Category Archives: Physiology

Physiology

Microphysiological Systems: Approaches, Applications and Opportunities – Technology Networks

Microphysiological systems (MPS), also commonly referred to as organ-on-a-chip or body-on-a-chip technologies, have gained considerable attention in recent years. They provide a more physiologically relevant setting compared to static two-dimensional cell culture assays or animal models, as they more closely recapitulate human physiology and the downstream effects of drugs on multiple tissues. The development of MPS technologies has been driven by advances in several areas 3D cell culture techniques, microfluidics, tissue engineering and bioprinting enabling the creation of various key components. In this article, we highlight advances in the field that have been instrumental to the development of MPS, as well as key applications and future opportunities.

However, building a device that encompasses several tissue constructs to produce an interconnected multi-organ environment is no easy feat, as Dokmeci explains, Finding a universal media that satisfies the needs of multiple cells or organs is one of the main challenges.

Also, being able to control the fluid flow between different systems sometimes requires microvalves, which enables automation but complicates the design and manufacturing of the system. Overall, adding more components complicates the design, he adds.

In recent years, there have been efforts to improve the in vitro models used in preclinical drug development and disease research. In particular the use of microphysiological systems (MPS), also sometimes referred to as organ-on-a-chip (OOC) technologies, has become more widespread. Download this app note to discover a gut MPS that has physiologically relevant morphology, reduced barrier integrity and mucus expression. It can also be used to predict drug permeability across an intestinal barrier.

To prevent loss of the drug compounds, the team chose to assemble their MPS using polymethyl methacrylate (PMMA) rather than polydimethylsiloxane (PDMS). While PDMS has been widely used to build microfluidic chips until now, it can cause small molecules to be absorbed into the walls of the chip, reducing the free concentration of drug within the circulated medium, affecting drug bioavailability.

Atala explains that to create the MPS they employed strategies like those used to implant engineered tissues in patients. We first determine the major cell types present in the specific organ, and we use normal cells in the same proportions as present in humans. We also use the tissue-specific glue that holds cells together, the extracellular matrix, he says. The team then combined the different organoids of interest into a single system by immobilizing them in hydrogels within individual chambers.

Atala elaborates, We can therefore test many parameters, such as the effects of one drug on a specific organ, and how the drug gets metabolized and processed, or its bystander effects on other organs. The system, depending on how many tissues it uses, can be designed to fit an area about the size of a matchbox.

This is one of the main promises of the organ-on-a-chip field being able to borrow cells from patients and test the drugs on individual patients beforehand, explains Dokmeci.

The invention of induced pluripotent stem cells (iPSCs) has helped to expedite research in this field, he adds. Personalized MPS can be created using blood samples, primary human tissue and cells derived from iPSCs, as Dokmeci emphasized above.

There are efforts by different groups in this area, explains Prof. Nureddin Ashammakhi, ex-associate director of the Center for Minimally Invasive Therapeutics, UCLA. Ashammakhis research is focused on 3D bioprinting and the development of organ-on-a-chip models for regenerative and personalized medicine.

In a recent study, published in Bio-Design and Manufacturing, Ashammakhi and colleagues reviewed the development of lung MPS to model the pathology of COVID-19. According to Ashammakhi, when designing a lung MPS it is important to mirror the organs unique organization and function.

This is achieved by designing a chip with one chamber for air, representing alveolus and one chamber lined with endothelial cells, representing the blood vessel. The two chambers are separated by a porous membrane that allows the movement of molecules between the two sides, says Ashammakhi.

It is even possible to emulate the motion of in vivo breathing by applying a vacuum to chambers surrounding the epithelialcapillary membrane, causing it to stretch. This is an important element as stress has been shown to influence permeability of the membrane and the release of reactive oxygen species, as well as other molecules.

COVID-19 pathology can be organized into the following stages: SARS-CoV-2 viral entry by the ACE2 receptor; inflammation or malfunction of the innate immune response; coagulopathy or clotting dysregulation; edema or swelling and fluid accumulation; and fibrosis or scarring through the buildup of fibrotic connective tissue, explains Ashammakhi.

While there are surely benefits to assessing COVID-19 using a single lung-on-a-chip device, as Ashammakhi eludes above, the systemic nature of the disease means that a multi-organ MPS would be needed to reflect secondary and systemic effects of the drugs being tested. The inclusion of other cell types such as immune cells is also of utmost importance in developing relevant models especially for infection-related studies, he stresses.

AI is very important in this sense, it can make the big data obtained from multiple MPS chips, for a multitude of variables comprehendible relations [can be] identified and conclusions can be drawn, says Ashammakhi.

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Microphysiological Systems: Approaches, Applications and Opportunities - Technology Networks

Physiology

A blood test for your body clock? It’s on the horizon – CU Boulder Today

What time is your body clock set on?

The answer, mounting research suggests, can influence everything from your predisposition to diabetes, heart disease and depression to the optimal time for you to take medication. But unlike routine blood tests for cholesterol and hormone levels, theres no easy way to precisely measure a persons individual circadian rhythm.

