Genetherapy

Stem Cell Differentiation | Stem Cells | Tocris Bioscience

September 13th, 2022

Stem Cell Differentiation Target Files

Stem cell differentiation involves the changing of a cell to a more specialized cell type, involving a switch from proliferation to specialization. This involves a succession of alterations in cell morphology, membrane potential, metabolic activity and responsiveness to certain signals. Differentiation leads to the commitment of a cell to developmental lineages and the acquisition of specific functions of committed cells depending upon the tissue in which they will finally reside. Stem cell differentiation is tightly regulated by signaling pathways and modifications in gene expression.

Stem cells can be categorized into groups depending on their ability to differentiate.

Embryonic stem cells (ESCs) are pluripotent cells that differentiate as a result of signaling mechanisms. These are tightly controlled by most growth factors, cytokines and epigenetic processes such as DNA methylation and chromatin remodeling. ESCs divide into two cells: one is a duplicate stem cell (the process of self-renewal) and the other daughter cell is one which will differentiate. The daughter cells divides and after each division it becomes more specialized. When it reaches a mature cell type downstream (for example, becomes a red blood cell) it will no longer divide. The ability of ESCs to differentiate is currently being researched for the treatment of many diseases including Parkinson's disease and cancer.

Adult or 'somatic' stem cells are thought to be undifferentiated. Their primary role is to self-renew and maintain or repair the tissue in which they reside.

View all pluripotent stem cell resources available from Bio-Techne.

Regenerative medicine is the repair or replacement of damaged or diseased tissue to restore normal tissue function. This blog post discusses the development of a new cell therapy product derived from PSCs for regenerative medicine use in Parkinson's disease.

Neurons derived from pluripotent stem cells (PSCs) are a source of considerable therapeutic potential for neurodegenerative diseases. This blog post outlines the development of a small molecule-based protocol for the differentiation of human induced PSCs into functional cortical neurons.

Tocris offers the following scientific literature for Stem Cell Differentiation to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.

This product guide provides a background to the use of small molecules in stem cell research and lists over 200 products for use in:

Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.

Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.

Written by Rebecca Quelch and Stefan Przyborski from Durham University (UK), this poster describes the isolation of pluripotent stem cells, their maintenance in culture, differentiation, and the generation and potential uses of organoids.

Link:
Stem Cell Differentiation | Stem Cells | Tocris Bioscience

Recommendation and review posted by Bethany Smith

Adult Stem Cells // Center for Stem Cells and Regenerative Medicine …

September 13th, 2022

Adult stem cells, also called somatic stem cells, are undifferentiated cells that are found in many different tissues throughout the body of nearly all organisms, including humans. Unlike embryonic stem cells, which can become any cell in the body (called pluripotent), adult stem cells, which have been found in a wide range of tissues including skin, heart, brain, liver, and bone marrow are usually restricted to become any type of cell in the tissue or organ that they reside (called multipotent). These adult stem cells, which exist in the tissue for decades, serve to replace cells that are lost in the tissue as needed, such as the growth of new skin every day in humans.

Scientists discovered adult stem cells in bone marrow more than 50 years ago. These blood-forming stem cells have been used in transplants for patients with leukemia and several other diseases for decades. By the 1990s, researchers confirmed that nerve cells in the brain can also be regenerated from endogenous stem cells. It is thought that adult stem cells in a variety of different tissues could lead to treatments for numerous conditions that range from type 1 diabetes (providing insulin-producing cells) to heart attack (repairing cardiac muscle) to neurological disease (regenerating lost neurons in the brain or spinal cord).

Efforts are underway to stimulate these adult stem cells to regenerate missing cells within damaged tissues. This approach will utilize the existing tissue organization and molecules to stimulate and guide the adult stem cells to correctly regenerate only the necessary cell types. Alternatively, the adult stem cells could be isolated from the tissue and grown outside of the body, in cultures. This would allow the cells to be easily manipulated, although they are often relatively rare and difficult to grow in culture.

Because the isolation of adult stem cells does not result in the destruction of human life, research involving adult stem cells does not raise any of the ethical issues associated with research utilizing human embryonic stem cells. Thus, research involving adult stem cells has the potential for therapies that will heal disease and ease suffering, a major focus of Notre Dames stem cell research. Combined with our efforts with induced pluripotent stem (iPS) cells, the Center for Stem Cells and Regenerative Medicine will advance the Universitys mission to ease suffering and heal disease.

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Adult Stem Cells // Center for Stem Cells and Regenerative Medicine ...

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What are Stem Cells? – Types, Applications and Sources – BYJUS

September 13th, 2022

Stem cells are special human cells that can develop into many different types of cells, from muscle cells to brain cells.

Stem cells also have the ability to repair damaged cells. These cells have strong healing power. They can evolve into any type of cell.

Research on stem cells is going on, and it is believed that stem cell therapies can cure ailments like paralysis and Alzheimers as well. Let us have a detailed look at stem cells, their types and their functions.

Global Induced Pluripotent Stem Cells Market (2022 to 2027) – Growth, Trends, Covid-19 Impact and Forecasts – ResearchAndMarkets.com – Business Wire

September 13th, 2022

DUBLIN--(BUSINESS WIRE)--The "Induced Pluripotent Stem Cells Market - Growth, Trends, Covid-19 Impact, and Forecasts (2022 - 2027)" report has been added to ResearchAndMarkets.com's offering.

The Induced Pluripotent Stem Cells Market is projected to register a CAGR of 8.4% during the forecast period (2022 to 2027).

Companies Mentioned

Key Market Trends

The Drug Development Segment is Expected to Hold a Major Market Share in the Induced Pluripotent Stem Cells Market.

By application, the drug development segment holds the major segment in the induced pluripotent stem cell market. Various research studies focusing on drug development studies with induced pluripotent stem cells have been on the rise in recent years.

For instance, an article titled "Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening" published in the International Journal of Molecular Science in October 2020 discussed the broad use of iPSC derived cardiomyocytes for drug development in terms of adverse drug reactions, mechanisms of cardiotoxicity, and the need for efficient drug screening protocols.

Another article published in the Journal of Cells in December 2021 titled "Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform-A Cardiac Perspective" focused on methods to reprogram somatic cells into human induced pluripotent stem cells and the solutions to overcome the immaturity of the human induced pluripotent stem cells derived cardiomyocytes to mimic the structure and physiological properties of adult human cardiomyocytes to accurately model disease and test drug safety. Thus, this increase in the research of induced pluripotent stem cells for drug development and drug modeling is likely to propel the segment's growth over the study period.

Furthermore, as per an article titled "Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells" published in the Multi-Disciplinary Publishing Institute journal of Cells in March 2022, preserved differentiation and physiological function, amenability to genetic manipulation via tools such as CRISPR/Cas9, and availability for high-throughput screening, make induced pluripotent stem cell systems increasingly attractive for both mechanistic studies of disease and the identification of novel therapeutics.

North America is Expected to Hold a Significant Share in the Market and Expected to do Same in the Forecast Period

The rise in the adoption of highly advanced technologies and systems in drug development, toxicity testing, and disease modeling coupled with the growing acceptance of stem cell therapies in the region are some of the major factors driving the market growth in North America.

The United States Food and Drug Administration in March 2022 discussed the development of strategies to improve cell therapy product characterization. The agency focused on the development of improved methods for testing stem cell products to ensure the safety and efficacy of such treatments when used as therapies.

Likewise, in March 2020, the Food and Drug Administration announced that ImStem drug IMS001, which uses AgeX's pluripotent stem cell technology, would be available for the treatment of multiple sclerosis. Similarly, REPROCELL introduced a customized iPSC generation service in December 2020, as well as a new B2C website to promote the "Personal iPS" service. This service prepares and stores an individual's iPSCs for future injury or disease regeneration treatment.

Thus, the increasing necessity for induced pluripotent stem cells coupled with increasing investment in the health care department is known to propel the growth of the market in this region.

Key Topics Covered:

1 INTRODUCTION

2 RESEARCH METHODOLOGY

3 EXECUTIVE SUMMARY

4 MARKET DYNAMICS

4.1 Market Overview

4.2 Market Drivers

4.2.1 Increase in Research and Development Activities in Stem Cells Therapies

4.2.2 Surge in Adoption of Personalized Medicine

4.3 Market Restraints

4.3.1 Lack of Awareness Regarding Stem Cell Therapies

4.3.2 High Cost of Treatment

4.4 Porter's Five Force Analysis

5 MARKET SEGMENTATION

5.1 By Derived Cell Type

5.2 Application

5.3 End User

5.4 Geography

6 COMPETITIVE LANDSCAPE

6.1 Company Profiles

7 MARKET OPPORTUNITIES AND FUTURE TRENDS

For more information about this report visit https://www.researchandmarkets.com/r/ylzwhr

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Global Induced Pluripotent Stem Cells Market (2022 to 2027) - Growth, Trends, Covid-19 Impact and Forecasts - ResearchAndMarkets.com - Business Wire

Recommendation and review posted by Bethany Smith

Bone Marrow market estimated to reach US$13899.60 Million during the forecast period – Digital Journal

September 13th, 2022

ThisBone Marrow MarketReport provides details on Recent New Developments, Trade Regulations, Import-Export Analysis, Production Analysis, Value Chain Optimization, Market Share, Impact of Domestic and Localized Market Players, Analyzes opportunities in terms of emerging revenue pockets, changing market regulations, strategic market growth analysis, market size, market category growth, niche and application dominance, product endorsements, product launches, geographic expansions , technological innovations in the market.For more information on the bone marrow market, please contact Data Bridge Market Research for a summary of theanalyst, our team will help you make an informed market decision to achieve market growth.

Bone Marrow Market is expected to experience market growth during the forecast period of 2021 to 2028. Data Bridge Market Research analyzes that the market is growing with a CAGR of 5.22% during the forecast period of 2021 to 2028 and it is projected to reach USD 13,899.60 Million by 2028. The increasing number of bone marrow diseases will help accelerate the growth of the bone marrow market.Bone marrow transplant also called hematopoietic stem cell.It is a soft vascular tissue present inside the long bones.It includes two types of stem cells, namely hematopoietic and mesenchymal stem cells.The bone marrow is primarily responsible for hematopoiesis (blood cell formation), lymphocyte production, and fat storage.

Get Report Sample PDF: https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-bone-marrow-market

The main factors driving the growth of the bone marrow market during the forecast period are the growth in the incidence of non-Hodgkins and Hodgkins lymphoma, thalassemia, and leukemia, as well as common bone marrow diseases worldwide, developments in technology and improvements.in health infrastructure.In addition, advanced signs of bone marrow transplantation for cardiac and neural disorders, increased funding for logistics services, and rising health care spending per capita are some of the other factors expected to further drive growth. growth of the bone marrow market in the coming years.years.However, the high costs of treatment,

Key Players Covered in the Bone Marrow Market Report are AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc., Astellas Pharma Inc., diaDexus, Illumina, Inc., QIAGEN, F Hoffmann-La Roche Ltd, Sanofi, Stryker Corporation, PromoCell GmbH, STEMCELL Technologies Inc., Lonza, ReachBio LLC, AllCells, ATCC, Lifeline Cell Technology, Conversant bio, HemaCare, Mesoblast Ltd., Merck KGaA, Discovery Life Sciences, ReeLabs Pvt. Ltd., Gamida Cell, among others national and global players.Market share data is available separately for Global, North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA), and South America.DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

For More Information On Market Analysis, View Research Report Summary At :-https://www.databridgemarketresearch.com/reports/global-bone-marrow-market

Bone MarrowMarket Scope and Market Size

The bone marrow market is segmented based on transplant type, disease indication, and end user.Growth between these segments will help you analyze weak growth segments in industries and provide users with valuable market overview and market insights to help them make strategic decisions to identify leading market applications.

Country-level analysis of thebone marrow market

The bone marrow market is analyzed and information is provided on market size and trends by country, transplant type, disease indication, and end user, as mentioned above.Countries Covered in Bone Marrow Market Report are USA, Canada, and Mexico, North America, Germany, France, UK, Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, the Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific region (APAC), Saudi Arabia, United Arab Emirates , South Africa, Egypt, Israel, Rest of the Middle East and Africa (MEA) under Middle East and Africa (MEA), Brazil,

Europe dominates the bone marrow market due to the proliferation of innovative health centers.Furthermore, the health systems have introduced bone marrow transplantation in their contributions and state-of-the-art public facilities that will further drive the growth of the bone marrow market in the region during the forecast period.North America is expected to witness significant growth in the bone marrow market due to increasing cases of chronic diseases such as blood cancer.In addition, the increase in the geriatric population is one of the factors that is expected to drive the growth of the bone marrow market in the region in the coming years.

Explore Full TOC At:- https://www.databridgemarketresearch.com/toc/?dbmr=global-bone-marrow-market

The country section of the Bone Marrow market report also provides individual market impact factors and regulatory changes in the country market that affect current and future market trends.Data points such as consumption volumes, production sites and volumes, import and export analysis, price trend analysis, raw material cost, Downstream and Upstream value chain analysis are some of the main indicators used to forecast the scenario. of the market for each country.Additionally, the presence and availability of global brands and the challenges they face due to significant or rare competition from local and national brands,

3D Printers in Zero-G Flights? There Have Been a Few of Those – 3DPrint.com

September 13th, 2022

In 2011, Made In Space created the first 3D printer for microgravity; what sounded like science fiction suddenly became a reality. Since then, at least 15 experimental 3D printers have been tested aboard Zero-G flights worldwide. Powered by companies, academic institutions, and space agencies, this type of 3D printing research has been successful, from a few printers occasionally tested between 2011 and 2018 to half a dozen in 2022 alone.

