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Genetic mapping of subsets of patients with fragile X syndro | TACG – Dove Medical Press

Introduction

Fragile X syndrome (FXS), OMIM # 300624, is a X-linked inherited genetic disease classified as a triplet repeat condition. FXS is the most common cause of inherited intellectual disability and autism in the world. It has a prevalence of 1 in 5000 men and 1 in 8000 women. Affected individuals are characterized by intellectual disability, autism, language deficit, typical facies, and macroorchidism.1,2

Alterations in the FMR1 gene with locus Xq27.3 are causative of Fragile X Syndrome and other disorders. This gene harbors a CGG repeat within the 5 untranslated region and, depending on the number of repetitions, 4 types of alleles are defined with different clinical manifestations:3 Normal alleles, which have up to 44 CGG repeats; grey zone or intermediate alleles that contain between 45 and 54 repeats; premutation (PM) alleles with between 55 and 200 repeats; and full mutation (FM) alleles, with more than 200 repeats. In most cases, this is due to an expansion of the CGG triplet from one generation to the next.4

The Fragile Mental Retardation Protein (FMRP) is coded by the FMR1 gene. The absence of FMRP expression is usually secondary to the methylation of the FMR1 gene that occurs when more than 200 CGG repeats are present in the 5UTR region; this can also be explained by a point mutation in the coding region for FMR1 or a deletion that includes this gene, but these changes have only been reported in a few cases. The absence of FMRP is related to the classic FXS phenotype.5,6

FMRP expression is slightly lower in the carriers of a PM allele. Lower levels of FMRP are found particularly in the upper premutation (PM) range however, they typically do not present the classic FXS syndrome phenotype.7 Furthermore, they have elevated FMR1 mRNA levels between 2 to 8 times normal levels, which also leads to RNA toxicity. These elevated levels of mRNA are a risk for a number of medical conditions that are not explained by decreased FMRP.2,4,8

FMRP has roles in chromatin dynamics, RNA binding, mRNA transport, and mRNA translation9,10 and for certain subgroups of cerebral transcripts.11

This protein is involved in the regulation of RNA stability, subcellular transport and translation of neural mRNAs that codify proteins involved in synapsis development, neural plasticity and brain development.8

In addition, FMRP interacts with at least 180 proteins expressed in the brain and connective tissue. This interactome comprises known FMRP-binding proteins, including the ribosomal proteins FXR1P, NUFIP2, Caprin-1, and other novel FMRP-interacting candidate proteins located in different subcellular compartments, including CARF, LARP1, LEO1, NOG2, G3BP1, NONO, NPM1, SKIP, SND1, SQSTM1 and TRIM28. This interactome suggests that, besides its known functions, FMRP is involved in transcription, RNA metabolism, ribonucleoprotein stress granule formation, translation, DNA damage response, chromatin dynamics, cell cycle regulation, ribosome biogenesis, miRNA biogenesis and mitochondrial organization.9

Several studies have shown that in the absence of FMRP, a wide range of neural mRNAs are affected, boosting neural protein synthesis, which results in dendritic spine dysmorphogenesis and glutamate/GABA imbalance, which in turn produce variations in neural excitation/inhibition, phenomena that are present in FXS. Dendritic spine dysmorphogenesis plays a role in the intellectual deficits and behavioral problems, due to the weak synaptic connections found in this syndrome.12,13

Fragile X syndrome (FXS) has incomplete penetrance and variable expressivity and biological sex is a decisive factor of the phenotype. Full mutation of the FMR1 gene has a 100% penetrance of intellectual disability in males and 60% in females. Other characteristics associated with FXS Appear with varying frequencies in affected individuals. Autism spectrum disorder (ASD) symptoms appear during early childhood in 50% to 60% of males and 20% of females with FXS.1417

Physical features include elongated face, large and prominent ears (7578% of affected males), mandibular prognathism (80% of adult men), hyperlaxity and macroorchidism (95% of adult men). Other characteristics also vary in their frequency of presentation: seizures (23%), strabismus (8%), and cardiac abnormalities such as abnormal aortic root dimensions (18%) and mitral valve prolapse (55%). In general, the female phenotype is less severe and less specific.4,18

The variation in the phenotype of monogenic diseases is common,19,20 it is explained by a combination of genetic, environmental, and lifestyle factors,21 and FXS is not an exception.

Here, we present a review of the knowledge about the molecular factors involved in the variable expressivity of FXS.

The presence of a full mutation in FMR1 is associated with the hypermethylation of a CpG island located in the promoter of the FMR1 gene. Methylation of DNA regions (mDNA) is one of the main epigenetic modifications related to transcription regulation.22 A CpG island is located proximal to the CGG repeat tract, which is expanded in FXS. Hypermethylation of the CpG island generates transcriptional silencing of the FMR1 gene.23 As a consequence, the Fragile Mental Retardation Protein (FMRP), codified by the FMR1 gene, is not produced24 and in turn, the absence or low expression of FMRP causes FXS.

CGG tract repetition expansion in the untranslated region (UTR) of exon 1 in the FMR1 gene generates instability of that region during the replication process, inducing size mosaicism, which is defined as the presence of premutation and mutation alleles in several cells.25

In males with FXS caused by full mutation, the detection of FMR1 mRNA levels in peripheral blood lymphocytes is common. This phenomenon is due to both size mosaicism and mDNA in the CpG island and nearby regions that vary between cells and tissues.26 Furthermore, longitudinal studies in women with FXS have shown that levels of mRNA transcribed from FMR1 decrease significantly with age.23 Complicating even more the behavior of mDNA and FXS, it has been found that in premutation alleles, a considerable number of cells have mDNA.27 The variation between methylation states of the CpG island and nearby regions among different cells and tissue of the same person is known as methylation mosaicism.28 It is estimated that around 50% of people with FXS have this type of mosaicism.29 In cells where mutated alleles are not methylated, they are transcriptionally active and can be expressed.30 However, in these cells there is no FMRP synthesis since mRNA with CGG expansion greater than 200 repeats is not translated efficiently in ribosomes.31,32

The absence or low levels of FMRP is a decisive factor for FXS development, as several studies have aimed to discover the relationship between protein levels and phenotypic characteristics of the patients. Since the late 1990s, correlations between FMRP levels and the neurological phenotype of FXS have been established.29,33,34 The first studies about this topic established the standard levels of FMRP in peripheral blood leucocytes through immunoblotting. When comparing protein levels with the allele type and the presence of size mosaicism, it was demonstrated that people with the lowest FMRP levels were males with FM. Males with size mosaicism and females with FM had slightly higher levels of FMRP than males with FM.33,35,36 Via multiple regression models, it was found that FMRP levels were significantly correlated with the intelligence quotient (IQ) of the patients in the study.33 However, studies did not identify the same relation between FMRP levels and behavioral symptoms.34,37 More recent evidence supports a partial overlap between the pathogenic mechanisms that lead to FXS and ASD.38 Lower FMRP levels have been documented in samples of individuals with FXS and ASD compared to patients with FXS only.29,34 The relation between FMRP levels and IQ in males and females with different expansions in CGG repeats was studied recently.39 This last study has two important advantages compared with previous studies: firstly, the use of fluorescence resonance energy transfer (FRET), which has a higher sensibility when measuring protein levels, and also FMRP levels were measured in dermal fibroblasts. Unlike leucocytes, fibroblasts derive from the ectoderm, the same germ layer from which nervous system cells originate. Researchers found a strong and positive relation between FMRP levels and cognitive skills in patients with levels below 30% of the standard levels in controls. Interestingly, above this level, there was a higher dependence between low FMRP levels and low IQ.39

In parallel with the aforementioned studies, researchers reported the incidence of size and methylation mosaicism in cognitive impairment severity.4042 The classic definition of premutation alleles behavior as non-methylated alleles, and mutated alleles as methylated or partially methylated ones in order to categorize premutation carriers and patients with FXS has been extended progressively to include a detailed classification that takes into account the existence of size and methylation mosaicisms.

Regarding size mosaicisms, different combinations have been described, including patients with some FM cells and other cells with PM. Indeed, patients with FM, PM, grey zone alleles and even alleles with normal size have been reported.40 The presence of size mosaicisms with PM and FM alleles is related with a less severe phenotype and a higher risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS).43

When exploring the possible relation between size mosaicisms and the intellectual functioning of patients with FXS disregarding sex, it was found that patients with FM/PM had better intellectual functioning and less maladaptive behavior, compared with FM-affected individuals.42 Interestingly, the same study found that ASD features and maladaptive behaviors were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning. A limitation of this study is that they used venous blood and real time PCR and Southern blot analysis to quantify the level of methylation.

Recently, methylation mosaicism has been taken into account as an important variable in phenotype traits. The most frequent mosaicism found in males is the presence of FM-methylated alleles and non-methylated FM and PM alleles (combination of size and methylation mosaicism).25,44 However, in patients with FM and not PM mosaicisms, methylated alleles do not express mRNA, while non-methylated alleles do. An aspect that highlights the importance of detecting the presence of this kind of mosaicism is the influence on phenotype severity. Additionally, according to some case reports, the presence of synthesized mRNA from PM and FM alleles increases the odds of developing the FXTAS phenotype.45,46 The final consequence of methylation mosaicism is the cells reduced ability to express FMR1 mRNA, measure mRNA and determine if there is a relation with phenotypic traits. When analyzing mRNA levels between males and females, it was found that females had higher levels. Also, in females, higher levels of FMR1 mRNA were related positively with age but not with intellectual functioning and autistic features. Males with FM that express FMR1 mRNA had significantly higher ADOS calibrated severity scores, when compared with males with fully methylated FM. Interestingly, no differences were found regarding intellectual functioning.41 Likewise, when contrasting FMR1 mRNA levels and scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-CfX) it was found that in males with FM, higher values of FMR1 mRNA were related with elevated irritability and lower health-related quality of life scores.47 This association was not found in males with PM/FM, suggesting that for improved genotype/phenotype associations, it is essential to take into consideration not only sex but also size and methylation mosaicism.

Recent investigations explored simultaneously how FMR1 mRNA levels of FMRP are related to phenotypic alterations in males with PM and FM.48 In a study composed of 14 cases of patients with PM or PM and FM mosaicism and mental illnesses such as bipolar disorder, schizophrenia and psychosis, among others, low levels of FMRP and increased FMR1 mRNA were evident in these patients. This combination of characteristics in patients with FM, decreased FMRP, PM and increased FMR1 mRNA represents a dual mechanism of clinical significance that may generate characteristics of both FXS and FXTAS.48 In a clinic-based ascertained group of patients with FXS of both gender, a significant difference was found between FXS with ASD and low levels of FMRP when comparing concentrations of the protein in patients with FXS without ASD.29 They found that the mean full scale IQ and adaptive skills composite scores were significantly lower in males than in females (p = 0.016 and p = 0.001, respectively, MannWhitney). Additionally, all individuals with moderate or severe ID were males. Not surprisingly, ASD was present more frequently in males with FXS (46% vs 20% females). This association was not found in males with PM/FM, suggesting that for improved genotype/phenotype associations is essential to take into consideration not only sex but size and methylation mosaicism.29

There is a small proportion of FXS patients without expansions in the CGG-repeat tract. In this group, the condition is caused by missense or nonsense mutations,5,16 or deletions in FMR1.1,6 Patients with these mutations have similar physical, cognitive and behavioral characteristics to FXS patients. With the increasing availability of diagnostic methods based on next-generation sequencing and comparative genomic hybridization, a higher rate of diagnosis of mutations causing FMR1 function loss is expected. This will allow a clear delimitation of the phenotype caused by the loss of the protein in the absence of CGG tract expansions.

For many monogenic diseases it is known that, besides the allelic variance, the effect of modifier genes has an important role in incomplete penetrance and variable expressivity. The identification of modifier genes that affect the phenotype in monogenic diseases has many challenges that complicate their description. A genetic variant can modify the effect in the phenotype of another variant in many ways, including epistasis and genetic interactions.49,50

In studies using FXS murine models, important new evidence was acquired in order to establish the importance of potential modifier genes and their impact on FXS phenotype development. The knockout mouse model for FXS was generated in the last decade of the XX century. Fmr1 KO mice had learning deficits, abnormal synaptic connections, seizures, hyperactivity and macroorchidism.51,52 When describing the mouse phenotype in detail, it was evident that abnormal phenotypic characteristics depend, at least in some proportion, on their genetic background.53

During the identification of modifier genes in the FXS phenotype, a large proportion of the research has aimed towards the susceptibility to developing certain clinical behavioral characteristics, such as aggression, ASD and seizures.34,5459 All of the studies use a similar methodological design: they arrange groups of people with or without a specific phenotypic trait and establish the frequency of specific variants in modifier gene candidates.

The possibility that Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene may modulate the epilepsy phenotype in FXS patients has also been investigated. The replacement of a methionine for a valine in the 66th position of the BDNF protein interferes with normal intracellular traffic and BDNF dependent secretory activity in cortical neurons.60 This polymorphism has been related to cerebral anatomy alterations61 and neuropsychiatric disorders.62,63 In a sample of 27 males with FXS from Finland, it was found that all the patients with epilepsy (15%) had the Met66 allele, whereas the prevalence of this allele is 20% in the normal population. Research suggests that the Met66 allele in BDNF interacting with FM in FMR1 may partially explain the higher incidence of seizures in patients with FXS.56 In a more recent study with a higher number of males with FXS (77 patients), the results were not replicated and there was no association between seizures and Val66Met polymorphism.58 These results show the importance of validating studies about modifier genes in different populations.

In research about genes that affect mood and aggression, such as the serotonin transporter (5-HTTLPR), the monoamine oxidase A (MAOA-VNTR) and COMT, conflicting results were found. All of those genes are involved in regulatory pathways for different neurotransmitters, and their variants have been associated with the development of behavioral phenotypes in different contexts other than FXS. In one group of 50 males with FXS, the relationship of 5-HTTLPR and MAOA-VNTR polymorphisms with the frequency/severity of aggressive/destructive, self-injurious and stereotypic behaviors was studied. It was found that the high-transcribing long (L/L) genotype in 5-HTTLPR was related with a higher frequency of aggressive/destructive and stereotypic behavior, while patients with the short (S/S) genotype had less aggression. The MAOA-VNTR genotype had no effect on behavior.55 On the other hand, in a study of 64 males with FXS where the COMT gene was also included, the results of the previous study were not replicated. There was no association between behavioral characteristics and either 5-HTTL PR (serotonin) or MAOA genotypes. Nevertheless, the A/A genotype in COMT that modifies dopamine levels was associated with greater interest and pleasure in the environment, and with less risk of property destruction, stereotyped behavior and compulsive behavior.54 The authors of the study suggest that the non-reproducibility of the results regarding MAOA-VNTR can be explained by differences in the prevalence of aggressive and stereotyped behavior among the studied populations or by differences in the measurements used to characterize each behavior.

The importance of identifying potential modifier genes was explored in a clinical trial. The researchers investigated the relation between polymorphisms in several genes and the response of sertraline in 51 children. They found that BDNF, MAOA, 5-HTTLPR, Cytochrome P450 2C19 and 2D6 polymorphisms had significant correlations with treatment response.64

Currently the knowledge about molecular causes of the variable phenotype in patients with FXS include characteristics associated with the FMR1 gene itself and to secondary, modifying gene effects.

Regarding FMR1, when the diagnosis is established, the type of mutation causing FXS is identified: CGG repeat tract expansion vs pathological variant causing loss of function in FMR1.

When the CGG is identified, is it expected that about half of the patients have size or methylation mosaicism or both.29 The presence of any of those mosaicisms determines the expression or not of FMR1 mRNA and FMRP. The quantity of FMRP is directly related with IQ.34,37,39 While the presence of size mosaicism is related with better intellectual functioning and less maladaptive behavior,29,42 elevated concentrations of FMR1 mRNA in patients with FM have been associated with a higher risk of developing FXTAS45,46,48 and with the severity of behavioral symptoms.47

The search for modifier genes affecting the phenotype has been carried out using the candidate genes strategy. Because high impact clinical manifestations in FXS are related with neurologic phenotypes, the studied candidate genes are involved in CNS development and the appearance of seizures (BNDF)56,6062 and associated with mood and aggression (5-HTTLPR, MAOA-VNTR y COMT).54,55 Recent research has been done with small groups of patients and there are no conclusive results about the importance of these variants in modifier genes.

Scientific and clinical evidence about molecular causes of variable expressivity in FXS is growing quickly. It is evident that aspects of the mutation type in FMR1 and the behavior of the CGG repeat tract are relevant in the presentation of the condition. Research about modifier genes is still emerging. There are important limitations such as sample size and comparability of different studies, mainly due to smaller groups of selected patients and the use of different tools for measuring the phenotypes.

Independent cohorts of patients with FXS across different continents have shown evidence that mosaicism, FMR1 mRNA or FMRP quantification are associated with the severity of the phenotype. However, this information cannot currently be used effectively in the integral management of patients. When intervention strategies become available in order to prevent the development of FXTAS, or when certain molecules can regulate levels of FMRP expression to measure FMR1 mRNA and FMRP, they could be crucial for selecting patients and identifying the best therapeutic intervention.

In clinical trials there is an important window of opportunity. Identifying mosaicism, measuring transcription/translation activity of FMR1 and stratifying patients by modifier genotypes29,65 will permit the identification of subgroups of patients with greater potential to respond to specific treatments.

The authors report no conflicts of interest in this work.

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55. Hessl D, Tassone F, Cordeiro L, et al. Brief report: aggression and stereotypic behavior in males with fragile X syndrome - Moderating secondary genes in a single gene disorder. J Autism Dev Disord. 2008;38(1):184189. doi:10.1007/s10803-007-0365-5

56. Louhivuori V, Arvio M, Soronen P, Oksanen V, Paunio T, Castrn ML. The Val66Met polymorphism in the BDNF gene is associated with epilepsy in fragile X syndrome. Epilepsy Res. 2009;85(1):114117. doi:10.1016/j.eplepsyres.2009.01.005

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Genetic mapping of subsets of patients with fragile X syndro | TACG - Dove Medical Press

‘Star Wars: The Bad Batch’ Who Is Omega? Inside the Magic – Inside the Magic

Michelle Angs Omega joins the Star Wars universe in the latest Disney+ television series from Lucasfilm, Star Wars: The Bad Batch. With voice actor veteran, Dee Bradley Baker, back as the titular Bad Batch, Angs character is stirring up some big questions for Star Wars fans namely, who is Omega in The Bad Batch?

Here is your guide to the new female clone in the Star Wars universe.

The Bad Batch premiere launched on Star Wars Day (May 4) and tells the story of a group of defective, genetically modified clones called Clone Force 99, or the Bad Batch. Made up of five mutated clone troopers Hunter, Tech, Echo, Crosshair, and Wrecker the squad partakes in numerous mercenary missions on behalf of the Republic, and are quickly becoming some of the best characters in the galaxy.

Dave Filonis (Star Wars Rebels, Star Wars Resistance) new animated series crosses over the events of Star Wars: The Clone Wars and Star Wars: Episode III Revenge of the Sith (2005) in the time before the original trilogy began. The season began with a feature-length episode titled, Aftermath, highlighting the historic moment of the Galactic Empires rise to power. Despite The Bad Batch controversy early on, the new series seems to have already built its fandom like many of the other Star Wars spinoffs.

When Chancellor Palpatine executed Order 66, overriding the Clone Armys programming to turn on their Jedi generals, Clone Force 99 was seemingly unaffected due to their enhancements. Although, as time wore on, some of the squad members did succumb to the Order 66 protocol before being saved by their brothers.

Omega, like the member of Clone Force 99, is a genetically enhanced clone. Essentially made from the DNA of bounty hunter Jango Fett, Omegas existence at least at first was seemingly unknown, but as the series progresses more and more is coming to light about the new character.

In the ninth episode of The Bad Batch, Bounty Lost, Omega was revealed to be a direct replica of Jango Fett, at least in terms of genetics. Only one other clone has this same link the bounty hunter, Boba Fett.

Arguably the new Grogu of Star Wars, Omega was introduced as a wide-eyed child intent on seeking a more adventurous life. Raised under the guidance of the Kaminoans on Kamino, Omegas first appearance came when the elite soldiers of Clone Force 99 returned to Kamino following the execution of Order 66. She was the medical assistant to Nala Se.

Hunter had just saved the Padawan Caleb Dume Kanan Jarrus in Star Wars Rebels after the murder of Jedi Master Depa Billaba, and upon returning to Kamino stumbled upon Omega. When Admiral Tarkin arrived on Kamino, Omega bonded with Hunter and the rest of Clone Force 99 before escaping the planet with them after Crosshairs chip activated, making him turn on his squad.

Many theories point to Omega being Force-sensitive. Her skill targeting a weapon in the premiere episode of the Star Wars animation, and more recently her ability to win every opponent at a game of dejarik, suggests there may be more than meets the eye with this honorary Bad Batch member.

What Star Wars fans do know, however, is that Omega is the daughter of Jango Fett and sister to Boba Fett. In Bounty Lost, after a near-death situation with the notorious Cad Bane and Fennec Shand, Tech revealed that Omegas genetic makeup is a direct replication of Jango Fetts. While the clone trooper armys genetics were slightly modified to grow quicker, Omega and Boba Fett were left completely untouched.