At least not yet.

New CU Boulder research, published in the Journal of Biological Rhythms, suggests that day could come in the not-too-distant future. The study found its possible to determine the timing of a persons internal circadian or biological clock by analyzing a combination of molecules in a single blood draw.

If we can understand each individual persons circadian clock, we can potentially prescribe the optimal time of day for them to be eating or exercising or taking medication, said senior author Christopher Depner, who conducted the study while an assistant professor of integrative physiology at CU Boulder. From a personalized medicine perspective, it could be groundbreaking.

For decades, researchers have known that a central master clock in a region of the brain called the hypothalamus helps to regulate the bodys 24-hour cycle, including when we naturally feel sleepy at night and have the urge to wake up in the morning.

More recently, studies reveal that nearly every tissue or organ in the body also has an internal timing device, synced with that master clock, dictating when we secrete certain hormones, how our heart and lungs function throughout the day, the cadence of our metabolism of fats and sugars, and more.

As many as 82% of protein-coding genes that are drug targets show 24-hour time-of-day patterns, suggesting many medications could work better and yield fewer side effects if administration was timed appropriately.

And when our internal rhythm is at odds with our sleep-wake cycle, that can boost risk of an array of diseases, said study co-author Ken Wright, a professor of integrative physiology and director of the Sleep and Chronobiology Laboratory at CU Boulder.

If we want to be able to fix the timing of a persons circadian rhythm, we need to know what that timing is, he said. Right now, we do not have an easy way to do that.

Even among healthy people, sleep-wake cycles can vary by four to six hours.

Simply asking someone, are you a morning lark, a night owl or somewhere in-between? can provide hints to what a persons circadian cycle is.

But the only way to precisely gauge the timing of an individuals circadian clock (including where the peaks and troughs of their daily rhythm) is to perform a dim-light melatonin assessment. This involves keeping the person in dim light and drawing blood or saliva hourly for up to 24 hours to measure melatoninthe hormone that naturally increases in the body to signal bedtime and wanes to help wake us up.

In pursuit of a more precise and practical test, Wright and Depner brought 16 volunteers to live in a sleep lab on the CU Anschutz Medical campus in Aurora for 14 days under tightly controlled conditions.

In addition to testing their blood for melatonin hourly, they also used a method called metabolomicsassessing levels of about 4,000 different metabolites (things like amino acids, vitamins and fatty acids that are byproducts of metabolism) in the blood.

They used a machine learning algorithm to determine which collection of metabolites were associated with the circadian clockcreating a sort of molecular fingerprint for individual circadian phases.

When they tried to predict circadian phase based on this fingerprint from a single blood draw, their findings were surprisingly similar to those using the more arduous melatonin test.

It was within about one hour of the gold standard of taking blood every hour around the clock, said Depner, now an assistant professor of kinesiology at the University of Utah.

He noted the test was significantly more accurate when people were well rested and hadnt eaten recentlya requirement that could make the test challenging outside of a laboratory setting. And to be feasible and affordable, a commercial test would likely have to narrow down the number of metabolites its looking for (their test narrowed it down to 65).

But the study is a critical first step, said Wright.

We are at the very beginning stages of developing these biomarkers for circadian rhythm, but this promising study shows it can be done.

Other research, including some from Wrights lab, is exploring proteomics (looking for proteins in blood) or transcriptomics (measuring the presence of ribonucleic acid, or RNA) to assess circadian phase.

Ultimately, the researchers imagine a day when people can, during a routine physical, get a blood test to precisely determine their circadian phaseso doctors can prescribe not only what to do, but when.

This is an important step forward in paving the way for circadian medicinefor providing the right treatment to the right individual at the right time of day, said Depner.

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A blood test for your body clock? It's on the horizon - CU Boulder Today

Physiology

Adapting Roots to a Hotter Climate Could Reduce Pressure on Food Supply – Technology Networks

The shoots of plants get all of the glory, with their fruit and flowers and visible structure. But it's the portion that lies below the soil the branching, reaching arms of roots and hairs pulling up water and nutrients that interests plant physiologist and computer scientist, Alexander Bucksch, associate professor of Plant Biology at the University of Georgia.

The health and growth of the root system has deep implications for our future.

Our ability to grow enough food to support the population despite a changing climate, and to fix carbon from the atmosphere in the soil are critical to our, and other species', survival. The solutions, Bucksch believes, lie in the qualities of roots.

"When there is a problem in the world, humans can move. But what does the plant do?" he asked. "It says, Let's alter our genome to survive.' It evolves."

Until recently, farmers and plant breeders didn't have a good way to gather information about the root system of plants, or make decisions about the optimal seeds to grow deep roots.

In a paper published this month in Plant Physiology, Bucksch and colleagues introduce DIRT/3D (Digital Imaging of Root Traits), an image-based 3D root phenotyping platform that can measure 18 architecture traits from mature field-grown maize root crowns excavated using the Shovelomics technique.