Looking back at 2011, we might remember it as a year of transition for the space industry, chiefly because it was the beginning of the end for NASAs Space Shuttle program, which took its final flight in July of that year. With a budget trim to go with it, NASA would soon turn to private industry for many of its space needs. One company, in particular, was keen to leave its mark. Known today as the firm that creates 3D printers for the International Space Station (ISS), Made In Space came out of Singularity University looking to fill a space manufacturing gap.

At its core, Made In Space founders believed that 3D printing and in-space manufacturing would dramatically change the way we look at space exploration, commercialization, and mission design today.

Like Made In Space (now part of Redwire), other companies also decided to test their 3D printing technology in parabolic flights. For example, in 2016, engineering firm and regular NASA contractor Techshot (also acquired by Redwire) partnered with manufacturer nScrypt to create the first microgravity bioprinter and tested it in an aircraft flown by the Zero Gravity Corporation, which operates weightless flights from U.S. airports.

Flying at 30,000 ft (roughly 9,144 meters) over the Gulf of Mexico, the plane simulated weightlessness while the bioprinter created cardiac and vascular structures using human stem cells. Like Made In Space, Techshot and nScrypt later sent the bioprinter to the ISS U.S. National Laboratory, where astronauts are using it for manufacturing human knee cartilage test prints and other human tissue.

The idea of manufacturing in space has long posed several obvious challenges, primarily gravity issues, quality controls, and raw material sourcing. However, once in place, in-situ manufacturing has the potential to relax the dependence on resource resupply from Earth, making survival in space a little bit easier.

For decades, in-space manufacturing has been investigated as a method for producing parts and components in orbit that would otherwise be almost impossible to obtain immediately or at all. In the late 1960s, Soviet cosmonauts conducted the first welding experiments in space as part of their space manufacturing research. In the next decade, the United States began experimenting with space manufacturing in Skylab, the first space station launched by NASA.

But the gateway to space manufacturing lies in the investigations of parabolic flights that can reproduce gravity-free conditions in an aircraft right here on Earth. By alternating upward and downward arcs, they provide the necessary microgravity environment for scientists to conduct research without actually traveling to space. This simulated weightlessness may have started in the 1960s with the first flying space labs aboard U.S. military planes. Still, it has expanded to incorporate several private businesses, like US-based company Zero-G and French-based Novespace.

With more options to recreate the unique weightlessness of space, we have witnessed a series of printers that have been successfully tested in parabolic flights. For example, in late 2016, Luke Carter of the Advanced Materials and Processing Laboratory (AMP Lab) at the University of Birmingham demonstrated metal 3D printing in microgravity aboard three separate parabolic flights. By creating a printing process much like directed energy deposition (DED), and using aluminum wire as feedstock, Carter and his team made a near-net shape part.

Then in 2017, the Canadian Reduced Gravity Experiment Design Challenge (CAN-RGX), supported by the National Research Council and the Canadian Space Agency, chose two teams to test their 3D printing experiments in parabolic flights. Team AVAIL (Analyzing Viscosity and Inertia in Liquids) from the University of Toronto built a system that controls the flow of a viscous liquid (corn syrup, in this case) through 15 different nozzles, and Team iSSELab (Interfacial Science and Surface Engineering Lab), hailing from the University of Alberta, collected data from 3D printing materials in a reduced gravity environment.

The following year, a European parabolic flight aircraft in New Zealand took scientists from the Technology and Engineering Center for Space Utilization of the Chinese Academy of Sciences (CAS) to test the first ceramic DLP 3D printer in microgravity. Following this successful event, NASA chose Associate Professor Gregory Whiting and his research group to test and model how 3D printing functional materials would work in lunar gravity. Whitings research group, the Boulder Experimental Electronics and Manufacturing Lab, geared up for two parabolic flights in 2021.

Around that time, engineering students of the Munich University of Applied Sciences built a 3D printer with an extruder to dispense a liquid photopolymer that took off on the European Space Agency (ESA)s 74th parabolic flight campaign from Paderborn-Lippstadt Airport in Germany.

A few memorable 3D printing experiments in zero gravity in 2022 include Space Foundrys testing of space-based electronic printing, supported by NASAs Flight Opportunities and Small Business Innovation Research (SBIR) programs. In addition, UC Berkeley research teams tested the replicator, a light-based 3D printer, on May 10, printing more than 100 objects. Also, a German consortium tested out its patented 3D printing process and, for the first time, used metallic powders to 3D print in zero gravity.

This is just a taste of what is possible here on Earth, thanks to gravity-free flights. These and other experiments that took place in the last few years can be found below.

Stay up-to-date on all the latest news from the 3D printing industry and recieve information and offers from thrid party vendors.

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3D Printers in Zero-G Flights? There Have Been a Few of Those - 3DPrint.com

Recommendation and review posted by Bethany Smith

Hair-bearing human skin generated entirely from pluripotent stem cells

September 13th, 2022

Figure 1 |. Surface ectoderm and CNCC co-induction leads to hair-bearing skin generation.

a, b

a, b, Overview of (a) study objectives and (b) skin organoid (SkO) protocol. c, Brightfield images of WA25 aggregates on days 12 and 30 in optimized culture. d, Immunostaining for KRT5+KRT15+ basal and KRT15+ peridermal layers at day-55. e, f, Representative HF-induction images (e) in brightfield of days 6585 WA25 SkOs and (f) max-intensity confocal image (endogenous DSP-GFP) of days 6595 DSP-GFP SkO. Dashed-box: magnified-HF; dashed-line: HF; dashed-circles: developing hair germs; asterisks: dermal papilla. g, h, Violin plots showing (g) frequencies of HF-formation in WA25 (average 87.4%, min=68.8%, max=100%, n=212 organoids), DSP-GFP (average 87.2%, min=66.7%, max=100%, n=212 organoids), and WA01 (71%, n=130 organoids) cultures, and (h) average number of HFs formed in WA25 (average 64 HFs/organoid, min=9, max=285, n=80 organoids) and DSP-GFP (average 48 HFs/organoid, min=7, max=128, n=80 organoids) cultures between days 75147. i-k, Immunostained day-75 WA25 SkO with hair placodes. Antibodies highlight epidermal (KRT5+KRT15+CD49f+) and periderm (KRT15+) layers, dermis (PDGFR+P75+), and DC cells (SOX2+PDGFR+P75+). Dashed-boxes: magnified-regions. l, Wholemount of day-85 WA25 SkO with head-tail structures. KRT5 highlights epidermis and HF outer root sheath. SOX2 marks DC, DP, Merkel cells and melanocytes. Dashed-box: area shown to the right. Abbr: frontonasal prominence (FNP); cranial neural crest cells (CNCCs); dermal papilla (DP); matrix (Mtx); periderm (PD); hair root (HR); dermal condensate (DC). Scale: 500 m (c), 250 m (l; left), 100 m (e; first three panels, f; third-panel, i-k; upper-panels), 50 m (d, f; second-panel, i-k; lower-panels, l; right), 25 m (e; last-panel, f; first/last-panels). See Statistics and Reproducibility for plot and experimental information.

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Hair-bearing human skin generated entirely from pluripotent stem cells

Recommendation and review posted by Bethany Smith

FACTORFIVE Skincare The Power of Stem Cells for Skin

September 13th, 2022

FACTORFIVE Skincare The Power of Stem Cells for Skin icon-star icon-bag icon-search icon-close icon-list icon-plus minus icon-loading arrow-left arrow-right chevron-left chevron-right mail linkedin facebook instagram pinterest tumblr youtube stumbleupon google print heart share icon-visa icon-mastercard icon-american-express icon-discover icon-paypal icon-apple-pay icon-stripe

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Anti-aging skincare to target the signs of aging: wrinkles, sun spots, tightness, thickness, texture, and more.

Growth factors help replenish a more youthful-looking eye area, where biotin and redensyl work together to quickly and safely enhance your lashes and brows.

Hydrating cream shown to visibly improve signs of aging such as redness, wrinkles, tightness, thickness, and texture.

Most labs use Fetal Bovine Serum(FBS) in their cultures. We do not.

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"The entire process of producing FACTORFIVE formulations is based on leading-edge science. Each bottle contains the highest quality of rich, active proteins produced by ethically-derived adult stem cells, comprehensively targeting specific areas to deliver accelerated and robust results. "

Dr. Annie BowlesStem Cell Scientist

Backed by years of scientific research, FACTORFIVE is committed to providing you with the most cutting-edge and innovative skincare on the market. Human growth factors are essential to your skins appearance and health, and now their regenerative powers have finally been harnessed. Not only have we developed an exceptional skin serum, we continue to leverage the latest scientific discoveries to shape the future of aesthetics.

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FACTORFIVE Skincare The Power of Stem Cells for Skin

Recommendation and review posted by Bethany Smith

Hematopoietic Stem Cells | Hematopoiesis | Properties & Functions

September 13th, 2022

Hematopoietic Stem Cells: In living organisms, a specialized system that consist of blood and its progenitors are referred to as the hematopoietic system.

In particular, this system is made up of cells with specialized functions such as the red blood cells (for carrying oxygen to tissues), white blood cells (for immune defense against pathogens, and foreign agents), platelets (for blood clotting), macrophages and lymphocytes (also for immune defense).

However, many of the said blood cells are temporary and need to be replaced with new ones continuously. But fret not because a single cell can solve the problem!

Every day, almost billions of new blood cells are synthesized within the body with each coming from a specific progenitor cell called the hematopoietic stem cell.

How to pronounce Hematopoietic Stem Cells?

What is Hematopoiesis?

The formation of all kinds of blood cells including creation, development, and differentiation of blood cells is commonly known as Hematopoiesis or Haemopoiesis.

All types of blood cells are generated from primitive cells (stem cells) that are pluripotent (they have the potential to develop into all types of blood cells).

Also referred to as hemocytoblasts, hematopoietic cells are the stem cells that give rise to blood cells in hematopoiesis.

Where Does Hematopoiesis Occur?

In a healthy adult, hematopoiesis occurs in the bone marrow and lymphatic tissues, where 1000+ new blood cells (all types) are generated from the hematopoietic stem cells to main the steady-state levels.

Where Are Hematopoietic Stem Cells Found?

They can also be found in the umbilical cord and in the blood from the placenta.

Who Discovered Hematopoietic Stem Cells?

It was long believed that the majority of hematopoiesis occurs during ontogeny (origination and development of organism) and that the mammalian hematopoietic system originated from the yolk sac per se.

Functions of Hematopoietic Cells

As alluded to earlier, blood cells and blood cell components are formed in a process called hematopoiesis.

Coming from the Greek words hemato and poiesis which mean blood and to make respectively, hematopoiesis occurs in the bone marrow and is responsible not only for the synthesis but also the multiplication, and differentiation of blood cells.

Shown below is a diagrammatic illustration of the different blood cell types that hematopoietic cells can give rise to:

Clinical uses of Hematopoietic Stem Cells

The mammalian blood system showcases the equilibrium between the functions of hematopoietic stem cells. Intensive studies have already shown the structures and molecules that control these stem cells, but the exact picture of the underlying molecular mechanisms is still unclear.

Above everything else, it is important to note that such issues are not just of academic interest but can also be relevant in devising future novel methods of diagnosing and treating various diseases associated with cells.

Key References

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Hematopoietic Stem Cells | Hematopoiesis | Properties & Functions

Recommendation and review posted by Bethany Smith

Stem cells: Sources, types, and uses – Medical News Today

September 13th, 2022

Cells in the body have specific purposes, but stem cells are cells that do not yet have a specific role and can become almost any cell that is required.

Stem cells are undifferentiated cells that can turn into specific cells, as the body needs them.

Scientists and doctors are interested in stem cells as they help to explain how some functions of the body work, and how they sometimes go wrong.

Stem cells also show promise for treating some diseases that currently have no cure.

Stem cells originate from two main sources: adult body tissues and embryos. Scientists are also working on ways to develop stem cells from other cells, using genetic reprogramming techniques.

A persons body contains stem cells throughout their life. The body can use these stem cells whenever it needs them.

Also called tissue-specific or somatic stem cells, adult stem cells exist throughout the body from the time an embryo develops.

The cells are in a non-specific state, but they are more specialized than embryonic stem cells. They remain in this state until the body needs them for a specific purpose, say, as skin or muscle cells.

Day-to-day living means the body is constantly renewing its tissues. In some parts of the body, such as the gut and bone marrow, stem cells regularly divide to produce new body tissues for maintenance and repair.

Stem cells are present inside different types of tissue. Scientists have found stem cells in tissues, including:

However, stem cells can be difficult to find. They can stay non-dividing and non-specific for years until the body summons them to repair or grow new tissue.

Adult stem cells can divide or self-renew indefinitely. This means they can generate various cell types from the originating organ or even regenerate the original organ, entirely.

This division and regeneration are how a skin wound heals, or how an organ such as the liver, for example, can repair itself after damage.

In the past, scientists believed adult stem cells could only differentiate based on their tissue of origin. However, some evidence now suggests that they can differentiate to become other cell types, as well.