While Star Wars fans dont know much else other than this familial connection to two of the galaxys most notorious bounty hunters, her relationship to Boba Fett provides the most interesting detail, and not just for Filonis The Bad Batch. With only six episodes left of the first season, her backstory could point to the animated reprisal of Boba Fett or likewise the live-action debut of Omega in a Star Wars series down the line like Robert Rodriguezs The Book of Boba Fett.

Back to The Bad Batch though, we know the Kaminoans have hired bounty hunters to capture and protect Omega reasons unknown so her existence in the animated series suggests that trouble isnt far away for Clone Force 99.

As well as discovering what she is, Omega is slowly building a life outside of Kamino. Still under the shadow of those who made her, Omegas burgeoning connection to the members of the Bad Batch is how she seems to be writing her own history. The character is always one to dive into adventure, and even though this causes despair for Hunter and the gang, she is proving herself to be a valuable part of this formidable crew.

From helping in the mission on Corellia to find and secure a tactical droid to being present for the removal of the clones inhibitor chips on Bracca, Omegas Star Wars story has only just begun.

Omega is sharp-minded and headstrong. Sometimes a little nave, the character often heads into trouble with the right intentions but not the military skill to back it up. However, her way to find good in everyone as well as passing no judgments on what Clone Force 99 has had to do to stay alive makes her one of the galaxys warmest hearts.

Omegas personality has been shaped by those around her. The individual members of the unique squad, all of which have their own personalities seem to have rubbed off on the young clone. It is in her difference now to when she first met Clone Force 99, that fans can get an idea of how sheltered her life was back on Kamino. Much like how Grogu was in hiding for so long in The Mandalorian, Omegas entry into the big wide galaxy is a point of much character exploration.

From the Bad Batch, she learned about teamwork and survival, and even from characters like Cid (Rhea Perlman) has Omega developed new traits for this example, it seems Cids abrupt nature and aloofness has given Omega some new street smarts if her dejarik winning streak is anything to go by.

While Omega is the one Clone Force 99 protects most of the time, her calmness and quality to not see everything from a military perspective has aided the group on many occasions. Her competitive kinship with Rafa and Trace Martez on Corellia helped bring the sisters and the Bad Batch together to battle the army of police droids.

Omegas caring nature and inability to leave those she loves also highlight how the young clone is adding something new to the squad. Even after Wrecker set out to kill her after his inhibitor chip activated, Omega stayed by his side following the chip removal surgery and wouldnt rest until her squadmate woke up.

Omega has learned much since joining Clone Force 99. On Bracca, Wrecker taught her how to disarm explosives while on Ord Mantell, she acquired a Zygerrian energy bow. Although at first a novice in combat, Omega has quickly learned new skills in order to survive the attacks of Crosshair and the Galactic Empire as well as the relentless confrontations with the galaxys most nefarious bounty hunters.

Omega picked up her energy bow on Ord Mantell and has become an adept user at handling the weapon, although she still needs much practice to use it confidently. As StarWars.com describes:

Firing sizzling laser bolts instead of arrows, a Zygerrian energy bow is a formidable weapon in a firefight if you have a sharp eye and strong arms to lend the weapon unwavering accuracy.

It is perhaps the mystery surrounding the possibility of Omega being Force-sensitive that is most interesting in her skillset. Some might say its beginners luck or youthful charm, but the way she successfully aimed, possibly the first weapon she has ever wielded, in the premiere episode or managed to win numerous back-to-back games of dejarik, alludes to the fact that Omega may not be any regular clone.

Whether she is connected to the Force or not, Omegas skills at negotiating with her team members and other allies, as well as her ability to quickly pick up military talents make her more than suitable to take up the opening Crosshair left in Clone Force 99 and become one of the new rebels of the galaxy.

With more yet to discover, Omega is perhaps one of Star Wars most interesting new characters, and with many more upcoming projects, fans might not have to wait long for some answers.

What is your favorite thing about Omega? Let us know in the comments!

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'Star Wars: The Bad Batch' Who Is Omega? Inside the Magic - Inside the Magic

Hair: Types and care instructions – Medical News Today

There are many different types of hair, including straight, curly, wavy, and coily.

Depending on a persons hair type, they may need to follow different care instructions.

This article will provide some general information about hair types and detail some specific care instructions.

Hair type typically refers to the shape of a persons hair. Hair can be straight, wavy, curly, or coily.

According to one 2020 article, hair consists of two structures: the strand of hair itself, or the hair shaft, and the hair follicle.

The hair shaft consists of different layers, including the cortex, the surrounding cells, and, in thicker hair, a central medulla.

A 2017 study notes that the shape of the hair follicle determines the shape of a persons hair. For example, the hair follicles for curly hair are in the shape of an S.

Genetic factors play a role in deciding the shape of a persons hair follicle.

Learn more about what determines hair shape here.

Hair shape refers to the degree of curliness of a persons hair.

One review article notes that different researchers have used different hair shape categorization systems in their research about hair. For example, some have used use labels such as:

Some hairstylists like to distinguish hair shapes into four categories. However, scientists do not use this categorization system in medicine or scientific research.

Hairstylists use the following categorization system:

Hair density refers to the number of hairs that a person has on their head. The more hairs a person has, the higher that persons hair density.

Hair structure refers to the thickness of the strands of hair. A persons hair can be:

According to the World Trichology Society (WTS), hair thickness varies depending on the person. Some people have finer hairs than others. The WTS also notes that the hair fibers become shorter and finer as a person ages.

Hair porosity is a measure of the amount of moisture that a persons hair can absorb.

Hair porosity depends on how many gaps or tears are present in the cuticle layer. The cuticle is the outer layer of the hair, which protects it from wear and tear.

According to one 2015 article, hair is naturally porous. However, hair that has sustained damaged due to bleaching or chemical treatments is more porous than untreated hair.

People may find it helpful to avoid strong chemical and high heat treatments to let their hair recover.

According to the American Academy of Dermatology (AAD), people can try the following when caring for their hair:

People should select their shampoo and conditioner based on their hair type.

If possible, they should try to limit:

There is some evidence to suggest that straight hair carries sebum more easily than curly hair. Sebum is a waxy, oily substance that a persons skin produces. This means that people with straight hair may be more likely to get oily hair than those with curlier hair.

For this reason, people with straighter hair may wish to avoid the excessive use of certain hair products. These include:

People with straight hair may also wish to wash their hair more frequently.

According to a 2015 article, a person with straight hair may need to use a more gentle approach to caring for their hair. This may involve:

Over-brushing can damage curl definition. Therefore, people with curly hair may need to experiment to find the right amount of brushing for their hair.

Some other care tips for curly hair include:

Some people may also wish to use hair mousses and gels that are intended for curly hair to maintain curl definition.

The AAD suggests the following tips for Black hair:

Additionally, people may wish to take care when using weaves or extensions. To prevent hair damage, they may wish to try:

Tight hairstyles can also lead to traction alopecia, which results in hair loss. People may wish to consider giving the hair a break after 23 months of wearing a weave or extension.

Learn more about Black hair care tips here.

People with thick hair may find it helpful to use denser hair products, such as:

Additionally, people with greater hair density may find it beneficial to use brushes that are designed for thick hair. These brushes have fewer spokes than others, which helps people remove knots without breaking the hairs.

There is anecdotal evidence to suggest that denser hair products, such as oils and butters, can weigh down thinner hair. For this reason, people with thin hair may wish to avoid these products.

People with thinner hairs may also benefit from:

The WTS notes that people shed approximately 50150 hairs per day. This can occur through hair washing, brushing, and combing. However, some people lose more hair than they can grow.

This can happen for various reasons. One common cause is androgenetic alopecia. This is a genetically predetermined condition that affects around 50% of people. In males, hair loss occurs at the temples and the top of the head. In females, hair loss can affect the crown.

Hair loss can also occur in females due to other health conditions, including:

A person should contact a doctor if they:

Some anecdotal evidence suggests that people can use certain shampoos, essential oils, and dietary supplements to thicken the hair. However, there is no scientific evidence to prove that hair care can prevent thinning hair.

That said, a person can take measures to help prevent some causes of hair loss, such as traction alopecia.

Learn more about stopping hair loss here.

Everyones hair is slightly different. A persons hair can be straight, curly, coily, or wavy, and each type benefits from different methods of care.

Although some hair loss is common, a person should contact a healthcare professional if they are concerned.

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Hair: Types and care instructions - Medical News Today

New laws hit the books in Mississippi on Thursday – Yall Politics

Check out what laws go into effect on July 1, 2021.

Dozens of Mississippi laws will go into effect on Thursday, July 1, 2021. Take a look at some of the most talked about bills of the 2021 session and how these new or revised laws could impact you.

Teacher Pay Raise

Probably one of the most talked about bill that passed from the House of Representatives was a raise for teachers and teaching assistants. HB 852, which had a nearly identical companion bill in the Senate, provided for a $1,000 raise for teachers at the start of the 2021-2022 school year and $1,100 for assistant teachers.

A teacher pay raise was on everyones mind entering the 2021 session and COVID-19 made it particularly important to lawmakers to see these funds diverted to teachers. In total, the raise made up an additional $50 million to education in the FY2022 budget.

Occupational Licensing Recognition

Workers in Mississippi and those who would like to come to the state but are licensed in other states, just got a helping hand. HB 1263, authored by Rep. Becky Currie, instated the Universal Recognition of Occupational Licensing Act. This bill allows individuals who work in other states and have a license that is in good standing with that agency to transfer for work to Mississippi with no additional loopholes.

RELATED: Governor Reeves on Universal Occupational Licensing Act: Mississippi is open for business

Just days before going into law, Governor Tate Reeves commented that this bill would allow workforce development to continue and labor shortages from the pandemic to decrease. He also said that it will reduce the red tape many professionals have to go through in order to work in Mississippi. That will include teachers coming from out of state to work here.

Election Qualifying

Planning to run for office in Mississippi? Well, take note of this bill lawmakers passed this session. HB 1048 effectively changes the qualification deadline to February 1 for some statewide, state district, county and county district offices.

Previously the deadline was not until March 1. This will bump the decision up for candidates considering a run for elected office by one month.

Appropriations bills

Mississippis budget was set during the 2021 session. The bills that pertain to appropriations for state agencies and such will all go into effect July 1, 2021. This marks the start of a new fiscal year in the state.

You can read more of those bills from the Senate and House here.

Alcohol Delivery

Many Mississippians have been pushing for more accessible ways to get their alcohol. The Legislature listened with HB 1135. This bill will allow the delivery of a particular wine, spirit or beer from a licensed retailer to a consumer. The retailer must also have a delivery service permit to participate in this service.

Those delivering can be current employees or contracted individuals who are at least 21 years old and receive proper training consistent with current programs. To place an order, you must be at least 21 years old.

Executive Sessions for Public Bodies

Speaker of the House Philip Gunn authored a bill, HB 1323, that will allow any public body to enter into executive session in order to develop a strategic plan to combat, eliminate, reduce or respond to human trafficking or the commercial sexual exploitation of children.

The reason these meetings would be necessary is to address a particular trafficking issue and attempt to provide an immediate solution.

MAEP Calculations

Over in the Senate, many lawmakers set their sights on improving education as well as helping the Mississippi Department of Education operate in unprecedented times.

SB 2149, which was authored by Sen. Dennis DeBar, provided that typical daily attendance rolls would not count against schools from the 2020-2021 school year.

Mississippis MAEP funding formula is calculated in part by daily attendance. Due to the unprecedented nature of the pandemic and virtual learning, daily attendance was unpredictable and, for many schools, impossible in-person during portions of the last year.

Teacher License Reciprocity

Similar to the removal of red tape for all occupational licensing, SB 2267 will allow reciprocity for teachers.

This bill will apply to any teacher coming from another state who already possess a teacher license and can pass a background check. Under the law, the Department of Education can grant a one-year extension to June 2022 to allow for that teacher to meet requirements in Mississippi.

The bill also implements the creation of a licensing and certification committee that will assist in streamlining the process for teacher certification in the state.

Earned Parole Eligibility

Possibly one of the most talked about pieces of legislation in general this year centered around the criminal justice system in Mississippi. SB 2795, or the Earned Parole Eligibility Act, was offered by Sen. Juan Barnett. He brought forward a similar bill in 2020 but it was vetoed by Governor Reeves.

Barnett said he took those critiques and perfected the language in order to have an agreement.

The Earned Parole Eligibility Act allows for particular non-violent, and some violent offenders, to be eligible for parole after a certain amount of their sentence has been served. The hesitation in 2020 centered around murderers being considered in the eligibility category, a move Barnet said was removed in the 2021 bill.

RELATED: Senate passes Mississippi Earned Parole Eligibility Act

Those not eligible include sex offenders, human traffickers, murderers, capitol, and habitual offenders. It is important to note that the bill does not grant any offenders parole; it only allows the possibility of parole in the event the individual has met the proper criteria for consideration.

The bill passed in both chambers and was later signed into law by Governor Reeves.

Medicaid Tech Bill

Every three years lawmakers are tasked with reconfiguring the guidelines for the Mississippi Division of Medicaid. This year it almost looked as if lawmakers would leave the 2021 session without a Medicaid Tech bill. However, at the final hour they were able to come to an agreement on the program with SB 2799.

RELATED: Medicaid will live on in the Governors office and with a budget

Though some attempts were made to remove the Division of Medicaid from under the Governors office, it remained housed there in the 2021 legislation. But the House did remove language that would have provided 12 months of postpartum care for mothers who receive the benefits.

Sen. Kevin Blackwell, Chairman of Medicaid, said the final bill included a 5% reimbursement for some providers, restored crossover claims for hospitals, nursing home and immediate care facility reimbursement days, and provided an additional 5% bump for dentists in 2022-2024 to cover preventative services.

RELATED: Senate passes bill to increase TANF benefits for Mississippians

Dept. of Public Safety

Many changes were made in regard to law enforcement and the Department of Public Safety. Perhaps the largest of note was the transfer of the Capitol Police from the Department of Finance and Administration to the Department of Public Safety. The law came by way of SB 2434.

The duties and abilities of the Capitol Police did not change with the bill, only the overseeing agency. The bill was offered by Sen. Brice Wiggins, Sen. Angela Hill and Sen. John Horhn.

Capitol Police monitor the Capitol Complex in Jackson.

Mississippi Fairness Act

Mississippi gained national attention with the passage of SB 2536, entitled the Fairness Act. The legislation, offered by Sen. Angela Hill, would prevent biologically male individuals from competing in female sports. This law will apply to K-12 schools as well as institutions of higher learning.

When defending her bill to those who claimed it was non-inclusive to transgendered athletes, Hill said those who were born physically a male have an advantage over female athletes simply due to genetics.

RELATED: Mississippi Governor signs Fairness Act into law barring biological men participating in women, girls sports

The bill was up in the air until the last minutes of the session when it was passed. Sen. Hill said the legislation was necessary in order to protect girls sports in the state under the current federal position toward transgendered persons competing among athletes that do not share their at-birth genetic makeup.

Name, Image, Likeness

Another bill that could impact Mississippi athletes is SB 2313. This bill will allow Mississippi collegiate athletes to receive compensation if their image, name or likeness is used in advertising.

RELATED: Reeves signs bill to allow college athletes compensation when their name, image or likeness is used

Mississippi lawmakers believe passing this legislation will keep Mississippi schools competitive in the event the U.S. Supreme Court rules in current court cases to allow for the compensation.

Weight Limits

Senator Jennifer Branning presented SB 2825, the Mississippi Infrastructure Act of 2021 which tackled several road, bridge and transportation issues the state faces.

Probably the most considerable change was that of the harvest weight limits being raised from 84,000 pounds to 88,000 pounds. The bill goes into effect July 1, 2021, but the harvest permit increase does not take effect until July 1, 2023. These weight limits would only apply to commercial truckers carrying a harvest permit.

The bill was argued by many in the Senate as it moved through the process.

While this story only highlights some of the more impactful bills going into effect on July 1, you can access information on all bills passed from the 2021 session, and when they will take effect you can visit the Mississippi Legislatures website HERE.

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Lawmakers will officially head back to the Capitol in January for the 2022 session.

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New laws hit the books in Mississippi on Thursday - Yall Politics

PATHWAY to Northern PROFITABILITY with Seifert Belmont Reds – Queensland Country Life

This article is branded content for Seifert Belmont Reds

Profit-making genetics are readily apparent in the 90 bulls and 10 PTIC heifers' that husband and wife team Ian Stark and Jeanne Seifert, have selected for their third annual Seifert Belmont Reds Sale.

Seifert Belmont Reds is the largest breeder of purebred registered Breedplan recorded Belmont Reds in Australia. Their aggregation of five properties totals approximately 10,000ha and is a mix of ticky and clean country from marginal iron bark breeder country to brigalow backgrounding country.

Mrs Seifert is particularly proud of their females who continue to naturally rebreed, even on the back of two of the driest years on record.

"Our genetics are produced from a tough, unpampered cow herd where females are managed under a single sire mating program, using Belmont Red bulls at 1 per cent - 2 per cent, for a nine or a twelve-week joining period.

"Our cattle are never ever treated for tick or fly, are rarely handled, and every female must wean a calf every year, off native pasture, without any special care," she said.

"Under this regime and dry years, our wet cows and heifers returned from 93.2 per cent to 98.5 per cent pregnancy rates this year."

Early puberty bulls are also used from 14 months old to produce higher fertility daughters and sons. These stringent 'survival of the fittest' breeding principles, ensure that the young bulls catalogued for the 2021 sale will provide valuable heritable traits including phenomenal fertility, excellent growth and carcase attributes, genuine docility, and the highest levels of environmental adaptation.

Of the 90 bulls, 44 are Homozygous Polls (PP) and offer phenomenal fertility, truetropical adaptation and parasite resistance, with muscling and marbling.

"To top it off , 44 bulls of the 90 bulls are homozygous (PP) polls, and an impressive 73 per cent of them are at or above the 50th percentile for the Breedplan export $index."

Mr Stark said their emphasis on real fitness for purpose, and their ability to reliably meet volume demand, plus JBAS 7 status, ensures Seifert Belmont Reds can sell Australia-wide including into the Northern Territory and Western Australia.

"The reputation for our bulls to deliver consistent lines of calves, stems from many decades of breeding, where our pedigrees can be traced back to the original CSIRO Africander cross breeding trials of 1954," Mr Stark said.

"I'm especially pleased with the progress our herd has made with respect to type, muscling, and eye muscle area.

"IVF (invitro fertilization), ET (embryo transfer), AI (artificial insemination) and cloning are used to create optimum genetic combinations and accelerate genetic progress."

The demand for tropically adapted Bos Taurus Seifert Belmont Red genetics is emphasised by their exportation to Papua New Guinea, New Caledonia, the Philippines, and South America.

In 2020 the stud also established a satellite purebred Belmont Red herd with partners in Paraguay.

"Our focus on personal and professional integrity, combined with trustworthy data, provides peace of mind to our buyers," he said.

"We have every confidence in this draft, and we're sure they will make a valuable contribution to your herd and your profitability."

The demand for tropically adapted Bos Taurus Seifert Belmont Red genetics is emphasised by their exportation to Papua New Guinea, New Caledonia, the Philippines, and South America.

The catalogue is available now on http://www.seifertbelmontreds.com with hardcopies mailed on request. Inspections are welcome at any time, on any day - call, text or email Ian 0439 632 113 or Jeanne 0427 632 113, jeanne@seifertbelmontreds.com.

Click here for sale catalogue.

Videos will be on the website and AuctionsPlus two weeks before the sale. The sale will be on AuctionsPlus and by Helmsman auction, from 12 noon Monday, August 2, on property at 'Wonga' Jandowae. Attendees are welcome from 7am with complimentary morning tea and lunch.

Free delivery to Charters Towers, Rockhampton, Roma and Dalby saleyards will be available. Outside agents welcome, contact Elders Michael Smith 0428 541 711 or Anthony Ball 0428 275 499.

This article is branded content for Seifert Belmont Reds

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PATHWAY to Northern PROFITABILITY with Seifert Belmont Reds - Queensland Country Life

In Memoriam: Jean Wilson, M.D., made scientific discoveries that led to effective prostate treatments, insights into sexual differentiation – UT…

DALLAS June 21, 2021 Jean D. Wilson, M.D., an internationally known endocrinologist whose scientific discoveries led to profound insights into the mechanisms underlying sexual differentiation and led to now widely used treatments for prostate disease, died June 13. He was 88.

Wilson, seen here in 1962, graduated from UTSouthwestern Medical School in 1955 and joined the faculty in 1960, where he began his studies of testosterone.

Wilson, professor emeritus of internal medicine at UTSouthwestern, was largely responsible for current understanding of the mechanisms by which steroid hormones induce male sexual differentiation. He also was instrumental in identifying the scientific underpinnings of a widely prescribed class of drugs known as 5-alpha-reductase inhibitors which include finasteride (Proscar, Propecia) and dutasteride (Avodart) to treat enlarged prostate and balding in men.

