asked to take a "visual test" in a room alongside several other observers. They did not know, however, whether the other participants were also students. Within this experiment, non-student observers gave wrong answers to 12 of 18 questions. They did this to see if the students would change their answers to match the rest of the group. What the study found was that although the students gave a correct answer at first, they then they gave the wrong answer based on the observer's answer.[12] This demonstrates the powerful effects of peer pressure and socialization on ones actions.According to another study conducted by Paul Willis showed that students from working-class families have a negative attitude towards education.[13] They may, for instance, disrupt class or not follow school rules. Willis argues that the reason why working-class people are more likely to engage in deviant behaviour than the other people from other classes is because of social inequality.[14] As working-class family do not have the financial means to provide quality education for their children as middle-class and upper-class families do, working-class families may expect their children to find work earlier in life to support their families. However, as they are less qualified, they often have to work in factories or manufacturing industries as labourers for very little pay. Conversely, children of other classes have the opportunity to study in higher education, and thus use their knowledge and experience to attain well-paid jobs. Yet when working class children communicate with middle class children during their school years, they realize that they can't get the same treatment and experience as other classes. This, in turn, leads to violence to vent their frustrations. Albert Cohen therefore argued that when students don't get the status they aspire to, they tend to form a criminal subculture.[15] This could explain why working-class children are more likely to commit crimes.Accordingly, if someone commits a moral error such as a crime, its only logical to offer them rehabilitation than handing out punitive punishments. Criminals are not entirely in control of their actions, as they may be influenced by family upbringing or congenital factors that manifest as psychological problems. According to psychologist Thomas Fagan, many prison systems in recent years have finally realised that psychological care for mentally illness in prisons is of great importance.[16] This entails that prisons should be similar in their scope and ethos to mental hospitals, regardless of the difference in damage they may have done to society. In fact, it can be further deduced that all the mental deficiencies of criminals in prison may have even more serious symptoms than those admitted to mental health facilities. Hence, whilst criminals are punished by the law in prison, they undoubtedly also require psychological rehabilitation from doctors.One case study of interest is on conducted by James O. Beasley II on Offender Number Five, one of seven serial murder cases. Offender Number Five is a black male who grew up in a very unstable home and lived with his grandmother.[17]After his grandmother died, he turned to a life of crime and violence. He was arrested for a number of juvenile offenses, namely robbery, sexual assault, murder, and multiple thefts. Following his release from prison, he immediately resumed his murderous activities. His level of brutality was distinctive and shocking, as he robbed his victims of their mobility, sexually assaulted them, and finally beat them to death. One of his surviving victims eventually took him to court and he was sent back to prison.[18] In the interview, the criminal admitted that he had a strong sense of loneliness, yet he refused to communicate with others and chose to digest these feelings on his own.[19] As he got older, however, he found that he couldnt satisfy his sexual desire unless it was accompanied by violence against others.[20] Upon examination, he scored 33 on the psychopathic checklist, which is well above the diagnostic criteria for psychopathy.[21] This means he had little control over his actions and showed little remorse for his violent actions. Accordingly, Offender Number Five is a prime example of how poor socialization in childhood can induce psychopathy and breed criminality.ConclusionTo conclude, this essay has explored the extent to which social environment, genetic predisposition, and mental illness can influence people's choices. It first explored some Jungian psychology, which suggested that ones personality is more complex and multifaceted than it might seem on the surface. This led the essay to modern theories that a poor social environment may lead to epigenetic predispositions that induce psychological problems of inferiority and vulnerability. This chain reaction results in worsening psychological problems, which leads people to lose themselves and engage in extreme behaviour that they do not expect and cannot control. Hence, as there is plenty of evidence that people do not necessarily have control over their actions and choices, it is logically unsound to hold them not responsible for their moral decisions. Therefore, prisons should allocate more resources towards psychological rehabilitation, namely psychological counselling or drug treatment, which may compensate for the psychological defects of the primary socialisation stage and allow them to recover quickly and return to society. Finally, further research into this topic may seek to explore the other extreme of the spectrum. What leads sometimes to a life of joy and success? What factors are present in their upbringing? Perhaps even a comparative study between negative and positive examples may be helpful to illuminate the contrasts. Nevertheless, there is plenty more cases or examples than can be unearthed to grant insights to this question and prove my conclusion further.References

Abrams, D. (2019). Deviance - Sociological perspectives | Britannica. InEncyclopdia Britannica. britannica.com/topic/deviance/Sociological-perspectivesBaker, L. A. (2007). THE BIOLOGY OF RELATIONSHIPS: WHAT BEHAVIORAL GENETICS TELLS US ABOUT INTERACTIONS AMONG FAMILY MEMBERS.De Paul Law Review,56(3), 837846. ncbi.nlm.nih.gov/pmc/articles/PMC4685725/Beasley, J. O. (2004). Serial murder in America: case studies of seven offenders.Behavioral Sciences & the Law,22(3), 405. doi.org/10.1002/bsl.595Benson, E. (2003, July).Rehabilitate or punish?Www.apa.org; American Psychological Association. apa.org/monitor/julaug03/rehabCherry, K. (2019).How the Just-World Phenomenon Explains Victim-Blaming. Verywell Mind. verywellmind.com/what-is-the-just-world-phenomenon-2795304Cherry, K. (2020, April 3).The Asch Conformity Experiments. Verywell Mind; Verywellmind. verywellmind.com/the-asch-conformity-experiments-2794996Gadek, R. (2019).Rehabilitation Versus Punishment in the Adult Justice System. Criminaljusticeonlineblog.com. criminaljusticeonlineblog.com/11/rehabilitation-versus-punishment-in-the-adult-justice-system/Hadberg, A. V. (2006). The methodology of Paul Willis. A review of Learning to Labor: How Working Class Kids get Working Class Jobs.Athenea Digital. Revista de Pensamiento E Investigacin Social,1(9). doi.org/10.5565/rev/athenea.275Khan Academy. (2008).Genes, environment, and behavior. Khan Academy. khanacademy.org/test-prep/mcat/behavior/behavior-and-genetics/a/genes-environment-and-behaviorKreitzer, M. J. (2016).What Impact Does the Environment Have on Us?Taking Charge of Your Health & Wellbeing. takingcharge.csh.umn.edu/what-impact-does-environment-have-usLerner, M. J., & Simmons, C. H. (1966). Observers reaction to the innocent victim: Compassion or rejection?.Journal of Personality and Social Psychology,4(2), 203210. doi.org/10.1037/h0023562Lumen. (2018).Functionalism and Deviance | Introduction to Sociology. Courses.lumenlearning.com. courses.lumenlearning.com/wm-introductiontosociology/chapter/theoretical-perspectives-on-deviance/Mcleod, S. (2020, January 21).Stanford Prison Experiment. Simply Psychology; Simply Psychology. simplypsychology.org/zimbardo.htmlPaul, S., & Repository, S. (2020). The Criminal Behavior of Genes | Role of genes in criminal activity.Www.sciencerepository.org. doi.org/10.31487/sr.blog.14Santa Clara University. (2015).The Just World Theory. @SantaClaraUniv. scu.edu/ethics/ethics-resources/ethical-decision-making/the-just-world-theory/Stein, M. (2017a).Jungs Map of th Soul : an Introduction(K. Zhu, Trans.; p. 143). General distributor of Daiwa Books and Newspapers, Xin Bei Shi. (Original work published 1998)Stein, M. (2017b).Jungs Map of the Soul : an Introduction(K. Zhu, Trans.; p. 70). General distributor of Yamato Books and Newspapers, Xin Bei Shi. (Original work published 1998)Stein, M. (2017c).Jungs Map of the Soul : an Introduction(K. Zhu, Trans.; p. 60). General distributor of Daiwa Books and Newspapers, Xin Bei Shi. (Original work published 1998)Stein, M. (2017d).Jungs Map of the Soul : an Introduction(K. Zhu, Trans.; pp. 5659). General distributor of Daiwa Books and Newspapers, Xin Bei Shi. (Original work published 1998)Stein, M. (2017e).Jungs Map of the Soul : an Introduction(K. Zhu, Trans.; pp. 6667). General distributor of Daiwa Books and Newspapers, Xin Bei Shi. (Original work published 1998)Thompson, K. (2016, May 31).Subcultural Theories of Deviance. ReviseSociology. revisesociology.com/2016/05/31/subcultural-theories-crime-deviance/tutor2u. (2019, April).Classic Texts: Paul Willis Learning to Labour 1977. Tutor2u. tutor2u.net/sociology/reference/classic-texts-paul-willis-learning-to-labour-1977tutor2u. (2020, March 8).Classic Texts: Albert Cohen Delinquent Boys. Tutor2u. tutor2u.net/sociology/reference/classic-texts-albert-cohen-delinquent-boys-1955Weinhold, B. (2006). Epigenetics: The Science of Change.Environmental Health Perspectives,114(3). doi.org/10.1289/ehp.114-a160

[1] Cherry, K. (2019).How the Just-World Phenomenon Explains Victim-Blaming. Verywell Mind. verywellmind.com/what-is-the-just-world-phenomenon-2795304[2] Ibid[3] Lerner, M. J., & Simmons, C. H. (1966). Observers reaction to the innocent victim: Compassion or rejection?.Journal of Personality and Social Psychology,4(2), 203210. doi.org/10.1037/h0023562[4] Stein, M. (2017b).Jungs Map of the Soul: an Introduction(K. Zhu, Trans.; p. 70). General distributor of Yamato Books and Newspapers, Xin Bei Shi. (Original work published 1998)[5] Ibid, pp. 5659[6] Ibid, pp. 6667[7] Baker, L. A. (2007). THE BIOLOGY OF RELATIONSHIPS: WHAT BEHAVIORAL GENETICS TELLS US ABOUT INTERACTIONS AMONG FAMILY MEMBERS.De Paul Law Review,56(3), 837846. ncbi.nlm.nih.gov/pmc/articles/PMC4685725/[8] Ibid, pp. 837-846[9] Weinhold, B. (2006). Epigenetics: The Science of Change.Environmental Health Perspectives,114(3). doi.org/10.1289/ehp.114-a160[10] Lumen. (2018).Functionalism and Deviance | Introduction to Sociology. Courses.lumenlearning.com. courses.lumenlearning.com/wm-introductiontosociology/chapter/theoretical-perspectives-on-deviance/[11] Stein, M. (2017a).Jungs Map of the Soul: an Introduction(K. Zhu, Trans.; p. 143). General distributor of Daiwa Books and Newspapers, Xin Bei Shi. (Original work published 1998)[12] Cherry, K. (2020, April 3).The Asch Conformity Experiments. Verywell Mind; Verywellmind. verywellmind.com/the-asch-conformity-experiments-2794996[13] tutor2u. (2019, April).Classic Texts: Paul Willis Learning to Labour 1977. Tutor2u. tutor2u.net/sociology/reference/classic-texts-paul-willis-learning-to-labour-1977[14] Ibid[15] tutor2u. (2020, March 8).Classic Texts: Albert Cohen Delinquent Boys. Tutor2u. tutor2u.net/sociology/reference/classic-texts-albert-cohen-delinquent-boys-1955[16] Benson, E. (2003, July).Rehabilitate or punish?Www.apa.org; American Psychological Association. apa.org/monitor/julaug03/rehab[17] Beasley, J. O. (2004). Serial murder in America: case studies of seven offenders.Behavioral Sciences & the Law,22(3), 405. doi.org/10.1002/bsl.595[18] Ibid, pp. 405[19] Ibid, pp. 405[20] Ibid, pp. 405[21] Ibid, pp. 405

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To what extent human beings are morally responsible for the actions they take as a result of their innate and acquired influences - Teen Ink

Do you have healthy hair? Do you suffer from hair fall? Are you trying to grow your hair fast?

Many people do not give a second thought to their hair growth. For them, the growth of their hair is not a matter of concern. But the people who experience hair fall, hair damage, or have extremely thin hair often brood about the growth of their hair and what they can do to attain it. They often wonder how long it will take to reach the desired length or how fast hair grows normally.

Heres everything to know about hair growth, the factors affecting the growth, and how fast hair really grows.

First things first! The growth of everyones hair is not the same. It will always vary due to various factors such as hormone levels, genes, age, etc. If you see your friends hair growing fast doesnt mean your hair will grow at the same frequency or vice versa.

That being said, studies have laid down an average rate of hair growth in humans. According to a scientific report, most peoples hair grows at the rate of half an inch per month. It further depends on how well you care for your hair. It means that if you treat your hair properly and care for it on time, your hair will grow six inches a year.

While some people may experience good growth in their hair, others may not.

If your hair is weaker and more brittle compared to previous years, there may be an imbalance or deficiency in your body, resulting in malnourished hair. The factors such as poor diet and lifestyle, thyroid imbalances, medications, and inflammation from stress often make your hair weak and slow down the process of hair growth. As a result, your hair tends to grow slower than ever.

The speed of your hair growth depends upon many factors ranging from genetic to environmental. We have listed down some of them.

According to a study, your ethnicity defines the growth of your hair to a great extent. For instance, Asian hair grows the fastest at about 411 micrometers a day. This steady growth rate in their hair results in 0.48 inches growth per month.

African hair has a slower growth rate than Asian, around 280 micrometers a day or 0.32 inches a month. The growth for Caucasian hair is somewhere around 367 micrometers a day or 0.42 inches a month.

The growth of your hair is also characterized by your gender. Many studies have determined that male hair grows faster than female hair. It moves through the hair cycle quicker, thus, not getting as long as female hair before shedding and starting over again.

The growth rate in male hair is faster than in females. Compared to the opposite gender, male hair grows 0.5 inches per month, while female hair grows 0.4 inches per month. It is why men need more frequent haircuts and trimming than women.

Your age is one of the primary factors affecting your hair growth rate. The growth of your mane is partially regulated by the hormones, of which your body adjusts production over time. It is found that your hair growth is at the peak between 15 to 30 years of age.

After your thirties, the follicles of your hair stop growing new hairs in their entirety. It means that some hair strands already been shed through the natural hair cycle will not grow back on your scalp. Now you know what causes thinning of hair!

Age-related hair loss is again influenced by genetic and environmental factors. Thus, some people may not experience a noticeable reduction in their hair growth as they age.

One of the essential factors that influence your hair growth is your diet. As your hair is composed of protein, it needs to get enough protein and other forms of nutrition such as amino acids, iron, zinc, niacin, fatty acids, etc. for proper growth. If you are not getting the desired amounts of nutrients, minerals, and vitamins in your diet, the growth of your hair may suffer at large.

People who reduce their calorie count all at once are at a higher risk of thinning their hair.

Your genetics are equally responsible for influencing the growth rate of your hair. Every individuals hair enters a growth or anagen phase. The phase is where the follicles produce new hair cells actively, resulting in longer strands. Your genetics may cause you to have a short anagen phase lasting only 2-3 years, while it could last as long as 6-7 years for others.

The longer your hair is in the anagen phase, the more opportunities it gets to grow before shedding and being replaced by new hair. If you suffer from any genetic disorder, it may affect your hair growth, on the whole, resulting in the conditions such as premature shedding and shorter growth phases.

If you are bothersome about the slow growth of your hair, fret not. Increasing the rate at which your hair grows is possible when you take all the factors affecting your hair growth into consideration. While you cannot alter some factors such as genetics, ethnicity, age, and gender, there are a couple of things that you can do to accelerate your hair growth.

Here are some tips to encourage faster hair growth.

As stated, nutrition plays an integral role in managing your hair. Your hair has a few nutrient requirements that need to be met if you expect hair growth at a proper rate. According to scientists, the below-listed nutrients help you grow hair and prevent hair loss.

Make it a point to consume healthy meals including all the above-listed nutrients to grow your hair and improve your overall health. You can include the food items such as eggs, fish, dairy products, green vegetables, and fruits into your diet. Adding nuts such as almonds and walnuts also helps you grow your hair and improve its quality.

Never take hair supplements without consulting your doctor or nutritionist. Consume proteins in higher amounts to keep hair fall at bay.

A few studies have laid down that regular head massages may help hair grow thicker. More research is required to prove this claim, but massaging your hair regularly may help you in many ways.

Hair massage is known to help ease stress, which is considered one of the biggest triggers of hair fall. Apart from this, massaging your hair always feels great. You can use hair oil and massage your hair weekly. You can also buy a scalp massaging tool from the market. You will feel relaxed immediately.

Sleeping on a silk or satin pillow for hair growth is trending all over social media platforms. While some people do not take it seriously, there are benefits of using this fabric to sleep.

Crisp cotton lines may feel comfortable and good against your skin, but they may not be the best choice if you have fragile hair. Some people wear a satin bonnet to bed or sleep on satin pillowcases. Although this hack doesnt make your hair grow faster, it reduces hair friction, frizz, and breakage.

Do you skip conditioning every time you wash your hair?

If yes, its about time you take this step seriously. Using conditioner every time after shampooing your hair strengthens it. A conditioner also helps your hair behave and look better. A good-quality conditioner protects your hair from harmful UV sun rays. If you have fine hair, applying a conditioner on the bottom of your hair helps avoid weighing it down. A conditioner also helps to nourish fragile hair.

Many studies claim that severe stress is one of the triggers for hair fall. It sends your hair into a resting phase, skipping the stage that coaxes your hair to grow. Stressing too much may also put you at a higher risk for a condition known as alopecia areata. Under this condition, your immune system starts affecting your hair follicles, thus leading to extreme hair loss.

Do not stress too much, and give yourself a break to save your hair from falling.

Bleaching your hair may make you look food and stylish, but do you know it may damage your hair?

Using chemical hair treatments that alter your hair permanently may weaken your hair. Consequently, your hair starts breaking before growing. Do not color your hair too often. Always choose a high-quality product claiming minimal damage to color your hair.

Heat styling may damage your hair in ways you cannot imagine. If you often get blow-outs or use a curling or straightening iron or even a hot comb on your hair, avoid doing it to save it from damage.

If you heat your hair regularly, put on a heat protectant first and use the coolest setting.

We hope that the above-listed article helps you learn everything about hair growth and how you can protect them from damage. Keep in touch for more.

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How Fast Does Hair Grow? Know These Easy-Peasy Tips to Grow your Tresses - TheTealMango

Sure, your heart has been warmed by the historic releases of four California condors into our region over the last couple months. But how much do you know about these birds individual personalities?

If you are just realizing that you are woefully unprepared to distinguish your new feathered friends from each other, never fear. The U.S. Fish and Wildlife Services Rebecca Fabbri files the following helpful Prey-go-neesh profiles so you may better grasp the temperaments of the specific majestic creatures soaring over your head:

For the first time in more than a century, endangered Prey-go-neesh (California condors) can now be seen flying over Northern Californias redwoods.

On May 3, 2022, the Yurok Tribe successfully released the first pair of condors, out of a group of four, in Redwood National and State Parks, establishing the northernmost condor release area to date, and reclaiming a significant part of their former historic range, from which theyve been absent since 1892.

This journey towards restoration began in 2003, when a panel of Yurok elders made the decision that Prey-go-neesh was the highest priority land-based animal to return to Yurok ancestral territory due to the Yuroks deep cultural connection to the birds, saidYurok Wildlife Department DirectorTiana Williams-Claussen.

The reintroduction effort builds on over a decades worth of planning and preparation initiated by the Yurok Tribe with support by the U.S. Fish and Wildlife Service, the National Park Service, State and other partners.

For countless generations, the Yurok people have upheld a sacred responsibility to maintain balance in the natural world, saidJoseph L. James, the Chairman of the Yurok Tribe, in the days leading up to release. Condor reintroduction is a real-life manifestation of our cultural commitment to restore and protect the planet for future generations.It is a historical moment in the Yurok Tribe, as we introduce our condors back home, providing that balance for us.Our prayers are answered.

The four condors, including one female and three males, are between two and four years old, an ideal age range where they would leave the care of their parents in the wild. Although it will take several years until these birds are at an age to reproduce in the wild, we believe we have a model for success with future northern reintroduction efforts. Learn a little more about each condor below.

# # #

Poy-we-son

Poy-we-son was the first California condor to take flight into wild. Photo courtesy of Matt Mais/Yurok Tribe

Hatched:Peregrine Funds World Center for Birds of Prey

Wing Tag: A3

Age: 2-year-old male

About me:First out the holding pen, we have Poy-we-son, which literallytranslates to, the one who goes ahead, but also harks back to the traditional name for a headman of a village, who helps lead and guide the village in a good way.

A3 is one of the more dominant birds, and I expect that hell be a leader amongst this flock and for new birds coming in, said Williams-Claussen.

True to his name, Poy-we-son was adventurous right from the start, boldly exploring the area surrounding the release facility for two weeks before returning to the release enclosures. His sojourn will have equipped him with valuable knowledge which he will share with his fellow cohort-members, as the small flock expands across the landscape.

Studbook number:1045

# # #

Nes-kwe-chokw perches outside of the flight pen. Photo courtesy of Patrick Myers/Yurok Tribe

Hatched:Oregon Zoo

Wing Tag: A2

Age: 2 1/2-year-old male

About me: Nes-kwe-chokw, which translates to He returns or He arrives, is a representative of the historic moment we just underwent, and condors return, free-flying, to the Yurok and surrounding landscape, said Williams-Claussen. He is a confident bird, often jockeying with A3 in play, but also to help establish his place in the hierarchy and with the will to do well in the wild.