From the very earliest stage of pregnancy, after the sperm fertilizes the egg, an embryo forms.

Around 35 days after a sperm fertilizes an egg, the embryo takes the form of a blastocyst or ball of cells.

The blastocyst contains stem cells and will later implant in the womb. Embryonic stem cells come from a blastocyst that is 45 days old.

When scientists take stem cells from embryos, these are usually extra embryos that result from in vitro fertilization (IVF).

In IVF clinics, the doctors fertilize several eggs in a test tube, to ensure that at least one survives. They will then implant a limited number of eggs to start a pregnancy.

When a sperm fertilizes an egg, these cells combine to form a single cell called a zygote.

This single-celled zygote then starts to divide, forming 2, 4, 8, 16 cells, and so on. Now it is an embryo.

Soon, and before the embryo implants in the uterus, this mass of around 150200 cells is the blastocyst. The blastocyst consists of two parts:

The inner cell mass is where embryonic stem cells are found. Scientists call these totipotent cells. The term totipotent refer to the fact that they have total potential to develop into any cell in the body.

With the right stimulation, the cells can become blood cells, skin cells, and all the other cell types that a body needs.

In early pregnancy, the blastocyst stage continues for about 5 days before the embryo implants in the uterus, or womb. At this stage, stem cells begin to differentiate.

Embryonic stem cells can differentiate into more cell types than adult stem cells.

MSCs come from the connective tissue or stroma that surrounds the bodys organs and other tissues.

Scientists have used MSCs to create new body tissues, such as bone, cartilage, and fat cells. They may one day play a role in solving a wide range of health problems.

Scientists create these in a lab, using skin cells and other tissue-specific cells. These cells behave in a similar way to embryonic stem cells, so they could be useful for developing a range of therapies.

However, more research and development is necessary.

To grow stem cells, scientists first extract samples from adult tissue or an embryo. They then place these cells in a controlled culture where they will divide and reproduce but not specialize further.

Stem cells that are dividing and reproducing in a controlled culture are called a stem-cell line.

Researchers manage and share stem-cell lines for different purposes. They can stimulate the stem cells to specialize in a particular way. This process is known as directed differentiation.

Until now, it has been easier to grow large numbers of embryonic stem cells than adult stem cells. However, scientists are making progress with both cell types.

Researchers categorize stem cells, according to their potential to differentiate into other types of cells.

Embryonic stem cells are the most potent, as their job is to become every type of cell in the body.

The full classification includes:

Totipotent: These stem cells can differentiate into all possible cell types. The first few cells that appear as the zygote starts to divide are totipotent.

Pluripotent: These cells can turn into almost any cell. Cells from the early embryo are pluripotent.

Multipotent: These cells can differentiate into a closely related family of cells. Adult hematopoietic stem cells, for example, can become red and white blood cells or platelets.

Oligopotent: These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this.

Unipotent: These can only produce cells of one kind, which is their own type. However, they are still stem cells because they can renew themselves. Examples include adult muscle stem cells.

Embryonic stem cells are considered pluripotent instead of totipotent because they cannot become part of the extra-embryonic membranes or the placenta.

Stem cells themselves do not serve any single purpose but are important for several reasons.

First, with the right stimulation, many stem cells can take on the role of any type of cell, and they can regenerate damaged tissue, under the right conditions.

This potential could save lives or repair wounds and tissue damage in people after an illness or injury. Scientists see many possible uses for stem cells.

Tissue regeneration is probably the most important use of stem cells.

Until now, a person who needed a new kidney, for example, had to wait for a donor and then undergo a transplant.

There is a shortage of donor organs but, by instructing stem cells to differentiate in a certain way, scientists could use them to grow a specific tissue type or organ.

As an example, doctors have already used stem cells from just beneath the skins surface to make new skin tissue. They can then repair a severe burn or another injury by grafting this tissue onto the damaged skin, and new skin will grow back.

In 2013, a team of researchers from Massachusetts General Hospital reported in PNAS Early Edition that they had created blood vessels in laboratory mice, using human stem cells.

Within 2 weeks of implanting the stem cells, networks of blood-perfused vessels had formed. The quality of these new blood vessels was as good as the nearby natural ones.

The authors hoped that this type of technique could eventually help to treat people with cardiovascular and vascular diseases.

Doctors may one day be able to use replacement cells and tissues to treat brain diseases, such as Parkinsons and Alzheimers.

In Parkinsons, for example, damage to brain cells leads to uncontrolled muscle movements. Scientists could use stem cells to replenish the damaged brain tissue. This could bring back the specialized brain cells that stop the uncontrolled muscle movements.

Researchers have already tried differentiating embryonic stem cells into these types of cells, so treatments are promising.

Scientists hope one day to be able to develop healthy heart cells in a laboratory that they can transplant into people with heart disease.

These new cells could repair heart damage by repopulating the heart with healthy tissue.

Similarly, people with type I diabetes could receive pancreatic cells to replace the insulin-producing cells that their own immune systems have lost or destroyed.

The only current therapy is a pancreatic transplant, and very few pancreases are available for transplant.

Doctors now routinely use adult hematopoietic stem cells to treat diseases, such as leukemia, sickle cell anemia, and other immunodeficiency problems.

Hematopoietic stem cells occur in blood and bone marrow and can produce all blood cell types, including red blood cells that carry oxygen and white blood cells that fight disease.

People can donate stem cells to help a loved one, or possibly for their own use in the future.

Donations can come from the following sources:

Bone marrow: These cells are taken under a general anesthetic, usually from the hip or pelvic bone. Technicians then isolate the stem cells from the bone marrow for storage or donation.

Peripheral stem cells: A person receives several injections that cause their bone marrow to release stem cells into the blood. Next, blood is removed from the body, a machine separates out the stem cells, and doctors return the blood to the body.

Umbilical cord blood: Stem cells can be harvested from the umbilical cord after delivery, with no harm to the baby. Some people donate the cord blood, and others store it.

This harvesting of stem cells can be expensive, but the advantages for future needs include:

Stem cells are useful not only as potential therapies but also for research purposes.

For example, scientists have found that switching a particular gene on or off can cause it to differentiate. Knowing this is helping them to investigate which genes and mutations cause which effects.

Armed with this knowledge, they may be able to discover what causes a wide range of illnesses and conditions, some of which do not yet have a cure.

Abnormal cell division and differentiation are responsible for conditions that include cancer and congenital disabilities that stem from birth. Knowing what causes the cells to divide in the wrong way could lead to a cure.

Stem cells can also help in the development of new drugs. Instead of testing drugs on human volunteers, scientists can assess how a drug affects normal, healthy tissue by testing it on tissue grown from stem cells.

Watch the video to find out more about stem cells.

There has been some controversy about stem cell research. This mainly relates to work on embryonic stem cells.

The argument against using embryonic stem cells is that it destroys a human blastocyst, and the fertilized egg cannot develop into a person.

Nowadays, researchers are looking for ways to create or use stem cells that do not involve embryos.

Stem cell research often involves inserting human cells into animals, such as mice or rats. Some people argue that this could create an organism that is part human.

In some countries, it is illegal to produce embryonic stem cell lines. In the United States, scientists can create or work with embryonic stem cell lines, but it is illegal to use federal funds to research stem cell lines that were created after August 2001.

Some people are already offering stem-cells therapies for a range of purposes, such as anti-aging treatments.

However, most of these uses do not have approval from the U.S. Food and Drug Administration (FDA). Some of them may be illegal, and some can be dangerous.

Anyone who is considering stem-cell treatment should check with the provider or with the FDA that the product has approval, and that it was made in a way that meets with FDA standards for safety and effectiveness.

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Stem cells: Sources, types, and uses - Medical News Today

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Top 3 grants in regenerative medicine: July 2022 – RegMedNet

September 13th, 2022

This months top grants in regenerative medicine, sourced from Dimensions, includes projects on: a novel platform to enhance single cell interrogation of nervous system development, human endothelial cell regulation of ossification and the development of a dynamic double network hydrogel for generating pancreatic organoids from induced pluripotent stem cells.

This project aims to investigate a strategy, which utilizes novel spatial transcriptomics approaches, integrated multiplexed RNA/protein detection and visualization and computational algorithms to identify and map molecular markers of the preganglionic neurons in the ventral spinal cord and progenitor cell populations of the sympathetic ganglia. If successful, the approach could provide a foundation for basic research of peripheral nervous system birth defects and repair using stem cell-based therapies, as well as future studies of neuroblastoma initiation.

Funding amount:US$206,000

Funding period: 8 August 2022 31 July 2024

Funder:Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Research organization:Stowers Institute for Medical Research (MO, USA)

Beauty maybe be skin deep, but AI finds revenue on the faces surface – Biometric Update

September 13th, 2022

A Taiwanese AI algorithm maker knows the value of the mind behind a face. The company says its software can perform virtual fashion try-ons and parse a consumers personality with the same selfie.

Perfect Corp. last week pushed a new AI and augmented reality makeup app and a fashion industry tie-in that could seed the market for high-end algorithmic social aspiration. In August, the company went down-market with a beard try-on product.

None of that is to take away from Perfects July decision to start selling the AI Personality Finder. It is a combination of facial-feature mapping and rudimentary psychological data that allegedly tells people not only how emotionally attractive they are, but also, what products to use to increase their visual likability.

At least in the United States, Perfect typically sells to fashion and makeup companies, but it also partners with some firms for their mutual marketing benefit.

For instance, the software firm has created a try-on app for toothpaste maker Colgate that reportedly will show people how much brighter their teeth would be by using a Colgate product.

A selfie and a little measure of insecurity is all that someone needs.

A day later, Perfect said it was working with Nolcha Shows on New York Fashion Week (September 9 to 14), a top appointment on many social calendars. Nolcha, a fashion events promoter, has added try-on features to some segments of the show via its YouCam Makeup app.

Then there is Perfects Personality Finder, a subscription service sold to vendors for use by adults and children. It purports to be a biometric recognition algorithm based on the idea that certain faces belong to certain kinds of minds.

The app could raise eyebrows the way that emotion recognition algorithms have done.

It scans a selfie for as many as 65 facial attributes. Out the other end come scores for neuroticism, agreeableness, openness, conscientiousness and extroversion.

It is not unlike another of Perfects apps, its Skin Analysis tool.

Although Perfect says it will remove from its servers information pertaining to children younger than 16, the primary model it uses to illustrate its software appears to be younger.

It was just in March that Perfect left its parent, CyberLink, to acquire Provident Acquisition in order to register for an IPO this year. Provident is referred to as a blank-check company, which makes it the investing version of stem cells. It has all it needs to be something and is waiting for a nudge.

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Beauty maybe be skin deep, but AI finds revenue on the faces surface - Biometric Update

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September is Blood Cancer Awareness Month: All You Need to Know – News18

September 13th, 2022

September is observed as Blood Cancer Awareness month all over the world. During this month, activists and stakeholders work to raise awareness about the disease and the efforts being taken to fight blood cancers including leukemia, lymphoma, myeloma and Hodgkins disease.

The term blood cancer is a general description of various hematopoietic cancers. Our blood flows through blood vessels to supply all tissues in the body with nutrients. In the approximately 5 litres of blood circulating in our body there are billions of blood cells that carry out various vital functions. All blood cells originate from hematopoietic stem cells.

Haematopoietic stem cells are known as mother cells and do not yet have a specific function. They are able to renew and differentiate into cells with a specific function, thus replacing cells that die. In bone marrow, blood stem cells divide and develop into progenitor cells. Through further division, the progenitor cells mature and transform into different types of blood cells and then enter the bloodstream, says Dr Nitin Agarwal, HOD, Donor Request Management, DKMS BMST Foundation India.

Blood cancer is an abnormal proliferation (abnormal growth) of cells in the bone marrow especially white blood cells (WBCs). Cancer cells flood the bloodstream and drive out healthy cells. As a result, the blood can no longer perform its basic tasks, such as transporting oxygen and protecting the body from infection.

LeukemiaThis cancer is found in the bone marrow and the bloodstream. It is caused by abnormal rapid production of WBCs and high number of abnormal WBCs which cannot fight against infection, and they impair the bone marrows ability to produce red blood cells and platelets, says Dr Jimmy Mirani, Consultant Onco Surgeon, Wockhardt Hospital, Mumbai Central.

LymphomaA type of blood cancer which affects the lymphatic system, which removes the risk excess fluids from body and generates immune cells. Lymphocytes are blood cells which are used to fight against infections. These abnormal lymphocytes become lymphoma cells which multiply and get collected in the tissues, adds Dr Mirani.

There are two types of lymphoma, namely, Hodgkins lymphoma and non-Hodgkins lymphoma.

Non-Hodgkins lymphoma:It mainly impacts the B-cell or T-cell. This type of lymphoma occurs more commonly than Hodgkins lymphoma. Can vary clinically and diagnostically into slow-growing ones to very aggressive types, notes Dr. Amrita Chakrabarti, Consultant, Haemato-Oncology & Bone Marrow Transplant, Max Hospital, Shalimar Bagh.

Hodgkins lymphoma This type of lymphoma affects the B cells. Broadly divided into classical Hodgkins and nodular lymphocyte predominant types. Occurs in the adolescence or elderly age group.

MyelomaIt is the cancer of plasma cells; WBCs which produce disease and infection fighting anti-bodies. Myeloma cells prevent the functions and productions of these antibodies leaving a week immune system.