Wilsons discovery of 5-alpha-reductase and the identification of dihydrotestosterone as the primary hormone associated with the growth of the prostate transformed our understanding of prostate gland growth and paved the way for new effective treatment of prostate disease, says Daniel K. Podolsky, M.D., president of UTSouthwestern. His findings led to the first medical therapy for benign prostatic hyperplasia, and also provided the basis for understanding of the mechanism underlying the differentiation of male and female genital development. His legacy will be found in the legions of patients who have benefited from the therapy made possible by his discoveries.

Wilson, seen in 1978, was a popular and highly sought-after attending physician on the wards of Parkland Memorial Hospital, valued for his vast expertise in endocrinology and medicine in general.

Jean Wilson was one of the most critical and helpful sources of information concerning the development of two important drugs we were developing at Merck the statins, for control of LDL cholesterol, and Proscar, for treatment of benign prostate enlargement. Wilson was always available to wrestle with problems that often arise in drug development. I needed expert friends in those early days, and probably still do, says P. Roy Vagelos, M.D., former chairman, president, and chief executive officer of Merck & Co. and now chair of the board of Regeneron Pharmaceuticals.

Wilsons research included the study of cholesterol metabolism and steroid hormone action. The UTSouthwestern Medical School graduate and former National Institutes of Health (NIH) researcher earned international prominence for his investigations of testosterone including its formation from cholesterol as well as its metabolism and action. His efforts elucidated disorders resulting from genetic defects that lead to disruption in sex hormone biosynthesis with corresponding alteration in development.

Collaborations at UTSouthwestern with David Russell, Ph.D., professor of molecular genetics, led to the cloning of the 5-alpha-reductase (5AR) gene, development of animal models for 5AR deficiency, and eventually the finding that a 5AR inhibitor blocked prostate growth, which resulted in clinical trials led by Claus Roehrborn, M.D., chair of urology. The human androgen receptor later was cloned in 1989, allowing Wilson and colleagues to identify the receptor as a transcription factor that could regulate both the receptor and 5AR expression in prostate cancer. Other scientists at UTSouthwestern expanded upon his research, identifying androgen involvement in virtually all aspects of prostate development, alternate mechanisms of androgen synthesis, and other forms of androgens related to castrate-resistant prostate cancer.

Among his numerous awards, Wilson received the Kober Medal from the Association of American Physicians (1999); the Fred Conrad Koch Award from The Endocrine Society (1993); Gregory Pincus Award from the Worcester Foundation for Experimental Biology (1992); Henry Dale Medal from the Society for Endocrinology (1991); Amory Prize from the American Academy of Arts and Sciences (1977); and the Eugene Fuller Award from the American Urological Association. He was elected as a member of the American Academy of Arts and Sciences (1982), the National Academy of Sciences (1983), and the National Academy of Medicine (1994) as well as the American Philosophical Society and served as president of the Endocrine Society, the American Society for Clinical Investigation, and the Association of American Physicians.

Wilson, seen in 1992, was elected as a member of the American Academy of Arts and Sciences (1982), the National Academy of Sciences (1983), and the National Academy of Medicine (1994).

Wilson, who had held the Charles Cameron Sprague Distinguished Chair of Biomedical Research, was known as a collaborative colleague and empathetic adviser to students and fellows. His approach with students and trainees was threefold find out what they want to do, encourage them to do it, and develop pathways to fulfill their goals, he said in an interview with The Journal of Clinical Investigation. He also noted that some of the most difficult students to counsel turned out to be late bloomers who really were worth an investment of time and effort.

At UTSouthwestern, he served as the first director of the Medical Scientist Training Program, and it was recently announced that the Physician Scientist Training Program in Internal Medicine would be known as the Jean Wilson Society. The Jean D. Wilson Center for Biomedical Research and The Jean D. Wilson, M.D. Award, which honor excellence in scientific research mentorship, are named in his honor. The center was established with support from Dr. Wilson and his sister, the late Dr. Margaret Sitton, to promote research in endocrinology, developmental biology, and genetics, along with the J.D. and Maggie E. Wilson Distinguished Chair in Biomedical Research. In addition, he served among editors of two landmark medical textbooks Williams Textbook of Endocrinology and Harrisons Principles of Internal Medicine and as editor for The Journal of Clinical Investigation, among other journals. He authored The Memoir of a Fortunate Man, which chronicles his life growing up in the Texas Panhandle through his rise to pioneering academic physician and researcher.

Jean was a popular and highly sought-after attending physician on the wards of Parkland Memorial Hospital, valued for his vast expertise in endocrinology and medicine in general, say Nobel Laureates Joseph Goldstein, M.D, chair of molecular genetics, and Michael Brown, M.D., director of the Erik Jonsson Center for Research in Molecular Genetics and Human Disease. He founded a diabetic foot clinic at Parkland and spent hours each week clipping toenails and treating ulcers on the feet of elderly diabetic patients. After long days on the wards, he would retire to his modest laboratory where he would spend half the night meticulously dissecting rabbit fetuses. Often, when we were just starting our careers, we would sit by his side while he dissected, receiving sage advice about our careers as physician-scientists and life in general. Later, he extended his fatherly role to generations of M.D./Ph.D. students when he became the founding director of our M.D./Ph.D. program.

He had a rich life outside of the Medical Center as well. An avid opera buff, Wilson collected antique gramophones that could play every type of recording that had ever been produced. His extensive collection of 3,500 old 78-rpm operatic recordings included a 1917 disc of Enrico Caruso singing songs of Irving Berlin the only record that Caruso ever recorded in English, they note.

An avid opera buff, Wilson, seen in 2019, collected antique gramophones. His extensive collection of 3,500 old 78-rpm operatic recordings included a 1917 disc of Enrico Caruso singing songs of Irving Berlin the only record that Caruso ever recorded in English.

He took memorable trips to places like the North Pole, Antarctica, the Galapagos Islands, and the Easter Islands. He often incorporated science into his trips, visiting the Kangaroo Island in Australia to study sexual development in wallabies, and to Kenya to biopsy the phallus of the spotted hyena. Fearless in the pursuit of knowledge, he performed a rectal examination on a lion to estimate the size of the prostate, Goldstein and Brown say. A dedicated bird watcher, he traveled the world to many exotic places, hoping to spot that rare bird. But in the end, the rarest of that rare bird was Jean Wilson himself.

Born in Wellington, Texas, in 1932, Wilson obtained an undergraduate degree in chemistry from UT Austin and graduated from UTSouthwestern Medical School in 1955. As a student, he studied the control of urinary acid secretion by adrenal hormones, and as a resident, he investigated cholesterol metabolism. After residency, he spent two years at the NIH, where he studied ethanolamine biosynthesis. He joined the UTSouthwestern faculty in 1960 where he began his studies of testosterone, and worked in 1970 at Cambridge University. In all, he spent 60 years at UTSouthwestern and was named professor emeritus of UTSouthwesterns storied internal medicine department in 2011.

Jean Wilson leaves us with a remarkable legacy a quintessential physician-scientist whose scholarship both inspires and continues to serve as a foundation for new advances, says Podolsky, also professor of internal medicine.

In a career spanning six decades at UTSouthwestern, Dr. Jean Wilsons discoveries included:

Cholesterol metabolism

Dr. Wilson developed methods for quantifying cholesterol synthesis, absorption, degradation, and excretion in lab animals. Together, these analytical methods served as tools for understanding the feedback control of cholesterol synthesis and turnover. In addition, Dr. Wilson demonstrated that plasma cholesterol is synthesized in the intestinal wall and liver, findings that helped researchers define the contributions of diet and endogenous synthesis to cholesterol turnover in humans and other primates.

Male androgens

Concurrently, Dr. Wilson studied the action of male androgens, focusing on testosterone and its metabolite, dihydrotestosterone. Starting with a collaboration with his postdoctoral fellow, Nicholas Bruchovsky, in 1966, the researchers discovered that testosterone is converted inside prostate cells into dihydrotestosterone, a more potent androgen that is responsible for most of male sexual maturation and male sexual function. Dr. Wilson and his colleagues later showed that mutations that impair either the synthesis of testosterone, the conversion of testosterone to dihydrotestosterone, or the function of this metabolites receptor protein are the most common cause of birth defects associated with incomplete development of the male urogenital tract, affecting about four in every 1,000 boys. Cloning these responsible genes eventually allowed researchers to identify asymptomatic carriers of these mutations.

Dihydrotestosterone

Dr. Wilson also discovered that excess dihydrotestosterone is responsible for benign prostatic hyperplasia (BPH), or prostate enlargement, a condition that affects about 210 million men worldwide. Dihydrotestosterone is responsible for prostate growth in all male mammals, but in humans and dogs, prostate growth continues throughout life. Wilson and his colleagues showed that local excess of this potent androgen leads to prostate overgrowth. By curbing its production by inhibiting 5a-reductase, the enzyme that converts testosterone to dihydrotestosterone, they were able to prevent BPH in dog models of this condition. These findings have been developed into multiple 5a-reductase-inhibiting pharmaceuticals to treat this condition in human patients.

Brown, a Regental professor and director of the Erik Jonsson Center for Research in Molecular Genetics and Human Disease, holds The W.A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research, and the Paul J. Thomas Chair in Medicine.

Goldstein, a Regental professor and chair of molecular genetics, holds the Julie and Louis A. Beecherl, Jr. Distinguished Chair in Biomedical Research, and the Paul J. Thomas Chair in Medicine.

Podolsky holds the Philip OBryan Montgomery, Jr., M.D. Distinguished Presidential Chair in Academic Administration, and the Doris and Bryan Wildenthal Distinguished Chair in Medical Science.

Russell holds the Eugene McDermott Distinguished Chair in Molecular Genetics.

About UTSouthwestern Medical Center

UTSouthwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 24 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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In Memoriam: Jean Wilson, M.D., made scientific discoveries that led to effective prostate treatments, insights into sexual differentiation - UT...

Aduhelm Is A New Option to Treat Alzheimer Disease – Pharmacy Times

About 5.8 million Americans in 2020 were living with the disease, according to CDC data.2

Estimates show that this number will nearly triple to about 14 million people by the year 2060. Although the disease occurs mostly in older individuals, symptoms sometimes also occur in younger patients.

AD is the sixth-leading cause of death in the United States and the third-leading cause of death for patients older than age 65 years.

The disease is named after physician Alois Alzheimer, MD, who in 1906 discovered changes in the brain of a female patient who had died of mental illness. This patient suffered from language problems, memory loss, and unusual behavior. While examining her brain, Alzheimer found a few abnormal clumps, also known as amyloid plaques, and tangled bundles of fibers called neurofibrillary tangles.

An early symptom of AD is forgetfulness. As the disease advances, the individual may develop more severe memory impairment and can become more debilitated, causing then to struggle with completing everyday tasks. Symptoms are typically noticed by close family members who interact with the individual frequently, and they may become severe to the point that the patients forget relationships and even sometimes the names of loved relatives. Changes in the brains of these patients can also affect their behavior and mood and include aggressiveness, delusions, depression, irritability, more distrust of others, and social withdrawal.

Causes of AD may be related to brain proteins that fail to function normally, causing neurons to not be able to perform their duties. This impairment can be caused by environment, genetics, and lifestyle. The damage starts earlier than the point that the symptoms start to show, and in late stages, the brain shrinks significantly from its normal size.

The proteins involved include beta-amyloid plaques, which when clumped together cause toxic effects on neurons and disrupt the cell-to-cell connection. Meanwhile, Tau proteins help carry essential minerals and nutrients to the brain, and in patients with AD, these proteins change shape and become entangled. This disrupts the nutrient transport system, affecting brain cell function.

Genetics play a role in a patient developing AD, specifically for those with first-degree relatives diagnosed with the disease. Gender also plays a role, with women diagnosed more often than men, though this may also be related to the fact that women tend to live longer.1

One genetic factor known to cause the disease is Apolipoprotein E gene, which with the e4 variation, increases the risk of AD exponentially. Additionally, patients with Down syndrome are more likely to develop AD than others. This is likely related to 3 copies of the chromosome 21, which connect with the creation of beta-amyloid.

Diagnosing AD may include neuropsychological testing and brain imaging, using amyloid positron emission tomography (PET), computer tomography, magnetic resonance imaging, PET scan, or Tau PET imaging.

Medications used to great AD include those that help with memory symptoms and treat cognitive changes. Two major types of the drugs available on the market for these patients include cholinesterase inhibitors and memantine. Cholinesterase inhibitors may help treat agitation and depression and commonly include donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon). Memantine (Namenda) and the combination of memantine and donepezil (Namzaric) combine a cholinesterase inhibitor with memantine to help with medication compliance and help slow the progression of disease symptoms.

On June 8, 2021, the FDA approved aducanumab injection (Aduhelm), an amyloid beta-directed antibody indicated for the treatment of AD. Aduhelm comes in 2 dosages of 170mg/1.7ml and 300mg/3ml solution. The recommended dosage for this drug is 10mg/kg as an intravenous infusion for more than 60 minutes every 4 weeks.

Aduhelm provides new hope for patients diagnosed with AD to have more treatment options available to them after many years of waiting for an FDA approval. The future for research in this area is promising and holds the key to more discoveries, including a cure for AD.

References

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Aduhelm Is A New Option to Treat Alzheimer Disease - Pharmacy Times

‘Unfair Biological Athletic Advantage’, Maltese S&C Coach Weighs In On Trans Weightlifter Competing At The Olympics – Lovin Malta

Kiwi trans woman weightlifter Laurel Hubbard has reignited debates on transgender participation in sports following the announcement that she would be allowed to compete in the womens category at the Summer Olympics in Tokyo this year.

The landmark decision is the first since the International Olympic Committee modified its guidelines in 2015 to allow trans woman athletes to participate if they showed testosterone levels of less than 10 nanomoles per liter for at least one year prior to competition.

Needless to say, allowing Hubbard to participate in the womens weightlifting category has sparked both praise and criticism, with one side commending its inclusivity, while the other side draws attention to an uneven playing field created, with concerns that trans women may have an advantage over their peers and competitors due to their physical abilities.

Malta is equally divided on the subject, with some activists on one side of the fence and sports professionals on the other.

Laurel Hubbard is the first trans woman to compete in an Olympic Games

When you look at a female-born athlete at a high level, they are competing at around three nanomoles per liter of testosterone which already indicates that the level of testosterone of a female athlete is three times lower than that of a transgender woman that has undergone hormone replacement therapy, renowned strength and conditioning coach Nigel McCarthy told Lovin Malta.

Amongst the benefits of having higher testosterone levels are increased muscle mass, bone density, decreased fat percentage and recovery time.

Apart from the latter, performance does not reflect what happened the previous year but is an accumulation of years of building, he continued. The blood, hormones and cell production in your body are all signaled by previous years of training.

Despite having to undergo hormone replacement therapy, a body of research indicates that trans women are still at a biological advantage when compared to other female athletes, McCarthy argued.

Not all the advantages are diminished and still a large overwhelming benefit remains from being male years prior when it comes to biological advantages of strength and power, he said.

This is clearly shown by the results of transgender athletes when competing in female categories winning by large distances and not just the mere half a second or a centimeter.

In 2019, transgender athlete Rachel McKinnon set a world record time in sprint cycling with a timing of 11.649 seconds. Her opponent, Dawn Owrick, came in second with a time of 12.063.

Those on the other side of the fence argue that the decision to allow Hubbard to compete in the womens category of the Olympic Games promotes inclusivity and that it is skill, rather than genetics, that determines a champion.

Unfortunately, we think of sports as being fair which in reality is not, it is all a natural genetic lottery you do not choose to be tall, have higher testosterone levels or respond to training as well as others, McCarthy said.

While acknowledging that sports should be accessible to all, the S&C coach also believes in preserving the right of fairness for those who are also competing.

More studies need to be done to test baseline level before and after therapies for transgender athletes, he continued. There also needs to be a better understanding of the biological differences between males and females which determines athletic ability.

Hubbard will be competing in the womens 87kg weightlifting category. Though she has the backing of the New Zealand government and Olympic Committee, the decision on her participation hasnt been welcomed by some of her peers, including Belgian weightlifter Anna Vanbellinghen, who claimed that this particular situation is unfair to the sport and to the athletes.

As things stand, an out-of-proportion and unfair biological athletic advantage is occurring at the expense of born female athletes when competing against transgender athletes, McCarthy continued.

Hubbard had competed in mens weightlifting competitions prior to coming out as transgender in 2013.

The current total weightlifting record for men competing in the 89kg category is 387kg consisting of a combination of clean & jerk and snatch.

Meanwhile, the total female world record for athletes competing in the 87kg category stands at 294kg.

On a personal note, this should really be discussed by female athletes and not by myself or by any outsider not knowledgeable or impacted by the decisions, McCarthy said.

Females are having their hard work and opportunities lost to transgender athletes who evidently have an unfair athletic biological advantage, he ended.

What do you make of this? Let us know below

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'Unfair Biological Athletic Advantage', Maltese S&C Coach Weighs In On Trans Weightlifter Competing At The Olympics - Lovin Malta

Lions, More Tigers, and Bears, Oh My! Meet PDZA’s Newest Resident Tiger – southsoundmag.com

Meet Raja, the newest resident of the Point Defiance Zoo & Aquarium. The 2-year-old critically endangered Sumatran tiger was revealed to the public last weekend (June 19-20) and could hold the key to protecting the Sumatran tiger species.

Rajas definitely not in Kansas anymore, but Tacoma welcomes the tiger with open arms and the possibility he brings.

Raja moved from Topeka Zoo & Conservation Center to Point Defiance Zoo in an attempt to boost breeding and ensure the future survival of the big cat species. With roughly 400 remaining, zoos joined the Species Survival Plan for Sumatran tigers to protect the critically endangered species from disappearing entirely because of habitat loss, poaching, lack of prey, and tiger-human conflict. Point Defiance Zoo has become a leader in Sumatran tiger conservation efforts, along with a list of other endangered species.

We are proud to be part of the conservation community working to ensure this species is around for future generations, Dr. Karen Goodrowe Beck, the general curator and Species Survival Plan coordinator for all tiger species at the Association of Zoos & Aquariums, said in a press release.

Rajas valuable genetics are vital to the survival of his species, Dr. Goodrowe Beck said. In the future, Raja will likely father the cubs of the three female Sumatran tigers housed at the zoo: Kali, Kirana, and/or Indah.

Visit Raja in the Asian Forest Sanctuary section of Point Defiance Zoo and stay tuned for news of Sumatran tiger cubs in the future.

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Lions, More Tigers, and Bears, Oh My! Meet PDZA's Newest Resident Tiger - southsoundmag.com

Female athletes at risk of bone fracture resistant to muscle injury : The Asahi Shimbun – Asahi Shimbun

Genetic factors appear to affect the risk posed to female athletesfor getting certain kinds of sport-related injuries, a new study suggests.

Scientists found that female athletes fortunate enough to be resistant to muscle dislocation are more prone to getting fatigue fractures.

The researchers said they discovered through their analysis that the genetic factors that help build tolerance against muscle fragmentation and fatigue fractures do not work at the same time.

The finding is expected to lead to the development of new methods for injury prevention based on patients genetic conditions.

However, that correlative relationship does not appear to exist in men.

Women have fewer proteins in their bones and muscles, and the differences come to the surface more easily, said Eri Miyamoto, an assistant professor of genetics at Juntendo University.

Miyamoto and her colleagues examined the genes of 1,667 male and female athletes primarily in their 20s and 30s. They compared their genetic makeup with their records of fatigue fractures, muscle dislocation and other kinds of myopathy, or muscle tissue problems.

The results revealed no fewer than 17.8 percent of women marked by a certain genetic composition had developed stress fractures, while the ratio of myopathy was as low as 9.9 percent for the group.

About 80 percent of the athletes had that genetic feature, which is associated with proteins that constitute bones and muscles.

Researchers found those athletes had lower bone density and more flexible muscles.

Women with another genetic element developed myopathy and fatigue fractures with a probability of 18.6 percent and 9.0 percent, respectively. This marked a sharp contrast to the results for the other group.

However, no significant differences in the development risks from the disorders were found among the male athletes, according to the study.

The teams findings were published in March in the online edition of the U.S. sports medical journal Medicine & Science in Sports & Exercise, available at: https://journals.lww.com/acsm-msse/Abstract/9000/Female_Athletes_Genetically_Susceptible_to_Fatigue.96070.aspx

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Female athletes at risk of bone fracture resistant to muscle injury : The Asahi Shimbun - Asahi Shimbun

Female Receding Hairlines, Explained: Here’s What Experts Say About the Condition, Including How to Reverse It – Yahoo Lifestyle

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If there's one thing quarantine has shown us, it's that at-home bang trims, root touch-ups, and DIY blowouts aren't as daunting as they seemed in those blissful pre-COVID days. And, now that you're a total hair pro, it only makes sense to keep the new at-home grooming going even if you're fully vaccinated. An easy and affordable way to do that is by stocking up on the essentials during Ulta Beauty's most hair-raising sale of the year, the Gorgeous Hair Event.For the uninitiated, the sale is similar to the iconic 21 Days Of Beauty promo instead, this time around the deal spotlight is shining on your locks. From now through May 29, you can expect half-off daily deals on hair tools, intensive treatments, styling products, and much more. Each promo only lasts for 24 hours, so shop quickly and confidently! To assist, we've corralled every major hair deal happening this month ahead. At Refinery29, were here to help you navigate this overwhelming world of stuff. All of our market picks are independently selected and curated by the editorial team. 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Female Receding Hairlines, Explained: Here's What Experts Say About the Condition, Including How to Reverse It - Yahoo Lifestyle

Why vaccine side effects really happen, and when you should worry – National Geographic

Side effects can be a powerful deterrent stopping people from getting vaccinated. To address this issue, in 1991, a group of scientists in Minnesotaat the Department of Veterans Affairs and the Mayo Clinicdevised an experiment to see just how frequent these unpleasant reactions were.