Also proving true to his nickname, Nes-kwe-chokw initially has stuck more closely to home, the release enclosure, seemingly awaiting the release of the rest of his flock. Though growing increasingly comfortable ranging farther from the release facility, he has largely shown himself content to stay close to the facility, visiting with the birds remaining in captivity and agreeably taking advantage of food proffered by biologists to keep the far-ranging birds interested in the facility, which will be used for ongoing management.

Studbook number:1010

# # #

Ney-gem Ne-chweenkah takes in her new home. Photo courtesy of Patrick Myers/Yurok Tribe

Hatched:Oregon Zoo

Wing Tag: A0

Age: 3-year-old female

About me:Ney-gem Ne-chweenkah which translates to She carries our prayers is the only female of the first released cohort. She represents the creative life-force energy that females bring to the world, said Williams-Claussen. Its powerful. I envision her as the start of a whole new life and possibilities, both for our flock and for condors throughout their range. We also imbue this name with our prayers for her specifically, her cohort brothers and for all condors. She carries those, wherever she goes. We are incredibly grateful that Prey-go-neesh have come home to carry our beliefs, our energy, and our prayers when were asking for the world to be in balance, as a critical part of ecological community.

Though she struggled a bit with the mechanics of flying free in her first forays, as her first time to spread her wings in the wild, shell figure it out soon and has integrated well with both Poy-we-son (A3) and Nes-kwe-chokw (A2). All three are comfortably sharing resources and will continue to learn from and teach each other.

Studbook number:969

# # #

Hlow Hoo-let was the last to join the cohort with his friends, who together will take flight toward reestablishing a California condor population in the Pacific Northwest. Photo courtesy of the Yurok Tribe

Hatched:Peregrine Funds World Center for Birds of Prey

Wing Tag: A1

Age:3-year-old male

About me:A1 has been nicknamed Hlow Hoo-let which means At last I (or we) fly! In line with the heavier names this first cohort carries, said Williams-Claussen. I interpret that as reference to the joyous day that all four of our first cohort fly free together.

On a lighter note, its definitely also a reference to poor A1s extended wait to be let out, due to his faulty transmitter! We welcome Hlow Hoo-let to the skies of Yurok and surrounding lands, and look forward to his journey with us.

On July 14, 2022, he was the last to join the cohort with his friends, who togetherwill take flight toward reestablishing a California condor population in the Pacific Northwest.

Studbook number:973

# # #

Paaytoqin was chosen as a mentor bird because of his calm nature and good disposition. Photo courtesy of Matt Mais/Yurok Tribe

Hatched:Peregrine Funds World Center for Birds of Prey

Age:8-year-old male

About me:His name Paaytoqin (pie-toe-quin) means come back in Nez Perce language because he returned to World Center Birds of Prey, one of the recovery programs captive breeding facilities, after being at Oregon Zoo for three years, saidLeah Esquivelfrom the Peregrine Fund.

Hatched in 2014, he was selected to be held back for captivity based on genetics and is unreleasable.

We do not release captive adults that have never had any wild experience, saidSteve Kirkland, California condor field coordinator for the U.S. Fish and Wildlife Service. He could be paired with a mate in the future, if necessary; however, as for now, his role as a mentor will be an important influence on the younger birds.

Paaytoqin was chosen as a mentor bird because of his calm nature and good disposition.Prior to arriving to the Northern California Condor Reintroduction Program Facility, he proved to be a steady and centering influence onyoung birds, helping them become acclimated to their new regionand with their development ofcritical social behavior before their release.He regularly charges turkey vultures outside of the pen feeding, showing the condors stature in the feeding order.

He will eventually return to captivity to help contribute to the health and vitality of the overall flock as part of the captive breeding program after his stint in Northern California, said Williams-Claussen.

# # #

Poy-we-son and Nes-kwe-chokw spotted exploring their new home. Photo courtesy of the Northern California Condor Restoration Program|Image Details

Comprised of biologists and technicians from the Yurok Tribe and Redwood National Park, the Northern California Condor Restoration Program will collaboratively manage this flock from a newly constructed condor release and management facility in Northern California, near the Klamath River in Redwoods National and State Park.

The return of the condors to the skies over the Redwoods represents a significant milestone in the restoration of this magnificent forest to its former glory, remarked Redwood National and State Park SuperintendentSteve Mietz. This project is a model for listening to and following the lead of the parks original stewards, healing both our relationship with the land and its original people.

With the release of these birds, the Northern California Condor Restoration Program team officially joins the larger California Condor Recovery Program led by the U.S. Fish and Wildlife Service. The recovery efforts include three additional release sites in California, one in Arizona and one in Baja Mexico. Each release site is championed by a partner in condor recovery.

The reintroduction of condors into Northern California is truly a monumental moment, saidPaul Souza, Regional Director for U.S. Fish and Wildlife Services Pacific Southwest Region. This effort builds upon the programs collective knowledge and history of releasing condors and showcases the benefit of partnering with tribes and others to implement recovery of listed species. We are proud to support this collaborative and innovative partnership with the Yurok Tribe and Redwood National Park. Together we can recover listed species for future generations.

PREY-GO-NEESH KEECH KE-ME-YEHL CONDORS HAVE COME HOME.The Yurok Tribe

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BETTER KNOW A PREY-GO-NEESH: Up Close and Personal With Your New Condor Neighbors - Lost Coast Outpost

In early June, three 2-year-old lion cub siblings were permanently relocated from the Pittsburgh Zoo to the Alabama Gulf Coast Zoo.

Adjusting to a new home is a feat for anyone, including the three young predators, Chadwick, Regina and Daniel.

Staff members at the zoo in Gulf Shores, Ala., worked hard to prepare for the cubs arrival. They made sure to have a pool in the cats enclosure to help battle the Southern heat.

They were much fluffier when they first got here, Ashlyn Kenwright, one of the zookeepers who interact with the cubs daily, said in mid-July. They quickly shed a ton to try to cool off naturally.

The keepers use other methods to keep the lions cool, such as freezing blocks of blood and giving them to the cats to enjoy like a carnivorous Popsicle.

Its something that they would lie down to eat, said Joel Hamilton, Alabama Gulf Coast Zoo director. They hold the block with their front paws and the ice cools down their arms as their internal temperature lowers with the intake of the cool moisture.

Introductions between the cubs and their keepers were a slow process. They started by helping the cubs get used to the keepers scents. This entailed the keepers entering the feeding building while the cubs were in another room.

In the beginning, doors leading from the feeding room to inside the enclosure were left open so the cats could leave if they felt uncomfortable. That slowly transitioned to the keepers being able to feed the cats inside and clean their enclosure while the cubs ate.

This is the first time that weve taken care of cubs that werent born in our zoo, said Caitland Dallas, another zookeeper who helps care for the lions. This was a new experience for us and the cats. The secret to most cats is not through their hearts, but their stomachs. Once they realized that we usually show up with food, they decided to let us stick around.

The three cubs are closely bonded with each other, especially Chadwick, who calls for his siblings when he cant see them. This usually only happens during feeding time. Sometimes the cat lets his nerves get the best of him and he can only eat a few pounds of meat before he begins to miss his brother and sister.

Keepers have been giving him a smaller diet with the hopes that his hunger will make him fully enter the feeding building, and he can learn that there is a full meal waiting for him there.

The Pittsburgh Zoo described Chad as a little insecure, said Kenwright. Were hoping that he gets more confident in his own skin. Their whole world just got changed, so he just needs a bit more time to get comfortable.

Chadwick was certainly at his brightest on a recent morning once his siblings came out from the feeding building. He bumped heads with Daniel encouraging his brother to play, and followed Regina as she investigated the milk bottle that Dallas gives them as a treat.

Dairy in large amounts can upset a cats stomach, she said. But a small amount like this is a good treat that they enjoy and it helps them cool off.

After the cubs had their fill of the spray-bottle milk, they cuddled in a pile for a nap.

The heat never stops them from sleeping on top of each other, said Kenwright. They could sleep a few feet apart and be much cooler, but they just want to be as close as possible.

The Alabama Gulf Coast Zoo looks to become a bigger part in breeding programs for lions in the Zoological Association of America. Director Hamilton took in the cubs hoping to find a cage mate for the zoos other female lion, Nandi.

African lions were officially put on the vulnerable species list in 2020. In response, ZAA has communicated with zoos around the country to help increase healthy breeding.

For lions to be bred, their family trees need to be mapped to avoid any inbreeding. Each zoo that would like to participate in the program must have their lions genetics mapped.

The whole point is to have a science- based breeding program, where animals are sent or received is all based on genetics, Hamilton said. Looking at who should be paired with who to keep genetic vigor going for several generations is all based on their family trees.

Once the cubs get a bit more settled, the zoo staff will begin the introduction process between Nandi and the male cubs. If she takes a liking to one, their breeding will help bolster the lion population.

Hamilton hopes there will be a successful mating and an opportunity to send the possible cubs to a zoo with eligible mates. With the widespread work of zoos across America, the African lion population will have a chance to increase so that the species is no longer considered vulnerable.

Hayley Daugherty is a contributing writer.

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From the 'Burgh to the Gulf: Lions relocated in zoo breeding program - TribLIVE

Introduction

More than 47% of less than five-year-old deaths globally occur in the neonatal period, resulting in 2.4 million deaths yearly.1 Most of these deaths usually occur in low-income countries, and almost one million deaths are attributed to infectious causes, including neonatal sepsis, meningitis, and pneumonia.1,2 On the other hand, the survivors of neonatal sepsis are vulnerable to short- and long-term neurodevelopmental morbidity.3

Pathophysiology of neonatal sepsis relies on the innate immunity of neonates as their adaptive immune response is not fully developed. A more rigorous evaluation of the possible association between genetic signatures and neonatal sepsis is critical. The related neonatal innate and adaptive immune responses showed impairment of some aspects of innate immunity to bacterial infection, particularly in low-birth-weight infants.46

The recently recognized family of non-coding RNAs, long non-coding RNAs (lncRNAs; >200 nucleotides), has been implicated in several biological processes, including innate immunity.7 The lncRNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) upregulation has demonstrated an independent predictive value as a biomarker for diagnosis, severity, and poor prognosis in adults with sepsis.8,9 Also, the antisense non-coding RNA in the INK4 locus (ANRIL) was implicated in regulating inflammation in rats with uric acid nephropathy,10 and the pro-inflammatory genes, including IL6 and IL8, in human endothelial cells under the control of the nuclear factor-B.11 Gui et al have identified its clinical utility as a biomarker of severity, inflammation, and prognosis in adult sepsis patients.12 Lastly, the lncRNA HOX Transcript Antisense RNA (HOTAIR) was observed to promote sepsis progression by regulating interleukin-6 receptor expression via microRNA-211 in a septic rat model.13 Additionally, it was reported to play a vital role in sepsis-induced acute kidney injury via regulating apoptosis.14,15

Although dysregulated expression of the lncRNAs mentioned above was associated with sepsis etiopathology in adults, no studies have explored their potential clinical utility as diagnostic and/or prognostic biomarkers in neonatal sepsis.16 To this end, the authors were inspired to explore the potential clinical utility of the lncRNAs MALAT1, ANRIL, and HOTAIR in a sample of neonatal sepsis to confirm their rules in this devastating disorder. The results of this work could help in risk stratification for this vulnerable group of population and provide preliminary data for future molecular targeted therapy.

A total of 124 neonates with sepsis (93 early-onset and 31 late-onset sepsis) and 17 healthy controls were enrolled in the current study after taking informed consent from all their parents or legal guardians. Cohorts were recruited from Suez Canal University Hospital, Egypt, between December 2018 and November 2019. Age enrollment starts from the day of life (DOL) 1 at delivery till DOL 7 of suspected neonates with any manifestations that enable physicians to diagnose neonatal sepsis. Neonates 28 weeks gestational age confirmed by New Ballard Score,17 of both sex diagnosed with sepsis (defined as bacteremia presented clinically with dysregulation of response to infection in the first four weeks of life),18 or suspected neonatal sepsis (defined as neonates who are delivered to a mother with risk factors for sepsis, including premature rupture of membrane (PROM) >18 hours, urinary tract infection, genital infections, fever, leukocytosis or chorioamnionitis),19 were enrolled. In addition, neonates presented with clinical indicators (ie, observations and events in the baby) of possible/suspected neonatal sepsis/infection, including red flag clinical indicators and other National Institute for Health and Care Excellence (NICE) guidelines-related clinical indicators, were recruited.20 Exclusion criteria included newborns with gestational age <28 weeks, gross congenital malformation/genetic syndromes, history of perinatal hypoxia, hypoxic-ischemic encephalopathy, maternal drug abuse, or maternal viral hepatitis. The study was executed following the Declaration of Helsinki guidelines and approved by the Ethics Committee of the Faculty of Medicine, Suez Canal University (approval no. 4463).

Early clinical diagnosis of neonatal sepsis is still highly suspected due to the lack of specific signs and symptoms as they are shared with various other neonatal diseases. Blood culture is the gold standard of lab diagnosis but has certain limitations, which delay early identification. Routinely, 713% of neonates are treated empirically for suspected sepsis because of these diagnostic limitations. In this sense, we included all neonates with sepsis, either diagnosed with +ve blood cultures or ve results.6,21

Prenatal maternal history was examined for maternal risk factors such as premature rupture of membrane, maternal diabetes, anemia, hypertension, pre-eclampsia, urinary tract infection, or triple I (intrauterine inflammation, infection, or both). Detailed obstetric history on the mode of delivery, weight at birth, antepartum hemorrhage, maternal antibiotics, or intrapartum fever were obtained. Putative neonatal risk factors were evaluated as preterm, intrauterine growth retardation, receiving total parental nutrition, mechanical ventilation, umbilical venous catheterization and other invasive procedures such as a urinary catheter, chest tubes, or long lines. Symptoms in neonatal sepsis are unspecific, as many non-infected neonates display similar symptoms. There is no single-point assessment of clinical signs to diagnose sepsis; hence, our clinical examination included the following: (1) gestational age assessment, weight, and sex of the full-term neonates, (2) general and systemic examination, including (a) the respiratory system: tachypnea, apnea, increased ventilator support, and oxygen desaturation, (b) the cardiovascular system: bradycardia, pallor, hypotension, persistent pulmonary hypertension (PPHN) and decreased perfusion, (c) metabolic changes: hypothermia, hyperthermia, glucose instability, metabolic acidosis, (d) gastrointestinal system: poor feeding, vomiting, diarrhea, jaundice, feeding intolerance, abdominal distension, and ileus (e) neurologic changes: lethargy, hypotonia, decreased activity, and seizures, (f) hematological: disseminated intravascular coagulopathy, purpura, petechiae, and bleeding.

Qualified nurses collected 5 milliliters of blood on several occasions (ie, not at one time) from a peripheral vein under an aseptic condition from the enrolled neonates upon admission for routine hematological, chemistry, immunological assessment, blood culture, and genetic analysis. Tubes for genetic analysis (1 mL on EDTA tubes) were transferred immediately to the genetic lab within 20 min to be centrifuged with separation of the buffy coat in sterile Eppendorf for the subsequent genetic analysis. Post-treatment samples were withdrawn three days after starting antibiotics (as post-treatment samples) for 43 neonates (only the available samples for comparison).

As blood culture is the gold standard to define neonatal sepsis, a blood culture sample (0.51 mL) taken from a normally sterile site under aseptic measures was taken in pediatric oxoid blood culture bottles and sent to the microbiology lab for cultivation. Blood culture time to positivity (TTP) or turn-around time technique was used. The blood cultures were incubated aerobically at 37C and observed daily for the first three days to identify any visible microbial growth (turbidity). A preliminary report of findings is available within 48 hours. However, even in the absence of turbidity, the blood was subcultured up to the seventh day, and the report depends on the growth result rather than the observation of the bottles. The final report is released after 57 days accordingly.

Extraction of total RNA from the buffy coat separated from the whole blood was carried out using PureLink RNA Mini Kit (Qiagen, Catalog no. 217184) according to the manufacturers instructions. RNA concentration and purity were assessed via NanoDrop ND-1000 spectrophotometer (NanoDrop Tech., Inc. Wilmington, DE, USA). Samples with a 260/280 nm absorbance ratio <1.8 were excluded. RNA was converted to complementary/copy DNA (cDNA) using the high-capacity cDNA Reverse Transcription (RT) Kit (Applied Biosystems, USA), as described in our previous work.22 The RT reactions were carried out in a Mastercycler Gradient Thermocycler (Eppendorf, Hamburg, Germany) at 25C for 10 min, 37C for 120 min, and 85C for 5 min, then held at 4C. No template and no enzyme samples as negative controls were included in each run. Gene expression of MALAT1, ANRIL, and HOTAIR compared to GAPDH was performed using quantitative real-time polymerase chain reaction (qPCR) following the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines.23 The PCR reactions were carried out in duplicate with a final volume of 20 L, including 1 L TaqMan assays (Hs00273907_s1, Hs03300540_m1, Hs05502358_s1, and Hs02786624_g1) that include the pre-designed primer and probe set (Thermo Fisher Scientific) for MALAT1, ANRIL, HOTAIR, and GAPDH, respectively, diluted in RNAse-free water, 1.33 L RT product, and 2 TaqMan Universal PCR Master Mix (Applied Biosystems, Waltham, MA, USA) following the previously described protocols.24 The fold change of the studied lncRNA expressions in each case with sepsis relative to the healthy controls was calculated via the Livak and Schmittgen method based on the quantitative cycle (Cq) value (2Cq); where Cq = (Cq lncRNA Cq GAPDH) sepsis cases (Cq lncRNA Cq GAPDH) healthy neonates.25

Statistical Package for the Social Sciences (SPSS) for Windows software (version 27.0; IBM SPSS Statistics, USA) and GraphPad Prism 9.1.2 software were used for data analysis. Data were presented as the median and interquartile range or frequency and percentage. Chi-square (2), Fishers exact, and MannWhitney U (MW) tests were used. Spearman correlation analysis was carried out to assess lncRNAs co-expression. Cox proportional regression analysis was performed to identify independent predictor risk factors for mortality. Hazard ratio (HR) and 95% confidence interval (CI) were reported. Statistical significance was set at a p-value<0.05. Heatmap, hierarchical clustering, box plots, and correlation matrix were generated using reshape2, scales, RColorBrewer, gplots, psych, factoextra, FactoMineR, and ggpubr R package.

The current study included 124 neonates with sepsis (93 early-onset and 31 late-onset sepsis). Two-thirds of them (65.3%) were males, and in-hospital mortality was reported in 29%. Table 1 demonstrates a comparison between 88 survivors of neonates with sepsis and 36 non-survivors. The non-survivors were more likely to be delivered by cesarean section (66.7% vs 46.6%, p=0.049), preterm (63.9% vs 34.1, p=0.002), with inserted umbilical venous catheter (44.4% vs 9.1%, p<0.001). Higher prevalence of deceased neonates presented with hypoxia (86.1% vs 65.9%, p=0.027) and respiratory distress syndrome (55.6% vs 30.7%, p=0.014). Mothers were more likely to have premature rupture of membranes (52.8% vs 28.4%, p=0.010), pre-eclampsia (13.9% vs 0%, p<0.001), and received amoxicillin (27.8% vs 8.0%, p=0.003). Higher frequency of non-survivors neonates required ventilation (63.9% vs 29.5%, p<0.001) and surfactant therapy (33.3% vs 10.2%, p=0.001). Non-survivors neonates were more likely to develop complications (75% vs 13.6%, p<0.001), such as pulmonary hemorrhage (16.7% vs 0%, p<0.001), air leak syndrome and pneumothorax (19.4% vs 3.4%, p=0.002), respiratory failure (22.2% vs 1.1%, p<0.001), necrotizing enterocolitis (11.1% vs 0%, p=0.002), and multiple organ failure (22.2% vs 0%, p<0.001).

Table 1 Characteristics of Sepsis Patients According to Survival

Compared to normal neonates, the three tested lncRNAs expression signatures were upregulated in the circulation of neonates presented with sepsis. Their median levels were as follows: median = 1.71, IQR: 0.5 to 3.27 for MALAT1, median = 1.09, IQR: 0.89 to 1.30 for ANRIL, and median = 1.83, IQR: 1.44 to 2.41 for HOTAIR (Figure 1A). Co-expression analysis showed a direct correlation between the three lncRNAs ranged from weak (r = 0.37) to moderate (r = 0.42 and 0.61) correlations (all p-values <0.001) (Figure 1B). Hierarchical cluster analysis classified patients into two clusters: the first cluster was characterized by high expression of all lncRNAs, and almost all patients died, while the second cluster, including those who survived, exhibited downregulation of at least one of the markers (Figure 1C). On comparison of gene expression levels of the studied lncRNAs pre- and post (three days)-treatment after initiating the antibiotic therapy, there was no observed significant change in their expression signature (Figure S1).