Multiple myelomaThis starts in the bone marrow when plasma cells begin to grow uncontrollably. As the cells grow, they compromise the immune system and impair the production and function of white and red blood cells causing bone disease, organ damage and anemia among other conditions, adds Dr Agarwal.

In most cases of blood cancer, the patient feels tired and weak. This happens because the number of red blood cells in the blood starts decreasing due to which there is a lack of blood in the person. Someof the commonsymptoms of blood cancers are fever, severe fatigue, bleeding from gums or skin, back ache, or bone pains, says Dr Pravas Mishra, Head Haematology/ Medical Oncology and BMT, Amrita Hospital, Faridabad.

Patients with myeloma might first present to an orthopaedical with a fracture originating from trivial trauma or to a nephrologist with a kidney dysfunction.Pain in bones and joints can be a symptom of not only arthritis but also blood cancer. Blood cancer is a disease in the bone marrow that is found in large amounts around the bones and joints.

Patientsmight present with nodes in the neck or axilla or groin or swelling in any part of the body. However most often a patientwith blood cancermight present with just a low haemoglobin. It is strongly advised not to ignore any anaemia, warns Dr Mishra.

A person suffering from blood cancer is prone to repeated infections. When leukemia cells develop in the body, then complaints of infection can be seen in the patients mouth, throat, skin, lungs, etc.

People who have cancer tend to have an abnormally low weight. If the body weight is reduced without any obvious cause, then it can be seen as the primary symptom of cancer.

The abnormal formation of leukemia cells in the body prevents the bone marrow from forming healthy blood cells such as platelets. Due to its deficiency, more bleeding problems can be seen from the nose of the patient, during menstruation and gums.

Blood cancer is diagnosed with the help of a wide range of diagnostic methods along clinical evaluation, such as blood tests, bone marrow tests, cytogenetic/karyotyping and molecular analysis, flow cytometry.

Myth: Blood cancer cannot be treated?

Fact: Once a patient is diagnosed with blood cancer, the first concern that comes to ones mind Is blood cancer curable?

Blood cancer is one type of cancer that has a high curability rate especially due to the advancement in the medical field, availability of newer, improved chemotherapy regimens, targeted therapy, and improved infection control measures. Timely diagnosis, especially early diagnosis, increases the chances of cure from blood cancer.Some of the other factors that impact the cure of blood cancer include the age of the patient, physical condition, presence of other comorbidities, stage of the disease, subtype of cancer, molecular factors, whether low grade/high grade, acute or chronic, the body parts that are affected and whether the disease is new onset or has come back after a previous cure.

You must understand that the cure or recovery from cancer is unpredictable, adds Dr. Chakrabarti.

There are cases when the patient has recovered even in the later stages of blood cancer. On the other hand, there are recorded cases where the patient couldnt recover even in the initial stages of blood cancer. So, its important to have realistic expectations and focus on following a healthy lifestyle with the advised treatment and measures. Early diagnosis and treatment play an important role in attaining cure.

Myth: All blood cancer patients need a bone marrow transplant

Fact: No, majority of patients suffering from blood cancers are treated without bone marrow transplant. A combination of chemotherapy, targeted therapy and immunotherapy is the best line of treatment.

Myth: Blood cancer occurs only in children?

Fact: No, blood cancers can occur in all age groups. All have a higher incidence in young children whereas Myeloid Leukaemia (MLL) is more frequently seen in senior citizens.

India is reeling under pressure of many misconceptions that exist amongst people about blood stem cell donation, its process and even its after-effects.

Myth: Once you donate blood stem cells, you will lose them forever.

Fact: Only a fraction of total stem cells is extracted during the process. Also, all the cells are naturally replenished within a few weeks

Myth: Donating stem cells is a really invasive and painful process

Fact: Blood stem cells are collected through peripheral blood stem cell collection (PBSC) which is completely safe and a non-surgical procedure. The process is similar to blood platelet donation that takes approximately three to four hours to complete and the donor can leave the collection center the same day.

Myth: Blood donation and a blood stem cell donation are same

Fact: Unlike blood collection for transfusion, blood stem cells are collected only when there is a match between the donor and patients human leukocyte antigen (HLA) combination (tissue type). So, you could be potentially the only match and life saver for a person with blood cancer in need of a transplant, adds Dr Nitin Agarwal. Blood stem cell donors donate only blood stem cells and the process is similar to a platelet donation.

Myth: Pregnant women cant register

Fact: This is untrue, a woman can register even during her pregnancy.

Myth: Stem cell donation leaves prolonged side-effects

Fact: No, there are no major side effects post blood stem cell donation. A person may only experience minor flu like symptoms because of the GCSF injections given to him/her before the donation, to mobilize blood stem cells in your blood stream.

Myth: Piercing and/or tattoo is a restricting factor

Fact: Piercing or a tattoo doesnt stop you from registering yourself to be a potential donor.

Myth: My blood stem cells can be stored

Fact: Your blood stem cells will not be stored. They last for around 72 hours and are delivered for the recipient straight to the hospital by a special courier. If the recipients body accepts them, the stem cells will start making healthy blood cells.

Myth: Joining a blood stem cell registry is no use. Most patients can find a stem cell donor within their own families

Fact: Per statistics, only 30% of blood disorder patients in need of a stem cell transplant are able to find a sibling match. About 70% of patients need an unrelated donor.

A registry like DKMS BMST Foundation India is a data bank of potential blood stem cell donors that houses details on thousands of committed blood stem cell donors. Any patient can benefit from this registry provided an HLA match.

Some of the blood cancer treatments include the following

Chemotherapy

This is the most important aspect of blood cancer treatment and involves using certain chemicals to kill the cancer-causing cells in the patients body. The prescribed drugs are given in a particular timeframe for the best possible improvement in the patients health. In some patients, a stem cell transplant is provided along with high dose chemotherapy.

Radiation therapyRadiation therapy helps to destroy cancer cells with the help of specific high-energy beams to kill cancer cells in precise areas of the body. This treatment is much beneficial for patients with lymphoma

Bone marrow transplantIn this procedure, healthy stem cells are utilized to replace the cells affected by cancer. This helps the patients recover in the best possible manner. Can be autologous (where stem cells are taken from the patients own body) or allogenic (when a healthy donor gives stem cells to the patient.)

Targeted Therapy

Usually in the form of oral medications or pills. They are given alongside chemotherapy/ or radiotherapy and affect specific cancer cells and help in destroying them.

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September is Blood Cancer Awareness Month: All You Need to Know - News18

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10 Facts That Prove Memory Is Not What You Think – Listverse

September 13th, 2022

Memory seems simple enough. For most people, its the ability to create and retrieve memories or information. In reality, memory is a mysterious rabbit hole. Its still not fully understood, especially in the natural world where strange forms of memory exist in chemical compounds and even rocks. There are anthills where memories outlast the ants, and some plants remember being dropped. These facts, and others, might just prove that memory is more amazing than we ever thought possible.

Related: 10 Weird Things You Did Not Know About Memory

A few years ago, evolutionary ecologist Monica Gagliano set out to prove that plants are more intelligent than we give them credit for. More specifically, she wanted to show that plants can learn and remember even though they have no brains. For her experiment, she chose the species Mimosa pudica, a plant that responds to touch by rapidly closing its leaves.

Gagliano created a custom shelf for the plants, one that would suddenly drop a few feet. At first, the plants reacted in a defensive manner and curled their leaves. But after a few drops, the plants seemed to realize there was no danger and stopped clamming up.

Gagliano halted the experiment for a month to give the plants enough time to forget, but they didnt. When the shelf dropped again, none of the Mimosas closed upa tantalizing sign that the plants remembered the falling shelf and that it was also a safe experience.[1]

For a long time, biologists believed that giant tortoises were about as intelligent as a cabbage. However, this misconception lost traction when two zoos tested Galapagos and Aldabra tortoises and discovered that the large reptiles were quick learners. After dangling food as a reward, the tortoises were given two tests. In one instance, they simply had to bite a ball on a stick to get a snack. In the second test, they were shown two balls, but in order to be fed, they had to bite the right color ball.

One zoo tested the animals one by one and got good results. The second zoo tested them in groups, and incredibly, these tortoises seemed to grasp what was expected of them by watching what their fellow tortoises did. Not only did this prove that these animals are capable of individual and social learning, but some of them even remembered to bite the correct color ball when they were tested again nine years later.[2]

In 2018, scientists tested a substance called vanadium dioxide (VO2). The compound was hiding a mystery. For some reason, VO2s resting state made it an insulator, but when heated to above 154.4F (68C), it turned into a conductor. The study revealed why; VO2 has atoms that are capable of rearranging themselves. When heated, they adopt a pattern that turns the compound into a conductor. As it cools, the atoms relax back into their original positions and turn the material back into an insulator.

Remarkably, when researchers heated the VO2 a second time, the atoms behaved as if they remembered the experience of shifting between the two states. Although the discovery is groundbreakingits the first material to behave in this wayVO2 wont win any memory contests. It only seems to remember the shift for three hours after the fact.[3]

Our skin contains plenty of stem cells. When there is a cut or infection, stem cells rush to repair the skin, and they remember the experience. This inflammation memory is mostly a good thing. It helps stem cells respond faster the next time they sense a wound, which speeds up healing times.

However, when researchers looked more closely at the process, they realized that it could be the smoking gun pointing to a new suspect behind inflammatory skin disorders such as psoriasis. In the past, the blame was squarely placed on immune cells. But new studies revealed that the same memory that makes stem cells more effective can also go haywire. As the theory goes, when this happens, the cells hijack the skins inflammatory process, which might either cause psoriasis or make the condition worse.[4]

When a caterpillar turns into a moth or butterfly, the metamorphosis is one of the most drastic in nature. Can memory survive a process that rearranges a creatures entire body? To find out, researchers knew they had to give the caterpillars an enduring memorylike a bad smell. Even better, a pong accompanied by pain. Soon enough, the caterpillars were exposed to light electric shocks accompanied by the smell of nail polish remover.

The caterpillars soon learned to avoid the odor, and remarkably, after they blossomed into moths, the memory and skittishness around the nail polish remover remained. This proved that moths, and probably butterflies too, can remember things from their caterpillar days even though their brains and nervous systems have undergone extensive reshuffling.[5]

Rocks have a curious ability. They can align their magnetic bits with the Earths magnetic field. The manner in which these bits arrange themselves and settle down can act like a snapshot of the planets field. Aptly called magnetic memory, the effect on a rock is permanent, and it gives geologists a way to see how strong or weak the Earths field was a thousand or even millions of years ago.

But when researchers looked at the Devonian period (420 to 360 million years ago), they discovered that rocks from this era have no magnetic memory. What caused this worldwide blank? Thus far, the entire thing remains a compelling mystery. But a leading theory suggests that Earths magnetic field was so disastrously weak that it had no influence on magnetic particles inside stones.[6]

The human brain and ant colonies have a few things in common. They operate without central control, and both also use chemical signals to alter the behavior of important interacting parts. The latter include neurons in brains and ants in colonies.

Researchers were curious to know if ant colonies could also remember things like a brain. To clarify, not the ants. The colony. In other words, could ants behave in a way that suggests they remain affected by something originally experienced by their long-gone predecessors? Incredibly, it would appear so.

Experiments showed that when some nests suffered a disturbance, the ants changed their behavior. Thats not really unusual. But in some cases, subsequent generations of ants also adopted the new behavior even though they were unaware of the disturbance. In this manner, it would appear that a colony can remember a threat when individual ants no longer do.[7]

A few years ago, scientists fitted mosquitoes with tiny helmets. No, really. The hats monitored the brain activity of each mosquito to discover more about its memory processes. The study, which placed the insects in a flight simulator and exposed them to different human chemicals, revealed something interesting.

First, it proved that an old wives tale was true. Mosquitoes find the blood of some people sweeter, and they remember these hosts, often snacking on the same person more than once. The helmets also revealed that mosquitoes are far from dumb because they also remember people who swat at them. Once they recognize the smell of a defensive food source, some mosquitoes abandon the person even though their blood is of the sweet variety.[8]

Gamma-aminobutyric acid (GABA) is a molecule that can be found in humans and animals. It acts as a messenger of the nervous system, which includes the brain. Plants lack brains, and yet, they also have GABA. It helps them with memory-like processes during times of drought, something that surprised the researchers who stumbled upon the fact in 2021.

With plants, GABA works in a simple yet ingenious way to help them limit their water loss in times of drought. During the day, the molecules accumulate within the plants tissues. The drier the weather, the more GABA molecules cram into the fibers. The total amount of GABA then acts like a memory the next day. For example, a dense cluster will remind the plant that yesterday was dry. As a result, the plant protects its internal moisture reserve by not opening its leaf pores too widely.[9]

Slime molds dont have brains or a nervous system. Despite these missing pieces, their minds are surprisingly sophisticated. Experts already knew that slime molds can learn things about their environment and even share these memories with their fellow slime balls. The question was how.

This riddle was cracked in 2019 when researchers noticed that members of one species, Physarum polycephalum, often fused their venous systems with each other. This suggested that individuals can teach other blobs by sharing information through their fused veins. But how do they learn something in the first place?