The study involved more than 300 veterans over the age of 65 who were given either a flu shot followed two weeks later by a placebo injection of salt water, or a placebo shot followed two weeks later by the real vaccine.

When the researchers unblinded the study to see who received the vaccine versus the placebo, the side effects were split equally between the two groups, says Robert Jacobson, medical director for the population health science program at the Mayo Clinic. About five percent said they got sicker than they ever had been in their entire life, says Jacobson. Half of these people had received the placebo and yet they complained of the worst headaches, or worst fever, of their lives. The take-home message here, says Jacobson: Its easy to confuse an allergic reaction with nervousness or emotions or even stomach upsets from anxiety.

Recent studies show some side effects, even ones from the COVID-19 vaccines, arent due to the shots at all, but to our own fears. Weve seen this in the military, when young recruits, who think they can tolerate anything, faint when they get the injections, because their body overreacts, says Jacobson.

Its a lesson that may be useful to medical professionals, who can reassure patients that most side effects are normal and predictableand may not even be caused by the shot. Case in point, in studies of the Pfizer/BioNTech vaccine, 23 percent of people aged 16 to 55 who received the placebo complained of fatigue after their second jab, and 24 percent noted headaches.

Studies do suggest that up to seven out of ten people getting their second shot have some type of reaction. Some feel a soreness at the injection site on their arm. They may experience itching or hives, or a range of flu-like symptoms, such as chills and fever, headaches, or debilitating fatigue, that can leave them bedridden for a day or two. Still, its important to put these side effects in perspective, says Jacobson, because these are mild, temporary, and transient reactions that disappear within a few days.

In the case of the authorized COVID-19 vaccinesPfizer, Moderna, and Johnson & Johnsonall contain a genetic blueprint for manufacturing spike proteins, which sit on the surface of the coronavirus and enable it to infect human cells. When human cells receive these instructions, they churn out copies of spike protein. But since the cells make only a piece of the virus, and not the whole pathogen itself, we dont get sick. But while the foreign spike cant cause disease, it can activate a two-step immune responseexactly as it is supposed to do.

The immediate physical reaction to the COVID-19 vaccine is caused by the innate immune system. When a person receives a shot, a flurry of white blood cells called macrophages and neutrophils arrive at the injection site and begin producing chemicals called cytokines. This response triggers a wide range of symptoms, from inflammation and swelling at the injection site to fever, fatigue, and chills.

As a result, side effects are a natural reaction to vaccination. This responsecalled reactogenicitymeans the vaccines instigate a strong, initial immune response and trigger a wide range of symptoms. Out of about 3,600,000 vaccinated people who participated in a survey in February, approximately 70 percent reported pain at the injection site, 33 percent felt fatigued, 29 percent suffered headache, 22 percent had muscle pain, and 11 percent experienced chills and fever after their first shot of a COVID-19 vaccine. The symptoms were even more pronounced after the second dose. Still, the innate immune response is short-lived, lasting only a few days.

But not everyone experiences side effects after a COVID-19 vaccine. Some feel fine after both doses. Scientists dont really know why, says Sujan Shresta, an immunologist at the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology, in California. But its not a surprise that each person mounts the immune response differently.

Several factors can contribute to this wide variation. Women, for example, typically have stronger immune reactions than men, which may be part of what makes them more prone to suffering from side effects from the shots.

We all have our own individualized immune system, says John Wherry, director of the institute for immunology at the University of Pennsylvania, in Philadelphia. Its almost like our own immune fingerprint thats driven by genetics, gender, diet, our environment, and even our life history, which are the things our immune system has been exposed to in the past and has been trained to respond to over the years.

Even if you dont have an unpleasant reaction, the vaccines are still doing their job, because the real work of the immune systemand of the vaccinestakes place during the second, or adaptive, phase of the immune response. During this phase, the spike protein generated via the vaccine trains the B-cells to produce antibodies that match the virus, and the T-cells to seek-and-destroy infected cells. But it takes days to weeks to provide this long-lasting protection against the virus.

This is also the reason why people often have more rigorous reactions to the second shot. Three weeks after the first shot, the immune system has already been primed, and the B-cells and T-cells are ready to fight. When the second shot is delivered, both the innate and adaptive systems respond.

Still, we dont really know if having a serious response to the vaccines is a measure of the strength of the immune system. We also dont know if it means that someone who doesnt have a strong innate response will be more vulnerable to COVID or more resistant. We really dont have any data in the field on thiswhether a person with strong side effects would have a more severe COVID infection and vice versa, says Wherry.

In a February study that looked at the data from the first 13.7 million COVID-19 vaccine recipients, the Centers for Disease Control and Prevention found that nearly 80 percent of the people reporting reactions were female, even though only 61.2 percent of the injections had been given to women. In a similar vein, the CDC reported that all anaphylactic reactions to the Moderna shot have been in women; 44 of the 47 people whove had these reactions to the Pfizer injection were female.

The majority of people who have experienced the severe blood clotting issues with the J & J vaccine, and also the AstraZeneca vaccine in Europe and the United Kingdom, have been women. There has been speculation about hormones playing a rolewhich is always the first culprit thats looked at when you see a major sex difference, says Penns Wherry.

Several other factors may also contribute to this gender imbalance. Women also seem to have a more robust immune system, both in their innate responses and in their adaptive immune reactions. Females mount a stronger antibody response than males but its a double-edged sword because this is why women have more auto immune disease than men, says Shresta of the La Jolla Institute for Immunology.

Other studies have shown that a womans response to half a dose of the influenza vaccine was the same as mens full dose, so females might not need full doses of the COVID-19 vaccines. We have this idea that one size fits all, but this may be part of whats contributing to the higher rate of reactions among women, says Rosemary Morgan, a scientist specializing in gender research at the Johns Hopkins Bloomberg School of Public Health. There is also a behavioral componentwomen are more likely to visit the doctor and to be more proactive about reporting unpleasant symptoms.

But side effects and adverse eventswhich often get conflatedare not the same, says Wherry. Side effects are pretty commonoccurring maybe 50 to 70 percent of the time. But adverse events are rare and unexpected, like the clotting disorders.

Immediately after injection, about two to five people per million experience anaphylaxis, a severe allergic reaction that causes a dramatic drop in blood pressure and difficulty breathing. But even this is easily treatable with an EpiPen and antihistamines, which is why everyone is asked to stick around for 15 minutes after their COVID-19 shots.

The blood clots associated with the Johnson & Johnson vaccines, that have occurred within six to 13 days of receiving the shot, can be dangerous and even life threatening. But the incidence is quite low; there are only 23 confirmed cases out of 8.4 million doses of the vaccine.

This is very rare, says Ofer Levy, director of the precision vaccines program at Boston Childrens Hospital and a professor of pediatrics at Harvard Medical School. The risk of getting COVID and possibly dying is much higher than getting blood clots from the vaccines.

There is some worry that there may be other adverse effects that have gone largely unreported.

The three COVID-19 vaccines that have been authorized in the United States have been tested on tens of thousands of people in clinical trials, and manufacturers were required to follow up with at least half the vaccine recipients for two months or more after they received both shots. But now that more than 116 million Americans have been fully vaccinated, rare side effects that dont show up in smaller human clinical trials can emergewhich is why surveillance systems are important.

Here in the U.S., we have a patchwork of systems: the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink, and the CDCs new phone-based tracking program, v-safe.

All of these have limitations, including that someone has to suspect these health outcomes are related to vaccination and go to the trouble of filling out the form, says Katherine Yih, a biologist and epidemiologist at Harvard Medical School, specializing in infectious diseases, immunization, and vaccine safety monitoring. We have a vigorous surveillance system in place. But we cant be sure its picking up everything.

Whats more, these incidents only show correlation. In other words, if someone died or had a stroke after getting vaccinated, physicians dont know if it was triggered by the shot. Only further study can reveal that.

The swift identification of the rare blood clotting disorder related to the J & J vaccine was reassuring. Initially, six cases were reported, prompting the FDA and the CDC to temporarily halt its use. When the CDCs Advisory Committee on Immunization Practices met in late April to determine the vaccines fate, 15 cases had been detected out of seven million people who had the shot. The discovery of that association with the J & J vaccinewhich is very rareis a real demonstration of how good our safety program is, says the Mayo Clinics Jacobson. At this point in the pandemic, a risk of less than three per million should not enter into our calculus of how to proceed.

Continue reading here:
Why vaccine side effects really happen, and when you should worry - National Geographic

5 things to know about the ‘conundrum’ of lupus – ABC17News.com

Lupus is unpredictable, triggering different symptoms in different patients. A chronic illness, it can even attack many different parts of the body.

The condition is an autoimmune disease, which means that a persons immune systemthe body system that usually fights infectionsattacks healthy tissue instead. It can cause inflammation and pain anywhere in a patients body.

Because the illness can look different in every patient, it can go undetected and undiagnosed for years.

The Lupus Foundation of America estimates that 1.5 million Americans and at least 5 million people worldwide have some form of lupus. There are four forms in all: systemic lupus erythematosus (SLE), lupus confined to the skin, lupus caused by some prescription drugs and a rare lupus that affects infants of women with the disease.

Despite ongoing research into how the disease manifests in patients and what causes it, scientists and other experts sometimes describe the disease as cruel mystery which is to say, they still have a lot to learn about it.

There is a lot about lupus that is still a conundrum to us, said Dr. Karen H. Costenbader, a professor of medicine at Harvard Medical School and director of the Lupus Program at Brigham and Womens Hospital in Boston.

Its treatable, but it can still be very painful and challenging to overcome, said Costenbader, who is also chair of the Lupus Foundation of Americas Medical-Scientific Advisory Council.

May 10 is World Lupus Day, and we recently caught up with Costenbader to learn more about the disease.

This conversation has been edited and condensed for clarity.

CNN: What does it mean that lupus is an autoimmune disease?

Dr. Karen Costenbader: It means the immune system is attacking healthy tissue inside the body instead of infections. With lupus, patients make antibodies against any different number of organs, cells, internuclear proteins and intercellular particles.

Any organ system can be involved. As a result, causes a wide range of different symptoms that can come and go over time and vary from person to person. These include extreme fatigue, pain or swelling in the joints, low-grade fevers and damage to internal organs like the kidneys, heart and lungs. Thats what makes it so difficult to diagnose and treat.

CNN: If lupus presents so differently in every patient, how do experts diagnose it?

Costenbader: The one thing all lupus patients have in common is that they have dealt with chronic pain and discomfort for a while. When lupus first presents, symptoms can include fever, joint pain and rashes. These symptoms are similar to symptoms of infections and other autoimmune diseases such as rheumatoid arthritis, so a diagnosis can be tricky. It takes an astute clinician and expert. Sometimes it also takes time(recent) research indicates it can take as long as (almost seven) years. As soon as symptoms involve three or more different organ systems, clinicians should start thinking about lupus.

CNN: What is the treatment? Does hydroxychloroquine, the drug that we learned doesnt work for Covid-19, really work on lupus?

Costenbader: Thankfully, today we have more and more treatments through clinical trials. Historically, though, the treatment has been hydroxychloroquine, the same drug that was touted for a while as a potential treatment for Covid-19. It turns out the drug doesnt work for Covid, but it does work well for lupus.

Last year during the pandemic, when people thought it worked for Covid, we had huge shortages of hydroxychloroquine, which was a problem for our patients. Anti-malaria drugs also help stabilize the disease, and steroids work, too. Steroids have a lot of side effects such as weight gain and glaucoma. The goal of some of the new treatmentstheyre all immunosuppressantsis to keep organ involvement under control.

CNN: Are men or women more likely to get lupus?

Costenbader: Lupus mainly strikes femalesnine of 10 people with lupus are female. It also commonly starts between ages 15 to 44 years. We dont know why this happens; it is one of the conundrums. A lot of autoimmune diseases have sex predilections. With lupus, incidence picks up during menstruation, decreases after menopause. Men who have two X chromosomes also have a high prevalence of lupus, so perhaps X chromosomes have something to do with it. This is one of the aspects of the disease were still studying.

CNN: What are some of the other conundrums experts have identified about lupus?

Costenbader: Lupus is two to three time more common among people of colorAfrican Americans, Hispanics/Latinos, Asians, Native Americans, Alaska Natives, Native Hawaiians and other Pacific Islandersthan among people of European ancestry. The real burden in this country is in young African American women. Lupus is one of the top 5 causes of death of young African American women. Were just starting to have large enough populations involved in the studies to see that the genetics involved with patients may be different.

CNN: Is lupus contagious?

Costenbader: Its not contagious. But it does run with other autoimmune diseasespeople who have lupus usually have family members with rheumatoid arthritis and other autoimmune diseases. For people who have lupus, relatives have a 5 to 20% chance of also developing it. Experts think it may develop in response to certain hormones (like estrogen) or environmental triggers.

An environmental trigger is something outside the body that can bring on symptoms of lupus or make them worse. For instance, we know smoking increases the risk of lupus and oral contraceptives might trigger it as well. Obesity, stress and post-traumatic stress disorder can be triggers. We know that if people have a genetic predisposition and they are in the wrong environment, their inflammatory pathways get triggered, and they are at risk.

CNN: What is the outlook for someone with lupus?

Costenbader: Lupus is not a death sentence. With the right meds, and the right physicians and caregivers involved, lupus patients can have kids, hold jobs, and lead productive lives like anybody else.

Visit link:
5 things to know about the 'conundrum' of lupus - ABC17News.com

People on the Move: Appointments, retirements, achievements – Beef Central

Beef Central publishes an occasional summary of appointments, departures and achievements occurring across the red meat and livestock supply chain. Send details for entries to admin@beefcentral.com

After six years at the helm of Stockyards Kerwee feedlot on Queenslands Darling Downs, Steve Martin recently stepped down from his role as general manager of feedlot operations.

Steven Martin

While he has been active in industry circles in recent weeks, attending both the Australian Wagyu Association conference and Beef 2021, Mr Martin is yet to make a decision on his future path, short of telling Beef Central he is keen to remain within the beef industry.

Suffice to say he was observed having lengthy discussions with some large Wagyu supply chain players during the recent Wagyu conference.

Mr Martin joined Stockyard in 2015 and steered the company through a major expansion in 2017 that doubled the capacity of the Kerwee feedlot; and more recently the establishment of Stockyards Fullblood and purebred Wagyu breeding and backgrounding business.

Following his departure, the Stockyard Group has promoted George Lubbe as general manager of feedlot operations. Mr Lubbe has previously worked since 2017 as Kerwees assistant manager.

George Lubbe

A South African by birth, Mr Lubbe previously worked with large-scale Queensland egg producer Mclean Farms, and civil engineers Ostwald Brothers, as well as his familys cattle trading business based near Texas on the NSW/QLD border.

Another long-term Kerwee staffmember, Stevie-Lee Wayman, has been appointed assistant manager of Kerwee feedlot, moving up from her livestock supervisor role. Both she and George Lubbe bring a wealth of experience to their new positions.

Good feedlot managers and grainfed supply chain managers were in high demand and short supply across the industry at present, one of Australias most prominent ag recruiters told Beef Central recently.

Northern Territory Livestock Exporters Association chairman David Warriner has confirmed the commencement of the organisations new CEO, Tom Dawkins, in Darwin last week. Mr Dawkins has previously held a number of senior industry affairs roles with national agricultural bodies the Australian Livestock Exporters Council, the Cattle Council of Australia and most recently Australian Pork Ltd.

Tom Dawkins

He began his career as a livestock markets reporter with Rural Press/Fairfax newspaper Stock Journal in his home state of South Australia in 2006. He was appointed editor of the masthead in 2008, before transferring to the editors desk at Victorian stablemate Stock & Land in 2010.

Mr Dawkins follows in the footsteps of numerous well-known export industry figures who have served terms heading-up the NTLEA, including regular Beef Central contributor Dr Ross Ainsworth, Patrick Underwood, Lach Mackinnon, Kevin Mulvahil and Bernie Brosnan. Mr Dawkins immediate predecessor Will Evans, who is now the CEO of the NTCA, followed on in the NTLEA position after Stuart Kemp, who is now based in Queensland as Livestock Manager North with Australian Country Choice.

Tracey Hayes, the first female chief executive officer of the Northern Territory Cattlemens Association and the facilitator of the successful class action against the 2011 suspension of the live cattle export trade to Indonesia, was awarded the Beef Achiever Award at a Beef 2021 dinner hosted by Rabobank and Queensland Country Life in Rockhampton last week.

NTCA executive director Tracey Hayes addresses a function at the Australian Embassy in Jakarta.

Tracey is regarded as a senior business and industry leader, having also previously served as chair of the Darwin Waterfront Corporation and as a Member of the Order of Australia Honours Council. She is a director of the Cooperative Research Centre for Northern Australia, sits on the board of the Australia Indonesia Institute and is a member of the advisory board of the National Drought and North Queensland Flood Response and Recovery Agency.

Tracey is also small business proprietor, a long-term former Territory pastoralist, pilot and Justice of the Peace, and ran against NT chief minister Michael Gunner as a candidate for the Country Liberal Party for the seat of Fannie Bay in the NT election last year.

Asked to reveal something about herself in an interview with the NT Independent last year, she noted that at one point in time she was licenced to operate and use aeroplanes, trucks, cars, motorbikes, boats, firearms, forklifts, and S7 pharmaceuticals and chemicals. Not unusual for bush women she added. Keep an eye on Beef Central for an upcoming interview with Tracey Hayes.

The Beef Industry Achiever award was initiated by Beef Central publisher Jon Condon back in 1997.

Two new councillors elected to the Australian Lot Feeders Association board in November have been out and about around the industry, since the lifting of the COVID curtain.

Attending Beef 2021 last week, coinciding with the launch of ALFAs new community-facing website, grainfedbeef.com.au was newly-minted councillor Daryle Belford, from Whyalla feedlot, near Texas Qld

Pictured on ALFAs stand during Beef 2021 were new ALFA councillor Daryle Belford, chief executive Christian Mulders, CARS Road Safety Ambassador Judy Lindsay, and ALFAs Elise Mizzi. Click on image for a larger view

Mr Belford managed cattle properties in Central Queensland between 1990 and 2004 before moving into an agribusiness and financial advisory role based in Emerald up to 2009. He entered the feedlot industry in 2010 with NH Foods Whyalla yard, having worked in numerous parts of the business up to his current position of assistant general manager. He replaces Whyalla general manager Tony Fitzgerald on the ALFA board.

Also joining the ALFA council lineup this year is was Tom Green, from Thomas Foods Internationals Iranda Beef feedlot in South Australia.

Tom worked in North America on large-scale bull breeding properties before entering the feedlot industry in 2012 when he joined Teys Australia at Jindalee feedlot as a Graduate Manager before becoming the Livestock Manager followed by the Operations Manager.

In 2016 he joined TFI as operations manager at Iranda Beef before being appointed General Manager of Feedlot and Farming in 2018. Tom was awarded Young Lot Feeder of The Year in 2017 and a Nuffield Scholarship in 2019. Tom has been an external representative on ALFAs Feedlot Management committee during 2019 and ALFAs R&D committee during 2020.

Angus Australia has appointed Jake Phillips as the breed societys new Breed Development Officer.

Jake Phillips

Mr Phillips grew up in South Australia and has spent considerable time working across the beef supply chain in various positions throughout Eastern Australia. After uni he joined ABRI as a BreedPlan consultant, followed by four years with Meat Standards Australia based in Queensland in the areas of the integrity and adoption. More recently he has spent the past seven years working for Teys Australia at Naracoorte in South Australia in a variety of roles including livestock procurement, branded beef, QA management and livestock strategic operations. His most recent Teys role was as livestock strategic operations manager.

Jake and his wife run a small seedstock operation near Naracoorte, recently added Angus genetics to their herd.

In his role with Angus Australia, he will work alongside existing Breed Development Officer, Matt Reynolds, in the delivery of education and extension programs that assist Angus breeders with the utilisation of genetic improvement technologies to enhance the profitability of Angus cattle and beef across the beef supply chain. He will be regionally based, working from Naracoorte in South Australia.

Meat & Livestock Australias Man in Singapore, Dr Michael Patching, has moved on to establish his own industry consultancy.

Michael Patching

Dr Patching has worked as MLAs livestock services manager and more recently market development manager for the Asia Pacific region for the past two and a half years, after earlier acting as market development manager for in-country operations in Vietnam for three years.

A Murdoch University and University of Edinburgh trained veterinarian with masters degree qualifications in international animal welfare, ethics and law, Dr Patching has worked closely with Australian live exporters and Vietnamese importers over the past six years, during the period of dramatic volume growth, more recently adding Indonesia and other southeast Asian customer countries to his responsibility. Click here to read Beef Centrals report from an interview.