Figure 1 The expression level of long non-coding RNAs in plasma of neonatal sepsis compared to normal neonates. (A) Box plot for fold change (log-transformed). All the three studied lncRNAs were upregulated in neonates with sepsis relative to controls. Mann-Whitney U-test was used. Cases are plotted compared to controls (set at zero line). All p-values were <0.001. (B) LncRNAs co-expression analysis. A direct correlation between the three studied lncRNAs was identified. The correlation coefficient (r) text color aligns with the degree of correlation. Spearman correlation analysis was employed. All p-values were <0.001. (C) Heatmap showing expression pattern in patients. Ward.D2 method and Euclidean distance measure were utilized. Hierarchical cluster analysis categorized cases into two distinct clusters: high expressors of all lncRNAs and those who exhibited downregulation of at least one of the studied lncRNAs.

The transcriptomic pattern of MALAT1 (p=0.93), ANRIL (p=0.69), and HOTAIR (p=0.98) did not show a significant difference between early-onset and late-onset sepsis groups. However, overall and stratification by sex revealed significantly higher levels of the three lncRNAs in deceased neonates compared to the survivor group (all p-values <0.001) (Figure 2AC). Analysis of the association of the three studied lncRNAs with other comorbidities in the study groups is presented in Table S1. Running a principal component analysis showed a clear demarcation between the two groups of cohorts in males and females (Figure 3A).

Figure 2 Association of long non-coding RNA expression with survival and gestational age in neonates with sepsis. (AC) Boxplots comparing non-survivors and survivors groups. Higher levels of the three lncRNAs in non-survivor neonates compared to the survivor group were observed. (D) The association between gestational age in neonates with sepsis and survival. Fold change was estimated using the formula of delta Cq = (Cq lncRNA Cq GAPDH) sepsis cases (Cq lncRNA Cq GAPDH) healthy neonates. The median and interquartile range are shown to the left of the corresponding boxplots. Mann-Whitney U-test was applied.

Figure 3 Multivariate analysis for predicting mortality. (A) Principal component analysis for data exploration showing clear demarcation between survivor and deceased infants based on the three lncRNAs. The expression levels of the three lncRNAs, demonstrated by the direction of their corresponding arrows, were pointing towards the cluster of the Died group. In contrast, the gestational age (GA) arrow pointed towards the Alive group, indicating that the higher the GA, the better survival. The length of the arrows indicates the weight of the variables. All points (round and triangle) represent each study subject and are of equal size. A large circle and triangle represent the centroid of the cluster. (B) Cox hazard proportional regression analysis was performed. Data are represented as hazard ratio (HR) and 95% Confidence intervals (CI). Non-survivor neonates were significantly more likely to be males and have upregulated circulating ANRIL and HOTAIR levels. Significant data with p-values less than 0.05 are red.

Abbreviations: LBWB, low birth-weight baby; ARDS, acute respiratory distress syndrome; PROM, Premature rupture of membrane.

As depicted in Figure 3B, Cox regression analysis revealed that non-survivor neonates were more likely to be male (HR = 6.43, 95% CI = 1.3115.7, p = 0.022) and presented with early-onset sepsis (HR = 4.18, 95% CI = 1.0511.6, p = 0.043). Cohorts with upregulated ANRIL (HR = 4.21, 95% CI = 1.1510.4, p=0.030) and HOTAIR (HR = 2.49, 95% CI = 1.026.05, p = 0.044) were at higher risk of mortality. On the contrary, higher gestational age, more than 33.5 weeks, were less likely to die (HR = 0.79, 95% CI = 0.640.96, p=0.020), and those who received surfactant therapy conferred protection (HR = 0.21, 95% CI = 0.060.76, p=0.017).

Neonatal sepsis contributes to global neonatal morbidity and mortality worldwide, with a higher burden, in particular, in low- and middle-income countries.26 The current study included 124 neonates with sepsis, two-thirds of them were males, and the non-survivor neonates were more likely to be male, as revealed by Cox regression analysis. This male predominance aligns with previous studies that revealed that females have a less exaggerated immune reaction to pathogens than males due to hormonal and genetic/epigenetic modifiers contributing to the observed immunological and survival rate differences.27,28 Also, Cox regression analysis revealed that non-survivor neonates were more likely to be presented with early-onset sepsis. This finding is congruent with recent Fleischmann et als meta-nalysis conclusion that in the overall time frame, estimated incidence and mortality was higher in early-onset than late-onset neonatal sepsis cases based on 26 studies from fourteen countries.26

In comparison between 88 survivors of neonates with sepsis and 36 non-survivors, the non-survivors were more likely to be delivered by cesarean section, preterm, and have a history of an inserted umbilical venous catheter. Their mothers were more likely to have premature rupture of membranes, pre-eclampsia, and received amoxicillin. Also, non-survivor neonates were more likely to develop complications such as pulmonary hemorrhage, air leak syndrome and pneumothorax, respiratory failure, necrotizing enterocolitis, and multiple organ failure as expected.

On exploring the association of the tested inflammation-related lncRNAs expression signature with neonatal sepsis and outcome, our results demonstrated that the three lncRNAs, MALAT1, ANRIL, and HOTAIR, were markedly increased in the plasma of cases with neonatal sepsis compared to healthy neonates. On correlating the expression signatures of the studied lncRNAs to the clinical features and outcome of the neonatal cases, we found significantly higher levels of the three lncRNAs in deceased neonates than in the survivor group. Furthermore, the cohorts with upregulated ANRIL and HOTAIR were at higher risk of mortality, as revealed by Cox regression analysis.

Given the high blood stability and detection sensitivity of lncRNAs in plasma compared with several traditional protein biomarkers,29 circulating lncRNAs show promising roles as adjunct diagnostic/prognostic epigenetic biomarkers in several disorders, including inflammatory conditions.3032 In the last years, the circulatory MALAT1 expression profile was screened mainly in adults with sepsis. Pellegrina et al identified that deregulated MALAT1 expression might contribute to gene expression changes associated with the poorer outcome of elderly patients with sepsis.33 In the present study, the expression signature of this lncRNA is uncovered for the first time in neonatal sepsis. Our finding could be supported by the vital role MALAT1 plays in regulating the lipopolysaccharide-induced inflammatory response via its interaction with nuclear factor (NF)-kappa B.34 It was also implicated in regulating the hyperglycemia-induced inflammatory process.35 Recent findings by Liu et al, in addition, confirm the substantial value of MALAT1 as part of the MALAT1/miR-125 axis in discriminating adult sepsis cases from a healthy population and demonstrate a significant correlation with disease severity, organ injury, and inflammation level.36

Several in vivo and in vitro studies suggested that ANRIL might mediate the inflammatory and immune responses associated with various diseases, including sepsis.10,12,37,38 In line with our findings, recently, Gui et al found overexpression of ANRIL in plasma of non-survivor patients with sepsis than survivors, and the accumulating survival was worse in patients with ANRIL high expression. They proposed that this action could be mediated via enhancing multiple signaling pathways, such as increasing NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome by regulating the miR-122-5p/BRCC3 (BRCA1/BRCA2-Containing Complex Subunit 3) axis.12

The lncRNA HOTAIR was upregulated and associated with neonatal survival in the present cohort. This finding aligns with the previous experimental studies that revealed the implication of HOTAIR in sepsis progression and outcomes.14,15 Through acting as a microRNA-211 sponge with subsequent interleukin-6 receptor induction, HOTAIR has been found to promote inflammation response, inhibit monocyte proliferation and induce monocyte apoptosis in the mice model of sepsis.13 Furthermore, Shen et al showed that HOTAIR could promote cell apoptosis via the microRNA-22/high mobility group box 1 (HMGB1) pathway in vivo and in vitro.15

Although this study is the first, up to the authors knowledge, to explore the implication of the studied lncRNAs in neonatal sepsis, some limitations should be considered. First, the relatively limited sample size, in particular, the healthy control group; Second, the short follow-up duration of hospitalized neonates and absence of testing multiple samples to unravel the stability of the studied lncRNAs in the blood along the progression of the disease. Third, the exploratory nature of the present study lacks explaining the molecular mechanisms by which the studied lncRNAs increase the risk of sepsis or are associated with poor prognosis/survival. Fourth, the specificity of the studied lncRNAs for other neonatal pathological entities is questionable. In this sense, further future studies in large-scale cohorts with long outcome evaluations and molecular experiments are required to unravel the biological significance of these lncRNAs and their potential target genes in neonatal sepsis and the precise underlying molecular mechanisms. Furthermore, replication studies in other neonatal pathological entities, and including pathological controls with multiple sample testing during the disease progress, are recommended to validate the studied lncRNAs specificity in neonatal sepsis.

The present results show upregulation of circulatory lncRNA MALAT1, ANRIL, and HOTAIR in neonatal sepsis compared to healthy neonates. The lncRNAs ANRIL and HOTAIR may have potential prognostic utility as biomarkers for survival in neonatal sepsis.

All data generated or analyzed during this study are included in this submitted article.

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Faculty of Medicine, Suez Canal University (approval no. 4463). Informed consent was obtained from all included neonates parents or legal guardians before participating in the study.

The authors thank all the parents who agreed to let their infants join the study.

This research received no external funding.

The authors declare no conflicts of interest in relation to this work.

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Just three short weeks ago the bee parasite Varroa destructor was detected in Newcastle, NSW. Beekeepers and government bodies have sprung into action to establish eradication, surveillance, and notification zones for areas surrounding colonies with identified mites.

At the time of writing, more than 38 premises had been identified, bee hives in large areas of the state have been locked down, and hundreds of colonies comprised of millions of bees have been destroyed.

If poorly managed, the forthcoming spring and subsequent migratory pollination could turn this outbreak into varroa superspreader events that will devastate the nations honey bee population and the livelihoods of the people who depend on them.

What are these dreaded mites, why are they so feared and now that theyre here, possibly to stay, how can beekeepers deal with them?

Varroa destructor (and related species)are parasites of the eastern honey bee, Apis cerana. Their long-standing relationship means Apis cerana has evolved a number of defences against varroa, but during the 20th century, on at least two occasions, the Varroa destructor mite switched hosts to the economically important and more familiar western honey bee, Apis mellifera. Humanitys love of honey and dependence on the western honey bee for crop pollination means theyve spread to six continents. And following close behind are the varroa mites. Some territories, especially islands such as Hawaii and New Zealand, avoided the mite for some time, leaving Australia as the only country without varroa. Until now.

The impressive parasitising ability of varroa comes from the two main components to its life cycle reproduction and dispersal. The varroa sex life is pretty wild it features a lot of incest and a communal faecal pile but the important thing is that a single female mite, known as a foundress, can produce an impressive number of offspring. And over a few short generations that single mite can propagate into thousands.

Varroa mites feed on the fat stores of developing larvae and pupae of the honey bees. In doing so they rob the developing bee of energy stores, while also serving as a vector for damaging viruses such as deformed wing virus and acute bee paralysis virus.

Varroa mites feed on the fat stores of developing larvae and pupae of the honey bees. In doing so they rob the developing bee of energy stores, while also serving as a vector for damaging viruses

As Apis mellifera has not evolved defences to varroa, or the viruses they carry, the colony can be overwhelmed, both by the mites feeding and the viruses they carry, leading to sick bees and a collapse of the colonys population. Unfortunately, the death of the resident bees often spells trouble for other nearby colonies, as they come to rob the failing colony of the precious honey stores and pick up waiting varroa mites at the same time. This dispersal phase is just one way the mites can spread, as they can hitch a ride from colony to colony on the male drone bees, or through hopping from one foraging worker bee to another on flowers.

The experience of beekeepers in New Zealand gives an indication of what the introduction of varroa can do to the honey bee population. Losses of feral colonies were estimated at 90% in the first few years of the incursion, and 2021 figures compiled for the Ministry of Primary Industries showed annual managed colony losses at around 13%, with the losses directly attributed to varroa growing annually. And beekeepers have to do a lot of work to keep losses this low.

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The challenges posed by the mites has necessitated the development of a number of chemical treatments. Organophosphorus and organofluorine compounds such as coumaphos and fluvalinate were commonly used as miticides, and they were initially very successful treatments. These molecules are highly fat soluble, and over time they accumulate in the wax that forms the structural matrix of the colony. The low-level persistence of these treatments in the colony has provided the opportunity for the rapidly reproducing varroa mites to evolve resistance. The miticides are also retained in the processed wax, contaminating downstream products such as cosmetics, food-wraps, candles and more. The miticides can also be spread to untreated colonies, as beeswax is commonly recycled as foundation hexagonally patterned sheets that are used inside other hives as a template for honeycomb production. Another synthetic miticide called Amitraz remains in common use, but resistance is also on the rise.

Many beekeepers want to keep bees as naturally as possible, and a number of bio-related miticide treatments such as thymol (found in many herbs) and beta hop acids (from hops used in brewing beer) have been developed. These compounds are appealing as they have known botanical sources, and established breakdown pathways in the environment. Beekeepers are also treating for varroa using small organic acids found in nature. Formic acid most associated with ant bites is quite volatile and can kill varroa mites on developing brood. The volatility of formic acid means it must be used within strict temperature ranges, and it can have a negative impact on queen bees, frequently leading to their replacement by the colony. Oxalic acid commonly associated with rhubarb and other plants is a less volatile option that can be applied in a sugar solution, or through a specialised piece of equipment that sublimes the solid acid to a gas at temperatures above 157C. The mechanism of action for these organic acids is thought to involve pH changes inside of the mite, which is considered less likely to promote resistance.

These treatments add to the cost and effort of beekeeping, and are not without safety hazards. Organophosphates are well-known neurotoxins, while the volatile formic acid and sublimed oxalic acid are hazardous to the skin, eyes and lungs and require specialised respirators for their safe use. At the time of writing only two chemical treatments for varroa have been approved by the Australian Pesticides and Veterinary Medicines Authority amitraz and thymol. One would hope that the current emergency will expedite the approval of other treatments so they are (legally) available to beekeepers for the upcoming season.

While chemical treatments can offset the worst of varroa in managed colonies, they are not a long-term solution. The best outcome is for Apis melifera to evolve to deal with the mite and its associated viruses. The devastation experienced by feral colonies has provided an extreme selection pressure for these colonies to evolve resistance. Commercially and backyard managed colonies are not under the same evolutionary selective pressures, and are often bred for gentle behaviour and honey production. So, the unintended consequence of the interventional chemical treatments is the perpetuation of poor varroa-resistant honey bee genetics in the environment.

Three main behaviours have been observed in varroa-resistant colonies. The first is grooming, where adult bees physically damage or kill varroa, preventing a foundress mite infesting a new larval cell. Bees with this trait can even request to be groomed by another worker by performing a long vibrating dance. The second is hygienic behaviour, where bees can detect diseased or dead young in their cells, and the third is varroa sensitive hygienic behaviour, where the bees are able to distinguish brood infested with multiple female mites or those with high numbers of viruses and uncap their cell. Foundress mites only carry a limited number of sperm, so if the bees can break their reproductive cycle they can limit their proliferation.

Beekeepers who are actively breeding for varroa resistant traits have had mixed success. A study in Sweden found that only 7% of colonies of an isolated population survived without treatment, but with the potentially negative consequence of significant inbreeding. And attempts to breed varroa resistance in commercial colonies is made difficult by the mating habits of queen bees as they fly long distances and mate with multiple drones from uncontrolled or genetically undesirable colonies. The heritability of certain honey bee traits are strongly linked to the drone colony genetics, making it more difficult to select for desirable traits without controlling both the queen and the drone genetics.

The best outcome is for Apis melifera to evolve to deal with the mite and its associated viruses.

Commercial beekeeper and entomologist Randy Oliver has publicly shared his own experiences through his website and online presentations, and annually takes some 1,500 colonies through selection trials for mite resistance. His own success rate of less than 1% at the beginning of his trials in 2017 has steadily increased towards 20% through annual selective breeding. It should be noted that this selective breeding doesnt mean that poorly performing colonies are left to wither and die. The weak colonies can be combined with resistant colonies, or requeened with more favourable genetics, helping the beekeeper to maintain their stock and continue to seek a profit through honey production or pollination contracts.

Regardless of whether the current outbreak is contained, varroa mites are coming. Australian beekeepers need to be ready to rapidly adjust the ways they look after their hives. Fortunately, they have available the scientific tools of chemistry in the short term, and the evolutionary biology for the long-term survival of their bees.

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Varroa and the threat of bee decimation has now arrived. What have we learned from other nations' - Cosmos

Uveal melanoma (UM) is an intraocular malignancy with poor survival rates due to the propensity for metastatic spread. Although treatment options exist for localized disease, there are fewer definitive guidelines for metastatic UM. Treatment involves a personalized approach that entails patient-specific aspects, including tumor genetics. This case highlights the disease course of a 60-year-old male diagnosed with stage IIB right eye choroidal melanoma. Despite successful therapy for localized UM, he developed widespread metastasis. He received dual immunotherapy and was ultimately maintained on a single-agent regimen. His prognosis has surpassed initial prognosis and survival expectations. This case highlights the use of immunotherapy, both dual and single therapy, to treat this rare malignancy and extend overall survival.

Melanomas of the choroid, ciliary body, and the iris of the eye are collectively known as uveal melanomas (UMs). UM is the most common primary intraocular malignancy. It is commonly seen in middle-aged Caucasian males with a median diagnosis between 55 and 60 years of age [1]. The most common site for UM is the choroid [2]. The diagnosis is made by ophthalmologic slit-lamp biomicroscopy. For small tumors, anterior-segment optical coherence tomography (AS-COT) is useful in making the diagnosis by showing high-resolution imaging of the anterior and lateral segments. For large lesions, ultrasound biomicroscopy and AS-COT assist in the visualization of the extent of the tumor in the posterior segment. Fine-needle aspiration biopsy can be utilized to confirm the diagnosis of small lesions [2]. UM commonly presents as painless loss or distortion of vision. Some lesions are asymptomatic and incidentally identified during routine ophthalmic screening [1]. The initial workup involves imaging of the abdomen to look for metastatic lesions due to the approximately 90% propensity of hepatic spread metastases by UM. Because these tumors are F-fluorodeoxyglucose (FDG)-avid, positron emission tomography/computed tomography (PET/CT) is often performed [1]. Treatment is individualized and follows general guidelines and principles from oncologists based on the underlying tumor, which ranges from close serial observation, laser therapy, radiation therapy, to surgery (enucleation) for large tumors [1]. In the case of metastatic UM (MUM), there is an ongoing search to establish an ideal systemic therapy. There is no role of chemotherapy in MUM because it is highly resistant to systemic cytotoxic chemotherapy [1]. Due to the growth of UM in one of the most capillary-rich tissues of the body (choroid), it provokes hematogenous spread. The UM cell lines also strongly synthesize and secrete vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) [3]. Increased angiogenesis is noted in cancer, with the growth of blood vessels supplying the nutritional and metabolic demands of tumors [3]. Therefore, inhibiting VEGF targets angiogenesis and inhibits tumor growth. Currently, immunotherapy with immune checkpoint inhibitors (ICIs), such as ipilimumab, is a therapeutic option as it has shown promising results in treating cutaneous malignant melanoma [2]. When looking at theprogrammed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immune checkpoint, it was noted to be less upregulated in UM compared to cutaneous melanoma. Therefore, ICI therapy is less effective in MUM [4]. Single-agent therapy ICI has shown low response rates, as noted with a 0% overall response rate (ORR) in one phase 2 trial and a 3.6% ORR in another trial [5]. Here, we present the case of a 60-year-old male who was diagnosed with choroidal melanoma in May 2017, subsequently developing MUM and undergoing treatment with dual immunotherapy.

A 60-year-old Caucasian male presented to his primary care physician in January 2017 with the chief complaint of blurry vision in his right eye, sinus pressure, and dizziness for three weeks. On the physical examination, he had right hemianopsia. He was referred to ophthalmology and subsequently to ocular oncology for a definitive diagnosis. In May 2017, through fluorescein angiography and biopsy, the following diagnosis was confirmed: stage IIB cT3a cN0 cM0 right eye choroidal melanoma, measuring 16 mm in base by 7.3 mm in thickness via fundoscopic examination. Treatment ensued with plaque radiation therapy (RT), followed by bevacizumab, a VEGF inhibitor, every three to four months.Genetic analysis was performed, noting monosomy 3 and gain of 8q. To exclude metastatic disease, he underwent magnetic resonance imaging (MRI) of the abdomen which showed a small lesion at the dome of the liver, suggestive of hemangioma and less likely a metastatic focus. He continued to follow up with ocular oncology from 2017 to 2019 and showed good response to RT and bevacizumab. The tumor size regressed from 7.3 mm to 7.1 mm in thickness.

In January 2020, he endorsed lower back pain, radiating down his right extremity to his knee. An MRI of the lumbar spine identified a vertebral L3 lesion measuring 2.8 3.6 cm with extension into the anterior epidural space. The MRI also revealed additional foci of the T1 marrow signal throughout the lumbar spine and sacrum. A computed tomography (CT) of the chest/abdomen/pelvis (CAP) in May 2020 confirmed findings suggestive of widespread metastatic disease with lesions in the lungs, liver, and adrenal glands (Figure 1). Brain MRI showed no intracranial metastasis. Tissue examination of a CT-guided L3 lesion biopsy revealed malignant cells consistent with melanoma. This prompted palliative RT to the spine from June 6, 2020, to June 15, 2020. Further genetic analysis of the vertebral biopsied tissue identified a GNAQ 11 mutation.