A test, which used salt as an obstacle to food, threw some light on the learning process. In essence, the blobs get their information by absorbing the item theyre investigating. In this case, they hoovered a little salt, realized it wasnt dangerous, and vein-mailed their fellow blobs the good news.[10]

Jana earns her beans as a freelance writer and author. She wrote one book on a dare and hundreds of articles. Jana loves hunting down bizarre facts of science, nature and the human mind.

Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV (enfortumab vedotin-ejfv) with KEYTRUDA (pembrolizumab) and PADCEV…

September 13th, 2022

BOTHELL, Wash. & TOKYO & RAHWAY, N.J.--(BUSINESS WIRE)-- Seagen, Inc.(Nasdaq:SGEN), Astellas Pharma US, Inc.(TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., Astellas) and Merck & Co. (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the phase 1b/2 EV-103 clinical trial (also known as KEYNOTE-869) Cohort K investigating PADCEV (enfortumab vedotin-ejfv) in combination with Mercks anti-PD-1 therapy KEYTRUDA (pembrolizumab) and PADCEV alone as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-based chemotherapy. The findings were presented today at the European Society for Medical Oncology (ESMO) Congress as part of a late-breaking abstract presentation (Abstract #LBA73).

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20220912005300/en/

In patients treated with enfortumab vedotin and pembrolizumab (n=76), results demonstrated a 64.5% confirmed objective response rate (ORR) (95% CI: 52.7 to 75.1) per RECIST v1.1 by blinded independent central review (BICR), the primary endpoint of Cohort K, with 10.5% of patients experiencing a complete response and 53.9% of patients experiencing a partial response. The median duration of response (DOR) per BICR was not reached (95% CI: 10.25 months to NR). All-grade treatment-related adverse events (TRAEs) of special interest for enfortumab vedotin in combination with pembrolizumab were skin reactions (67.1%), peripheral neuropathy (60.5%), ocular disorders (dry eye, blurred vision, and corneal disorders) (26.3%), hyperglycemia (14.5%), and infusion-related reactions (3.9%). Pembrolizumab adverse events of special interest were consistent with previously observed safety data from monotherapy with the exception of severe skin reactions. Overall, the results were generally consistent with previously reported efficacy and safety results of the EV-103/KEYNOTE-869 dose-escalation cohort and expansion Cohort A.1

Please see Important Safety Information at the end of this press release for both drugs, including BOXED WARNING for enfortumab vedotin and immune-mediated adverse reactions for pembrolizumab.

Cohort K also included a monotherapy arm in which patients were treated with enfortumab vedotin alone (n=73), though this study was not designed to support a formal comparison between the two arms. Results showed a 45.2% confirmed ORR (95% CI: 33.5 to 57.3) per RECIST v1.1 by BICR, with 4.1% of patients experiencing a complete response and 41.1% of patients experiencing a partial response. The median DOR was 13.2 months (95% CI: 6.14 to 15.97) per RECIST v1.1 by BICR. All-grade TRAEs of special interest for enfortumab vedotin were peripheral neuropathy (54.8%), skin reactions (45.2%), ocular disorders (dry eye, blurred vision, and corneal disorders) (28.8%), hyperglycemia (11.0%), and infusion-related reactions (5.5%).

Additional secondary endpoints in the EV-103 Cohort K trial included progression-free survival (PFS) and overall survival (OS). Among patients treated with enfortumab vedotin and pembrolizumab, median PFS was not reached (95% CI: 8.31 months to NR). Median OS was 22.3 months (95% CI: 19.09 to NR). Among patients treated with enfortumab vedotin, median PFS was 8.0 months (95% CI: 6.05 to 10.35) and median OS was 21.7 months (95% CI: 15.21 to NR).

TRAEs of any grade that occurred in more than 20% of patients treated with enfortumab vedotin alone or in combination with pembrolizumab were fatigue, peripheral sensory neuropathy, alopecia, rash maculo-papular, pruritus, dysgeusia, weight decreased, diarrhea, decreased appetite, nausea, and dry eye.

Results from EV-103/KEYNOTE-869 Cohort K support the ongoing investigation of enfortumab vedotin and pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who are in need of treatment options, and this combination may be an important therapeutic option for these patients, said Jonathan E. Rosenberg, M.D., Chief, Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology, and Enno W. Ercklentz Chair, Memorial Sloan Kettering Cancer Center and EV-103/KEYNOTE-869 Cohort K primary investigator. Dr. Rosenberg has consulting relationships with Seagen, Astellas and Merck.

Nearly sixty-five percent of patients who were treated with enfortumab vedotin and pembrolizumab responded to the combination, with almost eleven percent showing no detectable cancer following treatment. These study results represent an encouraging finding for people with advanced urothelial cancer who are not eligible for cisplatin treatment, said Marjorie Green, Senior Vice President and Head of Late-Stage Development, Seagen.

We're encouraged by these positive findings from the combination of enfortumab vedotin and pembrolizumab in people with advanced urothelial cancer who historically have had limited treatment options in the first-line setting, and we intend to discuss these results with regulatory authorities, said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas.

Were pleased that this combination provided a meaningful benefit to this group of advanced bladder cancer patients in this study, and we will continue to investigate enfortumab vedotin plus pembrolizumab through our collaboration, said Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories.

In February 2020, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for enfortumab vedotin in combination with pembrolizumab for patients with unresectable la/mUC who are ineligible to receive cisplatin-based chemotherapy in the first-line setting. The designation is based on results from the dose-escalation cohort and expansion Cohort A of the phase 1b/2 trial, EV-103/KEYNOTE-869 (NCT03288545), evaluating patients with la/mUC who are ineligible to receive cisplatin-based chemotherapy treated in the first-line setting with enfortumab vedotin in combination with pembrolizumab.

Seagen, Astellas and Merck are further investigating enfortumab vedotin plus pembrolizumab in Phase 3 studies, including EV-302/KEYNOTE-A39 (NCT04223856), which is intended to confirm these results for the investigational treatment combination in previously untreated la/mUC and in muscle-invasive bladder cancer in EV-304/KEYNOTE-B15 (NCT04700124) and EV-303/KEYNOTE-905 (NCT03924895).

About Bladder and Urothelial Cancer

It is estimated that approximately 83,730 people in the U.S. were diagnosed with bladder cancer in 2021.2 Urothelial cancer accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.3 Globally, approximately 573,000 new cases of bladder cancer and 212,000 deaths are reported annually.4

About the EV-103/KEYNOTE-869 Trial (Cohort K)

The EV-103 trial (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with locally advanced or metastatic urothelial cancer (la/mUC) and in patients with muscle-invasive bladder cancer.

Cohort K of the EV-103/KEYNOTE-869 trial is a randomized 1:1 cohort investigating enfortumab vedotin alone (n=73) or in combination with pembrolizumab (n=76) in adult patients with unresectable la/mUC who are ineligible for cisplatin-based chemotherapy and have received no prior treatment for la/mUC. The enfortumab vedotin monotherapy study arm is intended to characterize the activity of enfortumab vedotin alone in this patient population. The key outcome measure of EV-103/KEYNOTE-869 Cohort K is objective response rate (ORR) per blinded independent central review (BICR) using RECIST 1.1. Secondary endpoints include ORR per investigator assessment; duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS) per BICR and investigator assessment; overall survival (OS); and assessment of safety.

About PADCEV

PADCEV (enfortumab vedotin-ejfv) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).6

PADCEV (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information

BOXED WARNING: SERIOUS SKIN REACTIONS

Indication

PADCEV is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

Important Safety Information

Warnings and Precautions

Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN, occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 55% of the 680 patients treated with PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 13% of patients, including maculo-papular rash, rash erythematous, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. Withhold PADCEV and refer for specialized care for suspected SJS or TEN or for severe (Grade 3) skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN, or for Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C 8% were excluded from clinical trials. In clinical trials, 14% of the 680 patients treated with PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. The median time to onset of hyperglycemia was 0.6 months (range: 0.1 to 20.3). Hyperglycemia led to discontinuation of PADCEV in 0.6% of patients. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Pneumonitis Severe, life-threatening or fatal pneumonitis occurred in patients treated with PADCEV. In clinical trials, 3.1% of the 680 patients treated with PADCEV had pneumonitis of any grade and 0.7% had Grade 3-4. In clinical trials, the median time to onset of pneumonitis was 2.9 months (range: 0.6 to 6). Monitor patients for signs and symptoms indicative of pneumonitis, such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis.

Peripheral neuropathy (PN) occurred in 52% of the 680 patients treated with PADCEV in clinical trials, including 39% with sensory neuropathy, 7% with muscular weakness and 6% with motor neuropathy; 4% experienced Grade 3-4 reactions. PN occurred in patients treated with PADCEV with or without pre-existing PN. The median time to onset of Grade 2 PN was 4.6 months (range: 0.1 to 15.8 months). Neuropathy led to treatment discontinuation in 5% of patients. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade 3 PN.

Ocular disorders were reported in 40% of the 384 patients treated with PADCEV in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 34% of patients, and blurred vision occurred in 13% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19.1 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 680 patients, 1.6% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Adverse Reactions

Most Common Adverse Reactions, Including Laboratory Abnormalities (20%)

Rash, aspartate aminotransferase (AST) increased, glucose increased, creatinine increased, fatigue, PN, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase (ALT) increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin.

EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy.

Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (4%) were PN (23%), rash (11%) and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (2%) were PN (10%), rash (8%), decreased appetite and fatigue (3% each). Clinically relevant adverse reactions (<15%) include vomiting (14%), AST increased (12%), hyperglycemia (10%), ALT increased (9%), pneumonitis (3%) and infusion site extravasation (0.7%).

EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for platinum-based chemotherapy.

Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (3%) were pneumonia, sepsis and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), AST increased and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (3%) were PN (19%), rash (11%) and fatigue (7%). Clinically relevant adverse reactions (<15%) include vomiting (13%), AST increased (12%), lipase increased (11%), ALT increased (10%), pneumonitis (4%) and infusion site extravasation (1%).

Drug Interactions

Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)

Concomitant use with a dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

For more information, please see the full Prescribing Information including BOXED WARNING for PADCEV here.

About KEYTRUDA (pembrolizumab) injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

Non-muscle Invasive Bladder Cancer

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients with stage III melanoma, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE-716, when KEYTRUDA was administered as a single agent to patients with stage IIB or IIC melanoma, adverse reactions occurring in patients with stage IIB or IIC melanoma were similar to those occurring in 1011 patients with stage III melanoma from KEYNOTE-054.

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

See original here:
Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV (enfortumab vedotin-ejfv) with KEYTRUDA (pembrolizumab) and PADCEV...

Recommendation and review posted by Bethany Smith

NYC Dermatologist, Dr. Julie Russak, launches first Anti-Aging Wellness Program of its kind in the U.S. – PR Web

September 13th, 2022

Dr. Julie Russak, Board-Certified Dermatologist

NEW YORK (PRWEB) September 12, 2022

Julie E. Russak, M.D., FAAD., is a Board Certified Dermatologist, Founder of Russak Dermatology Clinic in Manhattan and specializes in general and cosmetic dermatology, regenerative aesthetic medicine, skin cancer and dermatologic surgery. Dr. Russak has received numerous honors and recognition of her clinical excellence, including being selected as a New York Super Doctor by New York Times Magazine.

An Integrative Approach to Aesthetic Medicine and Metabolic Aging on the Cellular LevelThe new physician and nutritionist-led program utilizes a 360 approach to aesthetics and longevity, designed to empower patients with the clinical data, tools and treatments to reverse the signs of aging and feel their best. The program was designed for patients who want to receive a custom plan on how to approach anti-aging and wellness together.- Dr. Julie Russak

In-house Board Certified Holistic Nutritionist & Celebrity Health Coach, Jennifer Hanway, alongside Dr. Russak, leads all patients through their highly-personalized testing analysis and develops customized nutrition, supplement, lifestyle and aesthetic treatment plans. Jennifers deep knowledge of hormonal imbalances, gut health and body composition informs her holistic approach.

Aging well is the mission of the program, and that requires more than skin deep procedures. We have the ability to reprogram gene expression to increase our healthspan, while resetting our cells to a more youthful state. Benefits of the program include slowing premature aging internally and externally, healthy skin and hair, hormone and metabolism optimization, weight loss, increased lean muscle mass, increased energy levels and mental clarity. - Jennifer Hanway.

Russak Dermatology Clinic works with leading integrative laboratories, specializing in epigenetic and functional testing including biological age, food intolerance, gut health, micronutrient and hormone panels. Hormones tell your tissues and organs what to do. A slight imbalance can cause fatigue, anxiety, acne, hair loss, weight change and more. Hormone health is a critical pillar of the program. -Jennifer Hanway.

A Regenerative ResetDr. Russaks Regenerative Aesthetics menu was designed to go hand-in-hand with the program. It includes therapies such as exosomes, stem cell facelift technology, platelet rich plasma (PRP), IV drips and bio-stimulatory injectables. The clinic carries clinical-grade skincare and nutraceuticals that boost the body's natural regenerative responses and have secured brand partnerships available to their patients, including health-expert designed, organic meal delivery service, Daily Dose and integrative supplement brand, Nutrafol.

Russak Dermatology Clinic ExpansionThe newly expanded aesthetic center will house the Anti-Aging Wellness Program and regenerative aesthetics offerings. The mission of the newly expanded space is to guide patients on how to harness the regenerative power of their own body. Think of your skins health, but elevated and enhanced through integrative and cutting-edge aesthetic treatments that address your bodys total wellness, inside and out.