Dr Patching is now moving on to start his own consultancy business, Beanstalk Agtech, based out of Singapore, where he will focus on filling a gap in trade facilitation work for companies seeking to develop commercial agricultural and food market opportunities in the ASEAN region.

His replacement in the MLA Singapore role has not yet been announced.

Roger Desailly

The Australian Meat Industry Council has appointed Roger Desailly as the organisations new state manager for Queensland. He replaces Peter Talbot, who filled the role for the past two years.

In his role, Mr Desailly works principally with independent retail butchers across the state, but also has a watching brief across AMICs country processor, wholesaler and smallgoods manufacturer member network.

He is a former chief executive of the industrys major Beef Australia expos in Rockhampton, and most recently has worked in his own agribusiness consultancy after a period as state education and training manager for the Queensland Agricultural and Training Colleges organisation.

Mr Desailly is operating from AMICs Brisbane office in Red Hill, but travels widely across the state.

Laura Penrose

The formal launch of the Australian Wagyu Associations major ten-year Progeny Test Program (click here for earlier story) at the 2021 WagyuEdge annual conference recently has coincided with the appointment of AWAs first genetics improvement program manager.

Laura Penrose took up her new position in March. A Bachelor of Science graduate from the University of New England, Laura previously worked as a project assistant at UNE, and as a technical officer with the NSW Department of Planning, Industry and Environment.

She will be based out of AWAs Armidale office.

Queensland agribusiness and agtech pioneer, William Harrington was recently awarded a prestigious Fulbright academic scholarship, sponsored by the Food Agility CRC.

Mr Harrington is studying for his Food Agility PhD at James Cook University in Townsville. His thesis topic is measuring and quantifying the benefits of improved internet connectivity in regional and remote Australia and its effect on adoption of technology.

William Harrington

My PhD project aims to understand how farmers use the internet, including how often, what a farmers typical data usage is, and what types of websites and applications they use, he said. At this point in time there is very little, if any research in this area and I am excited to be able to contribute.

Growing up on a remote cattle station in the north west of Queensland, Mr Harrington was an early agtech pioneer, developing animal ID and iSee remote monitoring and W-Sky connectivity technologies, despite his remote location.

I have always loved being able to bring together my two passions, technology and agriculture, he said, after being awarded his scholarship. Improved connectivity can make a tangible difference to the lives of people in regional Australia and enables the adoption of new technologies that improve efficiency, production and environmental outcomes. There has been a lot of talk in the media about connectivity in regional Australia, and I decided to do a PhD to try and produce scientific data that can be used to guide decision and policy makers.

Mr Harringtons Fulbright scholarship will involve study in the US, where he will be based at Ohio State University for four months, studying the US approach to rural broadband.

The US is a world leader in this area and I would like to use the opportunity to learn from institutions such as the Federal Communications Commission, US Department of Agriculture, and academic organisations such as the Perdue Centre for Regional Development, he said.

On completing his PhD, Mr Harrington plans to remain in regional Australia and continue to research topics that are related to farmers, connectivity and technology adoption.

Dr Robyn Cleland was recently appointed as the new chief environmental biosecurity officer with the Department of Agriculture, Water and the Environment in Canberra.

Deputy secretary of biosecurity and compliance, Andrew Tongue, said Dr Cleland brought a wealth of experience and expertise to the role, having held senior leadership roles in the Australian Public Service for more than a decade.

Dr Cleland has worked across the portfolios of agriculture, health and environment, working in policy, compliance and regulation.Her scientific expertise spans biosecurity, plant health, biotechnology, food, ecology and agriculture.

The role of the chief environmental biosecurity officer is to liaise between government, industry and the community to raise awareness and build Australias capacity to manage biosecurity risks.

This is a hugely important role, charged with protecting Australias unique wildlife, our way of life, and our status as a clean, green exporter of high-quality food, Mr Tongue said.

Dr Clelandhas worked with State and Territory jurisdictions, NGOs and the community across a number of national regulatory schemes and has extensive experience in engaging with diverse stakeholders across contentious issues. Before she joined the APS, she was a research scientist at the University of Cambridge, the University of Sheffield and the Australian National University.

Agtech developer Jock Lawrence last month received the Victorian Young Achiever Award in Small Business.

Mobble founder, Jock Lawrence

The 28-year-old co-founder of the Mobble farm management software platform, Mr Lawrence received the award at a gala dinner in Melbourne. The Young Achiever awards began in 2012 with the purpose of promoting, acknowledging and encouraging the positive achievements of young people in industry up to 30 years of age.

In his acceptance speech, he thanked the farmers who had supported his business through the years, as well as his team at Mobble for their commitment to the companys vision of making life easier for farmers and simplifying farm management.

He noted that farmers are the reason we get out of bed every day, to make their lives easier and more successful. Mobble is a centralised livestock farm management software platform, used by more than 500 farms across Australia and New Zealand, currently managing more than two million stock units across those properties. The software puts a focus on connection and simplicity by farmers for farmers.

Beau North from Sarina, Queensland was recently announced as the Lachlan Hughes Foundation 2021 Foundation Scholar. An independent selection panel identified Beau from a strong field of applicants from across Australia.

With his partner Katherine Fausett, Beau has recently purchased a grazing property in the Sarina area, which is the focus of his project for the scholarship. As a new landholder, Beau recognises that he has a duty of care to protect and enhance water quality but also mitigate erosion on his property.

He is embarking on a journey to retire areas on the property, which were farmed for sugar cane for 80 years, to a mixed species of perennial pastures and beneficial vegetation for grazing, diversity and ecological value. Using regenerative agricultural principles where possible and practical, Beau aspires to enhance water cycles on farm, slowing the runoff and returning it to the soils to support fertility and drought resilience.

The scholarship mentoring will provide access to expertise and training to refine his current property plan and support him on the ground as he furthers his long term dream of building a beef grazing business.

Beau knows first-hand how hard it is to get a start in the beef industry as grazing land has been expensive in his region. He and his partner have been leasing country for his small cattle herd for the past eight years. Learning a trade as an electrician has helped him build up the capital to help pursue his passion for grazing and allowed him to finally purchase his first property.

Beau also hopes that the scholarship will benefit other farmers, through growing the regen community in the wider region.

Beau follows in the footsteps of inaugural scholar Jack Groat, who shared his experiences at the MLA BeefUp event in Roma earlier this year. Jack spoke on how his journey to learn more about regenerative agriculture has been rapidly enhanced through the scholarship.

The opportunity provided by the Lachlan Hughes Scholarship has allowed me to give back to the regenerative agriculture movement as well. It has improved my focus on hydrating our landscapes through a multi lever approach, implementing rotational grazing, contours and leaky weirs to reduce run-off, soil erosion and keep ground cover better for the environment and better for business, Jack said.

The Darling Downs lost one of its greatest export superstars in April. Geraldine Doumany, or Gerry as she was known, spent her career assisting businesses experience international trade success and she was one of the regions strongest advocates for creating a thriving export community.

Raised on a farm near Cunnamulla in Western Queensland, and always maintaining a connection to regional and rural communities, Gerry held senior roles with government agencies Austrade and Trade and Investment Queensland. She also worked within the private sector, and most recently was leading Toowoomba and Surat Basin Enterprises (TSBE) export initiatives.

Gerry was adept at helping businesses understand how to export and how to navigate the many challenges that every export journey entails.

I remember many times hearing phone calls from panicked local exporters with Gerry calmly stepping in to locate products stuck on a wharf in China or fixing export documentation or using her many international contacts to smooth the way for Darling Downs products to reach overseas markets, TSBE CEO, Ali Davenport said.

Export is incredibly complicated, but Gerry was brilliant and could solve just about any export problem.

Last year, the Toowoomba Chamber of Commerces Business Excellence Awards introduced the Gerry Doumany Export Award, which was won by local beef export supply chain Mort & Co.

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People on the Move: Appointments, retirements, achievements - Beef Central

Genentech to Present Data From One of the Most Comprehensive Oncology Portfolios at the 2021 ASCO Annual Meeting Showcasing Advancements for People…

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that new data from clinical trials of 19 approved and investigational medicines across 20 cancer types will be presented at the 2021 ASCO Annual Meeting, which will be held June 4-8, 2021. A total of 132 abstracts that include a Genentech medicine will be presented at this year's meeting. These data advance oncology by showing the importance of making patient-centric treatment decisions and providing tailored medical care based on specific cancer types.

We will be presenting data from across our diverse oncology portfolio that has the potential to help more people living with many types of cancers, said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. We are particularly excited about our compelling immunotherapy data in lung cancer, which may provide new hope for patients with earlier stage disease.

Focusing on earlier treatment and targeted lung cancer care

Positive results from the Phase III IMpower010 study will be presented that show Tecentriq (atezolizumab) improved disease-free survival (DFS) in people with resected early-stage non-small cell lung cancer (NSCLC) compared to best supportive care - a first in cancer immunotherapy. This advance is significant, as half of all people with early-stage lung cancer today still experience a recurrence following surgery; therefore, treating lung cancer early, before it has spread, can provide the best opportunity for a cure. Additionally, updated data for GavretoTM (pralsetinib) in patients with advanced RET fusion-positive NSCLC, including in patients who are treatment nave, will be reported. These data highlight the need for early RET fusion-positive testing to identify candidates who may benefit from treatment with Gavreto.

Exploring personalized cancer care for more patients

Genentech will present several studies that take tumor-agnostic approaches to clinical development, and in breast cancer, that may benefit people with rare and common tumors alike. These studies bring together next-generation sequencing, targeted therapies and patient-centric clinical trial design that show how personalized treatment plans are helping to evolve the way people are treated. The Phase II ALPHA-T study, made possible through a collaboration with Foundation Medicine and Science37, is pioneering a decentralized approach to clinical trial design which enables patients to participate from their own homes while remaining under the care of their oncologist. The Phase II TAPISTRY study, a platform umbrella trial, will pair patients with immunotherapy, targeted therapy or treatment combinations based on distinct tumor biology characteristics. The similarly designed Phase II MyTACTIC study is enrolling a diverse population of patients to direct them to appropriately targeted treatments based on the results of comprehensive genomic profiling.

With our research we are contributing to the body of evidence in hormone receptor (HR)-positive breast cancer, the most prevalent type of all breast cancers. For giredestrant, a third-generation oral selective estrogen receptor degrader (SERD), we will present data further supporting the tolerable safety profile and single agent clinical activity, as well as pharmacodynamics data from studies in HR-positive early and metastatic breast cancer.

Defining new solutions for patients with difficult-to-treat blood cancer

New and updated data in non-Hodgkin lymphoma (NHL) will be shared, including data from the T-cell engaging CD20xCD3 bispecific antibody development program. Glofitamab and mosunetuzumab are both T-cell engaging CD20xCD3 bispecific antibodies that are being studied as single agents or in combination with other Genentech therapies. Together, they may offer a new immunotherapy-based approach to tackle a range of blood cancers. In addition, data exploring novel combinations with mosunetuzumab and Polivy (polatuzumab vedotin), an antibody-drug conjugate, will also be featured. These data demonstrate how Genentech continues to seek new solutions for people living with a range of malignant blood disorders, where treatment options are still limited and both relapse and treatment resistance are common.

Furthermore, Genentechs data showcase a commitment to health equity through medicine delivery approaches that reduce treatment time and cost, trial designs that help remove barriers to clinical trial participation, pioneering cancer immunotherapy to improve outcomes for earlier disease stages, and a focus on inclusivity through developing tumor-specific therapies and therapy combinations based on the specific characteristics of each persons disease.

Keep up to date with ASCO news and updates by using the hashtag #ASCO21 and follow Genentech on Twitter via @Genentech and on LinkedIn.

Overview of key presentations featuring Genentech medicines

Medicine

Abstract title

Abstract number

Lung cancer

Alecensa

Final OS analysis from the phase III j-alex study of alectinib (ALC) versus crizotinib (CRZ) in Japanese ALK-inhibitor nave ALK-positive non-small cell lung cancer (ALK+ NSCLC).

9022

Gavreto

Safety and efficacy of pralsetinib in patients with advanced RET fusion-positive non-small cell lung cancer: Update from the ARROW trial.

9089

Tecentriq

IMpower010: Primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (NSCLC).

8500

Tecentriq

Artificial intelligence (AI)powered pathologic response (PathR) assessment of resection specimens after neoadjuvant atezolizumab in patients with non-small cell lung cancer: Results from the LCMC3 study.

106

Tecentriq

Pooled analyses of immune-related adverse events (irAEs) and efficacy from the phase 3 trials IMpower130, IMpower132, and IMpower150.

9002

Tecentriq

CONTACT-01: A phase III, randomized study of atezolizumab plus cabozantinib versus docetaxel in patients with metastatic non-small cell lung cancer (mNSCLC) previously treated with PD-L1/PD-1 inhibitors and platinum-containing chemotherapy.

TPS9134

Tecentriq

Clinicogenomic real-world data analysis of patients (pts) with KRAS G12C-mutant advanced non-small cell lung cancer (aNSCLC) from the natural history cohort of the Blood First Assay Screening Trial (BFAST).

9023

Tecentriq

Real-world treatment patterns in stages IA-IIIB non-small cell lung cancer.

e20528

Blood cancer

Gazyva

Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.

7545

Glofitamab

Glofitamab step-up dosing (SUD): Complete response rates in updated efficacy data in heavily pretreated relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) patients (pts).

7519

Mosunetuzumab

Promising tolerability and efficacy results from dose-escalation in an ongoing phase Ib/II study of mosunetuzumab (M) with polatuzumab vedotin (Pola) in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkins lymphoma (B-NHL).

7520

Polivy

Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial.

7512

Venclexta

Measurable residual disease response in acute myeloid leukemia treated with venetoclax and azacitidine.

7018

Breast cancer

Giredestrant

acelERA Breast Cancer (BC): Phase II study evaluating efficacy and safety of giredestrant (GDC-9545) versus physicians choice of endocrine monotherapy in patients (pts) with estrogen receptor-positive, HER2-negative (ER+/HER2-) locally advanced or metastatic breast cancer (LA/mBC).

TPS1100

Giredestrant

persevERA Breast Cancer (BC): Phase III study evaluating the efficacy and safety of giredestrant (GDC-9545) + palbociclib versus letrozole + palbociclib in patients (pts) with estrogen-receptor-positive, HER2-negative locally advanced or metastatic BC (ER+/HER2 LA/mBC).

TPS1103

Giredestrant

Safety and activity of single-agent giredestrant (GDC-9545) from a phase Ia/b study in patients (pts) with estrogen receptor-positive (ER+), HER2-negative locally advanced/metastatic breast cancer (LA/mBC).

1017

Giredestrant

Evaluation of pharmacodynamic (PD) and biologic activity in a preoperative window-of-opportunity (WOO) study of giredestrant (GDC-9545) in postmenopausal patients (pts) with estrogen receptor-positive, HER2-negative (ER+/HER2) operable breast cancer (BC).

577

Kadcyla

Safety of trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive locally advanced or metastatic breast cancer (mBC): Final results from KAMILLA Cohorts 1 (global) and 2 (Asia).

1039

Phesgo

Potential non-drug cost differences associated with the use of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in the treatment of HER2-positive early breast cancer patients in Western Europe and the United States.

544

Tecentriq

The tumor microenvironment (TME) and atezolizumab + nab-paclitaxel (A+nP) activity in metastatic triple-negative breast cancer (mTNBC): IMpassion130.

1006

Colon cancer

Tecentriq

Phase Ib/II open-label, randomized evaluation of atezolizumab (atezo) + Imprime PGG (Imprime) + bevacizumab (bev) vs regorafenib (rego) in MORPHEUS: Microsatellite-stable (MSS) metastatic colorectal cancer (mCRC).

3559

Liver cancer

Tecentriq

IMbrave150: Exploratory analysis to examine the association between treatment response and overall survival (OS) in patients (pts) with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor).

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Tecentriq

IMbrave150: Exploratory efficacy and safety results of hepatocellular carcinoma (HCC) patients (pts) with main trunk and/or contralateral portal vein invasion (Vp4) treated with atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in a global Ph III study.

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Personalized healthcare and health equity

Association of electronic-health record (EHR)-derived race with BRCA testing in patients (pts) with breast cancer (BC) with similar genetic ancestry (GA) in a clinicogenomic database (CGDB).

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Racial, ethnic, and socioeconomic disparities in treatment outcomes in patients (pts) with diffuse large B-cell lymphoma (DLBCL): A U.S. real-world study using a de-identified electronic health record (EHR)-derived database.

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Tumor agnostic

Alecensa

Alpha-T: An innovative decentralized (home-based) phase 2 trial of alectinib in ALK-positive (ALK+) solid tumors in a histology-agnostic setting.

TPS3155

Gavreto

Clinical activity and safety of the RET inhibitor pralsetinib in patients with RET fusion-positive solid tumors: Update from the ARROW trial.

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Genentech to Present Data From One of the Most Comprehensive Oncology Portfolios at the 2021 ASCO Annual Meeting Showcasing Advancements for People...

President Biden, stop working to reverse the rights of half of America – msnNOW

Provided by Washington Examiner

President Biden ushered in his presidency alongside Americas first female vice president, pledging a message of unity and womens advancement. Yet, with a simple pen stroke, Biden set women back and effectively crippled the rights and dreams of millions of women and girls.

How? By signing an executive order to allow biological males to compete in female athletics. By siding with the few, Biden is decimating womens rights and their futures.

He need not look further than what this policy has already done to girls at the state level, and he should reverse course on this injustice rather than bringing it to the federal level.

Simply put, the policy he champions hurts Americas girls. Female athletes in Connecticut have been forced to face this sad reality for years. Just ask Selina Soule and Alanna Smith. Soule and Smith are two student athletes who, like many, dreamed of achieving success in sports. In 2017, after years of grueling practices and long nights, their goals finally seemed within reach.

Then the finish line was moved in the name of equity.

When these women took their spots at the starting line, they were lined up next to two biological males who identify as females. No matter their identity, the facts remain: Their genetics and physical bodies are equipped with athletic abilities unachievable to women. Unsurprisingly, these males defeated Soule and Smith and their dreams in the process.

This all began when the Connecticut Interscholastic Athletic Conference started accepting boys who identify as female in its competitions. The results have predictably been disastrous for the state of female sports.

These male athletes have gone on to claim 15 womens track championship titles in two years. And theyre not alone. Currently, 16 states allow full transgender participation in high school athletics, while an additional 10 states require medical documentation to participate.

In these female competitions, who won 15 titles? The boys.

Who set 13 individual track meet records? The boys.

Who lost out on their goals and dreams? The girls.

Fast forward to 2021, and our new administration is dead set on taking this injustice to the next level. Bidens nationwide inclusion mandate seeks to damage the very rights his party claims to champion.

This has gone on long enough.

As someone who enjoyed playing in sports in high school and coaching high school track for many years, I am well aware of the damage this executive order places on current and future generations of women. Sadly, this action by Biden will water down our hard-fought rights and protections while effectively denying female athletes fair competition.

When we misconstrue Title IX rules and morph them into an alternate reality, our girls are the ones who end up losing. This is unacceptable.

For our society to grow stronger, we need to build up the traits that make each of us unique, not walk back decades of female victories in order to minimize our differences. Americas girls deserve better than to become victims of political correctness.

Biden said, I will be a president for all Americans. If thats the case, he should stop working to reverse the rights of half of them.

Rep. Vicky Hartzler represents Missouri's 4th Congressional District in the U.S. House of Representatives.

Tags: Opinion, Op-Eds, Transgender Issues, Sports, Gender Issues, Joe Biden, Capitol Views

Original Author: Rep. Vicky Hartzler

Original Location: President Biden, stop working to reverse the rights of half of America

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President Biden, stop working to reverse the rights of half of America - msnNOW

Noninvasive probe monitors health of ‘friendly’ gut bacteria – Medical News Today

The gut microbiota is the community of bacteria, fungi, viruses, and other microorganisms that make their home in the human digestive tract.

In recent years, scientists have discovered an astonishing range of interactions between the gut microbiota and human health. These include effects on mood, eating disorders, and immunity.

A recent study reported by Medical News Today also found associations between particular bacterial species and the risk of developing diabetes, heart disease, and obesity.

Bacteria in the gut produce an enzyme called bile salt hydrolase (BSH) that may be essential to many of their beneficial effects.

For example, scientists have linked high BSH activity to decreased inflammation, reduced blood cholesterol levels, and protection against colon cancer and urinary tract infections.

Scientists still know surprisingly little about the complex interactions between the diet, the gut microbiota, and BSH activity.

Recently, an international team of researchers set out to study the effects of prebiotics insoluble dietary fibers that promote the growth of friendly bacteria on the activity of BSH.

They also wanted to develop a clinical test for assessing the enzymes activity in people with inflammatory bowel disease.

Microbiologists currently use indirect techniques to gauge the enzymes activity, for example by analyzing fecal samples or culturing bacteria in the lab. But these efforts do not reflect the diversity of bacteria and the chemical complexity of their natural environment, which varies according to where they live in the gastrointestinal tract.