In June 2020, he began dual ICI treatment with ipilimumab and nivolumab. Two months later, treatment was held during hospitalization due to suspicion of immune-mediated pneumonitis. CT CAP in August 2020 showed an interval decrease in the size of the hepatic lesions; more than 30 liver lesions measured less than 2 mm. His pulmonary nodules remained stable. He resumed treatment with ipilimumab and nivolumab.

In September 2020, he was hospitalized for non-severe Candida esophagitis, requiring a nasogastric tube and eventual G-tube placement. Immunotherapy was deferred for one month during hospitalization. Due to concern of increased toxicity from dual ICI, the patient resumed single-agent nivolumab in October 2020.

From October 2020 to January 2021, serial imaging continued to show a positive response to immunotherapy with complete regression of liver lesions and stable pulmonary nodules. However, in January 2021, CT CAP showed an increase in the size and number of pulmonary nodules within both lungs, concerning for progressive metastatic disease within the chest, whereas there was an interval improvement in metastatic disease within the patients liver. From January 2021 to July 2021, he continued to showimprovement and resolution of metastatic liver lesions, which remained stable (Figure 2).

The previously noted L3 vertebral tumor regressed. He currently continues immunotherapy with nivolumab. June 2022 marks his third year of ICI treatment. Furthermore, he has been referred to a national clinical trial seeking patients with comparable genetic mutations; he is pending evaluation for possible inclusion in the trial.

As opposed to the high incidence of cutaneous melanoma, UM is considered to be a rare disease with cases noted in 3-5% of the US population [6]. The initial presentation of this patient with a localized choroidal tumor is consistent with the typical UM disease course. Approximately 95% of patients present with uveal involvement, and more than 50% develop metastatic disease [7]. The most common site of metastasis is the liver [3]. Unfortunately, metastasis is associated with poor prognosis, with a five-year survival rate of less than 5% [3].

This patients initial tumor was consistent with stage IIB cT3a cN0 cM0 right eye choroidal melanoma. UM is typically staged based on tumor characteristics, with stages ranging from one to four [8]. CT CAP at the time of diagnosis was negative for metastatic disease. The choroidal tumor measured 16 mm in max diameter 7.3 mm thickness on fundoscopic examination. These measurements are within the National Comprehensive Cancer Network (NCCN) guideline threshold of 19 mm base diameter 2.5-10 mm thickness for options including plaque brachytherapy, particle beam radiation, and enucleation [8]. Intravitreal bevacizumab was administered every three months to prevent elevated levels of VEGFs. This was a prophylactic treatment due to the increase in VEGF with radiotherapy, potentiating radiation maculopathy [9]. Close follow-up ensued, and our patient showed slow regression over time. However, in January 2020, he was diagnosed with widespread metastatic disease.

The treatment options for metastatic melanoma are limited, and the literature does not support any specific agents with superior outcomes [8]. If metastatic disease is confined to the liver, liver-directed therapies can be considered, including regional isolation perfusion, embolization, ablation, resection, and RT [8]. Unfortunately, our patient had widespread metastases. One of the first reports of UM responding to immunotherapy was published by Kottsachade et al., where patients with metastatic disease were treated with pembrolizumab, a PD-L1 inhibitor. Half of the patients had rapidly progressive disease, while others had varying outcomes ranging from stable disease to complete response [10]. On the contrary, a study by Algazi et al. showed no durable remission in patients treated with single-agent PD-1 and PD-L1 antibodies [11]. Literature concerning PD-1 and PD-L1 inhibitors as treatment options is mixed. Other ICI therapies have been studied, including cytotoxic T-lymphocyte-associated antigen antibodies. The first large retrospective study demonstrated a durable response, with average overall survival (OS) of 9.6 months, in patients with MUM treated with ipilimumab [12]. Additionally, two phase 2 studies in 2014 and 2015 utilized ipilimumab for progressive metastatic disease, reporting similar OS of 9.8 and 6.8 months, respectively [13]. It is important to understand that the literature regarding immunotherapy for UM stems from the therapeutic response seen in cutaneous melanoma responding to this treatment. However, there are critical differences between the two malignancies. One such difference is the mutation rates, which are lower in UM. This leads to decreased neoantigens and a smaller chance of immune cell recognition [14].

Recentstudies are focusing on the use of dual-agent immunotherapy. The combination has shown an OS of 15 months which is higher than the average OS noted in single-agent therapy [15]. This prompted our decision to use both nivolumab and ipilimumab. Our patient has surpassed the average expected OS; he remains progression-free for two years.Immunogenetics are targetable characteristics for potential treatment options. Our patient was evaluated for high-risk genetic features using a microscopic needle aspirate sample for micro-assay analysis. Genetic expression analysis divides mutations into a binary classification, Class I and Class II genes [16]. Our patient tested positive for monosomy 3 and gain of chromosome 8q, classified as Class II genes [16]. This was performed at the initial diagnosis of localized disease, with localized disease. Class II genes are associated with poor prognosis [2]. This enforced the need for close monitoring of our patient to discover any potential metastatic disease as early as possible. After radiographic confirmation of metastasis, his spinal lesion was sent for genetic analysis, which confirmed a GNA11 mutation; a common oncogene identified in 80% of UM cases [17]. This oncogene activates the protein kinase C (PKC) and mitogen-activated protein kinase pathways inducing cell signaling and proliferation [18]. PKC inhibitors, individually and in combination with MEK inhibitors, have shown a synergistic effect in halting cell proliferation [18]. This prompted our patients timely referral to a national clinical trial currently in progress, seeking patients with similar presentations and assessing the use of PKC inhibitors.

The future of UM is currently under investigation with increasing clinical trials and hypothesized treatment approaches. Although most cases of UM have not shown a clear and consistent response to single-agent immunotherapy, it continues to be under investigation with dual ICI therapies. Based on oncogene findings and immunogenetics, there may be opportunities for targeted therapy with ongoing research. Our case presents a unique observation of successful treatment with ICI with a progression-free survival of almost two years. Our use of clinical and radiographic response, with the addition of genetic analysis, yields a personalized treatment approach beyond expected statistical survival.

Excerpt from:
A Rare Case of Metastatic Uveal Melanoma Responding to Immunotherapy - Cureus

Do you remember your science lessons from school? Do you remember learning about chromosomes? We were taught that there are two chromosomes X and Y and that each of us has a set of chromosomes. Individuals with XX (or two X chromosomes) are female, while those with XY (or one X and one Y chromosome) are male. A recently published study has now revealed that many men can actually carry an extra chromosome.The study was published in the journal Genetics in Medicine. It included data on more than 207,000 men. It was discovered that of the participants, over 350 had an extra chromosome, either X or Y.Very few of these men knew about this abnormality or had it mentioned in their medical records.

Talking to the Guardian Dr Ken Ong, co-senior author of the study who is a pediatric endocrinologist in the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge says that they were surprised at how common this abnormality is.

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The National Human Genome Research Institute reported that previous estimations indicated that approximately 100 to 200 men out of every 100,000 are XXY. An estimated 18 to 100 out of every 100,000 were believed to be XYY.

Having an extra chromosome can raise the risk of certain health conditions. Those having Klinefelter syndrome (KS) or an extra X chromosome are linked to reproductive problems like infertility and delayed puberty. According to the National Human Genome Research Institute, XXY men are four times more likely than XY men to have late puberty.

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On the other hand, with an extra Y chromosome or 47,XYY syndrome does not come with reproductive problems but was linked to learning disabilities, including delay in acquiring speech and motor skills. According to the Genetic and Rare Diseases Information Center, they also have unusually low muscle tone.

Additionally, both XXY and XYY men have a higher rate of type 2 diabetes, atherosclerosis (plaque buildup in the artery walls), pulmonary embolism (blood clots in the veins and lung arteries), and chronic obstructive pulmonary disease (which obstructs airflow to the lungs).

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In their report, the authors questioned: "why both KS and 47,XYY should show striking similarities in conferring substantially higher risks for many diseases in common." As per them, future research is needed to examine the reasons causing this elevated risk.

(With inputs from agencies)

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Until recently, many scientists had been skeptical about the value of attempting to sequence ancient DNA: Samples are often so old that the DNA strands have become degraded and fragile or else contaminated; the process is much more laborious and costly as a result.

Many early studies of ancient DNA were therefore done with mitochondrial DNA. This genetic materialhoused in the mitochondria, the power plants of our cells, and passed from mother to childoffered more reliable data. But advances in sequencing technology means more recent studies have also been able to use Y-chromosome (male) DNA, which is typically more repetitive and difficult to read. The result is a more accurate overview of genetic changes over time, and it is this approach that Shanidar Z should benefit from.

After Hunts unusual flight home, Shanidar Z made it safely to the University of Cambridge for digital scanning and will eventually be transferred back to northern Iraq to feature as the centerpiece of a new museum. The skeleton could be up to 90,000 years old, but its DNA will be used to further understanding of modern human historyby analyzing and statistically comparing the ancient DNA against the genomes of modern populations, to demonstrate when different population groups parted company, Hunt says.

Once a population splits into two or more reproductively isolated groups, the genes in each new population will evolve gradually in new directions as a result of random gene mutations as well as exposure to various environmental factors that prevent successful reproductioncoming into contact with new diseases, for instance.

Its through work like this that scientists have been able to chart the migration of different populations of humans and Neanderthal groups around the planet over the last 70,000 years, and also bust some myths about their habits and migration patterns. We now know that humans and Neanderthals interbred quite commonly, and that Neanderthal communities were likely more caring and intelligent than weve previously given them credit for. According to Hunt, evidence of burial rituals at the Shanidar Cave suggests memory, and that they looked after their injured and sick members.

Separately, analysis of ancient DNA against the modern human genome has revealed that we still carry some genetic sequences that were present in people living millennia ago. Such analysis even helped to identify a new subspecies of humans 12 years agothis discovery of Denisovans, believed to have existed across Asia around 400,000 years ago, demonstrates how much is still unknown about our human origins.

At the Francis Crick Institute in London, a major project is underway to create a reliable biobank of ancient human DNA to help build on such discoveries. Population geneticist Pontus Skoglund is leading the 1.7 million ($2.1 million) project, which will sequence 1,000 ancient British genomes by gathering data from skeletal samples from the past 5,000 years, with help from around 100 other UK institutions. From the database he hopes to determine how human genetics have changed over millennia in response to factors such as infectious diseases and changes in climate, diet, and migration.

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What the DNA of Ancient Humans Reveals About Pandemics - Wired.co.uk

Several months ago, a lab technologist at Barnes-Jewish Hospital mixed the blood components of two people: Alphonso Harried, who needed a kidney, and Pat Holterman-Hommes, who hoped to give him one.

The goal was to see whether Harrieds body would instantly see Holterman-Hommes organ as a major threat and attack it before surgeons could finish a transplant. To do that, the technologist mixed in fluorescent tags that would glow if Harrieds immune defense forces would latch onto the donors cells in preparation for an attack. If, after a few hours, the machine found lots of glowing, it meant the kidney transplant would be doomed. It stayed dark: They were a match.

I was floored, said Harried.

Both recipient and donor were a little surprised. Harried is Black. Holterman-Hommes is white.

Could a white person donate a kidney to a Black person? Would race get in the way of their plans? Both families admitted those kinds of questions were flitting around in their heads, even though they know, deep down, that its more about your blood type and all of our blood is red, as Holterman-Hommes put it.

Scientists widely agree that race is a social construct, yet it is often conflated with biology, leaving the impression that a persons race governs how the body functions.

Its not just laypeople its in the medical field as well. People often conflate race with biology, said Dr. Marva Moxey-Mims, chief of pediatric nephrology at Childrens National Hospital in Washington, D.C.

Shes not talking just about kidney medicine. Race has been used as a shorthand for how peoples bodies work for years across many fields not out of malice but because it was based on what was considered the best science available at the time.

The science was not immune to the racialized culture it sprung from, which is now being seen in a new light. For example, U.S. pediatricians recently ditched a calculation that assumed Black children were less likely to get a urinary tract infection after new research found the risk had to do with a childs history of fevers and past infections not race. And obstetricians removed race and ethnicity from a calculation meant to gauge a patients ability to have a vaginal birth after a previous cesarean section, once they determined it was based on flawed science. Still, researchers say those race-based guidelines are just a slice of those being used to assess patients, and are largely based on the assumption that how a person looks or identifies reflects their genetic makeup.

Race does have its place during a doctors visit, however. Medical providers who give patients culturally competent care the act of acknowledging a patients heritage, beliefs, and values during treatment often see improved patient outcomes. Culturally competent doctors understand that overt racism and microaggressions can not only cause mental distress but also that racial trauma can make a person physically sick. Race is a useful tool for identifying population-level disparities, but experts now say it is not very useful in making decisions about how to treat an individual patient.

Because using race as a medical shorthand is at best imprecise and at worst harmful, a conversation is unfolding nationally among lawmakers, scientists, and doctors who say one of the best things patients can do is ask if and how their race is factored into their care.

Doctors and researchers in kidney care have been active recently in reevaluating their use of race-based medical guidance.

History is being written right now that this is not the right thing to do and that the path forward is to use race responsibly and not to do it in the way that weve been doing in the past, says Dr. Nwamaka Eneanya, a nephrologist with Fresenius Medical Care, who in a previous position with the University of Pennsylvania traced in the journal Nature the history of how race a social construct became embedded in medicine.

The perception that there is such a thing as a Black or white kidney quietly followed patient and donor as Harried and Holterman-Hommes were on the path to the transplant in their medical records and in the screening tests recommended.

Medical records described Harried as a 47-year-old Black or African American male and Holterman-Hommes as a 58-year-old, married Caucasian female. Harried does not recall ever providing his race or speaking with his physicians about the influence of race on his care, but for two years or more his classification as Black or African American was a factor in the equations doctors used to estimate how well his kidneys were working. As previous KHN reporting lays out, that practice distinguishing between Black and non-Black bodies was the norm. In fall 2021, a national committee determined race has no place in estimating kidney function, a small but significant step in revising how race is considered.

Dr. Lisa McElroy, a surgeon who performs kidney transplants at Duke University, said the constant consideration of race is the rule, not the exception, in medicine.

Medicine or health care is a little bit like art. It reflects the culture, she said. Race is a part of our culture, and it shows up all through it and health care is no different.

McElroy no longer mentions race in her patients notes, because it really has no bearing on the clinical care plan or biology of disease.

Still, such assumptions extend throughout health care. Some primary care doctors, for example, continue to hew to an assumption that Black patients cannot handle certain kinds of blood pressure medications, even while researchers have concluded those assumptions dont make sense, distract doctors from considering factors more important than race like whether the patient has access to nutritious food and stable housing and could prevent patients from achieving better health by limiting their options.

Studying population-level patterns is important for identifying where disparities exist, but that doesnt mean peoples bodies innately function differently just as population-level disparities in pay do not indicate one gender is fundamentally more capable of hard work.

If you see group differences theyre usually driven by what we do to groups, said Dr. Keith Norris, not by innate differences in those groups. Still, medicine often continues to use race as a crude catchall, said Norris, a UCLA nephrologist, as if every Black person in America experiences the same amount and the same quantity of structural racism, individualized racism, internalized racism, and gene polymorphisms.

In Harried and Holterman-Hommes case, one striking example of race being used as shorthand for determining how peoples bodies work was an informational guide given to Holterman-Hommes that said African Americans with high blood pressure could not donate an organ, but Caucasians with high blood pressure might still qualify.

The perception that there is such a thing as a Black or white kidney quietly followed patient and donor as Harried and Holterman-Hommes were on the path to the transplant in their medical records and in the screening tests recommended. (Joe Martinez/Kaiser Health News/TNS)

I cant believe they actually wrote that down, said Dr. Vanessa Grubbs, a nephrologist at the University of California, San Francisco. That worries Grubbs because using race as a reason to exclude donors can create a situation in which Black transplant recipients have to work harder to find a living donor than others would.

I do think that criteria such as these become barriers for transplantation, said Dr. Rajnish Mehrotra, head of nephrology at the University of Washington. He said that type of hypertension distinction could exclude potential donors like the 56 % of Black adults with high blood pressure in the U.S. when more of them are sorely needed.

The inclusion of race did not necessarily affect Harrieds ability to receive a kidney, nor Holterman-Hommes ability to give him one. But following their case offers a glimpse into the ways race and biology are often cemented together.

Harried and Holterman-Hommes met 20 years ago when they worked together at a nonprofit that serves youth experiencing homelessness in St. Louis. Harried was the guy who pulled kids out of their ruts and into a creative mindset, from which they would write poems and songs and do artwork. Holterman-Hommes said he was the calm in their storm. Harried calls Holterman-Hommes big stuff because she is the nonprofits CEO who keeps the lights on and the donations coming in. You never knew that she was the president of the company, said Harried. There wasnt an air about her.

Harried resigned in 2018 as his health declined. Then in 2021, Holterman-Hommes saw a KHN article about Harried and decided to see if she could help her former colleague. Although Holterman-Hommes mother was born with one kidney, she had lived a long and healthy life, so Holterman-Hommes figured she could spare one of her own.

As Holterman-Hommes explored becoming a donor candidate, initial tests showed high blood pressure readings, in addition to lower-than-ideal kidney function. But I like to get an A on a test, she said, so she redid both sets of tests, repeating the kidney function test after staying better hydrated and the blood pressure test after a big work deadline had passed. She moved on in the screening process after her results improved.

Grubbs wonders whether, if Holterman-Hommes had been Black, they would have just dismissed her. Grubbs shared an instance in which she suspects thats exactly what happened to the wife of a patient of hers in California who needed a kidney transplant.

The wife, who is Black and was in her 50s at the time, wasnt allowed to give the patient a kidney because of her hypertension.

There are people in this country that will tell you that, Oh, white people donate kidneys, Black people dont donate kidneys, and thats not true, said Mehrotra. You hear that racist trope. But (there are) all of these barriers to kidney donation.

Barnes-Jewish Hospital later said it had given Holterman-Hommes an outdated guide, an unfortunate circumstance that is being corrected, and provided a new one that does not say Black people with hypertension cannot donate. Instead, it says that people cannot donate if they have hypertension that was either diagnosed before age 40 or requires more than one medication to manage.

But at some point, it was a policy, said Harried, whose kidneys have been failing for several years. And its unclear how many years that outdated guidance shaped perceptions among those seeking care at Barnes-Jewish, which performs more living-donor kidney transplants per year than any other location in Missouri, according to the Scientific Registry of Transplant Recipients.

There is little transparency into how medical centers incorporate race into their decision-making and care. Guidelines from the United Network for Organ Sharing, the national organization in charge of the transplant system, leave the door open for hospitals to exclude a donor with any condition that, in the hospitals medical judgment, causes the donor to be unsuitable for organ donation.

Tanjala Purnell, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health studying disparities in kidney transplantation, said she knows of several centers that used race-based criteria, though some have relaxed those rules, instead deciding case by case. Theres not a standard set to say, Well, no, you can absolutely not have different rules for different people, she said. We dont have those safeguards. Dr. Tarek Alhamad, medical director of the kidney program at the Washington University and Barnes-Jewish Transplant Center, said race-based criteria for kidney donations arent created to exclude Black people it was born of a desire to avoid harming them.

African Americans are more likely to have end-stage renal disease, they are more likely to have end-stage renal disease related to hypertension. And they are more likely to have genetic factors that would lead to kidney dysfunction, said Alhamad.

Compared with white and Hispanic donors, non-Hispanic Black donors are known to be at higher risk for developing kidney failure because of their donation, though its still very rare.

He said it feels unethical to take a kidney from someone who may really need it down the line. This is our role as physicians not to do harm.

Researchers are studying a possible way to clarify who is really at risk in donating a kidney, by identifying specific risk factors rather than pinning odds on the vague concept of race.

Specifically, a gene called APOL1 could influence a persons likelihood of developing kidney disease. All humans have two copies of this gene, but there are different versions, or variants, of it. Having two risk variants increases the chance of kidney injury.

The risk variants are most prevalent in people with recent African ancestry, a group that crosses racial and ethnic boundaries. About 13% of African Americans have the double whammy of two risk variants, said Dr. Barry Freedman, chief of nephrology at the Wake Forest School of Medicine. Even then, he said, their fate isnt sealed most people in that group wont get kidney failure. We think they need a second hit, like HIV infection, or lupus, or COVID-19.

Freedman is leading a study that looks, in part, at how kidney donors with those risk variants fare in the long term.

This is really important because the hope is that kidneys wont be discarded or turned down as frequently, said Moxey-Mims, who is also involved in the research.

Researchers who are focused on health equity say that while APOL1 testing could help separate race from genetics, it could be a double-edged sword. Purnell pointed out that if APOL1 is misused for example, if a transplant center makes a blanket rule that no one with two risk variants can donate, rather than using it as a starting point for shared decision-making, or if doctors offer the test based only on a patients looks it could merely add another criterion to the list by which certain people are excluded.