About Dr. Julie RussakJulie E. Russak, M.D., FAAD., is a Board Certified Dermatologist and Founder of Russak Dermatology Clinic. Dr. Russak serves as Faculty at Mount Sinai Hospital, where she teaches dermatology residents and medical students. Dr. Russak has distinguished herself in the medical community through her clinical research, scientific presentations, publications and aesthetic approach. She attends anti-aging, aesthetic and regenerative medical conferences around the world to incorporate advancements in these fields into her practice. Some notable conferences include the Aesthetic & Anti-Aging Medicine World Congress and the Annual Mount Sinai Winter Symposium Advances in Medical and Surgical Dermatology".

Dr. Russak is frequently sought out by beauty editors and industry outlets as an expert contributor, including Good Morning America, NewBeauty, Cosmopolitan, Forbes, and Marie Claire. Dr. Russak serves as a consulting Dermatologist and formulator to clean skincare brand, Covey.

For all marketing and media inquiries, please contact Gabrielle@RussakDermatology.com. Learn more at http://www.russakplus.com and IG: @russakderm

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3814-BRCA1 or BRCA2 risk management (female) | eviQ

September 13th, 2022

Breast cancerSurgical

Bilateral risk-reducing mastectomy reduces cancer risk by at least 90%rr(depending on the operation performed). Statistically significant survival benefit associated with bilateral risk-reducing mastectomy compared with surveillance is yet to be demonstrated.

While RRSOhad been reported to reducebreast cancer risk by 53% in BRCA1 and BRCA2pathogenic variant carriers,rthis protective effect has been questioned, with a prospective study showing no reduction in breast cancer risk in BRCA1pathogenic variant carriers with RRSO.rRecent data indicates the benefit for BRCA2 pathogenic variant carriers is restricted to the risk of breast cancer diagnosed before the age of 50.r

MRIis the preferred screening technique due to its high sensitivity compared with MMG or US. The addition of MMG is limited, and does not lead to a significant increase in sensitivity compared with MRIalone.rThere is no added value of ultrasound in women undergoing MRI for screening. MRI detects tumours which are smaller and more likely to be node-negative than MMG. MRI has a recall rate (requiring further investigation and/or biopsy) of 15% for initial screening, which decreases with subsequent rounds of screening to <10%.

Mammography screening is not recommended before age 40 years in BRCA1 and BRCA2 pathogenic variant carriers. The sensitivity of MRI is not influenced by age or breast density, being similar in women aged >50 yearsto those aged <50 years.On current evidence, it may be reasonable to offer breast MRI to women with BRCA1 and BRCA2 pathogenic variants beyond age 50 years.r

The rate of cancers occurring between annual screening (interval cancers) is higher in BRCA1 pathogenic variant carriers than other high risk populations.

Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high risk women. To date studies have not included enough BRCA1 or BRCA2 pathogenic variant carriers to determine if it is effective for primary prevention in this population. Tamoxifen use is associated with a reduction in contralateral breast cancer risk in BRCA1 and BRCA2 pathogenic variant carriers with breast cancer; such benefit is stronger if ovaries are still intact.r In view of the potential side effects associated with tamoxifen/raloxifene, risk-reducing medications should be discussed with an experienced medical professional to determine the relevant risks and benefits in an individual pathogenic variant carrier. See COSA - Medications to lower the risk of breast cancer: clinician guide.

Bilateral risk-reducing salpingo-oophorectomy (RRSO) significantly reduces the risk of ovarian and fallopian tube cancer in BRCA1 and BRCA2 pathogenic variant carriers.rThe residual risk of primary peritoneal cancer after RRSO is <2%.r

The effectiveness and safety of risk-reducing bilateral salpingectomy followed by delayed bilateral oophorectomy has not been established, and is not recommended for ovarian cancer risk management.

The decision to perform hysterectomy at the time of RRSO should be individualised. There is no evidence of an increased risk of endometrial cancer in Australian BRCA1 and BRCA2 pathogenic variant carriers, although there is some evidence that serous histology may be more common in BRCA1 pathogenic variant carriers.rrHysterectomy may simplify subsequent menopausal hormone therapy, or the use of tamoxifen for breast cancer risk or as adjuvant treatment of breast cancer, but it is not justified for endometrial cancer prevention alone.

For asymptomatic women annual transvaginal ultrasound (TVU) and serum CA125 levels have poor sensitivity and specificity for ovarian cancer. They do not reliably detect ovarian cancers at an early stage, nor do they affect outcomes. This is true of women in the general population and women at high risk of hereditary ovarian cancer. Effective ovarian cancer risk management relies on RRSO.

Although there is evidence that the combined oral contraceptive pill can reduce the ovarian cancer risk, it is significantly less effective than RRSO and it is not recommended for cancer prevention.

There is currently no effective surveillance that detects early pancreatic cancer.

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3814-BRCA1 or BRCA2 risk management (female) | eviQ

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Twins with different fathers: Case in Portugal highlights rare copulation event – Interesting Engineering

September 13th, 2022

All this is, of course, assuming that the father is the same. However, there have been more than one instance when the assumed father of the twins turns out to be the father of only one child. The scientific terminology for such an event is heteroparental superfecundation (HS).

Before we get into how HS occurs, a quick biology class.

During sexual intercourse, the human male deposits millions of sperm in the female reproductive tract. Inside the harsh environment of the female vagina, most sperm perish while whipping their tails to move up the female reproductive tract.

With the energy supplied by the mitochondria inside them, the sperm navigate the arduous path of the cervix and uterus and then up one of the fallopian tubes with the hope that they will meet the egg. Only a few hundred or perhaps even lesser reach this point.

To fertilize the egg, sperm needs to beat the odds of being in the correct fallopian tube, where the ovulated egg will be available. Further, it must defeat other sperm who have also beaten the previous odds and are now fighting to fertilize the egg. An egg is usually available for a brief period of 12-24 hours, so the sperm must be present at the correct time for pregnancy.

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Twins with different fathers: Case in Portugal highlights rare copulation event - Interesting Engineering

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The on-farm sexual revolution is getting closer to home – ABC News

September 13th, 2022

In 1995, an ordinary-looking lamb was born to a conventional Merino ewe.

But Larry the lamb was anything but ordinary. Larry made history as the world's first gender-selected sheep.

Scientists at the University of Sydney always knew they'd be getting a baby boy. They'd employed a process that sorted ram semen into male and female, and they chose to produce a male.

The scientists used a technique discovered in the USA in 1989 when Dr Larry Johnson developed a method to separate living female-producing (X-chromosome) and male-producing (Y-chromosome) sperm based on their DNA content.

Johnson had effectively turned nature on its head. Until then, it had been nature that determined whether you were born male or female.

The American scientists made their breakthrough using rabbits and then successfully applied the technology to cows and pigs.

Naturally, it was livestock industries that stood to be the biggest beneficiaries of this brave new worldand it was dairy farmers who most embraced it.

They want female calves to replenish their milking herds.

Male calves, largely unwanted, are known as bobby calves and can be sold for slaughter as young as five days of age.

Dairy Australia estimates that last year nationwide, about 300,000 bobby calves met that fate.

Worldwide, there's growing opposition to bobby calves. Many countries have banned the trade.

New Zealand is introducing tighter restrictionsand many believe Australia will soon follow.

Improving animal welfare is a major reason why more Australian dairy farmers are using "sexed"semen.

"The main sort of incentive to use the sexed semen was the plight of the poor male Jersey bobby calf. They don't really have any value in our industry," said Tess Butler, a veterinarian and dairy farmer at Jindivick east of Melbourne.

"Unfortunately, they get slaughtered at about five days old, off to the abattoirs, which is something that we don't really agree withand we really want to change."

Just now, it's calving season. In the farm's calf-rearing shed, there's a growing number of young Jersey calves.

So far, their use of sexed semen is achieving better than expected results.

"Last year, we ran at about 10 per cent bulls, which is what we were kind of promised, which is great," said Ms Butler.

"This year, we've only been calving for a week, but we've got about 5 per cent bull calves, so that's amazing as well."

"The technology has definitely got better over time," said dairy farmer Rowen Foote.

"We're seeing a lot better conception rates from the start of 2004 up to now. It has been massive."

Mr Foote runs a large, family-owned dairy farm at Fish Creek in South Gippsland. Opposed to bobby calves, he was an early adopter of the use of sexed semen.

Gender selection also means he can sell surplus dairy heifers to the lucrative export market.

About a quarter of Australian dairy farmers are now using sexed semen. In the United Kingdom, the figure is now 50 per cent.

"So this whole area of sexed semen is evolving at a great rate, and primarily its been so much research and the success of conception rates that is driving that engagement," said Paul Douglas of global company ST Genetics.

British dairy farmers got access to sexed semen in 1998 when UK company Cogent made the first commercial sales of sexed semen from dairy bulls.

In the early years, it was expensive to use, the conception rates weren't always goodand there was a limited range of available bovine genetics.

In 2017, US based-company ST Genetics bought a majority share in Cogent.

The company is rapidly expanding its semen sorting facilities around the globe.

"I think there's 40 plus labs in 33 countries now, most of them working 24 hours a day, seven days a week," said Peter Semmens, who heads up the company's Australian branch.

"The product is getting better every day, and the discerning breeder out there or the discerning farmer is making some pretty astute decisions," said Brad Aitken, whose company supplies genetics to livestock farmers across Australia.

To date, ST Genetics has focused on dairy genetics. But the company is targeting Australia's beef industry, which is rebuilding after severe droughts and floods.

Breeding more females through gender selection can accelerate that rebound.

The company has other species in its sights. Sheep producers are embracing the use of sexed semen, and pork and goat producers are poised to join them.

In the future, gender selection could be used to bolster populations of endangered animals by producing more breeding females.

And this new frontier of animal production is getting closer to home. The company is experimenting with sorting dog semen.

"It could be some ideal working dogs that become involved in a sexed semen situation. Who knows?" said Mr Douglas.

Watch this story on ABC TV's Landline at 12:30pm on Sunday, or onABC iview.

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One Gene, Variants Linked to Many Cases of Rare Hair Condition – Medscape

September 13th, 2022

One gene and pathogenic missense variants in that gene account for most cases of uncombable hair syndrome (UHS), a rare hair shaft anomaly that manifests during infancy, investigators have reported.

The findings are from a cohort study published in JAMA Dermatology that involved 107 unrelated children and adults suspected of having UHS, as well as family members, all of whom were recruited from January 2013 to December 2021. Genetic analyses were conducted in Germany from January 2014 to December 2021 with exome sequencing.

Senior author Regina C. Betz, MD, professor of dermatogenetics at the Institute of Human Genetics, University Hospital Bonn, Bonn, Germany, told Medscape that in 2016, she and her co-investigators authored a study on the molecular genetics of UHS. That study, which involved 18 people with UHS, identified variants in three genes PADI3, TCHH, and TGM3 that encode proteins that play a role in the formation of the hair shaft. The investigators described how a deficiency in the shaping and mechanical strengthening of the hair shaft that occurs in the UHS phenotype, which is characterized by dry, frizzy, and wiry hair that cannot be combed flat.

Dr Regina Betz

As a result of that previous work, "we base the assignment or confirmation of a clinical diagnosis of UHS on molecular genetic diagnostics," the authors write in the new study, rather than on the clinical appearance of the hair and the physical examination of the patient, with confirmation on microscopical examination of the hair shaft.

Following the 2016 study, Betz and colleagues were contacted by many clinicians and by the public through Facebook and other social media platforms with details about possible cases of UHS, an autosomal recessive disorder. Through these contacts, blood samples, saliva, or DNA was sent to the investigators' laboratory from 89 unrelated index patients (69 female patients, and 20 male patients) suspected of having UHS. This resulted in the identification of pathogenic variants in 69 cases, the investigators write.

"In the first study, we had 18 patients, and then we tried to collect as many as possible" to determine the main mechanism behind UHC, Betz said. One question is whether there are additional genes responsible for UHS, she noted. "Even now, we are not sure, because in 25% [of cases in the new study], we didn't find any mutation in the three known genes."

The current study resulted in the discovery of eight novel pathogenic variants in PADI3, which are responsible for 71.0% (76) of the 107 cases. Of those, "6 were single observations and 2 were observed in 3 and 2 individuals, respectively," the investigators write.

Children can grow out of this disorder, but it can persist into adulthood, Betz noted. Communication that investigators had with parents of the children with UHS revealed that these children are often the targets of bullying by other children, she added.

She and her and colleagues will continue this research and are currently studying adults who have UHS.

Jeff Donovan, MD, FRCPC, FAAD, a dermatologist and medical director of the Donovan Hair Clinic in Whistler, British Columbia, described these findings as fundamental to understanding UHS and creating pathways to possible treatments.

Dr Jeff Donovan

The study "identifies more about the genetic basis of this challenging condition," said Donovan, who is also clinical instructor in the Department of Dermatology at the University of British Columbia, Vancouver, and president of the Canadian Hair Loss Foundation. "We really need this type of information in order to have any sort of clue in terms of how to treat it," he told Medscape.

"In the hair loss world, it's pretty clear that if you can understand the genetic basis of things, or the basic science of a condition, whether it's the basic genetics or the basic immunology, you give yourself the best chance to develop good treatments," said Donovan.