So the team, led by researchers at the University of Missouri, in Columbia, and the Swiss Federal Institute of Technology, in Lausanne, developed a noninvasive chemical probe that measures the activity of BSH along the entire length of the gut.

They have published their findings in the journal Science Advances.

The probe relies on a natural compound called luciferin, which emits light in the presence of oxygen, and the enzyme luciferase, which originates in fireflies.

To create the probe, the researchers chemically caged the luciferin by combining it with a small molecule that shields it from luciferase.

They designed the cage so that only the enzyme BSH can liberate the luciferin molecule from the probe. As a result, the amount of light that a fecal sample produces in the presence of luciferase is proportional to the amount of BSH along the length of the gut.

The scientists first tested their probe on samples in the lab. A female volunteer then swallowed two capsules containing the probe, and these successfully measured the enzymes activity as they passed through her gut.

Until now, we have not had any ways to noninvasively monitor activity in the intact gastrointestinal tract, given the unique chemical environment, variable distribution, and highly dynamic nature of the gut microbiota, says Dr. Elena Goun, an associate professor in the universitys department of chemistry and the senior author of the paper.

In another experiment, in mice, the team used the probe to test the ability of different types of prebiotic supplement inulin and fructo-oligosaccharides (FOSs) to boost the production of BSH.

They discovered that inulin produced no significant change in BSH levels in the animals guts, but FOSs doubled these levels.

Dr. Goun explains the significance of her teams results:

Prebiotics are often used in combination with probiotics to enhance their functions in the body. [] We show, for the first time, that certain types of prebiotics alone are capable of increasing [BSH] activity of the gut microbiota, which, among other health benefits, has been shown to decrease inflammation, reduce blood cholesterol levels, and protect against colon cancer and urinary tract infections.

The senior researcher adds that there could also be important cost benefits, as prebiotics are less expensive to produce and store than probiotics.

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Noninvasive probe monitors health of 'friendly' gut bacteria - Medical News Today

Suza: Self-reflection strengthens diversity and inclusion | Opinion | iowastatedaily.com – Iowa State Daily

Columnist Walter Suza encourages to strengthen diversity and inclusion in institutions by beginning at an individual level.

There will be progress. Like after the Obama administrations effort to make college more affordable and accessible to low-income students and students of color.

There will be setbacks. Like after Trumps executive order threatened diversity training in U.S. colleges.

The impact of such external factors is hard to miss. Yet its internal factors that can escape our attention because theyre deeply ingrained in our normal way of operating.

Imagine a stellar high school student with a dream of attending her favorite university, which is predominantly white. The aspiring student visits the university and hears more about various great programs and activities. The visit seals the deal.

The student enrolls as an undeclared major.

A class in philosophy introduces the student to George Berkeley, who tried to put God in the center of philosophy, and Immanuel Kant, who believed that moral principles must be followed unconditionally.

Martin Heidegger also captures the students attention with his idea that: We do not experience mere sensations abstracted from the real objects of the world; rather, our experiences are of everyday objects in all their richness and complexity.

From Heidegger's thinking, the student recognizes that theres complexity in our humanness, and richness in our cultures, backgrounds and experiences.

Yet upon looking around the department, the student sees more vividly that the department is homogeneously white. The student wonders: How can I experience the richness and complexity of a professor of color if I dont interact with such a professor?

The student looks white and also is Jewish, and upon further research she learns that Heidegger was supportive of the Nazis. The student wonders: Why was this not mentioned in class?

Unfortunately, what was also left out in the discussion was the fact that modern philosophy has ties to racism and bigotry. Upon this realization, the student decides to take a course in genetics.

In genetics she learns about the amazing work of James Watson and Francis Crick to unravel the structure of the genetic code. The student is elated that knowledge of the genetic code made it possible to create the COVID-19 mRNA vaccine.

Upon further research the student finds out that Watson and Crick relied on the work of a female scientist, Rosalind Franklin, yet Franklin wasnt considered for the Nobel Prize. Another student whos Black shares that Watson was stripped of his numerous accolades because of his racist views against Black people. The students wonder: Why were these things not acknowledged in class?

In the genetics class, the students read research papers on bone development and biological networks and are upset to discover that the terms master and slave are used with impunity in biology and computer science.

The Black student raises more concern about the term breeding used in crop and animal science. The term breeding reminds the students of a dark past in America involving the creation of slave breeding farms to supply Black slaves to plantations. The students wonder: Why is the term breeding still used to describe improvement of the genetics of animals and crop plants?

The students browse the internet and learn that in French, Spanish and Portuguese languages, the term breeding is not used, instead, the term improvement of plants is used.

The students meet at a coffee shop with other concerned students to discuss the use of offensive terms in courses. They also discuss circulation of hate speech on social media.

A student from journalism warns the group that controversial social media posts are protected by the First Amendment. The Black and Jewish students are appalled by this and ask: How about the protection of those affected by hate speech?

A professor in agronomy who happens to be at the coffee shop overhears the conversation and approaches the students and says:

I am sorry for the hurtful experiences you have endured in our institution. I have also been complicit in this. I was educated and Im working in the area we call plant breeding. I also use the term "breeding" in my teaching and research. Now I see better and I want to do something about this. I am sorry for perpetuating the pain.

The Black student turns to the professor and says: Imagine having a guest in our home. If we are good hosts, we would prepare a room for our guest, we would make sure our guest has food to eat, we would spend time with our guest, we would show that were interested in their well-being, we would make sure our guest feels safe in our home.

There is a lot of work to be done in academic institutions such as this one to make the learning environment safe.

The work starts at the individual level.

First by imagining being in the underrepresented and having to deal with racism. This will help us become aware of beliefs and stereotypes about those different from us.

Next, by looking inward for our own unconscious biases because learning that we have unconscious bias can help us to develop compassion.

Compassion helps us gain the courage to accept that prejudice lives and breathes in academia.

Compassion helps us become willing to address offensive content in our lectures and speeches.

Compassion helps us become willing to address controversial monuments on our campus.

Compassion helps us realize that we are at our best when we treat others the way we would like them to treat us.

Walter Suza is an adjunct associate professor in the department of agronomy.

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Suza: Self-reflection strengthens diversity and inclusion | Opinion | iowastatedaily.com - Iowa State Daily

[Full text] Extra-Hepatic Hepatoid Carcinomas in Female Reproductive System: Three | CMAR – Dove Medical Press

Introduction

Extrahepatic hepatoid carcinomas (HCs) are a rare group of aggressive tumors with clinical and pathologic features similar to hepatocellular carcinoma (HCC). Ishikura and Scully first proposed the concept of a hepatoid carcinoma in 1987 when they described a case involving the ovary that was immunopositive for -fetoprotein (AFP).1 Positive staining for AFP by immunohistochemistry was considered to be an essential feature of this tumor.2 Another case of AFP-producing endometrial adenocarcinoma was reported in 1988. These tumors can arise in many tissues outside the liver (most commonly in the stomach) but rarely occur in the female reproductive system.35 Here we report 3 such cases that were treated at Qilu Hospital of Shandong University. The patients were aged 48, 56, and 67 years; 2 had hepatoid carcinoma of the ovary (HCO), with negative staining for AFP in 1 case; and the third patient had hepatoid carcinoma of the uterus (HCU).

A 66-year-old postmenopausal female (G2P2L2) was admitted to our hospital with abdominal pain and distension that had persisted for 20 days and emesis that had lasted for 7 days. The patient had a history of bilateral tubal ligation but no family history of gynecologic cancer, hepatitis, or any other hepatopathy, and was negative for hepatitis B surface antigen (HBsAg) at admission. Physical examination revealed a giant (1015 cm) irregular lump in her abdominopelvic cavity but no hepatosplenomegaly or lymphadenopathy. Her cervix uteri was atrophic and the uterus was undetectable to the touch. The shifting dullness test yielded a positive result.

A heterogeneous hypoechoic solid tumor measuring 13128.1 cm with unclear margin was observed in the bottom left area of the abdominal cavity by color Doppler ultrasound. The tumor contained a few liquid dark areas and streaked bloodstream signals. The uterus was contracted to 4.33.92.8 cm. A sonolucent area of fluid was observed in the abdominal cavity at a depth of 7.1 cm, which increased to about 11 cm after 15 days. An enhanced computed tomography (CT) scan of the abdomen and pelvis revealed multiple masses with heterogeneous density, with the largest measuring 13.8 cm in diameter. The omentum and peritoneum were thickened, but the liver and lymph nodes showed no abnormalities (Figure 1A). Levels of tumor markers were as follows: cancer antigen (CA)125, 795.40 U/mL (normal: <35 U/mL); CA153, 735.52 U/mL (normal: <25 U/mL); CA199, 162.80 U/mL (normal: <39 U/mL); and cytokeratin 19 fragment (CYFRA21-1), 18.54 ng/mL (normal <3.3 ng/mL). Serum AFP level was 2.05 ng/mL, which was within the normal range (<20 ng/mL).

Figure 1 CT and MR images of cases: (A) for CT image of case 1; (B) for CT image of case 2; (C) for MR image of case 2; (D) for CT image of case 2; (E) for MR image of case 3; (F) for MR image of case 3.

The patient was diagnosed with a malignant ovarian tumor and underwent hysterectomy as well as dissection of bilateral adnexa, greater omentum, and metastatic nodules on the mesentery and in the pelvic cavity. About 2 L of pale bloody ascites was removed. Bilateral ovaries were slightly enlarged with cauliflower-like neoplasms on the surface. The right oviduct was thickened but the left oviduct was normal. An enormous cystic solid tumor measuring 15109 cm was found beside the colon sigmoideum that was tightly adhered to the mesentery and had an 8-cm long crevice. A cauliflower-like neoplasm approximately 87 cm in size was observed near the splenic flexure of the colon, but excision was not attempted because of its tight adhesion to the spleen and transverse colon. Numerous tumor nodules were present on the omentum majus, with the largest one approximately 56 cm in diameter in the omental bursa. Friable cauliflower-like neoplasms of variable size were observed on the peritoneum and mesentery. The gall bladder was enlarged to about 55 cm and the vermiform appendix was tortuous and thickened. No abnormalities were observed in the liver. Histopathologic analysis of frozen sections strongly suggested the possibility of sex cord stromal tumors. The final diagnosis was stage IIIC HCO.

The patient completed 1 cycle of carboplatin (450 mg) and docetaxel (90 mg) but refused additional cycles of chemotherapy because of serious side effects. The patient died 3 months after her surgery. The pathologic findings are shown in Figure 2 and supplementary Figure 1.

Figure 2 Pathological findings for case 1: (A) (H&E100), (B) (H&E200), Microscopically, tumor cells are large and polygonal, with abundant and eosinophilic cytoplasm. The nuclei were lightly stained and appeared round or ovoid, some cells were binucleated, the nucleoli were obvious, mild atypia, and mitotic figures were seen. The nuclei are lightly stained, round or ovoid, with obvious nucleoli, and some of the cells are binucleate. Slight atypia and mitotic figures are visible. The tumor has an infiltrative growth and is poorly demarcated from normal tissue. (C) negative stain for AFP(100). (D) partial positive stain for Hepatocyte-paraffin 1(100). Besides, we got immunohistochemical analysis as follows: PAX8(-), P53(-), P16(-), ER(-), PR(-).

A 48-year-old postmenopausal female (G5P2A3L2) was admitted to our hospital with a left lower abdominal mass with tenderness that had persisted for 5 days. The patient had a history of Budd-Chiari syndrome and no family history of gynecologic tumors. She had no history of hepatitis or any other hepatopathy, and was negative for HBsAg at admission. Physical examination revealed a hard 8910 cm mass in the left adnexa area along with tenderness. No abnormality was found in the right adnexa or uterus.

Ultrasonography showed a 10.38.6 cm solid mass in the left adnexa area. High blood flow signals were observed and the depth of the sonolucent area of fluid in the abdominal cavity was about 4.0 cm. There was no significant abnormality in the liver. The enhanced CT scan revealed a lesion in the subcapsular area of the right lobe of the liver that was highly suggestive of a metastatic tumor (Figure 1B). Enhanced magnetic resonance imaging (MRI) showed circular T1 and T2 signals and an annular high diffusion-weighted imaging (DWI) signal in the subcapsular area of the right lobe of the liver, with uneven annular enhancement and a diameter of about 2.2 cm that supported the possibility of a metastatic tumor (Figure 1C). Portal hypertension and cholecystitis were observed. In the left adnexa area, there was a round cystic mass about 9.58.8 cm in size with uneven density, unclear boundary, and uneven slight enhancement (Figure 1D). The tumor was considered as originating in the ovary. The density of fat space in the peritoneal cavity around the tumor was increased, and the boundary between the colon and surroundings was unclear. There were no enlarged lymph nodes in the pelvic cavity. Serum levels of biochemical markers were as follows: CA125, 81.95 U/mL (normal: <35 U/mL); CA724, 8.73 U/mL (normal: <6.9 U/mL); and anti-Mllerian hormone, 0.01 U/mL (normal: 0.052.06 ng/mL). Serum AFP was extremely elevated at >24,200.00 ng/mL, which decreased to 3334.00 ng/mL 12 days after the surgery.

The patient underwent exploratory laparotomy. There was cystic enlargement of the left ovary, which was about 886 cm with an incomplete capsule and anabrotic surface. No obvious abnormalities were found in the appearance of the right adnexa and uterus, and there were no visible tumors or other abnormalities in the liver and intestines.

Frozen sections from the left adnexectomy showed poorly differentiated adenocarcinoma. The patient underwent extrafascial hysterectomy, bilateral bilateral adnexectomy, greater omentum resection, pelvic lymph node dissection, para-aortic lymph node sampling, and appendectomy.

The final pathologic diagnosis was stage IC2 HCO. Tumor cells were large and polygonal with cytoplasm ranging from pink and granular to clear. Nuclei are round to oval with distinct nucleoli. The cells resembled those of HCC. Immunostaining results were as follows: AFP(+), arginase (Arg)-1(+), glypican (GP)3(+), hepatocyte paraffin 1 (+), cytokeratin (CK)8/18(+), Sal-like protein (SALL)4(), cluster of differentiation (CD)117(), CD30(), AFP(+), -inhibin(), CK(), CK7(), octamer-binding protein (OCT)4(), chromogranin (Cg)A (), synaptophysin (Syn)(), paired-box (PAX)8(), estrogen receptor (ER)(), progesterone receptor (PR)(), Wilms tumor (WT)(), and Ki67(40%+).

The patient completed 6 cycles of intravenous chemotherapy with paclitaxel liposome (270 mg) plus carboplatin (600 mg). Serum AFP level decreased to 127.00 ng/mL after the first cycle and was normal after the second cycle. The enhanced CT scan showed a small liver-occupying lesion and enlarged retroperitoneal lymph nodes 4 months after the operation. After consulting with the surgeon, the lesion was determined to be metastatic disease. The patient underwent radiofrequency ablation of the lesion and is alive over 22 months later. At the most recent physical re-examination, no obvious abnormality was found in her pelvic cavity. The pathologic findings are shown in Figure 3 and supplementary Figure 2.

Figure 3 Pathological findings for case 2: (A) (H&E100), (B) (H&E200),Microscopically, tumor cells are large and polygonal, with abundant and eosinophilic cytoplasm. The nuclei lightly stained are round, elliptic or irregular in shape, with inconspicuous nucleoli. Some of the nuclei are vacuolated with chromatin squeezed under the thickened nuclear membrane. The nuclei are highly heteromorphic, with active mitoses and some of the cells are binuclear or multinucleate. The tumor has an infiltrative growth and is poorly demarcated from normal tissue. (C) positive stain for AFP(100). (D) positive stain for Hepatocyte-paraffin 1(100). (E) negative stain for SALL-4(100). Besides, we got immunohistochemical analysis as follows: PAX8(-), P53(-), P16(-), ER(-), PR(-).

A 48-year-old premenopausal female (G3P2A1L2) was admitted with menostaxis and menorrhagia. The patient had a history of bilateral tubal ligation and no family history of gynecologic malignancies. She had no history of hepatitis or any other hepatopathy and was negative for HBsAg at admission. Physical examination revealed a tumor in the external cervix about 4.5 cm in diameter with an ulcerated surface that bled on contact. Her uterus size was equivalent to about 2 months of pregnancy, with regular shape, good movement, and mild tenderness. Ultrasonography showed that the size of the uterus was increased to 11.07.56.2 cm, with a regular shape and a 2.92.6-cm low-echo area whose pedicle was connected to the uterine cavity. The liquid dark area in the abdominal cavity had a depth of 7.1 cm that increased to about 11 cm after 15 days. An enhanced MRI scan of the pelvis and abdomen revealed an irregular mass in the uterine cavity near the uterine isthmus with a clear boundary and a size of about 32.52.6 cm, showing a high DWI signal with the same degree of enhancement as the myometrium (Figure 1E). No abnormal signals were found in bilateral adnexa and rectum, and multiple small lymph nodes <1 cm in diameter were present in the pelvic cavity. The signal of the liver parenchyma was nonhomogeneous (suggesting fibrosis), and no abnormal enhancement was observed in any phase of the enhanced scan (Figure 1F). There were no abnormalities in the intra- and extrahepatic bile ducts or gallbladder and no obvious enlargement of lymph nodes in the abdominal cavity and retroperitoneum. Serum levels of carcinoembryonic antigen (CEA), CA125, CA153, CA199, CA724, and a CYFRA21-1 were within normal ranges. Two months before admission, the patients serum AFP level was 1210 ng/mL (normal: <20 ng/mL), and the maximum level before surgery was 8191 U/l.

The patient had been treated by curettage at a local hospital, and pathologic analysis of the biopsy indicated a malignant tumor. Pathologic findings from another hospital suggested the possibility of metastatic HCC, while primary hepatoid yolk sac tumor (HYST) could not be excluded. A tentative diagnosis of placental site trophoblastic tumor with focal infiltration of muscle tissue was made after 1 week based on the following immunohistochemistry results: CK(+), AFP(+),human chorionic gonadotropin (hCG)(), human placental lactogen (hPL)(), smooth muscle actin (SMA)(),-inhibin (), hepatocyte paraffin 1 (-), and GP3(). Clinical examination was necessary in order to exclude liver cancer metastasis. Histopathologic examination at our hospital revealed epithelioid cells with abundant cytoplasm in the endometrial tissues, and hepatoid adenocarcinoma was considered based on immunohistochemical analysis at our hospital, which yielded the following results: CK(+), AFP(+), epithelial membrane antigen (EMA)(+), vimentin(), OCT4(), 1 antitrypsin(), hepatocyte paraffin 1(-), and GPC3().

The patient was diagnosed with endometrial cancer and underwent modified radical hysterectomy, bilateral adnexectomy, pelvic lymph node dissection, and anterior sacral lymph node resection. Bilateral adnexa appeared normal, and there were several enlarged lymph nodes in the pelvic cavity. By dissecting the uterus, a dark purple neoplasm about 433 cm in size was found in the upper part of the uterine cavity near the fundus that had invaded the superficial muscle layer and caused local necrosis, with no obvious abnormalities in the cervix. Frozen sections showed localized endometrial carcinoma infiltrating into the superficial muscle layer. The final pathologic diagnosis was stage IA HCU.

The patients serum AFP level gradually decreased to 4212 ng/mL on the second day after the operation and to 680.6 ng/mL 7 days later. She received 6 cycles of intravenous chemotherapy with taxol (240 mg) and carboplatin (600 mg). After the first cycle, serum AFP decreased and after the second cycle, the level was below the normal range. There were no abnormalities in serum AFP level or by liver imaging during follow-up, and the patient remains alive over 63 months later. Pathologic findings are shown in Figure 4 and supplementary Figure 3.

Figure 4 Pathological findings for case 3: (A) (H&E100), (B) (H&E200),Microscopically, tumor cells are large and polygonal, with abundant and eosinophilic cytoplasm. The nuclei were round or oval in shape, varied in size, and some cells were binucleate. The nuclear membrane was thickened, the nucleus was pale stained, the nucleolus was obvious, atypia was not obvious, and mitotic figures were seen. The tumor tissue is poorly defined from normal tissue and shows infiltrative growth. (C) positive stain for AFP(100). (D) negative stain for Hepatocyte-paraffin 1(100). Besides, we got immunohistochemical analysis as follows: PAX8(-), P53(-), P16(-), ER(-), PR(-).

Ovarian cancer is one of the most common gynecological malignancies, accounting for 2.5% of all female cancers and 21% of malignancies of the female genital tract. It is often diagnosed in the late stages and has poor prognosis, with a low cure rate (<40%) and accounting for 5% of total cancer deaths in women in the United States.6 Five subtypes of ovarian carcinoma that together account for over 95% of cases have been distinguished based on histopathologic, immunohistochemical, and molecular genetic featuresnamely, high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous (<5%) carcinoma.7 Primary HCO is a rare, aggressive tumor that shares clinical and pathologic features with HCC and is thought to have 2 histogenic originsie, superficial epithelium and germ cells, although neither of these are supported by conclusive evidence.8 This tumor type was labeled as HC because it lacked an adenocarcinomatous component,1 until the possibility of a surface epithelial origin was suggested.9,10

Only 39 cases of HCO have been reported to date; most patients have been postmenopausal females ranging in age from 27 to 78 years, with a median age of 55 years. Most cases were diagnosed at a late clinical stage and presented with abdominal distension and lower abdominal pain with rapid progression of the disease. Primary HCU is also rare, with only 11 cases reported in the literature. Most patients were postmenopausal women except for our 48-year-old patient, with an average age of 64 years. The adenocarcinomatous component coexisted in all cases, and sarcomatous components were observed in 2 cases. HCU has very poor prognosis, with the majority of patients experiencing tumor recurrence or death within 12 months of diagnosis (Tables 1 and 2).