We have to do our due diligence, said Purnell, to ensure that any effort to be protective doesnt end up making the pool of available donors for certain groups smaller and smaller and smaller. Purnell, McElroy, and others steeped in transplant inequities say that as long as race which is a cultural concept defining how someone identifies, or how they are perceived is used as a stand-in for someones ancestry or genetics, the line between protecting and excluding people will remain fuzzy.

Thats the heart of the matter here, said McElroy.

So where does race belong in kidney transplant medicine? Many of the physicians interviewed for this article many of them people of color said it primarily serves as a potential indicator of hurdles patients may face, rather than as a marker of how their bodies function.

For example, McElroy said she might spend more time with Black patients building trust with them and their families, or talking about how important living donations can be, similar to the ways she might spend more time with a Spanish-speaking patient making sure they know how to access a translator, or with an elderly patient emphasizing how important physical activity is.

The purpose is not to ignore the social determinants of health of which race is one, she said. Its to try to help them overcome the race-specific or ethnicity-specific barriers to receiving excellent care.

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While all the science gets sorted out, Eneanya is trying to get the message out to patients: Just ask the question: Is my race being used in my clinical care? And if it is, first of all, what race is in the chart? Is it affecting my care? And what are my options?

Just keep your eyes open, ask questions, said Harried.

In late April, a kidney from Holterman-Hommes body was successfully placed into Harrieds. Both are home now and say they are doing well.

KHN ( Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF ( Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.)

___

2022 Kaiser Health News. Visit khn.org. Distributed by Tribune Content Agency, LLC.

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Race is often used as medical shorthand for how bodies work. Some doctors, researchers want to change that. - The Virginian-Pilot

Measuring how old a persons sperm is could help predict the chances of them getting pregnant, according to a new study. But sperms age isnt just how many birthdays its had. It takes about 64 days for a sperm cell to mature, and depending on how much sex youre having (or how much youre masturbating), its released into the world shortly thereafter. But a sperms age has nothing to do with that cycle. Instead, it has to do with the aging process that occurs at the cellular level. And that biological age is linked to how long it takes a couple to conceive.

Chronological age, or how much time a person has lived, is an important factor when it comes to pregnancy especially for pregnant people, who have a finite number of egg cells. But it doesnt tell the whole story.

All your friends from high school, they're the same age, right? says J. Richard Pilsner, Ph.D., director of Molecular Genetics and Infertility at Wayne State University in Detroit, Michigan, and lead author of the study. But that number doesn't capture some of the genetic differences they have or environmental factors like smoking or exercising, which can have major impacts on the aging process, Pilsner says.

Chronological age is actually somewhat of an arcane way of thinking about aging. If we have a precise measurement of the biological age, that's going to give us more information, he says.

Thats why his team developed a novel technique to read the true biological age of sperm cells. They measured this age by reading how much DNA methylation a sperm cell has how many of a type of chemical called methyl groups are attached to the sperms DNA, which alters how its genes are expressed. The more methylation, the older the sperm. Using this method, the researchers can tell whether sperms biological age is up to nine years younger or older than its makers chronological age.

Pilsner and his team used this technique to analyze the sperm of 379 people from 16 different locations across the U.S. from 2005 to 2009, then followed the participant couples for up to 12 months or until they got pregnant. They compared the sperms biological age against the ability of the couple to get pregnant. Couples with older sperm took 17% longer to get pregnant than people with younger sperm.

17%

How much longer it took people with older sperm to get their partners pregnant compared to people with younger sperm.

A sperms biological age can match up with a persons chronological age, but it doesnt necessarily have to. A man could be 30 years old, but his sperm's epigenetic age may be 35, and that's causing a lower pregnancy probability, Pilsner says.

Lifestyle choices can advance the biological aging of sperm. For example, the study found that men who smoked had older sperm.

Pilsner will be conducting more research on what can speed up or slow down sperm aging in the coming months, but he notes that the basics of a healthy lifestyle, sleep, diet, and exercise are important for ensuring that your cells dont mature too quickly. Future research could also shed light on whether sperms age affects the babys health.

Knowing sperms true age could also help couples get pregnant faster. If a person has very old sperm, for example, they may decide to look into assisted reproductive technology sooner.

There's very little screening for male reproductive health, Pilsner says. He hopes that the new technique for determining sperms age could one day help doctors diagnose clinical infertility, given that the semen parameters currently used have been shown to be poor predictors of reproductive success. We need this new biomarker that really captures what's happening biologically within the cell, he says.

The next step? After validating these findings, Pilsners lab will run experiments on mice to see whether there could be pharmacological options for rejuvenating older sperm cells. One day, its possible that men having trouble getting their partners pregnant could turn back the clock on their sperm to increase their chances of getting pregnant.

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The "Age" Of Your Sperm Could Predict Your Chances Of Pregnancy - Fatherly

Calves are one of the most stubborn muscle groups. Many people find it hard to make them grow, irrespective of how hard or often they train them in the gym.

Are big calves only for improving your physique aesthetics? Not really.

A study conducted on 6,265 people found that the bigger a persons calves, the smaller their risk of stroke. Regardless of age, sex, body mass index, and other vascular risk factors, those with bigger calves had fewer fatty deposits known as plaques built up in their arteries. It means they have a lower risk for stenosis, carotid artery disease, and strokes. [1]

If you do not wear shorts to the gym as you fear ridicule because of your tiny calves, you have come to the right place. In this article, youll learn about the average calf size for men and women of different ages, how to measure your calf circumference correctly, and how to increase your calf size.

Youve probably heard of the unwritten rules you should never ask a woman her age, a man his salary, and agym bro his calf size. Okay, we just came up with the calf size part, but make no mistake, it can be even more offending than the first two questions.

Your calf size is determined by your genetics and daily activity levels, especially if youre not a gym regular. You could alter your calf circumference with calf exercises, but it requires hard work in the gym.

According to data based on a sample of 4,303 men aged 20 years and above, the Center for Disease Control and Prevention (CDC)suggests that the average male calf size is15.5 inches. [2]

On average, men between 20 and 29 had 15.5-inch calves, while men aged 30 to 39 had 15.6-inch calves. Average male calf circumference peaks at15.8 inchesfor the40 to 49 age group.

Although men undergo a gradual increase in calf size up to the age of 49, the drop in calf circumference is comparatively drastic. Per the survey, men between 50 and 59 have 15.6-inch calves. It drops down to 15.4 inches by the time they enter their 60s.

In their 70s, men, on average, have 14.9-inch calves, which further drops to 14.2 inches by the time they are in their 80s.

Related:Ronnie Coleman Hits Calf Raises for Reps: Trying My Very Best with My Feet Totally Numb

Per the same CDC research cited above (based on the sample size of 4,133 women aged 20 and above), the average female calf size is 15 inches. [2]

For women between the ages of 20 to 29, the average calf size is 14.8 inches. It increases to 15.2 inches for women between 30 and 39 before peaking at15.4 inchesfor females aged between40 and 49.

After peaking around 50, womens calf size, on average, decreases to 15.1 inches between the age of 60 and 69. The calf size drops to 14.4 inches as women enter their 70s and hits its low at 13.9 inches in their 80s.

Although men have larger calves than their counterparts of the same age, the difference isnt as big as some might have imagined. Notably, age plays an important role in determining your calf size.

Related:The 13 Best Calf Raise Machine Alternatives for Bigger, Stronger Lower Legs

There are a few different ways of measuring your calf size. Some people like to get their calves measured while seated, while others prefer doing it standing. Calf measurements taken seated are usually bigger than those recorded standing up.

Like in the case of other muscle groups like the biceps and chest, many people like to get their calves measuredafter they have a good muscle pumpfrom performing a few sets of the lower leg exercises.

Nonetheless, it does not matter if you choose to get your calves measured standing or seated, with or without a pump, or contracted or relaxed. Make sure you do it in the same position every time for consistency.

Here is how to measure your calves correctly:

Competitive bodybuilding is a game of aesthetics, symmetry, and illusions. You do not have to build your calves to a certain size to be able to win bodybuilding shows. However, you should focus on building proportions and balance.

Arnold Schwarzenegger summed it up the best when he said

When I went to train with my hero, Reg Park, he pulled out a tape measure and measured my calves and biceps. He said, Arnold, your calves are 19 inches, and your biceps are 21 inches. You might win Mr. Universe like this, but youll never go all the way. You need to build up your calves. Every step you take is a 250-pound calf raise. So to grow, you are going to have to go as heavy as possible, and youre going to need to do 10-15 sets every single day.'

If you are a bodybuilding fan, make sure your calves are as big as your biceps. If your upper arms are bigger than your lower legs, your body might appear disproportionate.

Check Out:14 Best Legs in Bodybuilding History

Building bigger calves is easier said than done. Youll have to undergo strict training, diet, and recovery regimen to put muscle mass on your lower legs. Here is an effective calf training workout you should try the next time you hit the gym:

Next Read:15 Ways To Turn Your Calves Into Full Grown Bulls

If your calves are slightly over or under (up to 0.3 inches, either way) the average size for your age and gender, your calves will still be considered normal. However, if your calves are smaller, you should follow the workout listed above to add mass to your lower legs.

For men of average height (five-foot-nine) and weight (194.7 pounds), 16-inch calves or bigger can be considered big. On the other hand, 15.5-inch or bigger calves can be considered big for women of average height (five-foot-four) and weight (170.6 pounds). [2]

Knowing the average calf size for your age and gender gives you a good idea of where you stand in terms of your lower leg gains.

If you want to add size to your calves, you should add the workout mentioned above to your training regimen and follow a high-protein diet. On the other hand, you should switch to acalorie-deficit dietand spike your cardiovascular workouts to lose a few inches off your lower legs.

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The Average Calf Size for Men and Women Fitness Volt - Fitness Volt

image:Small carpenter bee on a flower. view more

Credit: York University

TORONTO, June 17, 2022 The local environment plays a pivotal role in the health and diversity of the gut microbiome of wild bees which could help detect invisible stressors and early indicators of potential threats, say York University scientists in a new study.

Piloting a new frontier of metagenomics, the researchers sequenced whole genomes of three species of carpenter bees, a type of wild bee, in North America, Asia and Australia. This analysis allowed them to gain insights into the bees gut microbiome (bacteria and fungi), diet and viral load, as well as their environmental DNA.

Unlike social bees (like honeybees and bumblebees), the researchers found solitary bees get their microbiome, which is important for health, from their environment where they forge for food, rather than inheriting it from their nest mates. Carpenter bees burrow into woody plant stalks to lay eggs rather than in hives.

This may make them better bio-indicators as they are much more sensitive to their environment, says Faculty of Science Associate Professor Sandra Rehan, corresponding author of the research, Comparative metagenomics reveals expanded insights into intra- and interspecific variation among wild bee microbiomes, published today in the journal CommunicationsBiology.

In Australia, the local populations had highly distinctive metagenomes and microbiomes; so much so that machine learning tools were able to reliably predict from which population each bee was drawn.

The research team also discovered crop pathogens in the microbiomes of carpenter bees which were previously only found in honeybees.

These pathogens are not necessarily harmful to bees, but these wild bees could potentially be vectoring diseases that might have negative effects on agriculture, says Rehan. Finding out how these pathogens are spreading in wild bees is important as bees contribute to ecological and agricultural health worldwide in addition to more than $200 billion in annual agricultural services.

Establishing a baseline of what a healthy microbiome looks like in wild bees allows scientists to compare species across continents and populations, and to figure out how diseases and harmful microbiota are being introduced and transmitted.

We can really dissect bee health in a very systematic way looking at population genetics and parasite pathogen loads, healthy microbiomes and deviations, says Rehan, whose Postdoctoral Research Associate, Wyatt Shell, led the study. The long-term goal is really to be able to use these tools to be able to also detect early signatures of stress and habitats in need of restoration or conservation. To develop it almost like a diagnostic tool for bee health.

Researchers believe they have captured the core microbiome of carpenter bees for the first time. They found beneficial bacteria in all three carpenter bee species which helped with metabolic and genetic functions. They also detected species of Lactobacillus, which is an essential beneficial bacteria group, imperative for good gut health and found across most bee lineages. Lactobacillus may protect against prevalent fungal pathogens, boost the immune system, and facilitate nutrient uptake.

However, a recently published paper in the journal Environmental DNA by Rehan and her graduate student Phuong Nguyen, Developmental microbiome of the small carpenter bee, Ceratina calcarata, which studied the microbiome in brood and adult carpenter bees in cities, found they were lacking Lactobacillus.

This raises red flags, says Rehan. We are continuing those studies to look at more nuanced urban, rural comparisons and long-term data to really understand these environmental stressors. Anytime we characterize a microbiome and see deviations from what we know to be normal, it can give us an indication of a population or species in threat.

Overall, the results show metagenomic methods could provide important insights into wild bee ecology and health going forward.

We've been piloting this research approach in a few species, but we're aiming to study dozens of wild bee species and broader comparisons are coming. These two studies are really establishing the foundation," she says. The long-term goal is really to be able to use these tools to detect early signatures of stress in wild bees and thereby identify habitats in need of restoration or preservation. We are excited to be building the tools for a new era of wild bee research and conservation.

The work was funded by NSERC Discovery Grants, Weston Family Foundation Microbiome Initiative funds, and the NSERC E.W.R. Steacie Memorial Fellowship to Rehan.

PHOTOS: Small carpenter bee - https://www.yorku.ca/news/wp-content/uploads/sites/242/2022/06/860-header-Small-carpenter-bee.jpg

Male carpenter bee (certina calcarata) - https://www.yorku.ca/news/wp-content/uploads/sites/242/2022/06/Male-ceratina-calcarata-side-copy-scaled.jpg

Carpenter bee (ceratina australensis) nest - https://www.yorku.ca/news/wp-content/uploads/sites/242/2022/06/Ceratina_australensis_nest.jpg

Carpenter bee (ceratina japonica) - https://www.yorku.ca/news/wp-content/uploads/sites/242/2022/06/Ceratina-japonica.jpg

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York Universityis a modern, multi-campus, urban university located in Toronto, Ontario. Backed by a diverse group of students, faculty, staff, alumni and partners, we bring a uniquely global perspective to help solve societal challenges, drive positive change and prepare our students for success. York's fully bilingual Glendon Campus is home to Southern Ontario's Centre of Excellence for French Language and Bilingual Postsecondary Education. Yorks campuses in Costa Rica and India offer students exceptional transnational learning opportunities and innovative programs. Together, we can make things right for our communities, our planet, and our future.

Media Contact:Sandra McLean, York University Media Relations, 416-272-6317,sandramc@yorku.ca

Communications Biology

Animals

Comparative metagenomics reveals expanded insights into intra- and interspecific variation 2 among wild bee microbiomes

17-Jun-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Clues to bee health found in their gut microbiome - EurekAlert

When you consider how babies are made, you bump up against a basic math problem. No need for calculus here, or even the mental gymnastics of carrying the one. Its a problem of doubling.

A mother has 23 pairs of chromosomes. A father also has 23 pairs of chromosomes. When sperm meets the egg, you would expect the embryo, and thus the fetus, and thus the baby to have 46 pairs of chromosomes. And when that baby grows up, one of its eggs, filled with 46 pairs of chromosomes, might meet-cute a sperm, carrying its own 46 pairs of chromosomes, and the result would be a baby whose cells hold onto 92 pairs of chromosomes.

Given humanitys long history on this planet and its propensity to make babies, our cells would have, by now, exploded with chromosomal goo. This surplus of DNA would be unmanageable from a containment perspective, let alone what it would do to the body. We simply do not need that much DNA. When we have one extra chromosome, such as in trisomy 21, the effects are appreciable. What would happen if we had dozens upon dozens of extra chromosomes, or hundreds?

In order to figure out natures answer to this quandary, someone needed to crawl under the metaphorical bed sheets and figure out just how babies are made. That man was Oscar Hertwig, and the procreators that captured his attention were spiny globules we call sea urchins.

Hertwig was born in 1849 in Friedberg, Germany. He and his brother Richard, one year his junior, attended university together, and Oscars curiosity was later piqued by the question of just what happened when a sperm cell and an egg cell met. Two main theories were fighting it out in academic circles at the time. The first was that the sperm touched the egg and basically vibrated against it, which spurred the egg into becoming an embryo. In this scenario, sperm was a sort of alarm clock loudly buzzing and prodding the egg to wake up and fulfill its destiny.

The second hypothesis was that the sperm penetrated the egg and their raw materials mixed and became the embryo.

Hertwig saw the evidence that had been published for this second theory but was not happy with it. When he heard that his brother was leaving for the Mediterranean to work on a research project with the preeminent biologist they had both studied under, Oscar decided to join them. And he made an important observation while there: sea urchins, which can be found on the Mediterranean seashore, had transparent embryos.

With the veil of fertilization thus lifted, Hertwig was able to witness sea urchin sperm entering a sea urchin egg cell and fusing with its nucleus, which contains the chromosomes. Sperm was no alarm clock; it mixed with the egg. Once a single sperm cell had penetrated the egg, a force field called the vitelline membrane was erected by the egg to block out the remaining sperm cells.

This is now common knowledge, but what Hertwig didnt know then was exactly what was happening to the contents of the sperm and egg when they met and what strange chromosomal dance had taken place before the sperm and egg were even created. Because that would prove to be the answer to the problem of DNA doubling up all the time.

Lets start with sperm, the simpler of the two.

Inside the testis of an adolescent male, we look for a regular cell that is about to become a sperm cell. We race past the complex structures that bring this dynamic cell to life and enter its nucleus, the command center of the cell which contains the chromosomes. We focus on chromosome 1. There are two of them, joined at the hip. Lets call them Dwayne and Matthew. Matthew was inherited from the teenage boys mom (hence the M" name), while Dwayne was a gift from his dad. They are, in a manner of speaking, fraternal twins: the same age, with similar enough features, but with important differences.

Cells, which contain Dwayne and Matthew and nearly two dozen other pairs of chromosomes, divide, like a soap bubble being pinched into two. In order to make sure that the cells that result from this division both carry Dwayne and Matthew, Dwayne and Matthew need to be copied.

And so, through the magic of molecular biology, Dwayne and Matthew, joined at the hip, find themselves next to Dominic and Marc, also joined at the hip and looking like clones of Dwayne and Matthew. We have now doubled the amount of DNA inside this cell in preparation for that bubble pinch.

But before this can happen, a critical event takes place. It does not happen in any other cell of the boys body, but strictly in those that are to become sperm cells.

Matthew, originally inherited from Mom, and Dominic, a copy of Dwayne which was inherited from Dad, get together. Its not exactly love, but more akin to one of Dr. Frankensteins experiments. A part of Matthew goes to Dominic and vice versa, creating new chromosomes: Matthinic and Domew.

What happens next is simple. Dwayne and the new chromosome Matthinic move to one end of the cell, while Domew and Marc shuffle over to the other side. The cell splits into two, and these cells then each split into two, creating four sperm cells.

There is a name for this entire process of a cell swapping material between Mommys and Daddys chromosomes after it has doubled up its DNA, then twice halving its content. Its called meiosis (pronounced my-OH-sis) and it means a lessening. It takes place in cells that are meant to become sex cells, i.e. sperm and egg in humans.

Figure 1: A simplified illustration of meiosis, using the development of sperm cells as an example. 1) Each chromosome consists of two halves, one inherited from Daddy (labelled Dwayne here) and the other inherited from Mommy (labelled Matthew), and identical copies of them are made at the beginning of this process (Dominic and Marc). 2) One of the halves inherited from Mommy swaps material with one of the halves inherited from Daddy. 3) This creates new recombinant chromosomes. 4) Eventually, each one of these chromosomes finds itself in a single sperm cell. Created with BioRender.com.

Cells which contained both Dwayne and Matthew now only contain either Dwayne or a modified version of Matthew. Where once there were two chromosomes 1 in the same cell, there is now only one. The same process concurrently affects chromosomes 2 to 22 and the sex chromosomes as well. Sperm cells thus have half as much DNA as any other cell in the body.

Meiosis also takes place in females, though the process stops-and-goes over the course of many years to eventually create egg cells that also contain half as much DNA as any other cell. (To be more accurate, some cells in our body actually contain even more DNA than regular cells, for example up to half of our liver cells.)

This is why, when a sperm penetrates an egg, we do not get 46 pairs of chromosomes.

The 23 single chromosomes of the sperm are matched with the 23 single chromosomes of the egg, and this creates a new combination of 23 pairs of chromosomes in the embryo. Only Dwayne becomes part of the embryo, or Marc, or Matthinic, or Domew, or any one of a near-infinite combination of Matthew and Dominic chromosomes, or of Dwayne and Marc recombined chromosomesall depending on which sperm wins the race.

And the egg they will fertilize will contain May, or Dawn, or Darilyn, or Marlene, or any combination of Marilyn and Darlene and of May and Dawn.

And these recombinationscreating Matthinics and Darilynsare critical events because they engender genetic diversity. Without these DNA swaps, the same chromosomes would get passed down, intact, from generation to generation. Instead, a mothers and fathers genetic contributions are scrambled inside their children when the latter start making sexual cells. This diversity benefits us: it gives us a better chance to survive when our environment changes and helps reduce the chances of our children inheriting certain genetic diseases. And this perk is not just for us. Meiosis takes place in plants and animals more broadly.