The article provides advanced genetic information of the condition, such that geneticists can test for at least three markers if they are suspecting UHS, Donovan observed.

Donovan also commented that UHS can have a detrimental impact on children with regard to socializing with their peers. "Having hair that sticks out and is very full like this is challenging because kids do get teased," he said.

"It is often the parents who are the most affected" when a child aged 2 to 5 years has a hair condition such as UHS. But at age 5 to 9, "children are developing self-identity and an understanding of various aspects of self-esteem and what they look like and what others look like. And that's where the teasing really starts. And that's where it does become troublesome."

Betz and Donovan have disclosed no relevant financial relationships.

JAMA Dermatol. Published online August 31, 2022. Abstract

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How a small, unassuming fish helps reveal gene adaptations – University of Wisconsin-Madison

September 13th, 2022

Jesse Weber collects stickleback with a minnow trap in the Kenai Peninsula of Alaska. Photo by Matt Chotlos

At first blush, sticklebacks might seem a bit pedestrian. The finger-length, unassuming fish with a few small dorsal spines are a ubiquitous presence in oceans and coastal watersheds around the northern hemisphere. But these small creatures are also an excellent subject for investigating the complex dance of evolutionary adaptations.

A new study published Sept. 8 in Science sheds light on the genetic basis by which stickleback populations inhabiting ecosystems near each other developed a strong immune response to tapeworm infections, and how some populations later came to tolerate the parasites.

Evolutionary biologist Jesse Weber, a professor of integrative biology at the University of WisconsinMadison, is one of the studys lead authors. Sticklebacks have long been a source of fascination not only for Weber, but for biologists all over the world so much so that the fish are among the most closely studied species.

An aerial view of an experiment in the Kenai Peninsula of Alaska studying changes in stickleback traits in response to a new environment. Photo by Andrew Hendry

We arguably know more about stickleback ecology and evolution than any other vertebrate, says Weber.

This is in part because of sticklebacks rich abundance in places like Western Europe, where the fish have long been involved in biological study, Weber says. But the reasons for the species star status go well beyond happenstance.

Sticklebacks are also just super charismatic, Weber adds, noting the species complex courtship and territorial behaviors, as well as their diverse colors, shapes and sizes, all of which vary depending on the specific ecosystem they inhabit.

While sticklebacks diversity provides a foothold for understanding why animals evolve different traits, their value for scientists like Weber is boosted by their genetics. The fish have approximately as many genes as humans, but their genetic material is packed much more tightly sticklebacks genome is about one-sixth the size of the human genome.

Their genome is amazingly useful, Weber says. As far as we can tell, its just packed more densely. This means we can efficiently investigate their genetic diversity, allowing us to ask not only, Why do new traits evolve? but also, How are adaptations programmed into the genome?'

On top of all that, sticklebacks take well to captive breeding. A single female can produce hundreds of offspring multiple times over the course of just a few months.

All these traits make stickleback an almost uniquely valuable species for studying the genetic basis for many types of biological adaptations. So, when Weber arrived at UWMadison in the fall of 2020 from the University of Alaska Anchorage, he came with an entire fish colony in tow. Living in tanks, the colony contains fish from genetically distinct populations originating from different lakes and estuaries dotting northwestern North America.

A three spine stickleback with tapeworms recently dissected from the body of the same animal. Photo by Natalie Steinel

In their quest to understand why and how the fish sometimes evolve to look and behave very differently even in relatively nearby lake systems, Weber and his colleagues can crossbreed these populations in various ways and map changes to their genomes across multiple generations relatively quickly.

Much of Webers scientific career to this point has focused on developing tools to make this type of work more efficient. More recently, Weber has turned to using these tools to investigate coevolution the process by which two species adapt to the presence of one another within a shared habitat.

Specifically, Weber and his colleagues have sought to understand why sticklebacks in some lakes are much more likely to be infected with tapeworms than their counterparts in nearby lakes where the tapeworms are also present.

These investigations are beginning to bear fruit. Weber, along with colleagues at the University of Connecticut and University of Massachusetts Lowell, recently identified key genetic differences between the populations.

These differences indicate that all fish populations developed a robust immune response to the tapeworms when they first moved from the sea to new freshwater habitats near the end of the last ice age. But the immune response is costly in terms of both energy and reproduction. It also leads to a large amount of inflammation and internal scarring.

Webers work and that of his colleagues suggest that numerous populations eventually evolved to avoid these costs by ignoring, or in the lingo of immunologists tolerating, the parasite infestation. But the tolerant population still carries the genes that produce the immune response to the tapeworms.

While they havent yet tested it, Weber says it appears that these sticklebacks may have mutations to these fibrosis-associated genes that render them non-functional.

While the results are exciting for Weber, hes already looking toward future research that he hopes will further tell the genetic story of sticklebacks abundant adaptations, and by extension reveal biological processes with implications across the wide diversity of life on Earth.

Read more about the study and its findings from the University of Connecticut.

This study was supported by the Howard Hughes Medical Institute Early Career Scientist fellowship, as well as grants from the National Institutes of Health (1R01AI123659-01A1, 1R01AI146168 and 1R35GM142891).

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Gout and Weight Loss: What You Need to Know – Healthline

September 13th, 2022

Gout is an inflammatory form of arthritis that affects the joints, often the big toe. An estimated 36% of men and 12% of women per year in Western countries experience gout.

This condition occurs when a waste byproduct known as urea builds up in your body, leading to hyperuricemia. Its caused by overproduction of urea or an inability to excrete it through urine.

While genetics play a large role in gout, other factors can also increase your risk, such as your diet and, potentially, your weight.

You may wonder, then, if you should attempt to lose weight to help manage your gout.

This article tells you all you need to know about gout and weight loss.

Gout is caused by hyperuricemia, or high urea levels.

Certain hereditary and lifestyle factors can increase your risk of hyperuricemia, such as:

While these factors may play a role, gout is hereditary, which means you may still develop it regardless of your lifestyle habits or weight.

The American College of Rheumatology currently recommends that people with overweight or obesity who have gout lose weight to help manage the condition and reduce their risk of flare-ups.

One large study found a link between body mass index (BMI) and gout incidence and flare-ups. Over the course of 7 years, people with obesity were significantly more likely to develop gout than people with normal BMIs (less than 25 kg/m2).

In addition, those whose BMIs decreased by 5% had 39% lower odds of gout flare-ups, while those whose BMIs increased by 5% had a 60% increased risk.

Another study that included 11,079 people also found a relationship between obesity and gout. Study participants who had obesity throughout adulthood and those who gained weight in adulthood had an 84% and 65% increased risk of gout, respectively.

A review of 10 studies on gout and weight loss found that losing 7.7 pounds (lbs.) (3.5 kg) or more may reduce gout attacks.

However, the authors argue that most studies on this topic are small and low quality, and they suggest that we need larger, higher quality clinical trials.

Further, a large 27-year study among 44,654 men found that 77% of gout cases may have been prevented through strategies such as maintaining a normal BMI, following a nutritious eating pattern, and limiting alcohol and diuretics.

In particular, the study found that excess adiposity, or fat stores, was one of the largest risk factors. Interestingly, adopting healthier lifestyle habits did not seem to be beneficial in men with obesity if their weight was not also reduced.

Ultimately, it appears that weight loss, and particularly fat loss, may help people with obesity and gout manage their symptoms.

If you want to lose weight to help manage gout symptoms, its important to do so in a safe and healthy way. That means its best to skip fad diets, which can lead to mental health challenges, nutrient deficiencies, weight gain, metabolic issues, and other effects.

For sustainable weight loss, try to adopt habits that you can continue to follow in the long term. Consider:

You may also wish to work with a registered dietitian, who can make personalized recommendations based on your medical history, food preferences, and budget.

In addition, its important to make sure youre staying active when you can.

The Centers for Disease Control and Prevention recommends getting at least 150 minutes of moderate-to-vigorous physical activity per week, but any increase in physical activity is a great starting point.

Getting proper sleep and doing your best to manage stress are also important for well-rounded health and may support weight loss, if you choose to pursue it.

For most people, its generally safe to lose around 12 lbs. (0.450.9 kg) per week from a calorie deficit.

While losing weight may help with gout symptoms, there are other tips you can follow to manage the condition:

Gout is an inflammatory form of arthritis that can result from genetics or lifestyle factors.

While genetics play a large role, overweight or obesity can increase your risk of developing gout and experiencing recurring flare-ups. Thus, losing weight may be beneficial for some people.

However, keep in mind that gout is hereditary and may not be related to your weight or lifestyle habits.

If you want to manage your gout symptoms, there are other things you can do besides losing weight, such as eating a nutritious diet, limiting foods high in purines, avoiding alcohol, and managing any other chronic conditions you may have.

Its best to work with a healthcare professional such as a physician, as well as a registered dietitian, who can make personalized recommendations for your treatment including a nutritious, culturally appropriate eating pattern that can help you manage gout.

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Gout and Weight Loss: What You Need to Know - Healthline

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Everything You Should Look At Before Buying Cannabis Indica Seeds – Caribbean and Latin America Daily News – News Americas

September 13th, 2022

News Americas, NEW YORK, NY, Mon. Sept. 12, 2022: There is no better time to cultivate cannabis Indica seeds than at the start of the year. Whether you are new to this practice or well-established in the industry, you will agree that finding these seeds is not an easy job.

Before going on your way to buy indica seeds, you need to do a little research on what factors to consider before you make the purchase. Navigating the cannabis seed market can be daunting as every state has different laws regarding the legality of the herb.

This article will discuss some of the things you should consider before buying cannabis Indica seeds.

Since the legality of cannabis can vary in every state, you need to figure out what the status of cannabis is in your state. If you live in a state with adult-use legalization, you have the ability to buy, produce, and sell cannabis in your own state as long as the seeds dont make it to other states.

Other states have medical marijuana legalization, which only allows people to buy cannabis if they have a medical card that states their disorder and the need for the herb.

Still, some other states have completely banned the use and sale of cannabis seeds, and in these state lines, you are not allowed to own, grow, buy, or sell marijuana. In case you are found to be in possession of these seeds, they are confiscated, and you will have to serve an appropriate sentence.

Before buying marijuana seeds, make sure you ask the breeder who produced them if they can mention the origin of the seeds, where they were grown, how they were crossed, or how they were backcrossed.

This information is essential because it allows you to spot poor breeding practices, which can result in unstable genetics. Some inexperienced breeders may cross a male and female plant only once, which will create a new hybrid, but unless they backcross it several times, you wont get consistent plants with the same genetic properties.

One of the most common problems that buyers face when buying cannabis autoflower seeds is scamming incidents. Especially when buying seeds online, make sure you are contacting a trusted seller. Make sure you do thorough research regarding the seller by visiting their website, checking reviews, and reading up on customers feedback to confirm the legitimacy of the seller.

After that, pick a seller with a good reputation and good-quality products that previous buyers have endorsed.

Growing marijuana demands you to have sufficient space and resources to successfully cultivate and store them. Since you are looking for cannabis Indica seeds, it is okay if you have limited space since these strains are usually smaller and take less space. Moreover, Indica strains typically grow faster and smaller.

Secondly, you need expert advice on how to nurture a specific strain of cannabis. Before buying the seeds, get in touch with a professional breeder who can help you understand the standard practices to grow Indicas and give you tips on the growing requirements.

Before buying weed seeds from a seller, you should compare their delivery periods to other sellers. It is obviously better to pick a seller that delivers quicker so that you dont have to wait around for weeks for your package. Ideally, the seller should deliver your product within seven days after you place the order.

Another crucial factor to consider is the packaging of the seeds. Sellers should ensure that the packaging they choose for the seeds is durable enough that it doesnt damage the seeds during transportation. Moreover, the packaging should be discreet in order to not raise suspicion.

Choose a seller that agrees with your payment method. You can detect a good seller by the way they offer multiple payment methods in order to make shopping convenient for their customers. It is better to opt for a seller that offers credit card or debit card options.

Purchasing cannabis Indica seeds is not an easy job, especially if you are a newbie. It takes time to learn how to navigate the market, so the best thing you can do is research and go with your instincts.

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Everything You Should Look At Before Buying Cannabis Indica Seeds - Caribbean and Latin America Daily News - News Americas

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Why Are There More Lonely, Single Men Than Ever Before? – Evie Magazine

September 13th, 2022

Today, we have more lonely, single men than ever before. This is particularly concerning as, unlike many women, men struggle to be on their own and suffer more as a result. In heterosexual relationships, women usually maintain friendships for the couple, but when men are single, they dont have someone pulling them to socialize with other people (usually another couple), causing loneliness.

The obvious cost of loneliness is the emotional turmoil it causes a person, however, the relationships we have in our lives have more of an impact on our physical health than many realize. In fact, the longest study on happiness showed that even the role of genetics proved less important to longevity than the level of satisfaction with relationships.

But this isnt just a concern for men. On a societal level, men who are single and unhappy cause issues because men are naturally more aggressive. As a result, theyre more likely to act out with violence.

Psychologist Dr. Greg Matos says that because men make up the majority of dating apps (upwards of 62%), women are overwhelmed by the number of options they have. Competition is greater than ever before and the chances of meeting someone in person are rarer, especially in the post-Covid, remote-working world we find ourselves in.