Table 1 Clinical Features, Treatment, and Outcomes of HCO

Table 2 Clinical Features, Treatment, and Outcomes of HCU

Most HCO patients have a higher-than-normal serum AFP level, with only 3 recorded cases of normal AFP levels. CA-125 levels were also higher than normal in most patients. CT and ultrasound imaging showed a unilateral (occasionally bilateral) mass that was generally solid or accompanied by partial cystic components. Both of our HCO patients had solid pelvic masses that were partially cystic with abundant blood flow signals by ultrasound examination. Microscopically, primary HCO behaves like HCC, with tumor cells arranged in sheets, cords, or trabeculae, sometimes with glandular and papillary structures. Cells usually have an eosinophilic cytoplasm with large and irregular nuclei that show high mitotic activity. Both of our patients showed typical pathologic manifestations. AFP is the most commonly used biochemical marker for HCO and is negative in rare cases. Despite negative immunostaining for AFP, these carcinomas with typical histologic features of a HC have been classified as HC1 as was undifferentiated carcinoma with abundant eosinophilic cytoplasm and immunonegativity for AFP.2 In our patient who was negative for AFP by immunohistochemistry, the tumor consisted of solid sheets of cells with abundant eosinophilic cytoplasm, distinct cell borders, and centrally located nuclei with prominent nucleoli, which is a typical histologic feature of HC. AFP production is closely coupled to cell division and the degree of cell differentiation; neoplastic cells only transiently produce AFP, leading to negative AFP staining. Thus, AFP immunopositivity is not essential for diagnosing AFP-secreting tumors such as HCO.2

HYST is another ovarian tumor characterized by hepatoid differentiation and AFP production that should be distinguished from HCO, which is relatively straightforward.12 HCO can be distinguished from HCC based on detection of hepatocyte paraffin 1 and the presence of bile, microscopic findings, and immunonegativity for CA125.46 In addition to hepatocyte paraffin 1, HCC is positive for SALL4, a frequently used marker of germ cell tumors.47 We consider that diffuse positivity for SALL4 is suggestive of HYST rather than HCO, especially in women of childbearing age. However, immunopositivity for SALL4 has been reported in HCO cases. Our case 2 was negative for SALL4. The presence of a surface epithelial carcinoma component strongly favors a diagnosis of HC over HYST.11 One study suggested that immunohistochemical detection of hepatocyte nuclear factor (HNF)-4 may be helpful in distinguishing between hepatoid adenocarcinoma and the solid component of high-grade endometrioid adenocarcinomas, because all examined cases of endometrioid adenocarcinoma were negative for HNF-4; these authors speculated that liver-enriched nuclear factors such as HNF-4 may be involved in hepatic differentiation of the tumor,8 although the underlying molecular mechanism is unclear.

According to our review, survival time in patients with HCO ranged from 1 month to 5 years (2- and 5-year survival rates <50% and <10%, respectively). The prognosis of patients with HCU is equally poor, with only one patient (our case 3) surviving >5 years. The optimal treatment for HCO remains to be determined. Most cases are treated as ovarian-like cancerie, with surgery plus chemotherapy (carboplatin plus paclitaxel). The tyrosine kinase inhibitor sorafenib has been used as a second-line treatment but its efficacy is undetermined; in one study, second-line sorafenib was discontinued because AFP level increased and the disease progressed,12 and in another study the patients condition deteriorated after 2 months of treatment and the chemotherapy regimen was switched to carboplatin plus paclitaxel.13 However, one case treated with sorafenib achieved a progression-free survival of 7 months.48 All of our patients underwent cytoreductive surgery for their tumor and received postoperative chemotherapy with carboplatin/docetaxel and carboplatin/paclitaxel liposome. The patient with HCU who was treated with carboplatin plus paclitaxel liposome responded well to this regimen and achieved a progression-free survival >56 months. Hysterectomy and bilateral adnexectomy were performed in all cases of HCU reported to date and most patients received adjuvant chemotherapy while some were treated with radiotherapy. Two of our patients were treated with 6 cycles of chemotherapy and did not receive radiotherapy; our case 3 was diagnosed with stage IA HCU and achieved a good clinical outcome after treatment.

Based on our 3 cases and review of the literature, we conclude that first-line treatment for both HCO and HCU should be staging surgery followed by platinum-based chemotherapy.

All patients (or next of kin for the deceased patient) provided written informed consent for the case details and images to be published. This research was conducted according to the guidelines put forth in the Declaration of Helsinki. Institutional approval to publish the case details is exempt.

The authors report no conflicts of interest in this work.

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[Full text] Extra-Hepatic Hepatoid Carcinomas in Female Reproductive System: Three | CMAR - Dove Medical Press

The Importance of Seed Banks for Our Future – Agweb Powered by Farm Journal

Today, three major food crops--corn, rice, and wheat--provide more than 60 percent of the calories consumed by the more than seven billion people around the world on a daily basis, according to the UNs Food and Agriculture Organization (FAO). Just 15 crop plants provide 90 percent of the world's food energy intake, including some crops that many Americans have never heard of, such as teff, millet, plantains, and cassava, which are all staple crops in parts of Africa. Most agricultural research funding, especially in the private sector, focuses on the top six or so food crops, as those are the ones they see the opportunity to gain profits from selling farmers improved versions of those seeds. In order to conduct effective research on all domesticated crops, scientists need access to germplasm from a wide variety of cultivars with various characteristics, so as to be able to select the best of the traits they are seeking to introduce or enhance. A common source of that germplasm is seed banks, which are generally publicly funded and operated, to preserve a variety of seeds from both well-known and obscure plants.

Botanic gardens in Europe collected seeds from plants with medicinal properties as early as the 16th century. Some of them, such as the Royal Botanic Gardens in Kew in southwest London, were established by grants from royal or noble families, while several were associated with European universities such as the University of Leiden in the Netherlands.

One of the first known broad-based seed banks was established in Leningrad in what was then the Soviet Union in 1917 by botanist Nikolai Vavilov and his colleagues, who traveled around the world collecting a wide variety of seeds. The original institution, the Bureau of Plant Botany, was established under the Russian Empire in 1894, but their work originally focused largely on collecting seeds from within the country. Vavilov was sentenced to death in July 1941 by Russian dictator Josef Stalin, who had embraced the false theory of plant genetics promulgated by Vavilovs former student, Trofim Lysenko. Vavilovs sentence was commuted but he died in prison in 1943. His colleagues protected the seed collection during the 28-month long siege of Leningrad by the German army during World War II, even as nine of them died of starvation.

The first U.S. seed bank was established at a USDA facility in Ames, IA in 1947. That facility, still operated by the Agricultural Research Service, maintains a collection of more than 53,000 unique accessions of 1,400 distinct crop species. It is one of 20 gene banks in operation in this country, including a back-up collection at the National Laboratory for Genetic Resources Preservation in Fort Collins, CO.

Scientists began to raise concerns about the limited genetic diversity of major food crops about fifty years ago, after a major crop failure in the United States was determined to have resulted from the fact that most public corn breeders of the era used a single parental type of corn, known as Texas cytoplasmic male sterile (Tcms), to conduct their breeding practices. This variety had been favored by crop breeders because production of such corn seed did not require the labor of large numbers of young people to detasslefemale corn plants. In 1970, a disease that became known as Southern corn leaf blight (SCLB) caused by the fungus Bipolaris maydis that had been viewed previously as only a minor pathogen affecting corn grown in Southern states swept across the country into the Corn Belt region due to the presence of the wet, warm growing conditions in which the fungus thrived. Many cornfields in the South were totally wiped out, while Midwest corn farmers also experienced significant yield losses. It is estimated that the U.S. corn crop was reduced by at least 700 million bushels in that year, which amounted to about a 15 percent decline compared to the 1969 U.S. corn crop. Crop breeders began to respond immediately by using alternative germplasm as the foundation for corn seed sold to U.S. farmers in subsequent years.

There are more than 1,750 seed banks operated around the world, including several associated with member centers of the CGIAR system, such as the International Potato Center (CIF) in Peru and the International Institute of Tropical Agriculture (IITA), headquartered in Nigeria. Transfer of genetic materials held by these facilities is governed by provisions of the International Treaty for Plant Genetic Resources for Food and Agriculture, which entered into force in 2004 and now has 148 contracting parties. The United States joined the treaty in March of 2017. The treaty was established in order to ensure the establishment of a global system to provide farmers, plant breeders and scientists with access to plant genetic materials, and that recipients share benefits they derive from the use of these genetic materials with the countries where they have been originated.

The most famous seed bank is probably the Svalbard International Seed Vault, also known as the Doomsday Vault, which opened for storage in February 2008. The facility is constructed inside a mountain in Norway which is inside the Arctic Circle, intended as a backup collection in case other facilities are damaged or destroyed as a result of climate change or other catastrophes. The facility was built by the government of Norway and its operations are funded through donations to the Global Crop Diversity Trust. The vault holds varieties of more than 5,000 crop species. In 2020, the Cherokee Nation made a deposit of ancestral varieties of corn, beans, and squash seeds in the facility, to protect their cultural heritage.

One major component of biodiversity that gene banks are often lacking are crop wild relatives the undomesticated, but related, strains of staple food crops like corn and wheat. A recent study conducted by the Crop Trust looked at 1,076 wild relatives related to 81 species of some of the most important staple crops in the world. The researchers found that 70 percent of those wild relatives are insufficiently represented in the worlds gene banks.

As crop breeders search for varieties to help them incorporate drought or salt tolerance in crops to help with adaptation against the effects of climate change, all such samples will become even more important.

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The Importance of Seed Banks for Our Future - Agweb Powered by Farm Journal

Women Changing the Face of Science in the Middle East and North Africa – The Media Line

For International Day of Women and Girls in Science, four inspiring women scientists tell their stories

Despite making up a little more than half of the globes population, women remain underrepresented in the fields of science, technology, engineering and mathematics (STEM). In fact, a 2017 UNESCO report found that only 35 percent of STEM higher education students globally are women.

However, those numbers are significantly better in many countries in the Middle East and North Africa, where women account for nearly 50% of the STEM student population.

To mark International Day of Women and Girls in Science, held annually on February 11, The Media Line reached out to four inspiring women who are changing the face of science in the region.

Making Moroccos First Humanoid Robot

Prof. Hajar Mousannif has the distinction of having helped build the first Moroccan-made humanoid robot.

Mousannif, 39, is a professor and coordinator of the Data Science Masters Program at Cadi Ayyad University in Marrakech, Morocco. On the forefront of artificial intelligence (AI), Mousannifs team of researchers last year unveiled Moroccos first robot, called Shama.

Hajar Mousannif is a professor of computer science and data science at Cadi Ayyad University in Morocco. (Courtesy)

In 2020, Mousannif won the WomanTech Global AI Inclusion Award, which honors women around the world who are leaders in AI innovation.

In developing countries especially, its not common to see women excelling in such fields because its usually a male world so [the award] meant a lot to me, Mousannif told The Media Line. It opened the door to fruitful collaborations.

For example, last month the US-based company FotaHub announced that it would invest $100,000 to help with the creation of a more advanced version of Shama.

In addition to her groundbreaking work in robotics, Mousannif is involved in a number of other significant initiatives, including using AI to help health officials craft efficient measures to contain the spread of COVID-19, as well as a project in collaboration with the Moroccan government aimed at improving road safety.

Our team of researchers succeeded in developing algorithms that predict road crashes before they occur just by analyzing driver behavior, she said.

In recent years, a growing number of Moroccan women have entered STEM university programs. In Mousannifs data science masters program, for instance, roughly half of all the students are women.

In Ph.D.s the story is different, Mousannif said. Ph.D. students, she added, are 23 or 24 years old and women prefer to get married and have kids.

Still, Mousannif has taken it upon herself to set an example for female students and encourage them to pursue scientific careers.

Im married and have three kids, she said. I keep inspiring them and telling them that they can be good mothers, organize their time and achieve whatever they want.

Solving the Mystery of Diabetes Prevalence in the UAE

The United Arab Emirates has one of the worlds highest rates of diabetes, according to 2019 data from the International Diabetes Federation, affecting 16.3% of the countrys adult population.

A few years ago, Dr. Habiba Alsafar, director of the Center for Biotechnology at Khalifa University in Abu Dhabi, led research that found that types of genes commonly found in Emiratis make them more susceptible to the disease.

Dr. Habiba Alsafar, director of Khalifa University Center for Biotechnology in Abu Dhabi, UAE. (Courtesy)

Born in Dubai, Alsafar showed promise in science at a young age and received numerous scholarships to study in the United States. An expert in genetics and molecular biology, her research into the genetic risk factors for Type 2 diabetes was the first of its kind to delve into the genetic makeup of an Arab population in connection to diabetes.

It was one of a kind in the Middle East, Alsafar told The Media Line of the research.

In her role at Khalifa University, Alsafar teaches students biochemistry, chemistry, forensic science and genetics.

I mentor a lot of science and Ph.D. students, she said. We also work on COVID-19: We sequenced the virus and we looked at the different profiles of severity in patients.

Alsafar has helped the UAE government design a response plan to the coronavirus pandemic. For all of her game-changing work, in 2016 she was awarded the International LOral-UNESCO Fellowship for Women in Science, which is presented annually to five outstanding women scientists.

These awards empower women as there are a lot of awards out there for both genders, she said. Women are always doing a lot of multitasking: they are mothers, sisters and daughters. But they can also be very successful scientists that contribute to the development of the economy or the country.

In order to attract women and girls to the STEM field, Alsafar believes that it is very important to have role models. The leadership in the UAE, she added, has encouraged women to pursue scientific careers as well.

In my lab and technology center, 90% are women, Alsafar said. Its not an issue now compared to the past.

Understanding Cancer Genetics in Saudi Arabia

Wake up to the Trusted Mideast News source Mideast Daily News Email

It may come as somewhat of a surprise, but Saudi women outnumber men in graduating with science degrees, a new report by the kingdoms education ministry revealed.

Dr. Malak Abed AlThagafi is one of the many female scientists in Saudi Arabia leading this charge.

Dr. Malak Abed AlThagafi is an American Board-certified physician-scientist specializing in molecular and cancer genetics. (Courtesy)

An American board-certified molecular neuropathologist and a physician-scientist, AlThagafi is the director of the General Directorate for National RDI Coordination at King Abdulaziz City for Science and Technology (KACST) Research Center in Riyadh. She is also the director of Satellite Research Administration at King Fahd Medical City, where she oversees several departments, including genomics, neuroscience research and research collaboration.

With these numerous achievements under her belt, AlThagafi, 39, considers herself a strong advocate of women in science.

She first became interested in becoming a scientist as a young girl in the 1980s, when her parents took her to see a leading genetics specialist in the kingdom after she was diagnosed with a rare genetic disease. The specialist who treated her was a woman named Nadia Awni Sakati. In Sakati, AlThagafi found a strong role model, she told The Media Line.

We always hear about Western women who did great things but [theyre from] a different background and culture, AlThagafi said. But when you see someone from your own culture its very inspiring and motivating.

Much of AlThagafis research has focused on decoding genetic mutations in tumors. She spent many years in the US completing her clinical training and working at several prestigious universities, among them Johns Hopkins, Harvard and Georgetown. Nevertheless, while the promise of a successful career in America was undoubtedly enticing, five years ago AlThagafi decided to leave it all behind and return to Riyadh. This is where she felt she could make a difference.

Its very enjoyable when you do something for your community, she said. When I came back it was a difficult decision because I was in Harvard and was appointed as junior faculty there. Everybody said: Why did you leave Harvard and come to Riyadh?

Aside from her clinical practice, AlThagafi is also part of the Saudi Human Genome Program, an ambitious national initiative that aims to build a genetic database of the Saudi population in the hope of better understanding and preventing certain genetic diseases.

According to AlThagafi, Saudi society was much more conservative in the late 80s and 90s but the situation for women has improved in recent years.

In terms of undergraduates, up to 60% of medical and health care students are women now, she said, adding that, as in other countries, most leadership and senior positions are still mainly held by men.

In my time [women] only went into biology and health care; now many go into physics and engineering and IT, AlThagafi said. These career options just became available a few years ago in Saudi Arabia for women, she added.

Investing in the Leaders of Tomorrow in Israel

In the world of venture capital firms looking to change the face of health care innovation and entrepreneurship, Dr. Irit Yaniv undoubtedly stands out.

Together with her two business partners Amir Blatt and Tzahi Sultan Yaniv recently founded Almeda Ventures, an equity partnership fund that first went public last October. Almeda Ventures is the first R&D partnership of its kind to focus on life sciences, specifically on medical devices and digital health.

Dr. Irit Yaniv, founding partner and CEO of Almeda Ventures and the co-founder of WE@HealthTech. (Courtesy)

Yaniv, 56, studied medicine at Ben-Gurion University of the Negev in southern Israel and served as a medical doctor in the army for four years. After her initial foray into medicine, she decided to pursue a career path in the private sector, working in the pharmaceutical and medical device industries along the way.

Eight years ago, I decided that I would like to look at the industry from a different angle, Yaniv told The Media Line. I had this feeling that in order to be able to make an impact you also have to understand investments.

So far, Almeda Ventures has invested in five Israeli companies. The most recent is Virility Medical, which is in the process of developing a single-use patch that can help with premature ejaculation.

As a woman in the VC arena, Yaniv is very much in the minority. Last year, Tel Aviv-based firm Qumra Capital found that women make up only 8% of partners in Israeli VC firms.

Being in the VC and upper management side, I find myself most of the time being the only woman in the room, Yaniv said. It became an issue and I wanted to do something about it.

With this in mind, she joined together with other female industry leaders Dorit Sokolov, Yael Gruenbaum-Cohen and Ronit Harpazto establish WE@HealthTech, a program geared toward helping junior female managers get the tools they need to reach more senior positions.

When you look at the life sciences [field], you see many women in junior positions: junior researchers, biology and chemistry graduates, laboratory technicians, clinical managers and so on, Yaniv said. But when you look at the other end management, investors and CEOs you see very few. So somewhere in the middle we are losing them.

The WE@HealthTech program teaches women how to speak, conduct negotiations and improve their business profiles online. It also helps them build up their professional networks and connect to other influential women in Israel and abroad.

Out of 21 participants who recently completed the pilot initiative, five have received promotions at work, Yaniv said. Yaniv, who has two children, believes that many women in STEM simply need a gentle push in the right direction.

Sometimes you need someone else that did it to tell you that this is right and that it is ok to do it, she said. It is ok to split yourself between career and home. You can find a balance between the two without giving up on one of them.

From left, Dorit Sokolov, Yael Gruenbaum-Cohen, Ronit Harpaz and Irit Yaniv, the founders of WE@HeathTech. (Courtesy)

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Women Changing the Face of Science in the Middle East and North Africa - The Media Line

Menstrual cycles and lunar cycles: Is there a link? – Medical News Today

For centuries, scholars and writers have speculated about the possibility of a link between lunar cycles and menses. And in 2021, it seems that the potential synchronicity between the two continues to fascinate.

Menstruation is a cyclical process, as are the phases of the Moon from new moon to waning crescent. Little wonder, then, that poets, philosophers, and scholars have, over the centuries, drawn parallels between the two, suggesting that they might be connected.

The mystique of the Moon and that of female bodies at a time when medicine was in its infancy led Greek philosopher Aristotle to claim, in the 4th century before the common era, that:

[T]he menses tend to occur naturally during the waning moon []. For this time of the month is colder and more humid because of the wasting and disappearance of the Moon.

Age-old parallels between the menstrual cycle and the phases of the moon have likely also led to some females referring to their periods as moon cycles to this day.

Is there really a link between lunar cycles and menstrual cycles? In this Special Feature, we investigate.

Popular belief and many works of literature suggest that there may be some synchronicity between menses and the phases of the Moon.

That may be based on the similarity of duration between menstrual cycles and lunar cycles.

One full revolution of the Moon around the Earth takes 27 days, 7 hours, and 43 minutes. A moon phase cycle, during which the amount of Moon surface that we are able to see from Earth waxes and wanes, takes 29.5 days.

The length of menstrual cycles can be in the range of 2530 days, with the median duration of a menstrual cycle being 28 days.

One 1986 study which Sung Ping Law, from the Department of Gynecology at the Canton Traditional Chinese Medical College in Guangzhou, conducted did seem to find a link between menstrual and lunar cycles.

The research, which appears in the journal Acta Obstetricia et Gynecologica Scandinavica, studied the cycles of 826 female participants, aged 1625 years, over 4 lunar months in different seasons.