One of the core principles of toxicology is that its the dose that makes the poison. In a way, it holds true in genetics. We could not withstand a growing accumulation of chromosomes from generation to generation. Meiosis is thus key in keeping the number of chromosomes constant and helping ensure diversity.

Take-home message:- Without a special process in place, every child would receive all of its mothers and fathers DNA and thus end up with twice as much DNA as each parent- What actually happens is that sperm cells and egg cells wind up with half of the DNA of regular cells through a process called meiosis- During meiosis, equivalent chromosomes inherited from different parents swap parts of each other, which contributes to genetic diversity

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How Nature Solved the Problem of Too Much DNA - Office for Science and Society

The novel coronavirus SARS-CoV-2, which causes COVID-19, has caused millions of infections worldwide. As time has passed, it has become increasingly clear that COVID-19 is not a cookie-cutter disease.

People vary significantly in their susceptibility to infection, symptoms, and disease severity. Certain risk factors clearly play a role. Could genetics also play a part?

Researchers are examining the role of genetics in peoples reactions to the virus. While far from conclusive, data indicates that some of your genes may influence how SARS-CoV-2 affects your health.

Read on to learn what research has uncovered.

To look for genes that may influence the impact of COVID-19, geneticists scan the DNA of large study groups. This helps them find and identify connections between specific DNA sequences and disease characteristics.

Early genetic studies have uncovered compelling clues that certain genomic variants and blood types may play a role in how people react to the SARS-CoV-2 virus.

Angiotensin-converting enzyme 2 (ACE2) receptors are proteins found on the surface of certain cells. ACE2 receptors generate other proteins that regulate cell function. ACE2 receptors also allow the SARS-CoV-2 virus to enter your cells.

ACE2 receptors are located in the lungs, blood vessels, kidneys, and other parts of the body. They help regulate blood pressure, wound healing, and inflammation.

Everyone has ACE2 receptors, but their amount and locations vary. Multiple studies, including a 2021 study reported in the European Journal of Medical Research, found a link between ACE2 levels and vulnerability to COVID-19.

The same study also found that people with a specific type of genetic variation in ACE2 are at higher risk of SARS-CoV-2 infection. Another finding was a heightened susceptibility to SARS-CoV-2 infection in men compared to women.

Cytokines are proteins released by cells. Cytokines help cells communicate with each other. They also work to regulate inflammation and the bodys immune response to infection.

A cytokine storm is an overreaction of the immune system to infection from an invading host, such as SARS-CoV-2. During a cytokine storm, your cells release too many cytokines. This causes high levels of inflammation and the overactivation of certain immune cells.

The results of a cytokine storm can be severe and include tissue damage, organ failure, and sometimes death.

A review of multiple studies found that several genetic variants in cytokine genes may be related to cytokine storm and disease severity. Studies also found that these variants might be related to COVID-19 complications, including venous thrombosis.

A large study analyzed genes found along a stretch of chromosome 3. The study found compelling information about specific genes and their potential impact on respiratory failure caused by COVID-19.

Researchers identified a gene cluster on chromosome 3 linked to susceptibility to respiratory failure in COVID-19 patients. According to researchers, the gene cluster confirmed that ABO blood type played a role, indicating a higher risk for respiratory failure from COVID-19 for people with type A blood.

The HLA gene helps regulate your bodys immune response. Decades of research have found that people with certain HLA alleles (slight gene mutations, or variations) are prone to various autoimmune, inflammatory, and malignant diseases. Scientists call this phenomenon HLA disease association.

A 2021 review found that people with certain HLA alleles were more vulnerable to COVID-19 and severe illness than the general population.

If you were assigned male at birth, you might be at higher risk for serious illness from COVID-19. While some data points to lifestyle factors more common in men (such as smoking or drinking alcohol), genetic factors are also at play.

Men tend to express higher amounts of ACE2, making them more susceptible to COVID-19. A 2021 study suggests that this alone doesnt account for the difference in response.

The study also highlights genes present in men that might make them more prone to infection and genes present in women that may help them fight off infection.

There are also genes on the X-chromosome that influence your immune response. There are about 55 times as many of these genes on the X-chromosome as on the Y-chromosome.

As men only have one copy of the X-chromosome, variants in genes on this chromosome may have a greater effect on how COVID-19 progresses.

Its also important to remember that genetic traits are sometimes clustered among people with the same nationality, ethnicity, or culture. This can skew study results, especially in places where poor living conditions or poverty are factors.

Still, three 2021 studies (1, 2, 3) state that we cant ignore ethnic differences in COVID-19 susceptibility. Some genes that influence the course of COVID-19, such as HLA alleles, are more prevalent in certain ethnicities.

Another study noted that Black people tend to have more variations in the genes that affect ACE2.

Again, more research is needed before we fully understand the true impact.

COVID-19 is known to present with a wide variety of symptoms. While some symptoms are common, the virus tends to affect people in many different ways. Your genetics may play a role here too.

A 2021 study linked COVID-19 with altered gene expression in specific tissues or cells. This suggests that certain genetic variations may make you more likely to experience certain symptoms.

The study also noted that some of the genes they studied were also linked to ethnicity. This means that some symptoms may be more common in certain ethnic groups.

Researchers and geneticists are sharing their findings on genetics and COVID-19 through the COVID-19 Host Genetics Initiative.

As more studies take place, the biological pathways that affect your susceptibility or natural immunity to this disease may become more apparent.

This research may help generate new types of drugs that can treat COVID-19. It may also help determine why some people have a severe reaction to infection, and others experience mild to no symptoms.

While exciting and compelling, its important to remember that the research on genetics and COVID-19 is still new. We need more research before we can fully understand the impact of genes on this disease.

Knowing your risk factors can help you make decisions concerning exposure to the virus. Risk factors for COVID-19 and severe symptoms include:

No gene makes you fully immune to COVID-19. No matter what your own risk may be, these measures can help protect you from infection:

A growing body of evidence has linked certain genes and gene mutations to COVID-19 susceptibility. While compelling, this information is still new. We need more research to fully understand how our genes affect our response to the coronavirus.

As this body of science grows, it may better inform us on how to treat or even prevent COVID-19.

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Genetic Susceptibility to COVID-19: What We Know So Far - Healthline

Participants

For factor analyses, we restricted our analyses to autistic individuals from the SSC and SPARK cohorts. Participants had to have completed the two phenotypic measures (details are below) to be included in the factor analyses. We also excluded autistic individuals with incomplete entries in either of the two measures (n=5,754 only in the SPARK cohort). This resulted in 1,803 participants (n=1,554 males) in the SSC, 14,346 participants (n=11,440 males) in SPARK version 3 and 8,271 participants (n=6,262 males) in extra entries from SPARK version 5 (SSC, mean age=108.75 months, s.d.=43.29 months; SPARK version 3, mean age=112.11 months, s.d.=46.43 months; SPARK version 5, mean age=111.22 months, s.d.=48.19 months). Only the SCQ was available for siblings in the SPARK study.

We conducted analyses using data from four cohorts of autistic individuals: the SSC (n=8,813)30, the Autism Genetic Resource Exchange (AGRE, CHOP sample) (nmax=1,200)64, the AIMS-2-TRIALS Longitudinal European Autism Project (LEAP) sample (nmax=262)65 and SPARK (n=29,782)31. For sibling comparisons, we included siblings from the SSC (n=1,829) and SPARK (n=12,260) cohorts. For trio-based analyses, we restricted to complete trios in the SSC (n=2,234) and SPARK (n=4,747) cohorts. For all analyses, we restricted the sample to autistic individuals who passed genetic quality control (QC) and who had phenotypic information.

We conducted factor analyses using the SCQ29 and the RBS28. The SCQ is a widely used caregiver report of autistic traits capturing primarily social communication difficulties and, to a lesser extent, repetitive and restricted behaviors29. There are 40 binary (yes-or-no) questions in total, with the first question focusing on the individuals ability to use phrases or sentences (total score, 039). We used the Lifetime version rather than the current version as this was available in both the SPARK and SSC studies. Of note, in the Lifetime version, questions 119 are about behavior over the lifetime, while questions 2040 refer to behavior between the ages of 4 to 5 years or in the last 12 months if the participant is younger. We excluded participants who could not communicate using phrases or sentences (n=217 in the SSC and n=17,092 in SPARK) as other questions in the SCQ were not applicable to this group of participants. The RBS is a caregiver-reported measure of presence and severity of repetitive behaviors over the last 12 months. It consists of 43 questions assessed on a four-point Likert scale (total score, 0129). Higher scores on both measures indicate greater autistic traits.

We conducted exploratory factor analysis on a random half of the SSC (n=901 individuals, of which 782 were males) using promax rotation to identify correlated factors as implemented by psych (ref. 66) in R. We conducted three sets of exploratory correlated factor analyses: for all items, for social items and for non-social items. Previous studies have provided support for a broad dissociation between social and non-social autism features12,23 and have conducted separate factor analyses of social (for example, refs. 67,68) and non-social autism features (for example, refs. 69,70). Thus, we reasoned that separating items into social and non-social categories might aid the identification of covariance structures that may not be apparent when analyzing all items together. We divided the data into social (all of the SCQ except item 1 and nine other items and item 28 from the RBS) and non-social (nine items from the SCQ (items 8, 11, 12 and 1418) and all items from RBS except item 28) items, which was carried out after discussion between V.W. and X.Z. The ideal number of factors to be extracted was identified from examining the scree plot (Supplementary Fig. 2), parallel analyses and theoretical interpretability of the extracted factors. However, we examined all potential models using confirmatory factor analyses as well to obtain fit indices, and the final model was identified using both exploratory and confirmatory factor analyses.

We then applied the model configurations from promax rotated exploratory factor analysis for bifactor models to explore the existence of general factor(s). In addition to a single general factor bifactor model, we divided the data into social and non-social items as mentioned earlier and applied bifactor models separately for the social and non-social items. Hierarchical values and explained common variances were then calculated for potential models as extra indicators of the feasibility of bifactor models, but hierarchical values were not greater than 0.8 for most of the models tested, and explained common variances were not greater than 0.7 (refs. 71,72,73) for any of the models tested (Supplementary Table 2).

Three rounds of confirmatory factor analyses were conducted: first for the second half of the SSC, followed by analysis of SPARK participants whose phenotypic data were available in version 3 of the data release and, finally, analysis of SPARK participants whose phenotypic data were available only in version 4 or version 5 of the data release and not in the earlier releases. To evaluate the models, multiple widely adopted fit indices were considered, including the comparative fit index (CFI), the TLI and the root mean square error of approximation. In CFA, items were assigned only to the factor with the highest loading to attain parsimony. We conducted three broad sets of confirmatory factor analyses: (1) confirmatory factor analyses of all correlated factor models, (2) confirmatory factor analyses of the autism bifactor model and (3) confirmatory factor analyses of social and non-social bifactor models. For each of these confirmatory factor models, we limited the number of factors tested based on the slope of the scree plots and based on the number of items loading onto the factor (five or more). For the confirmatory factor analyses of social and non-social bifactor models, we iteratively combined various numbers of social and non-social group factors. In bifactor models, items without loading onto the general factor in the correspondent EFA were excluded. Items were allocated to different group factors, which were identified based on the highest loading (items with loading <0.3 were excluded). Due to the ordinal nature of the data, all CFAs were conducted using the diagonally weighted least-squares estimator (to account for the ordinal nature of the data) in the R package lavaan 0.6-5 (ref. 74). We identified the model most appropriate for the data at hand with TLI and CFI>0.9 (TLI and CFI>0.95 for bifactor models), low root mean square error of approximation and good theoretical interpretability based on discussions between V.W. and X.Z. Additionally, as sensitivity analyses, the identified model (correlated six-factor model) was run again with two orthogonal method factors mapping onto SCQ and RBS-R to investigate if the fit indices remained high after accounting for covariance between items derived from the same measure, as these measures vary subtly during the period of time evaluated. We also reanalyzed the identified model after removing items that were loaded onto multiple factors (>0.3 on two or more factors) to provide clearer theoretical interpretation of the model. For genetic analyses, we used factor scores from the correlated six-factor model without including the orthogonal method factors and without dropping the multi-loaded items.

QC was conducted for each cohort separately by array. We excluded participants with genotyping rate <95%, excessive heterozygosity (3s.d. from the mean), non-European ancestry as detailed below, mismatched genetic and reported sex and, for families, those with Mendelian errors >10%. SNPs with genotyping rate <10% were excluded, or they were excluded if they deviated from HardyWeinberg equilibrium (P<1106). Given the ancestral diversity in the SPARK cohort, HardyWeinberg equilibrium and heterozygosity were calculated in each genetically homogeneous population separately. Genetically homogeneous populations (corresponding to five super-populations: African, East Asian, South Asian, admixed American and European) were identified using the five genetic principal components calculated using SPARK and 1000 Genomes Phase 3 populations75 and clustered using UMAP76. Principal components were calculated using linkage disequilibrium-pruned SNPs (r2=0.1, window size=1,000kb, step size=500 variants, after removing regions with complex linkage disequilibrium patterns) using GENESIS77, which accounts for relatedness between individuals, calculated using KING78.

Imputation was conducted using the Michigan Imputation Server79 with 1000 Genomes phase 3 version 5 as the reference panel49 (for AGRE and SSC), with the HRC r1.1 2016 reference panel80 (for AIMS-2-TRIALS) or using the TOPMed imputation panel81 (for both releases of SPARK). Details of imputation have been previously reported82. SNPs were excluded from polygenic risk scores if they had minor allele frequency <1%, had an imputation r2<0.4 or were multi-allelic.

We restricted our PGS associations to four GWAS. First, we included a GWAS of autism from the latest release from the iPSYCH cohort (iPSYCH-2015)83. This includes 19,870 autistic individuals (15,025 males and 4,845 females) and 39,078 individuals without an autism diagnosis (19,763 males and 19,315 females). All individuals included in this GWAS were born between May 1980 and December 2008 to mothers who were living in Denmark. GWAS was conducted on individuals of European ancestry, with the first ten genetic principal components included as covariates using logistic regression as provided in PLINK. Further details are provided elsewhere49. We additionally included GWAS for educational attainment (n=766,345, excluding the 23andMe dataset)35, intelligence (n=269,867)34, ADHD (n=20,183 individuals diagnosed with ADHD and 35,191 controls)36 and schizophrenia (69,369 individuals diagnosed with schizophrenia and 236,642 controls)37. These GWAS were selected given the relatively large sample size and modest genetic correlation with autism. Additionally, as a negative control, we included PGS generated from a GWAS of hair color (blonde versus other, n=43,319 blondes and n=342,284 others) from the UK Biobank, which was downloaded from https://atlas.ctglab.nl/traitDB/3495. This phenotype has SNP heritability comparable to that of the other GWAS used (h2=0.15, s.e.=0.014), is unlikely to be genetically or phenotypically correlated with autism and related traits, and has a sample size large enough to be a reasonably well-powered negative control.

PGS were generated for three phenotypes using polygenic risk scoring with continuous shrinkage (PRS-CS)84, which is among the best-performing polygenic scoring methods using summary statistics in terms of variance explained85. In addition, this method bypasses the step of identifying a P-value threshold. We set the global shrinkage prior () to 0.01, as is recommended for highly polygenic traits. Details of the SNPs included are provided in Supplementary Table 3.

De novo variants were obtained from Antaki et al.19. De novo variants (structural variants and SNVs) were called for all SSC samples and a subset of the SPARK samples (phase 1 genotype release, SNVs only). To identify high-impact de novo SNVs, we restricted data to variants with a known effect on protein. These are damaging variants: transcript_ablation, splice_acceptor_variant, splice_donor_variant, stop_gained, frameshift_variant, stop_loss, start_loss or missense variants with MPC86 scores >2. We further restricted data to variants in constrained genes with a LOEUF score <0.37 (ref. 87), which represent the topmost decile of constrained genes. For SVs, we restricted data to SVs affecting the most constrained genes, that is, those with LOEUF score <0.37, representing the first decile of most constrained genes. We did not make a distinction between deletions or duplications. To identify carriers, non-carriers and parents, we restricted our data to samples from the SPARK and SSC studies that had been exome sequenced and families in which both parents and the autistic proband(s) passed the genotyping QC.

For genes associated with severe developmental disorders, we obtained the list of constrained genes that are significant genes associated with severe developmental disorders from Kaplanis et al.27. To investigate the association of this set of genes with autism and developmental disorders, we first identified autistic carriers with a high-impact de novo variant and then divided this group into carriers who had at least one high-impact de novo variant in a DD gene and carriers with high-impact de novo variants in other constrained genes.

Only individuals with undiagnosed developmental disorders are recruited into the Deciphering Developmental Disorders study, and, as such, known genes associated with developmental disorders that are easy for clinicians to recognize and diagnose may be omitted from the genes identified by Kaplanis et al.27. To account for this bias, we ran sensitivity analyses using a larger but overlapping list of genes identified from the Developmental Disorder Gene-to-Phenotype database (DDG2P). From this database, we used constrained genes that are either confirmed or probable developmental disorder genes and genes for which heterozygous variants lead to developmental phenotypes (that is, mono-allelic or X-linked dominant).

We identified 19 autism core and associated features that (1) are widely used in studies related to autism; (2) are a combination of parent-, self- and other-reported and performance-based measures to investigate if reporter status affects the PGS association; (3) are collected in all three cohorts; and (4) cover a range of core and associated features in autism. The core features are

ADOS88: social affect

ADOS88: restricted and repetitive behavior domain total score

ADI89: communication (verbal) domain total score

ADI89: restricted and repetitive behavior domain total score

ADI89: social domain total score

RBS28

Parent-reported Social Responsiveness Scale-2 (ref. 90): total raw scores

SCQ29

Insistence of sameness factor (F1)

Social interaction factor (F2)

Sensorymotor behavior factor (F3)

Self-injurious behavior factor (F4)

Idiosyncratic repetitive speech and behavior (F5)

Communication skills factor (F6).

The associated features are

Vineland Adaptive Behavior Scales91: composite standard scores

Full-scale IQ

Verbal IQ

Nonverbal IQ

Developmental Coordination Disorders Questionnaire92.

Measures of IQ were quantified using multiple methods across the range of IQ scores in the AGRE, SSC and LEAP studies. In the SPARK study, IQ scores were available based on parent reports on ten IQ score bins (Fig. 1c). We used these as full-scale scores. For analyses involving the SPARK and SSC cohorts, we converted full-scale scores from the SSC into IQ bins to match what was available from the SPARK study and treated them as continuous variables based on examination of the frequency histogram (Supplementary Fig. 8). For the six factors, we excluded individuals who were minimally verbal (Factor analyses), but these individuals were not excluded for analyses with other autism features.

We identified seven questions relating to developmental delay in the SPARK medical screening questionnaire. These are all binary questions (yes or no). Summed scores ranged from 0 to 7. The developmental phenotypes include the presence of

ID, cognitive impairment, global developmental delay or borderline intellectual functioning

Language delay or language disorder

Learning disability (learning disorder, including reading, written expression or math; or nonverbal learning disability)

Motor delay (for example, delay in walking) or developmental coordination disorder

Mutism

Social (pragmatic) communication disorder (as included in DSM IV TR and earlier)

Speech articulation problems.

We included the age of first words and the age of walking independently for further analyses. This was recorded using parent-reported questionnaires in the SPARK study and in ADI-R89 in the SSC study. While other developmental phenotypes are available, we focused on these two, as they represent major milestones in motor and language development and are relatively well characterized.

Before any statistical analyses, we visually inspected the distributions of the variables. All continuous variables were approximately normally distributed with the exception of the age of first words, the age of walking independently and the count of co-occurring developmental disabilities. For these three variables, we used quasi-Poisson or negative binomial regression to account for overdispersion in the data and because the variance was much greater than the mean. These models produced the same estimate but modestly different standard errors. Both have two parameters. However, while quasi-Poisson regression models the variance as a linear function of the mean, the negative binomial models the variance as a quadratic function of the mean. The model that produced the lower residual deviance was chosen between the two. For all other continuous variables, we used linear regression and parametric tests. For binary data, we used logistic regression as there was not a large imbalance in the case:control ratio.

For each cohort, PGS and high-impact de novo variants were regressed against the autism features with sex and the first ten genetic principal components as covariates in all analyses, with all continuous independent variables standardized. In addition, array was included as a covariate in SSC and AGRE datasets. This was performed using linear regression for standardized quantitative phenotypes, logistic regression for binary phenotypes (for example, association between PGS and the presence of a high-impact de novo variant), Poisson regression for count data (number of developmental disorders or delays, not standardized) and negative binomial regression for the age of walking independently or the age of first words (not standardized; MASS93 package in R).

For the association between genetic variables and core and associated autism phenotypes, we first conducted linear regression analyses for the four PGS first using multivariate regression analyses with data from SPARK (waves 1 and 2), SSC, AGRE and AIMS-2-TRIALS LEAP. This is of the form:

$$yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{textrm{intelligence}} + {textrm{sex}} + {textrm{age}} + 10 {textrm{PCs}},$$

(1)

where EA is educational attainment and 10PCs are ten principal components. For the negative control, we added the negative control as an additional independent variable in equation (1):

$$begin{array}{lll}yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{textrm{intelligence}} \+ {textrm{PGS}}_{textrm{hair color}} + {textrm{sex}} + {textrm{age}} + 10{textrm{PCs}}.end{array}$$

(2)

For the AGRE and SPARK studies, we ran equivalent mixed-effects models with family ID modeled as random intercepts to account for relatedness between individuals. This was carried out using the lme4 (ref. 94) package in R.