The problem with dating apps (among many) is that if a man is unable to present himself properly online, hes less likely to get matches. He may be more attractive in person, but if he cant take a decent picture or write a coherent bio, then women will swipe past him.

Before the rise of social media, men and women would typically settle down with someone in their local area. Now, with apps such as Instagram, women can build a profile and interact with high-status men from around the globe. This means that the man in a stable job who lives just down the road may not be as attractive a relationship prospect as he would have been for previous generations.

With a greater dating pool size, women are becoming increasingly more selective.

With a greater dating pool size, women are becoming increasingly more selective. According to Dr. Matos, women want men who are emotionally available, good communicators, and who share their values. They have less patience for poor communication skills today, which is creating a relationship skills gap that, if not addressed, will lead to fewer dating opportunities for some men.

Gone are the days when women would have to rely on a man to support them financially. Before women had equal access to education and jobs, they had no choice other than to settle down and marry a man with a stable income. This meant that even unattractive men who didnt have a lot going for them could offer financial security, at the very least. Now, what do they have to offer?

According to British journalist James Bloodworth, this is just one of the contributing factors to the growing number of single men. The low success on dating apps perpetuates the idea theyre undesirable to all women. With so few matches, they transpose this onto real life, believing they will be alone forever. When these men turn to mainstream outlets for advice, theyre provided with a Disney-fied version of the dating realm and are told to just be themselves and the right person will come along and love them as they are.

The low success on dating apps perpetuates the idea they're undesirable to all women.

These men soon realize that this is, in fact, not true and so go in search of alternative views, where they come across the manosphere. Bloodworth defines the manosphere as made up of pickup artists (PUAs), involuntary celibates (incels), mens rights activists, as well as Men Going Their Own Way (MGTOW). PUAs try to lure women into bed with tactics and manipulation, whereas incels blame womens sexual liberation for their failure to find a partner. Mens rights activists express [] a nostalgic yearning for ancient societal rules and stereotypes, while MGTOWs aim to live their lives free from female contact.

For incels, in particular, they become part of an echo chamber that perpetuates the idea they all have no hope of ever finding a woman who will commit to them and will forever be alone. Many in the incel community blame feminism and the sexual revolution for their difficulties in finding a woman (and to a certain extent, this has influenced it), believing that there should be a mandated redistribution of sex to solve the issue. However, alongside enforced monogamy (this is culturally enforced monogamy, where men and women are encouraged by society to commit to one person, not the act of physically forcing women to be with undesirable men), the real answer to the problem lies with men themselves.

Contrary to the manosphere encouraging men to be emotional robots, Dr. Matos recommends men level up [their] mental health game. That means getting into some individual therapy to address [their] skills gap. It means valuing [their] own internal world and respecting [their] ideas enough to communicate them effectively. It means seeing intimacy, romance, and emotional connection as worthy of [their] time and effort.

Men can generate the love life they want.

Self-improvement seems to be a consistent message to the men suffering from fewer dates. During a conversation on the Triggernometry podcast, Bloodworth, who has done extensive research into the manosphere, recommends these men make a conscious effort to improve their lives in order to be more attractive to women. Going to the gym, picking a hobby, starting a business, and dressing well will not only make these men happier in themselves, but they may find women are more attracted to them too.

Although dating apps offer a quick, convenient solution to finding a partner, these apps omit the best parts of a person. Those with the most attractive photo may not have the kindest heart, and the guy with a poorly written bio might be the funniest person in every room. These are things we only learn from face-to-face interactions with people.

The constant rejection many men are facing on dating apps doesnt necessarily correlate to how successful they will be when meeting women in person, and its important men realize this. Daters filter out many suitable matches when swiping on dating apps, but attraction grows easier in real-life situations.

Luckily, its not all doom and gloom like the manosphere claims, and men can take this situation into their own hands and improve their chances of finding love. Whether thats through therapy or going to the gym, or both, by committing to themselves and their mental health, men can generate the love life they want. But will they step up to the plate?

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Why Are There More Lonely, Single Men Than Ever Before? - Evie Magazine

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‘Call me Tumi,’ says the young female scientist lea… – Daily Maverick

September 13th, 2022

Call me Tumi, says Boitumelo Semete-Makototlela. This, after an awkward do we shake hands nowadays or not? in the doorway of her Centurion home. Unexpected winter rain had clogged up the roads and drawn out the school run, putting Tumi, casually dressed in a grey workout tracksuit, slightly behind schedule.

I drop the two of them off at school myself every morning because its important to me that we use that time to connect, she says, adjusting her stylish spectacles.

Semete-Makokotlelas son (7) and daughter (11) have left half-packed bags in the den ahead of a week with their paternal grandparents. I am going away with Khotso [her husband, a civil engineer]. If we didnt schedule time away together, we would quickly become strangers. Of course the kids are insisting we install Wi-Fi at gogos, Semete-Makototlela laughs.

Their 43-year-old mother got the job of running the countrys medicines regulator, the South African Health Products Regulatory Authority (Sahpra), at a pivotal point: three months before Covid hit South Africa in 2020.

At the age of 39, considerably younger than many of her predecessors, the relatively obscure public entity Semete-Makokotlela was leading was transformed practically overnight into a household name in the middle of a political maelstrom.

SARS-CoV-2, the rapidly changing virus that causes Covid-19, triggered a noisy scramble for the approval of Covid tests, jabs and treatments within a year of her appointment, leaving the relatively young scientist with the task of not only reducing Sahpras approval processes from years to months, but also facing extreme political pressure from parties such as the Economic Freedom Fighters (EFF) to approve the use of jabs from countries such as China and Russia, whose products the EFF believed were deliberately being overlooked in exchange for shots from Western countries.

No medicine or health product can be used in South Africa without the manufacturers of such goods submitting data for Sahpra to review. Sahpra then studies the information to see if it accurately reflects how effective (or not) the product is, and if its safe to use.

In June last year, EFF leader Julius Malema threatened Semete-Makokotlela with militant mass action if Sahpra didnt approve the Russian and Chinese jabs within seven days.

Semete-Makokotlela held the line. I was worried about the safety of my children and husband, but I wasnt scared. I was going to stand up against improper influences. To me it was clear: we were going to make decisions based on science, and no movement or political party was going to change that.

Although Sahpra gave Chinas Sinovac jab conditional emergency approval that July, it rejected Russias Sputnik V four months later because of a lack of safety data.

Semete-Makokotlelas smooth handling of things wasnt unexpected.

According to her PhD supervisor, Antonel Olckers (Semete-Makokotlela received a doctorate in biochemistry from North West University in 2005), [With Tumis appointment] people were asking, dont you think shes too young? Arent you worried shell fail?

But Olckers simply shook her head and responded: Give this woman the tools and get out of her way.

Semete-Makokotlela was born in Soweto in 1979, the first child of Benjamin and Sheila Semete. She starts to say it was a typical upbringing, but catches herself and instead says: Well, South Africas an interesting place it was, even then. Her parents lived and worked (mostly worked) with the single-minded purpose of buying a good education for their three children.

To enable their work, I was sent to live with my aunt in Orlando, sleeping on the kitchen floor because the house was small and very full. I laugh about this all the time with my cousins, and wecanlaugh because it was a joyful time.

The phrase joyful time often precedes the telling of less happy times, and in Semete-Makokotlelas case, the event that marked the end of her carefree childhood was a move to Zone 2, Diepkloof.

My mom wanted to move us to a better school a Catholic school.

She liked the school I loved what the nuns were about the order and the cleanliness but Diepkloof? Not so much.

The area was largely Tsonga-speaking, but I didnt speak Tsonga. And being from this prim and proper school, we were given a hard time by kids from less privileged schools.

Semete-Makokotlelas response was to stay indoors and dream of leaving.

The rejection of ones circumstances can be such a powerful driver in life, and it can do that positively or negatively. I think my own life has been greatly shaped by a desire to escape.

Political unrest in the late 1980s led to repeated school shutdowns and stayaways, compelling Semete-Makokotlelas parents to place their three children in suburban schools nearer central Johannesburg. Leaving for school at dawn and arriving home at dusk became the norm, and with her sports bag in hand and wearing her Northview High blazer, Tumis alienation intensified.

Soweto is a very open and communal society, and the unsaid expectation is that you will socialise quite well, but I didnt fit in. Even now, when I go back, it is just to visit my

Her voice trails off, until with the resolve of someone who had contemplated not mentioning it, she says: My father passed away a month ago yesterday.

He was a good man. People, especially moms friends, keep saying that he was such a good father, a good husband.

In her eulogy, Semete-Makokotlela said she is who she is because of the sacrifices her father made.

I dont have memories of going on holiday with my dad, because he chose to work. He missed my PhD graduation. I was shattered.Does work mean that much to you, that you cant come, just today?But that is the man he was; so many big moments that he contributed to financially, yet was never present for. It created a void, but you get over it because you realise thats how he loves.

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From her father, Semete-Makokotlela learnt a work ethic that would serve her well at the University of Pretoria. The institution accepted her application to study biomedical technology, a choice inspired by the most fantastic Standard 8 (Grade 10) biology teacher, who introduced the subject of genetics.

But for this self-described girl from Soweto, Tuks was freedom an almost disastrous dose, in fact.

I loved the diversity of the place and the fact that I was side-by-side with the [prestigious] St Marys girls Id envied from a distance at high school. I loved partying in Hatfield, too, and failed the first semester.

Fearing her parents judgement, Tumi pivoted.

I was, like, this is it Im going to create structure and I am going to learn to self-regulate, and I did.

Semete-Makokotlelas focus is legendary among those who know her. Unparalleled, is how Olckers describes it. The mention of her masters and doctoral thesis supervisor elicits a grin from Tumi.

Wooh, that woman! She made us work, hey. When you submitted a thesis chapter, you just knew it was coming back with red marks all over, to the point where, today, I use a blue pen when critiquing students work!

If her fathers example taught her about hard work, it was in Olckers lab that she learnt about uncompromising standards.

Tumi says: Sometimes we would sleep in the lab, rush home in the morning to shower, and come back whatever it took to avoid disappointing Antonel. She was very firm, but you knew it was well intended she really wanted all of us to succeed. And we have.

Olckers has a photo from Tumis graduation ceremony where she stands alongside fellow students Marco Alessandrini, now the chief technical officer of a biosciences company in Switzerland, and (now professor) Wayne Towers, who chairs the ethics committee at North West University.

They were an exceptional class, come to think of it, says Olckers, who demands three things of her students that they write a paper, present at a conference and, if at all possible, work overseas, because a doctorate isnt a Nobel prize it doesnt set you up for life. As a scientist, you compete internationally. Its not enough to be the best in South Africa.

After receiving her doctoral degree in biochemistry, Semete-Makokotlela joined the Council for Scientific and Industrial Research (CSIR) as a researcher and then took up a postdoctoral research fellowship with the Swiss Federal Institute of Technology in Lausanne.

She recalls: Man, it was a massive confidence boost for me to realise that we are on par in South Africa. The equipment was the same they just had more of it, and from a knowledge perspective I found I knew the same things, and some things I knew better.

The sometimes reclusive scientist also came to a new appreciation of her home countrys social warmth.

Switzerland, for all its virtues, is a terribly lonely place people keep to themselves. I missed being in a taxi with people chatting away.

Semete-Makokotlela returned to South Africa in 2011 mindful of something Olckers used to repeat: that most students will always be followers only a few have what it takes to lead.

I have never felt that I am innately a leader, she says, explaining that her confidence in this regard built gradually, with tenure.

I am an introspective person and as I gained in experience, I realised I do bring a few things to an organisation, like an ability to articulate clearly what I want to get done in the current moment, and to then follow through and get things done.

A two-year stint as a Mckinsey Leadership Fellow exposed Semete-Makokotlela to the world of management consulting, where she witnessed first-handhow biotechnology businesses operate. This, as much as her experience as a researcher, caught the attention of McLean Sibanda, who recruited Tumi to lead a biotechnology incubator within a Gauteng provincial government project called the Innovation Hub. Here, she helped small and medium-sized businesses with the commercialisation of their biotech innovations.

Sibanda found Tumi to be teachable, a great listener, but also someone with strong ideas all good traits for any leader in a fast-moving industry.

He wasnt surprised to learn, after two years, that the CSIR wanted Tumi back, this time in an executive role as the head of the biosciences department. In many ways, it was a foreshadowing of the scrutiny Tumi would come under at Sahpra.

When Tumi learnt of the Sahpra opportunity from a pharmacist friend, she was initially sceptical.

I had never seen myself in a regulatory space, but the more I thought about it, the more I realised I understand something of the role and workings of the national health products regulator, and I care about its proper functioning.

She applied for the job, thinking, I know Im a person that gets things done at least I can make a small difference.

According to Professor Helen Rees, who chairs the Sahpra board, Tumi was appointed primarily because her vision of what she wanted to do was so clearly and powerfully articulated.

Semete-Makokotlela knew she needed to get myself a good team and she did. But, she says, they probably didnt like me much the first two years. I mean, we didnt sleep, we worked over weekends, we worked at night.

And its that type of determination, Rees says, that Tumi uses to pull through difficult times.

You might not know this, but shes a serious triathlete, as is her husband. When she gets home, she doesnt sit on the couch shes talking to you from her bike. If her phones off, shes probably swimming across some or other dam. DM/MC

This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.

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'Call me Tumi,' says the young female scientist lea... - Daily Maverick

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