The study concept, the author writes, was based on the concept of traditional Chinese medicine that human physiological rhythms display synergism with other natural rhythms.

Law found that, in the study cohort, a large proportion of menstruations occurred around the new moon. This led the researcher to deduce that ovulation periods tended to coincide with the full moon.

However, more recent research contradicts the notion that menstrual cycles often synch with moon phases.

For example, a year-long retrospective study from 2013 which appears in the journal Endocrine Regulations found no synchrony of lunar phases with the menstrual cycle.

This study monitored 980 menstrual cycles in 74 females of reproductive age over a calendar year. The authors say that the findings came in defiance of traditional beliefs.

A more recent study, which the company who program the period tracking app Clue commissioned in 2016, also concludes that synchrony between menstrual and moon cycles is a myth.

This research, which analyzed over 7.5 million menstrual cycles, suggests that periods most likely do not sync with the lunar cycle.

The researchers collected data on menstrual patterns from 1.5 million Clue users. Clue data scientist Dr. Marija Vlajic Wheeler analyzed them.

Looking at the data, we saw that period start dates fall randomly throughout the month, regardless of the lunar phase, says Dr. Wheeler.

Clues raw data and subsequent analysis are not available to the public.

A new study in the journal Science Advances, however, suggests that there may be more to the idea of synchrony between lunar phases and menstrual cycles than previous research may have indicated.

This small-scale study analyzed the menstrual patterns of 22 participants who had kept track of their period onset for up to 32 years.

Together, we had recordings of 15 women aged [35 years and younger] and of 17 women aged [over] 35 years, the researchers write.

Their study found that those whose menstrual cycles were longer than 27 days had intermittent synchrony with two of the Moons cycles: the luminance cycle and the gravimetric cycle.

The luminance cycle refers to the Moons different light intensity as its position in relation to the Sun changes and it passes through its different phases, from new moon to full moon.

The gravimetric cycle refers to the cyclical difference of the Moons pull on the Earth as it orbits around our planet. Since the Moons orbit is elliptical, sometimes it is more distant from the Earth, and sometimes it comes closer.

Its cycle from perigee (when it is closest to the Earth) to apogee (when it is farthest from the Earth) lasts 27.5 days. Depending on where it is in its orbit, the Moon exerts a different gravitational pull on different parts of the Earth.

A third lunar cycle the tropical month, or the mean time of the Moons revolution from any one point in its orbit back to that same point also seemed to be linked to period onset, though to a lesser degree, according to the study authors.

The team also notes that, while menstrual cycles intermittently synched with the Moon cycles, the likelihood of synchrony faded as the participants got older.

Overall, the researchers observed that the Moons light intensity cycle seemed to be the most influential lunar cycle in terms of its effect on menses onset.

We hypothesize that in ancient times, human reproductive behavior was synchronous with the Moon but that our modern lifestyle, notably our increasing exposure to artificial light, has changed this relation, they explain.

Medical News Today spoke to first study author Prof. Charlotte Frster, from the Neurobiology and Genetics Biocenter at the Julius-Maximilians University of Wrzburg in Germany.

We asked her what spurred her research interest in the possible synchrony between moon cycles and the menses.

As a chronobiologist, I am interested in all kind[s] of rhythms, and I was always fascinated by the coincidence of the lunar cycle length and the menstruation cycle length, she told us.

At the same time, she went on, it was very clear that most women appear not to be in synchrony with the moon at least not permanently. This brought me to the idea to investigate whether menses onset couples intermittently to the moon, and I started to ask women about long-term records of their menses onset.

Although her and her colleagues study may be small-scale, sourcing the necessary data to conduct it was no mean feat.

It took more than 10 years until I had collected the data from these 22 women, Prof. Frster explained.

Their study taps into much debated questions regarding how and to what extent human circadian rhythms or our body clocks, which regulate our biological patterns relate to cycles from our natural environment.

Previous studies, including a recent one in the Journal of the Endocrine Society, have looked at fluctuations in melatonin levels in the blood throughout the menstrual cycle.

These have shown that levels of melatonin which is a hormone key to regulating circadian rhythms, and especially the sleep-wake cycle peak just before the onset of menses and decline, overall, the closer a female gets to menopause.

There is also some evidence to suggest that a full moon influences sleep, essentially disrupting sleep duration and quality. One 2013 study in the journal Current Biology suggests that participants slept less on a full moon night, and their melatonin levels also decreased.

Furthermore, there is some evidence to suggest that artificial light can disrupt sleep-wake cycles and have a negative impact on sleep duration and quality.

However, is there any evidence in support of Prof. Frster and colleagues hypothesis that exposure to artificial light has affected females natural synchronicity with lunar cycles over time?

Why and how might exposure to artificial light affect menstrual cycles? MNT asked Prof. Frster. This is a difficult question, and I cannot answer it yet, she replied.

Despite existing evidence that suggests that artificial light affects various aspects of circadian rhythms, research into how it might interfere with menstrual cycles is lacking, she explained.

What we know from circadian rhythms is that their period is strongly affected by light. Depending on the species, [this] period becomes shorter or longer with increasing light intensity. Obviously, this also applies to monthly rhythms, such as the menstruation cycle. In circadian rhythms, light interferes with the molecular mechanisms that generate them. For monthly rhythms, the molecular mechanisms are not yet known. Therefore, I also dont know the mechanisms [underlying] how light affects them.

Prof. Charlotte Frster

The intermittent synchrony between menstrual cycles and lunar cycles is not coincidental, though, the researcher maintains. We performed sophisticated statistical tests that revealed that the intermittent synchrony does not occur by chance, she told us.

Although this new study may have opened up new avenues for research into menstrual patterns, much more work is necessary to confirm whether or not there is a synchrony with moon cycles and, if so, what biological mechanisms might be at play.

Further research should include a larger and more inclusive cohort, the investigators note in their study paper. Aside from the limited number of participants in the recent study, there was also a dearth of variance in participant diversity.

This cohort is not at all representative of the global female population, because the majority of women are white and stem from Europe, Prof. Frster told MNT.

Using a more diverse cohort is important, as previous research has suggested that menstrual cycle length may vary by race or ethnicity.

Prof. Frster believes that learning more about the environmental factors that may influence menstrual cycles could come in handy under certain circumstances.

What applications might this and further studies on this topic have, in the context of womens health? we asked her.

I think that it is still too early to [draw] conclusions. There are so many factors that influence health, and the absence of a synchronization with the moon is for sure a minor contributor to health problems, she told us.

Nevertheless, women who have difficulties [in getting] pregnant and could exclude all other medical reasons might wish to consider a more natural life without too much artificial light at night, she suggested.

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Menstrual cycles and lunar cycles: Is there a link? - Medical News Today

A new candidate vaccine for human brucellosis based on influenza viral vectors: a preliminary investigation for the development of an immunization…

To our knowledge, this study is the first trial conducted in guinea pigs to evaluate the protective properties of a new candidate for vector vaccine against human brucellosis. This phase in vaccine trials is an important step in making an experimental vaccine a promising candidate for further human clinical trials to determine its effectiveness. In this study, double i.n. immunization with a vector vaccine based on influenza viral vectors expressing the immunodominant brucellosis proteins Omp16, L7/L12, Omp19 and CuZn SOD at a dose of 106 EID50 ensured protection against B. melitensis 16M infection comparable to the effect of commercial B. melitensis Rev.1 vaccine.

The choice of guinea pigs as model animals for evaluation of body gain changes and vaccine candidate protection was determined by their natural resistance to influenza infection in comparison with laboratory mice. In this case, the use of a more resistant model animal seemed to be a key condition in the study of protection, since, in the long run, the vaccine is designed for humans.

The previous success of using IVV in the development of the anti-brucellosis vaccine Flu-BA for cattle [12], which is now at the stage of commercialization in Kazakhstan, served as the basis for this study. The idea of developing an anti-brucellosis human vaccine is that the high efficacy of the vaccine is achieved in cattle which naturally resistant to influenza infection (i.e., as a non-replicable viral vector), and, in our opinion, should be even more pronounced in humans. This assumption is based on the fact that humans are a natural host for the influenza virus (Influenza A), including the influenza viral vectors we use.

It should be noted that we used an influenza viral vector (IVV) of the H5N1 subtype, because there is no immune background to this type of pathogen [22] in the human population and IVV of the H5N1 subtype has a greater potential as a vaccine vector.

We began the process of creating an effective anti-brucellosis vector vaccine for humans with the formation of requirements for the developed product, production technology and methods of its application and testing in healthcare practice. To this end, we have accumulated the existing experience in the development of vector vaccines for public health, have chosen the most generally accepted requirements for such vaccines and their manufacturing technologies, the method and frequency of their use and have developed criteria for assessing the effectiveness and safety of vaccine candidates.

An analysis of the compliance of the developed vaccine with the above requirements (which are more general in nature than specific) showed that the viral vectors we selected, as well as the method for preparing and using the vaccine, correspond to them. In particular, we use non-pathogenic influenza viral vectors, the general safety of which has been confirmed by studies on guinea pigs with various ways of administering and dose of immunization.

In order to obtain influenza viral vectors (IVV), we used A/Puerto Rico/8/34 (H1N1) with a length-modified NS1-80 gene encoding 80 amino acids in the N-terminal region of the protein as the initial strain. The surface genes of hemagglutinin (HA) and neuraminidase (NA) were taken from A/chicken/Astana/6/05 strains (H5N1, with the HA cleavage site preliminary removed). The safety or attenuation of IVV is ensured by the truncated NS1 protein (interferon antagonist), which results in their limited replicative capabilities (they make one cycle of reproduction in the cell and do not leave it) [14]. It is known that the degree of IVV attenuation is directly dependent on the length of the NS1 protein [23]. We have an IVV with NS1 length in 80 amino acid. NS1-124 was used to create a veterinary brucellosis vaccine as it for use in cattle a more aggressive IVV was required. As for humans, far preferable may be IVV with NS1-80. With IVV subtype H5N1 (a pathogenic variety of influenza virus), the attenuation was additionally achieved by removing the proteolytic cleavage site in the HA protein, that is, double attenuation was performed. During repeated re-inoculation in chick embryos, IVV retained all their basic biological properties, including signs of attenuation, and did not lose the brucellosis insertion segment [14], which indicates their genetic stability. In addition, the influenza viral vectors we use are RNA-containing viruses that are limited to cytoplasmic replication, thus eliminating the risk of integration and long-term persistence.

The next important phase of our research was devoted to the study of the general safety control of the vaccine candidate at the early stage with different ways of administration and dose of use in guinea pigs. The vaccine has been found to be safe for guinea pigs when administered c., i.n. and s.l. The experimental animals did not show death or signs of any disease; by the end of observation (on day 14 after the prime-boost vaccinations), the body weight gain in guinea pigs was observed both after prime and after boost immunization. At the same time, the increase in body weight of guinea pigs in the experimental groups was comparable to the control group of animals that were injected with PBS. As a result of this work, the vaccine was recognized as a safe drug and was used in the future to assess its protectiveness depending on the immunization schedule.

Further assessment of the effectiveness of the vaccine with different routes of administration to mucosal areas was determined using c., i.n. and s.l. methods of vaccine immunization in prime-boost mode. Since the influenza virus has a tropism for mucosal surfaces, it was assumed that the optimal way to administer a vaccine based on an influenza viral vector would be one of the tested mucosal routes. Since Brucella should be considered as a mucosal pathogen penetrating mucous surfaces, the gates of infection are the mucosal surfaces of the nose or mouth. Consequently, mucosal vaccination is capable to generate protective responses against pathogens at the site of the infection gate [24]. Our bacteriological study demonstrated that significant protection of guinea pigs after challenging with virulent strain of B. melitensis 16M infection was achieved through i.n. administration of the vaccine in comparison with other methods of application.

The next important step in our study was devoted to the choice of the vaccination dose and, at the same time, the frequency of vaccination, where the study of the protection and immunogenicity of the vaccine candidate was evaluated in animals by the ability to retain bacteria in organs and lymph nodes after animal infection with standard methods. Another distinctive feature of our studies was that the vaccine protection was assessed not only by the Brucella culture isolation from the tissues of vaccinated and unvaccinated animals, but also by such aspects as vaccination efficiency and infection index. It is believed that these indicators jointly provide a more complete and objective characterization of the vaccine protection. The new vaccine induced significant protection in response to B. melitensis 16M infection within a range of 6080% when administered i.n. in a double vaccination mode for all tested doses, and it was not inferior in efficiency to B. melitensis Rev.1, which is currently used in veterinary practice as the most immunogenic brucellosis vaccine. The level of protection of the B. melitensis Rev.1 vaccine obtained in our studies corresponds to the science literature data [25]. At the same time, it was found that the new vaccine candidate does not possess protection after primary vaccination, regardless of the dose. When choosing an immunizing dose of the vaccine, it is recommended to use a vaccination dose of 106 EID50, since the protection at the 106 EID50 dose (80% efficiency) was higher than 105 EID50 (60% efficiency) and similar to 107 EID50 (80% efficiency). The choice of an immunizing dose of 106 EID50 is determined by the reduction of possible adverse effect of vaccination and the cost of the production process of the vaccine. The vaccine is targeted at a specific risk grouplaboratory scientists working with the pathogen, veterinarians, slaughterhouse workers and people involved in animal care industry. The next step in the further vaccine development will be devoted to the preclinical studies where will be evaluated the safety, immunogenicity and protectiveness of a new human vaccine candidate against brucellosis.

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A new candidate vaccine for human brucellosis based on influenza viral vectors: a preliminary investigation for the development of an immunization...

Gene editing to enhance production in developing nations – Poultry World

Poultry production in low to middle income nations could substantially benefit from transferring beneficial genes between breeds to produce offspring with useful characteristics, researchers claim.

Sterile male and female chicken eggs have been implanted with reproductive cells from donor birds with the resulting chickens mated together to produce chicks of the donor breed. The chicks showed characteristics inherited from their real patents, the donor birds, along with the edited change to their DNA, rather than their surrogate parents. The gene editing outcome demonstrates an efficient way to introduce beneficial characteristics, the scientists claim, such as tolerance for warm climates or disease resistance.

Poultry production in low to middle income nations could benefit from gene editing, researchers claim. Photo: Mark Pasveer

Beneficial genes can be transferred from one breed into another via gene editing of embryos, in a single generation, and the method to control the reproductive genes can be carried by both parents known as Sire Dam Surrogate (SDS) mating can ensure that offspring will inherit a desired gene from both parents, and exhibit the characteristic associated with that gene. Commercial partner Cobb-Europe worked with a team from the Centre for Tropical Livestock Genetics and Health and the Roslin Institute to demonstrate their approach by using sterile male and female chickens, known as empty nest chickens, to transfer feather characteristics between breeds.

They removed reproductive stem cells (i.e. early stage cells that later develop into sperm and eggs) from chicken embryos using gene-editing technology, and used the same technology to introduce gene-edits into these reproductive cells from another breed. The altered reproductive cells were then implanted into surrogate parents the embryos of chicks and cockerels that were bred to be sterile. These surrogates were then hatched and mated with one another. Resulting offspring were of the donor breed and not that of their surrogate parents. They also had the new traits created by the gene-editing.

Researchers demonstrated their approach by repairing a natural generic change that causes distinctive white plumage in the White Leghorn breed. Chicks born to the sterile chickens now had a black plumage. Similarly, the team introduced a distinctive curly feather, which is believed to help Western African breeds cope with hot climates, into chicks bred from Light Sussex chickens a British breed. The concept could allow the transfer of useful traits among the worlds 1,600 chicken breeds and could boost animal productivity and welfare as well as safeguarding against changing environmental conditions.

Welcoming the developments, Professor Appolinaire Dijkeng, director of the Centre for Tropical Livestock Genetics and Health, said: Poultry is a key livestock animal for millions of smallholder farmers in low- and middle- income countries. Any gains in efficiency, productivity and health from introducing useful traits from other poultry breeds could significantly improve the lives of these farming families through increased food production and income.

Dr. Mike McGrew, one of the scientists who worked on the study, said: The SDS technique is being used now to test genetic variants present in different breeds of chicken and to improve our ability to 'biobank' breeds of chicken. Genome-edited chickens are not allowed in the food chain. However, we can still use the techniques presented in the paper to quickly validate genetic variants which can then be used in conventional breeding programmes. Selective breeding programmes use genotyping data of animals to identify animals and offspring of merit. The idea is to know which genetic sequences are important.

We can inform these breeding programmes that specific DNA sequences in their animals are beneficial and they can then pick the offspring carrying these DNA sequences for their breeding populations."

Heat resistance and disease resistance are the most important traits for our work with the Centre for Tropical Livestock Genetics and Health. For instance, the Frizzle feather genetic variant or 'trait' is hypothesised to cause the frizzly feather phenotype. Sometimes the background breed genetics of the animal is also important for the trait. We can now test now proven that a genetic variant or DNA sequence is causative for the trait. We have introduced the frizzle feather gene into the Light Sussex chicken and we will test if these chickens thrive at higher temperatures directly compared to Light Sussex chicken without the frizzle feather gene. This will prove that the frizzle feather gene on its own is beneficial for tropical environments.

The study was published in Nature Communications and the work was funded by the Bill and Melinda Gates Foundation and the UK Foreign, Commonwealth and Development Office through CTLGH as well as UKRI and Innovate UK.

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Gene editing to enhance production in developing nations - Poultry World

Meet the all-female team at this Dubai school’s science department – Gulf News

At GEMS International School (GIS), the science team is made up of women teachers only. Image Credit: Supplied

Dubai: A Dubai school has plenty to celebrate this International Day of Women and Girls in Science today. Its science department comprises an all-female teaching staff.

Many people may expect greying men in lab coats tinkering around in the science department, but at GEMS International School (GIS), the science team is made up of women teachers and instructors only. They are led by head-of-the-department Tanja Kolarov, who specialises in biology and integrated sciences.

I fell in love with science

Tanja Kolarov

As a small child, I used to sit on the white desks of my grandfathers pharmaceutical lab and watch him make creams and shampoos for my sister and myself. This is where I fell in love with science. My background is in biochemistry, with a deep interest in genetics. Genetics and the ability to change genetic information fascinate me, said Kolarov, who has been at GIS for four years.

She added that science has always been a male-dominated profession. Women scientists have been around, Kolarov said, but had to work really hard to get acknowledged. Women have to empower other women. My mother always said that if you set your mind to it, you can do anything. With STEM [science, technology, engineering, maths] being an equal-opportunities field, more and more women are joining the science profession and wanting to teach science to promote it amongst girls.

The UAEs Minister of State for Advanced Technology is a young woman, Sarah Al Amiri. Still in her early 30s, Al Amiri is also the chairperson of the UAE Space Agency and credited with leading the countrys Mars mission, which on Tuesday achieved the rare success by inserting the Hope Probe into Martian orbit to study the Red Planets atmosphere in unprecedented detail.

Paradigm shift

Hiba El Majzoub

At GIS, chemistry teacher Hiba El Majzoub has witnessed an exponential increase in girls participation in STEM in recent times. We need to have a paradigm shift as there is a misconception around this career being a mostly male domain of work. Yet, throughout history, numerous female scientists have had valuable contributions to science and to the industry as well, she said.

Once such scientist, her favourite, is Marie Curie, the only woman to win Nobel prizes in two sciences (chemistry and physics). El Majzoubs favourite subject, of course, is chemistry. She said: Chemistry is a central and pivotal experimental science that supports our deeper understanding of our biological systems as well as our physical environment. This is why chemistry is the foundation for many disciplines such as medicine, biological and environmental sciences, engineering, and materials.

Quite debatable

Hoda Alawady

GIS science teacher Hoda Alawady said the lack of female representation in STEM occupations is quite debatable. She explains: Although science is one of the fields that is dominated by males, this is currently changing dramatically. More female students are choosing to study science for many reasons. Young girls are now exposed to STEM subjects and are encouraged to study science in schools and higher education. Teachers strive to create environments that are equally appealing to females and males. With more women in the field, young girls are able to recognise the career opportunities open to them. This encourages girls to earn more college and graduate degrees and pursue a science career.

Welcome dividend

Sangita Thakrar

Fellow science teacher Sangita Thakrar teaches chemistry, biology and physics up to grade 10. She said women have to work hard to fit into all-male or majority-male departments. This extra effort has led to a dividend. Many female scientists have to blaze their own trail and become pioneers in their own field. This does, however, allow for more creativity, said Thakrar. She is currently following the work of Tiera Guinn Fletcher, 22-year-old MIT graduate working for Nasa as a rocket structural analyst. She is a relatable inspiration to all the young aspiring scientists, especially girls, added Thakrar.

Priti Suresh

The GIS science team also includes physics teacher Priti Suresh. Reacting to a query on whether more and more girl students were opting for science studies and also whether more and more women were opting to teach science, Priti said: "It is encouraging to see more women as science educators in recent times.However, a lot of young girls are still reticent to pursue a career in science owing to decades of gender-biased conditioning that a profession in the sciences requires longer work-hours and tougher working conditions. On a positive note, the last few years have seen substantial encouragement from educators across curricula from primary school through high school, in addition to a host of universities offering scholarships and waivers to further the role of women in science."

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Meet the all-female team at this Dubai school's science department - Gulf News

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