For high-impact de novo variants, we included the count of high-impact de novo variants as an additional independent variable in equation (1) and ran regression analyses for SPARK (wave 1 only) and SSC. To ensure interpretability across analyses, we retained only individuals who passed the genotypic QC, which included only individuals of European ancestries. Family ID was included as a random intercept:

$$begin{array}{l}yapprox {textrm{PGS}}_{textrm{autism}} + {textrm{PGS}}_{textrm{schizophrenia}} + {textrm{PGS}}_{textrm{EA}} + {textrm{PGS}}_{{mathop{{{rm{intelligence}}}}} } \+ {textrm{high-impact de novo count}} + {textrm{sex}} + {textrm{age}} + 10{textrm{PCs}.}end{array}$$

(3)

Effect sizes were meta-analyzed across the three cohorts using inverse-variance-weighted meta-analyses with the following formula:

$$begin{array}{l} {w_{i}} = {{mathrm{SE}}_{i}^{-2}} \ {{mathrm{SE}}_{mathrm{meta}}} = {surd}left(left({Sigma}_{1} w_{i}right)^{-1}right)\ {{beta}_{mathrm{meta}} = {Sigma}_{i}{{beta}_{i}}{{w}_{i}}{left({{Sigma}_{i}}{{w}_{i}}right)}^{-1}},end{array}$$

(4)

where i is the standardized regression coefficient of the PGS, SEi is the associated standard error and wi is the weight. P values were calculated from Z scores. Given the high correlation between the autism features and phenotypes, we used BenjaminiYekutieli false discovery rates to correct for multiple testing (corrected P<0.05). We calculated heterogeneity statistics (Cochrans Q and I2 values) for the PGS meta-analyses but not for the associations with high-impact de novo variants, as the latter were calculated using only two datasets (SSC and SPARK).

For the SPARK and SSC studies, we investigated the association between PGS (equation (1)) and being a carrier of a high-impact de novo variant (equation (3)) and the age of first walking and first words using negative binomial regression and conducted inverse-variance meta-analyses (equation (4)). We ran the same analyses for the SPARK study to investigate the association between PGS (equation (1)) and high-impact de novo variants (equation (3)) and counts of co-occurring developmental disabilities (quasi-Poisson regression). Leave-one-out analyses were conducted by systematically excluding one of seven co-occurring developmental disabilities and reconducting the analyses.

To investigate additivity between common and high-impact de novo variants, we conducted logistic regression with carrier status as a dependent binary variable and all PGS included as independent variables and genetic principal components, sex and age included as covariates. This was carried out separately for SPARK (wave 1) and SSC and meta-analyzed as outlined earlier.

Statistical significance of differences in factor scores between sexes were computed using t-tests. Associations with age and IQ bins were conducted using linear regressions after including sex as a covariate.

Matrix equivalency tests were conducted using the Jennrich test in the psych66 package in R. Power calculations were conducted using simulations. Statistical differences between pairwise correlation coefficients (carriers versus non-carriers) in core and associated features were tested using the package cocor95 in R. Using scaled existing data on full-scale IQ, adaptive behavior and motor coordination, we generated correlated simulated variables at a range of correlation coefficients to reflect the correlation between the six core factors and the three associated features. We then ran regression analyses using the simulated variable and high-impact de novo variants as provided in equation (3). We repeated this 1,000 times and counted the fraction of outcomes for which the association between high-impact de novo variant count and the simulated variable had P<0.05 to obtain statistical power. Differences in the age of walking and the age of first words between groups of autistic individuals and siblings were calculated using Wilcoxon rank-sum tests.

Polygenic transmission deviation was conducted using polygenic transmission disequilibrium tests14. To allow comparisons with midparental scores, residuals of the autism PGS were obtained after regressing out the first ten genetic principal components. These residuals were standardized by using the parental mean and standard deviations. We obtained similar results using PGS that had not been residualized for the first ten genetic principal components. We defined individuals without co-occurring ID as individuals whose full-scale IQ is above 70 the SSC and SPARK studies. Additionally, in the SPARK cohort, we excluded any of these participants who had a co-occurring diagnosis of intellectual disability, cognitive impairment, global developmental delay or borderline intellectual functioning. Analyses were conducted separately in the SSC and SPARK cohorts and meta-analyzed using inverse-variance-weighted meta-analyses. We additionally conducted pTDT analyses on non-autistic siblings to investigate differences between males and females.

For sex differences in high-impact de novo variants, we calculated relative risk in autistic females versus males based on (1) all carriers, (2) carriers of DD genes and (3) carriers of non-DD genes (SPARK wave 1 and SSC). For sensitivity analyses, we conducted logistic regression with sex as the dependent variable and carrier status for DD genes and either full-scale IQ and motor coordination scores (in SPARK wave 1 and SSC) or number of developmental disorders (only in SPARK wave 1) as covariates. For each sensitivity analysis, we provide the estimates of the unconditional analysis as well (that is, without the covariates).

We opted to conduct heritability analyses using unscreened population controls rather than family controls (that is, pseudocontrols or unaffected family members), as this likely reduces SNP heritability96 owing to parents having higher genetic likelihood for autism compared to unselected population controls55 and due to assortative mating97. Casecontrol heritability analyses were conducted using the ABCD cohort as population controls; specifically, the ABCD child cohort in the USA, recruited at the age of 9 or 10 years. This cohort is reasonably representative of the US population in terms of demographics and ancestry. As such, it represents an excellent comparison cohort for the SPARK and SSC cohorts. The ABCD cohort was genotyped using the Smokescreen genotype array, a bespoke array designed for the study containing over 300,000 SNPs. Genetic QC was conducted identically as for SPARK. Genetically homogeneous groups were identified using the first five genetic principal components followed by UMAP clustering with the 1000 Genomes data. We restricted our analyses to 4,481 individuals of non-Finnish European ancestries in the ABCD cohort. Scripts for this are available at https://github.com/vwarrier/ABCD_geneticQC. Imputation was conducted, similar to the analysis of SPARK data, using the TOPMed imputation panel.

For casecontrol heritability analyses, we combined genotype data from the ABCD cohort and from autistic individuals from the SPARK and SSC cohorts. We restricted the analysis to 6,328,651 well-imputed SNPs (r2>0.9) with minor allele frequency >1% in all datasets. Furthermore, we excluded multi-allelic SNPs and SNPs with minor allele frequency difference of >5% between the three datasets and, in the combined dataset, were not in HardyWeinberg equilibrium (P>1106) or had genotyping rate <99%. We additionally excluded related individuals, identified using GCTA-GREML, and individuals with genotyping rate <95%. We calculated genetic principal components for the combined dataset using 52,007 SNPs with minimal linkage disequilibrium (r2=0.1, 1,000kb, step size of 500 variants, removing regions with complex long-range linkage disequilibrium). Visual inspection of the principal-component plots did not identify any outliers (Supplementary Fig. 9). While our QC procedure is stringent, we note that there will be unaccounted-for effects in SNP heritability due to fine-scale population stratification, differences in genotyping array and participation bias in the autism cohorts. However, our focus is on the differences in SNP heritability between subgroups of autistic individuals, and unaccounted-for casecontrol differences will not affect this.

We calculated SNP heritability for autism and additionally in subgroups stratified for the presence of ID, sex, sex and ID together, and the presence of high-impact de novo variants. We also conducted SNP heritability in subgroups of autistic individuals with scores >1s.d. from the mean for each of the six factors, autistic individuals with F1 scores>F2 scores and autistic individuals with F2 scores>F1 scores.

We calculated the observed-scale SNP heritability (baseline and subgroups) using GCTA-GREML52,53 and, additionally, using PCGC54. In all models except for the sex-stratified models, we included sex, age in months and the first ten genetic principal components as covariates. In the sex-stratified models, we included age in months and the first ten genetic principal components as covariates. For sex-stratified heritability analyses, both case and control data were from the same sex. For GCTA-GREML, the observed-scale SNP heritability was converted into liability-scale SNP heritability using equation (23) from Lee et al.98. PCGC estimates SNP heritability directly on the liability scale using the prevalence rates from Maenner et al.99. For all analyses, we ensured that the number of cases did not exceed the number of controls, with a maximum case:control ratio of 1.

We used prevalence rates from Maenner et al.99, which provides prevalence of autism among 8 year olds (1.8%). The study also provides prevalence rates by sex and by the presence of ID. However, there is wide variation in autism prevalence. We thus recalculated the SNP heritability across a range of state-specific prevalence estimates obtained from Maenner et al.99. For estimates of liability-scale heritability for subtypes defined by factor scores >1s.d. from the mean, we estimated a prevalence of 16% of the total prevalence. For F1>F2 and F2>F1, prevalence was estimated at 50% of the total autism prevalence. Estimating approximate population prevalence of autistic individuals with high-impact de novo variant carriers is difficult due to ascertainment bias in existing autism cohorts. However, a previous study has demonstrated that the mutation rate for rare protein-truncating variants is similar between autistic individuals and siblings from the SSC and autistic individuals and population controls from the iPSYCH sample in Denmark, which does not have a participation bias100, implying that the de novo mutation rate in autistic individuals from the SPARK and SSC cohorts may be generalizable. Using the sex-specific proportion of de novo variant carriers and autism prevalence, we calculated a prevalence of 0.2% for being an autistic carrier of a high-impact de novo variant.

For sex-stratified SNP heritability analyses, we additionally calculated SNP heritability for a range of state-specific prevalence estimates to better model state-specific factors that contribute to autism diagnosis. In addition, using a total prevalence of 1.8%, we estimated SNP heritability using a male:female ratio of 3.3:1 (ref. 51) to account for diagnostic bias that may inflate the ratio.

We used GCTA-GREML to also estimate SNP heritability for the six factors, full-scale IQ and the bivariate genetic correlation between them. We used the same set of SNPs used in the casecontrol analyses. We were unable to conduct bivariate genetic correlation for the casecontrol datasets due to limitations of sample size.

We received ethical approval to access and analyze de-identified genetic and phenotypic data from the three cohorts from the University of Cambridge Human Biology Research Ethics Committee.

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

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Genetic correlates of phenotypic heterogeneity in autism - Nature.com

Height is typically a predestined characteristic in most people. According to Medical News Today, up to 80% of someone's height is based on their DNA. If you come from a tall or short family, you are more likely to be taller or shorter. Yet despite baseline genetics, there are a variety of actions to take during childhood and teen years to ensure that your reach your maximum potential height according to your DNA.

Basically, it's the health advice you've likely heard several times before but not everyone follows. Obey a nutritious dietby eating lots of fruits and veggies every day. Make sure you have enough calcium to grow healthy bones as well as plenty of protein. Get adequate exercise to strengthen bones and muscles.

One of the biggest things teens need to reach optimal height is sleep. A growth hormone is released while you're in certain sleep stages (via Verywell Health). If sleep is insufficient, a body won't likely reach maximum growth.

There are numerous ways to predict how tall a boy will be as he grows. The Mayo Clinic outlines two different techniques. In the first prediction, add the mother's height to the father's height and then add 5 inches for boys. (Subtract 5 inches for girls). Then just divide by two. The second way to estimate height is to find a boy's height at age 2 and then double it. (For girls, do the same at age of 18 months.)

As a general rule, men stop growing when they're 18. There is a slight possibility that if a teen boy began puberty late, he may grow a bit in his early 20s, but that is unusual. The reason is simple and it has to do with growth plates (via Healthline). That's the area of the bone made of cartilage that continues to grow. However, they meld together right after puberty, meaning there is no more potential to grow once they have fused.

Over the years the average height of men has grown and that's because men are now getting better nutrition, exercise, and sleep both as children and teens. In the early 1900s, men were averaging 5 feet, 8 inches tall (via A Hundred Years Ago). Currently, in the United States, the average height for men is approximately 5 feet, 9 inches tall, according to the Centers for Disease Control and Prevention (CDC)while the average weight for menrests at 197.9 pounds.

Oddly enough, there are certain states where heights differ. According to the World Population Review, the U.S. states with the tallest men, averaging 5 feet, 10.8 inches or more, are Alabama, Iowa, Kentucky, Montana, Nebraska, North Dakota, South Dakota, Tennessee, Utah, West Virginia, and Wyoming. The states with the shortest average male heights, averaging below 5 feet, 10 inches, are New York, New Jersey, California, Nevada, New Mexico, Hawaii, and Texas. All the remaining states lie somewhere in between.

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What Is The Average Height For Men In The US? - The List

Among neurologic complaints, migraines are the most common cause of productivity loss and emergency room visits. Migraines may be the most painful type of headache, increasing stroke, and heart attack risk in men.

While migraines tend to affect more women, migraines in men do happen. About 9% of men are regular sufferers (vs. 17% of women), and certain types of headaches like cluster headaches are more common in men. Genetics also play a role since approximately 70% of sufferers have a close relative with the problem.

Today, some consider chronic migraine (>15 migraine days per month) as an individual and societal burden as it is more disabling than episodic migraine. A hypothesis to this higher probability of progression could be that men are often not diagnosed or misdiagnosed. The theory may be that they are less likely to report or seek medical treatment for migraines.

It is a false notion that migraine is a women's disease- This stigmatizes the disorder and denies men access to proper care. It is important to be aware of these statistics and seek help if you suffer with migraines. Read on to find out moreand to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID.

A few years ago, scientists started looking at the influence of female hormones in men with migraine. This study reports that men with migraine displayed an increased level of estradiol (type of estrogen hormone) and clinical evidence of androgen deficiency (less male hormones). If you are having more than 15 headaches a month that are debilitating and interfere with your daily functioninga visit is warranted to your physician. Once the initial workup is normal, they can refer you to a migraine specialist once conservative measures fail. Looking at medications, supplements and your daily triggers will help you reduce pain and frequency of attacks. There are daily medications and well as preventive prescription medications that can control the overactivity of migraine attacks.

Use a migraine app to track your symptoms so you can make a correlation to your triggers and symptoms as they occur. The first thing I start with my patients are lifestyle changes to ensure better overall health. Daily habits can go a long way to help you have fewer, less-severe migraines.6254a4d1642c605c54bf1cab17d50f1e

Sleep cycle regulation is very important, go to bed at the same time every day, including on weekends and holidays. The brain's pathways responsible for sleep if disrupted can contribute to migraines.

It is important to seek out complementary medicine that is proven effective in migraines:

Apply lavender oil or peppermint to the base of your neck or use aromatherapy. Inhaling lavender essential oil may ease migraine pain.

Acupuncture can help to mitigate pain and the severity of attacks in many patients.

Ginger prevents nausea that can occur in many migraine patients.

Yoga and biofeedback help many patients cope with pain along with complimentary as well as medication management.

There are many migraine-specific vitamins that your migraine neurologist can recommend along with treatment.

There are also devices for migraines that attempt to interrupt pain signals, more specifically an external trigeminal nerve stimulation (eTNS) unit. The premise of the Cefaly is similar to that of other neurostimulators being tested for migraine treatment. SpringTM may be another option. You hold this device at the back of your head at the first sign of a headache, and it gives off a magnetic pulse that stimulates part of the brain. In addition, there is a noninvasive vagus nerve stimulator called gammaCore. When placed over the vagus nerve in the neck, it releases a mild electrical stimulation to the nerve's fibers to relieve pain. Nerivio is a wireless remote electrical neuromodulator.

Avoid certain foods. Diet plays a vital role in preventing migraine attacks. Your diet plays a part, too. In about 10% of people with these headaches, food is a trigger. Choose better food. Eat as much wholesome, fresh food, like fruits and vegetables, as you can. Avoid processed and packaged foods.

Some common trigger foods include:

Tyramine is a natural compound that forms in protein-rich foods as they age. It's also a trigger for migraines. These cheeses are high in tyramine:

Chemicals added to food to enhance their flavor or help them stay fresh longer may bring on a headache:

Limit stress as tension's a common trigger. Using mediation, music, meditation, yoga, and massage to relieve tension can help. There are many evidence-based complementary techniques. Along with your prescribed treatment, you might want to try one of these to help prevent migraines, such as acupuncture, massage & cognitive behavioral therapy

It is wise to avoid a drop in blood sugar which can set off a migraine. My patients know to drink at least 4-5 glasses of water to avoid dehydration, which can trigger headaches.

Exercise regularly, many of my patients are afraid it might trigger a migraine. Overdoing a workout may trigger a headache for some people, but research suggests regular, moderate aerobic exercise may make migraines shorter, less severe, and happen less often for many people. Vigorous exercise might be a trigger in migraineurs, but overall the benefits of physical activity far outweigh the risk for people with migraine.

Regular exercise is associated with a reduction in the frequency and intensity of migraines, says. Avoid exercise if you're in the middle of a migraine attack, as it can make the pain worse. When you're exercising it can help keep future away attacks by relieving stress, a common migraine trigger.

Exercise also stimulates the release of feel-good hormones called endorphins and enkephalins which are our natural painkillers and natural antidepressants. Migraines share brain receptors with serotonin responsible for our mood.

Preventive or good habits can go a long way to prevent migraines. Yet, it is not a substitute for a proper evaluation by a migraine neurologist. Good sources of information are the American Headache Society (AHS) and the American Migraine Foundation (AMF). The most important thing I keep in mind when treating my patients is that everyone is unique and the approach is never a one size fits all solution. Be aware of overusing over-the-counter pain relievers as they can actually trigger medication overuse headaches and cause stomach upset and ulcers. There is hope for your pain and you do not have to suffer in silence. And to protect your life and the lives of others, don't visit any of these 35 Places You're Most Likely to Catch COVID.

Shae Datta, MD, co-director, NYU Langone's Concussion Center, and director of cognitive neurology at NYU Langone HospitalLong Island.

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Best Habits to Prevent a Migraine, Says Neurologist Eat This Not That - Eat This, Not That

Research News

The subfossil jawbone of a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. A genomic study includes an analysis of DNA extracted from a tooth attached to this jawbone, which is now housed at the Natural History Museum at the University of Oslo. Photo: Karsten Sund, Natural History Museum, University of Oslo

By CHARLOTTE HSU

A new study is providing an enhanced look at the intertwined evolutionary histories of polar bears and brown bears.

Becoming separate species did not completely stop these animals from mating with each other. Scientists have known this for some time, but the new research draws on an expanded data set including DNA from an ancient polar bear tooth to tease out more detail.

The story that emerges reveals complexities similar to those that complicate human evolutionary history.

The formation and maintenance of species can be a messy process, says Charlotte Lindqvist, associate professor of biological sciences, College of Arts and Sciences, and an expert on bear genetics. Whats happened with polar bears and brown bears is a neat analog to what were learning about human evolution: that the splitting of species can be incomplete.

As more and more ancient genomes have been recovered from ancient human populations, including Neanderthals and Denisovans, were seeing that there was multidirectional genetic mixing going on as different groups of archaic humans mated with ancestors of modern humans. Polar bears and brown bears are another system where you see this happening.

We find evidence for interbreeding between polar bears and brown bears that predates an ancient polar bear we studied, she says. And, moreover, our results demonstrate a complicated, intertwined evolutionary history among brown and polar bears, with the main direction of gene flow going into polar bears from brown bears. This inverts a hypothesis suggested by other researchers that gene flow has been unidirectional and going into brown bears around the peak of the last ice age.

A mother polar bear and her 2-year-old cubs in northwestern Greenland. Photo: ystein Wiig

The study was published June 6 in the Proceedings of the National Academy of Sciences. It was led by Lindqvist; Luis Herrera-Estrella at the National Laboratory of Genomics for Biodiversity (LANGEBIO) in Mexico and Texas Tech University; and Kalle Leppl at the University of Oulu in Finland. Tianying Lan, a former UB postdoctoral researcher now at Daicel Arbor Biosciences, was co-first author with Leppl.

The concept of Arctic-adapted polar bears capturing genetic material from brown bears, which are adapted to life in lower latitudes, is one of several findings of possible interest for scientists concerned with climate change impacts on threatened species.

As the world warms and Arctic sea ice declines, polar bears and brown bears may run into each other more frequently in places where their ranges overlap. This makes their shared evolutionary history a particularly intriguing subject of study, Lindqvist says.

An adult male polar bear in northwestern Greenland. Photo: ystein Wiig

Splitting of species can be messy process

As Lindqvist explains, scientists once thought modern humans and Neanderthals simply split into separate species after evolving from a common ancestor. Then, researchers found Neanderthal DNA in modern Eurasian people, implying that modern human populations received an influx of genes from Neanderthals at some point in their shared evolutionary history, she says.

Only later did scientists realize that this genetic intermingling also supplemented Neanderthal populations with modern human genes, Lindqvist adds. In other words, interbreeding can be complex, not necessarily a one-way street, she says.

The new study on bears reveals a remarkably similar story: The analysis finds evidence of hybridization in both polar bear and brown bear genomes, with polar bears in particular carrying a strong signature of an influx of DNA from brown bears, researchers say. Earlier research proposed the inverse pattern only, Lindqvist says.

Its exciting how DNA can help reveal ancient life history. Gene flow direction is harder to determine than merely its presence, but these patterns are vital to understanding how past adaptations have transferred among species to give modern animals their current features, says Leppl, postdoctoral researcher in the research unit of mathematical sciences at the University of Oulu.

Population genomics is an increasingly powerful toolbox to study plant and animal evolution, and the effects of human activity and climate change on endangered species, says Herrera-Estrella, Presidents Distinguished Professor of Plant Genomics and director of the Institute of Genomics for Crop Abiotic Stress Tolerance in the Texas Tech Department of Plant and Soil Science. He is also a professor emeritus at LANGEBIO. Bears dont provide simple speciation stories any more than human evolution has. This new genomic research suggests that mammalian species groups can hide complicated evolutionary histories.

The subfossil jawbone of a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. Photo: Karsten Sund, Natural History Museum, University of Oslo

Evidence from modern bear genomes and DNA from an ancient tooth

The study analyzed the genomes of 64 modern polar and brown bears, including several new genomes from Alaska, a state where both species are found.

The team also produced a new, more complete genome for a polar bear that lived 115,000 to 130,000 years ago in Norways Svalbard archipelago. DNA for the ancient polar bear was extracted from a tooth attached to a subfossil jawbone, which is now housed at the Natural History Museum at the University of Oslo.

Using this data set, researchers estimate that polar bears and brown bears started to become distinct species about 1.3 to 1.6 million years ago, updating prior assessments made by some of the same scientists. The age of the split has been and remains a topic of scientific debate, with past interbreeding and limited fossil evidence for ancient polar bears among factors that make the timing hard to pinpoint, Lindqvist says.

In any case, after becoming their own species, polar bears endured dramatic population decline and a prolonged genetic bottleneck, leaving these bears with much less genetic diversity than brown bears, the new study concludes. The findings confirm past research pointing to the same trends, and add evidence in support of this hypothesis.

Genomes analyzed in a new study on bears include that of this bear, pictured here in 1995 on Alaska's North Slope. Scientists had wondered if this bear might be a brown bear-polar bear hybrid, but the new research finds that, This bear is not a hybrid, but simply a light-colored brown bear, says UB biologist Charlotte Lindqvist. Photo: Richard Shideler, Division of Wildlife Conservation, Alaska Department of Fish and Game

Together with the analysis of gene flow, these findings are providing new insights into the messy, intertwined evolutionary history of polar bears and brown bears.

The international research team included scientists from UB, LANGEBIO, Texas Tech, the University of Oulu, the Far Northwestern Institute of Art and Science, the Alaska Department of Fish and Game, the Natural History Museum at the University of Oslo, Nanyang Technological University, University of Helsinki and Aarhus University.

The research was funded by the National Fish and Wildlife Foundation, U.S. National Science Foundation, Alaska Department of Fish and Game, and U.S. Geological Survey.

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Study offers better look at tangled evolutionary histories of polar bears, brown bears - UB Now: News and views for UB faculty and staff - University...

TWH Extreme weather sometimes reveals unknown or unexplored archaeological sites. A prolonged drought in Iraq has threatened its harvest and resulted in authorities releasing water from the Mosul reservoir for crop irrigation.

As the waters receded, the ruins of a Bronze Age, Mitanni city emerged. Archaeologists excavated the site and found defensive walls, towers, a multi-story warehouse and more than 100 cuneiform boards.

Archaeologists have dated the ruins to around 1400 B.C.E. The ruins are those of Zakhiku, a city in the Mitanni Empire. That empire controlled parts of northern Syria and Mesopotamia from 1550 to 1350 B.C.E.

In 2018, when an earlier drought had lowered the water height in the reservoir, the palace of Zakhiku emerged. Archaeologists seized the opportunity to examine its ruins.

In 2019, The University of Tbingen reported that this palace had walls up to seven meters tall (22.9 feet). They partially excavated eight rooms of the palace. Its inner, plastered walls had heights and thicknesses of up to two meters (6.6 feet). Vivid reds and blue murals covered those walls. Archaeologists think that such murals would have been common. Few Mitanni buildings, however, have survived.

Only three other Mitanni palaces have ever been found, but they were all from the outskirts of the empire. In contrast, Zakhiku lies close to the Mitanni heartland.

They also found ten cuneiform tablets. One of these tablets identified the site as the ancient city of Zakhiku. Other Mitanni records from 1800 B.C.E. refer to Zahiku. As these ruins date to roughly 1400 B.C.E, Zakhiku lasted for, at least, four-hundred years.

The palace had stood on an elevated platform, 20 meters (65.6 feet) from the east bank of the Tigris. The city lay to the palaces north.

In 2021, the waters of the reservoir had receded enough to expose the ruins of Zakhiku. Archaeologists knew that the water levels in the reservoir would begin to rise soon. They decided to excavate the ruins while they were above water. Kurdish archaeologist, Dr. Hasan Ahmed Qasim, joined two German archaeologists, Professor Dr. Ivana Puljiz of the University of Freiburg, and Professor Dr. Peter Pflzner of the University of Tbingen. Oasim chairs the Kurdistan Archaeology Organization.

In their excavations, they found a massive fortification with walls and towers, as well as a multi-story warehouse, and a complex of workshops.

In 2022, the University of Tbingen reported on the significance of that warehouse. The size of the warehouse indicated that it stored a large number of goods. For Qasim, this capacity showed that the site was an important center in the Mitanni Empire.

Inside the warehouse, excavators found five ceramic jars containing more than 100 cuneiform tablets. These tablets do not date from the Mitanni period. They date from the latter Middle Assyrian period from 1350 to 1100 B.C.E.

The Mitanni Empire collapsed around 1350 B.C.E., and Zakhiku fell under Assyrian control. The cuneiform tablets may contain information about that transition.

A strong earthquake struck the region around 1350 B.C.E. which destroyed the city. The upper walls of buildings collapsed and buried the lower parts of the building which may have helped to preserve the structures.

Dried bricks formed the main building material in Zakhiku. The lack of water damage stunned the research team.

After excavation, archaeologists covered most of the site in tight-fitting plastic. Then they covered the buildings with gravel. The Mosul reservoir has returned to capacity. Now, water covers Zakhiku once more, at least until the next drought strikes.

The Mitanni Empire extended from the eastern Mediterranean to northern Iraq. Its center lay in northeastern Syria.

Egyptian texts record that Mitanni had a similar status to that of Babylon, Egypt, and the Hittites. Mitanni rulers intermarried with Egyptian pharaohs.

The Smithsonian Magazine reported that the Mitanni produced the worlds oldest horse training manual. Masters of horsemanship, the Mitanni developed improved wheel technology for their war chariots.

Of all the kingdoms of the Bronze Age in Anatolia, Mesopotamia, and the Levant, the Mitanni Empire remains one of the least known. Very few of their records have survived and their religion left few remains. Surviving mentions of the Mitanni Empire mainly occur in treaties with Egypt, the Hittite Empire, or Assyria. Their Empire combined elements of the indigenous Hurrian culture with migrating or invading Indo-Aryan culture.

Map of Eastern Mediterranean and Middle East in 14th century Image credit: Alexikoua, CC BY-SA 3.0

Indo-Aryan refers to a branch of the Indo-European languages. That branch spread from the steppe region of Eurasia into south and western Asia. Another branch of that language spread into Europe.

Humans being human, people mix genetics and cultures. Languages can spread from one population to another, without one genetic population replacing another. Indo-European is a linguistic, not a genetic concept.

In their paper, About the Mitanni-Aryan Gods, Arnaud Fournet argued that Indo-Aryan words appear in surviving Mitanni texts. Those tablets include what may be the worlds oldest horse training manuals. Two surviving Hittite-Mitanni treaties mention major gods of the RigVeda, and specifically name Mitra, Varuna, Indra, and the Nasatya.

Other words in other surviving texts appear to be Hurrian. That language has no relation to any Indo-European or Semitic languages.

In The Storm-Gods of the Ancient Near East: Summary, Synthesis, Recent Studies, Daniel Schwemer argues for the prominence of storm gods in Upper Mesopotamia. Among the Hurrians, the major storm god had the name, Teub. [Variations on spellings include: Teshub which is also written as Teshup,Teup, orTeup] Schwemer called Teub, the head of the Hurrian pantheon, a divine king.

Chamber A, main scene depicting (left to right) the God Kumarbi (chief god of the Hurrians), the weather and storm god Teshuba, the earth goddess Hepat, Sharumma (son of Teshuba & Hepat) and Alanzu (daughter of Teshup Hepat), Yazlkay in Hittite capital city of Hattusa, Image credit: Carole Raddato, FRANKFURT, Germany CC BY-SA 2.0

The main, barely-surviving Hurrian myth involves generational conflict. It only survives in fragments, mostly written in Hittite. The sky god, Anu, deposes his father, the primeval god, Alahu.

Kumarbi, of the same generation as Anu, then fights Anu and overthrows him. In that fight, Kumarbi bites off (and maybe eats) Anus genitals. That act of castration and absorption brings the divine line into the usurper, Kumarbi.

Anu, apparently still male, gives birth to a new generation of gods, including Tessub. His children, including Tessub, defeat Anu. Tessub becomes the new King of the Gods. Kumarbi returns and makes an alliance with the sea and underworld gods. Tessub eventually defeats that alliance.

This mythic complex has obvious parallels with the Uranus-Cronus-Zeus cycle. Modern Pagans may choose to view this myth cycle through a genderqueer lens. Scholars have studied its fragmentary sources, however, through a reconstructed language. A certain humility is in order. Some things are forever lost in the past, and we may never know.

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Mitanni City emerges from the Mosul Reservoir - Middle East, News, Paganism, Science, US, Uncovering the Past, World - The Wild Hunt

23 May 2022

Male breast cancer accounts for around one percent of breast cancer cases in the UK and a newstudy suggests that men with infertility are twice as likely to develop it.

There is little awareness of the condition due to its rarity. Men who have it are often older at first presentation than women with breast cancer, and they haveless favourable outcomes than women. Researchers from the Institute of Cancer Research, London have recently published the results of their breast cancer in men casecontrol study.

'Our study suggests that infertile men may be twice as likely as those without fertility issues to develop breast cancer. The reasons behind this association are unclear, and there is a need to investigate the fundamental role of male fertility hormones on the risk of breast cancer in men. We hope this could lead to insights into the underlying causes of male, and possibly even female, breast cancer', said Dr Michael Jones, study senior author and staff scientist in genetics and epidemiology at the Institute of Cancer Research.

Nearly two thousand men from England and Wales who had been diagnosed with breast cancer between 2005-2017, and 1597 controls, were included in the study recently published in the journal Breast Cancer Research. They took part in interviews with a nurse where they provided information on whether or not they had children or had ever sought fertility treatment. They also provided a blood or saliva sample.

Analysis showed men who reported they had been diagnosed as having infertility had double the odds of developing breast cancer when compared with those without fertility issues. Furthermore, men without offspring had 50 percent increased odds of developing breast cancer, and this difference remained significant even if restricting the analysis to married men alone.

Researchers did not look at reasons for the link but suggested that hormones could play a role, and there is already some understanding that testicular problems that could lead to infertility could also affect hormonal production.

Dave, a former police officer from Bristol, was diagnosed with breast cancer in 2015 and said: 'My mother died from ovarian cancer when she was 68-years-old, and I knew there was a link between ovarian and breast cancer, but generally little is known about male breast cancer. People will say 'I didn't realise men could get that' and to be honest, I didn't think I would ever get it!'

'It's really interesting that if you're affected by fertility issues, you could be more likely to be affected by breast cancer. I'm lucky that I haven't been impacted by fertility problems, but it's important scientists build on Breast Cancer Now's research as it could help to find out what causes some male breast cancers and one day even lead to developing new treatments.'

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Men with infertility could have double the risk of breast cancer - BioNews

This kind of first-degree offspring is extraordinary, only having been cited in royal families of the past headed by god-kings such as the Egyptian pharaohs seeking to maintain a pure dynastic bloodline. (It is known, for instance, that Akhenaten married his eldest daughter, Meritaten, and much later, Ptolemy II married his sister, Arsinoe II hence his nickname, "Philadelphus" or "sibling loving.") It has been suggested that this Neolithic elite may have claimed to possess divine powers to ensure the continuity of agricultural cycles by keeping the Sun's movements going.

The findings support the notion that these Neolithic communities were socially stratified and that the massive stone structures were used to bury transgenerational patrilineal members of these clans. Perhaps equally interesting is the fact that in one case relatives were separated by up to 12 generations, pointing to an unusual stability through time of both the funerary tradition and the stratified society where they lived.

We have seen several case studies of past inequality correlating funerary archaeology with genetics that might no longer apply today, where legal regulations (and also the exponential increase of cremations) represent a certain degree of standardisation in funeral practices. Nevertheless, an opposite trend could shape thefuture of the archaeology of death: the trend toward personalised coffins, unconventional funerary memorials, and special grave goods. One way or another, mortuary archaeology will always be an important subfield of this discipline, and one that will need to rely on the hard sciences such as genetics and forensics.

Perhaps one encouraging conclusion is that despite what we have seen on the archaeology of past inequality, societies have been able to evolve and change their social stratifications. One example is Iceland the country has become one of the most egalitarian societies in the world. In 2018, Iceland passed a law that all companies employing more than 25 people will have four years to ensure gender-equal payment because, according to the head of the Equality Unit at Iceland's Welfare Ministry, "equality won't come about by itself, from the bottom up alone".

* This is an edited version of an article thatoriginally appearedinThe MIT Press Reader, and is republished with permission.

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Carles Lalueza-Foxis Research Professor and Director of the Paleogenomics Lab at the Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra) in Barcelona. He participated in the Neanderthal Genome Project and led the first retrieval of the genome of an 8,000-year-old European hunter-gatherer. He is the author of Inequality: A Genetic History, from which this article is adapted (this is an edited version of the original MIT Reader piece).

--

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Why some ancient societies were more unequal than others - BBC

Sample and design

We used data from the Longitudinal Aging Study Amsterdam (LASA). LASA is an ongoing, prospective cohort study, based on a representative sample of the older population in the Netherlands. LASA focuses on the determinants, trajectories and consequences of changes in physical, cognitive, emotional, and social functioning in older adults aged 55years or older. Measurements are conducted approximately every three years and include a main face-to-face computer assisted interview, a face-to-face computer assisted medical interview in which clinical measurements are performed and additional questions are asked, and a self-administered questionnaire. The study received approval by the medical ethics committee of the VU University medical center. Signed informed consent was obtained from all study participants. Sampling, response and procedures are described in detail elsewhere [28].

For the current study, we adopted a lagged-effect design, because we expected that with ageing, older workers would increasingly be affected by their gender role (our main determinant) and working conditions (our moderator/mediator), and that this would result in higher depressive symptoms scores in the course of time. Thus, we assumed a temporal precedence of gender roles and working conditions, as opposed to an immediate effect on depressive symptoms. Accordingly, data from 20122013 (T1) and 20152016 (T2) were used. At T1, 1023 respondents participated in the LASA study. We excluded those who did not have a paid job at T1 (n=395), those who did not participate at T2 (n=93), and those who did not have a paid job at T2 (n=222). We ended up with a sample of 313 older workers.

Our outcome measure was depressive symptoms, measured using the Center for Epidemiologic Studies Depression Scale (CES-D) [29]. The CES-D is a 20-item self-report scale ranging from 0 to 60, with higher scores reflecting more depressive symptoms. The outcome was measured at T2 (2015/2016).

All independent variables were measured at T1 (2012/2013).

We included biological sex, derived from the population registers, as an independent variable.

We constructed a gender index, based on the work of Smith and Koehoorn [9] on gender roles in the labour market. Smith and Koehoorn included four gender items in their index: responsibility for caring for children, occupation segregation, number of working hours, and level of education. Because in our sample of older workers responsibility for caring for children was not applicable, we chose to include a measure of informal caregiving. Providing informal care is much more common among women compared to men and is seen as a more feminine role [30, 31]. As suggested by Smith and Koehoorn, we also included a measure of household responsibilities. Furthermore, Smith and Koehoorn suggested to include a measure for primary earner status. Unfortunately this information was not available in our data. We therefore chose to include income in our index. While Smith and Koehoorn use relative measures (relative to the partner) for educational level and number of working hours, we use absolute measures for these items, because we consider absolute measures to reflect broader societal gender roles rather than gender roles within the household.

The gender index consisted of the sum score of six items: number of working hours, income, occupation segregation, level of education, informal caregiving, and time spent on household chores. For each gender item, a higher score represents more femininity and a lower score represents more masculinity.

Respondents were asked about their number of working hours per week. Responses were categorised into quartiles and recoded so that a higher score (i.e. a lower number of working hours) represents more femininity.

To assess the income of the household, respondents were asked what their monthly household income was, choosing from 24 categories, with the lowest category being 454-567 and the highest category 5446 or more. To ensure comparability of income between persons with and without a partner in the household, income was multiplied by 0.7 for respondents with a partner in the household. The factor 0.7 is the inverse of the squareroot of 2, i.e., the number of household members. This correction makes the incomes of all respondents equivalent to one-person household incomes [32]. Income was categorised into quartiles and recoded so that a higher score (i.e. a lower income) represents more femininity.

Occupation segregation was measured by the percentage of female workers in the sector. Using data from Statistics Netherlands, we assigned each sector to one of four categories in accordance with Smith and Koehoorn [9]: (0)25% female workers, (1) 2650% female workers, (2) 5175% female workers, and (3)76% female workers.

Respondents were asked about their highest completed level of education. We used the International Standard Classification of Education 2011 [33] to categorise educational level into three groups: (0) low (up to lower secondary education, ISCED 02), (1) intermediate (upper secondary education or post-secondary non-tertiary education, ISCED 34), and (2) high (short cycle tertiary and higher, ISCED 56). Again, scores were recoded so that a higher score (i.e. lower educational level) reflects more femininity.

Respondents were asked if they recently provided help with household chores to somebody outside the own household, and whether the respondent provided help with personal care to somebody inside or outside the own household. If so, questions were asked about the intensity (hours) of care. Informal caregiving was categorised into (0) not giving informal care, (1) giving<8h of informal care per week, and (2) giving8h of informal care per week.

Respondents were also asked about the time spent on light and heavy household chores. Time in minutes per day, averaged across the past 14days, was categorised into quartiles.

The gender index ranged from 022 and was dichotomised at the median into masculine (scores 07) and feminine (scores 822) to enable comparison of its association with depressive symptoms with the association of biological sex with depressive symptoms.

We used a written questionnaire to obtain data on working conditions [34]. Respondents could answer (1) never, (2) sometimes, (3) often, or (4) always to all questions on working conditions.

To measure physical demands five items were used: use of force, using tools that cause vibration or shaking, working in an uncomfortable position , standing for a long time, and kneeling down or squatting. Psychological demands consisted of two items: working very fast, and having to do a lot of work. For cognitive demands, six items were used: think of solutions, learn new things, requires creativity, requires thinking intensively, requires focus, and requires attention. Autonomy was measured with three items: control over how to do the job, control over sequence of tasks, and control over when to take time off. For variation in tasks one item was used: having variation in tasks. And for social support four items were included: help and support of colleagues, colleagues willing to listen to work related problems, help and support of supervisor, and supervisor willing to listen to work related problems.

Sum scores were made for each type of working conditions and scores were dichotomised using the median due to non-linearity.

Age was derived from the population registers.

Multiple imputation (MICE) was used to deal with missing values, which were assumed to be missing at random. All independent, control and the outcome variables were included in the imputation process and the number of imputations was set to 30, based on the percentage of missing values (28%) [35]. To assess to what extent the separate gender items as well as the gender index are associated with sex, we conducted logistic regression analyses [36]. We used Structural Equation Modeling (SEM) to estimate the associations visualised in Fig. 1. All analyses were adjusted for age. Separate models were examined for sex and gender. We used tobit regression analyses to estimate the associations of sex/gender and the working conditions with depressive symptoms, because the depressive symptoms scale is skewed to the right due to the detection limit at the lower end of the scale. Tobit models account for this left-censoring by assuming a normal distribution that is cut off (censored) at zero.

Visual representation of the moderation and mediation models

To test whether gender/sex is a moderator in the association between working conditions and depressive symptoms, we built models with an interaction between sex/gender and the working conditions (Fig.1A). In case of a statistically significant interaction, the association between the working conditions and depressive symptoms varies across sexes/genders.

To investigate whether working conditions explain the association between sex/gender and depressive symptoms, we built single mediator analyses (Fig.1B). To estimate the c paths (total effect of sex/gender on depressive symptoms) and the b paths (effect of the mediators on depressive symptoms, while controlling for sex/gender), we used tobit regression analyses, and for the a paths (the effect of sex/gender on the mediators), we conducted logistic regression analyses. We used causal mediation analyses to estimate the indirect effects [37]. We used bootstrapping techniques (500 repetitions) to calculate the 95% confidence intervals around the indirect effects. All analyses were carried out in Stata version 14.

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Sex and gender differences in depressive symptoms in older workers: the role of working conditions - BMC Public Health - BMC Public Health