In their experiments, the system reliably computed all traits, including the distance between whorls and the number, angles, and diameters of nodal roots for 12 contrasting maize genotypes with 84 percent agreement with manual measurements. The research is supported by the ROOTS program of the Advanced Research Projects AgencyEnergy (ARPA-E) and a CAREER award from National Science Foundation (NSF).

"This technology will make it easier to analyze and understand what roots are doing in real field environments, and therefore will make it easier to breed future crops to meet human needs " said Jonathan Lynch, Distinguished Professor of Plant Science and co-author, whose research focuses on understanding the basis of plant adaptation to drought and low soil fertility.

DIRT/3D uses a motorized camera set-up that takes 2,000 images per root from every perspective. It uses a cluster of 10 Raspberry Pi micro-computers to synchronize the image capture from 10 cameras and then transfers the data to the CyVerse Data Store the national cyberinfrastructure for academic researchers for 3D reconstruction.

The system generates a 3D point cloud that represents every root node and whorl "a digital twin of the root system," according to Bucksch, that can be studied, stored, and compared.

The data collection takes only a few minutes, which is comparable to an MRI or X-Ray machine. But the rig only costs a few thousand dollars to build, as opposed to half a million, making the technology scalable to perform high-throughput measurements of thousands of specimens, which is needed to develop new crop plants for farmers. Yet, the 3D scanner is also enabling basic science and addresses the problem of pre-selection bias because of sample limitations in plant biology.

"Biologists primarily look at the one root structure that is most common what we call the dominant root phenotype," Bucksch explained. "But people forgot about all of the other phenotypes. They might have a function and a role to fulfill. But we just call it noise," Bucksch said. "Our system will look into that noise in 3D and see what functions these roots might have."

Individuals who use DIRT/3D to image roots will soon be able to upload their data to a service called PlantIT that can perform the same analyses that Bucksch and his collaborators describe in their recent paper, providing information on a wide range of traits from young nodal root length to root system eccentricity. This data lets researchers and breeders compare the root systems of plants from the same or different seeds.

The framework is made possible by massive number-crunching capabilities behind the scenes. These are provided by the Texas Advanced Computing Center (TACC) which receives massive amounts of data from the CyVerse Cyberinfrastructure for computing.

Though it takes only five minutes to image a root crown, the data processing to create the point cloud and quantify the features takes several hours and requires many processors computing in parallel. Bucksch uses the NSF-funded Stampede2 supercomputer at TACC through an allocation from the Extreme Science and Engineering Discovery Environment (XSEDE) to enable his research and power the public DIRT/2D and DIRT/3D servers.

DIRT/3D is an evolution on a previous 2D version of the software that can derive information about roots using only a mobile phone camera. Since it launched in 2016, DIRT/2D has proven to be a useful tool for the field. Hundreds of plant scientists worldwide use it, including researchers at leading agribusinesses.

The project is part of ARPA-E's ROOTS program, which is working to develop new technologies that increase carbon storage within the soil and root systems of plants.

"The DIRT/3D platform enables researchers to identify novel root traits in crops, and breed plants with deeper, more extensive roots," said ARPA-E ROOTS Program Director Dr. David Babson. "The development of these kind of technologies will help promote climate change mitigation and resilience while also giving farmers the tools to lower costs and increase crop productivity. We're excited to see the progress that the team at PSU and UGA has made over the course of their award."

The tool has led to the discovery of several genes responsible for root traits. Bucksch cites a recent study of Striga hermanthica resistance in sorghum as the kind of outcome he hopes for users of DIRT/3D. Striga, a parasitic weed, regularly destroys sorghum harvests in huge areas of Africa.

The lead researcher, Dorota Kawa, a post-doc at UC Davis, found that there are some forms of sorghum with Striga-resistant roots. She derived traits from these roots using DIRT/2D, and then mapped the traits to genes that regulate the release of chemicals in the roots that triggers Striga germination in plants.

DIRT3D improves the quality of the root characterizations done with DIRT/2D and captures features that are only accessible when scanned in 3D.

The challenges facing farmers are expected to rise in coming years, with more draughts, higher temperatures, low-soil fertility, and the need to grow food in less greenhouse-gas producing ways. Roots that are adapted to these future conditions will help ease pressure on the food supply.

"The potential, with DIRT/3D, is helping us live on a hotter planet and managing to have enough food," Bucksch said. "That is always the elephant in the room. There could be a point where this planet can't produce enough food for everybody anymore, and I hope we, as a science community, can avoid this point by developing better drought adapted and CO2 sequestering plants."

Reference:Liu S, Barrow CS, Hanlon M, Lynch JP, Bucksch A. DIRT/3D: 3D root phenotyping for field-grown maize (Zea mays). Plant Physiol. 2021;(kiab311). doi:10.1093/plphys/kiab311

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Adapting Roots to a Hotter Climate Could Reduce Pressure on Food Supply - Technology Networks

Physiology

In the hot seat: U of T expert on Tokyo’s weather and how athletes can beat the heat – News@UofT

This week, Spanish tennis player Paula Badosa was forced to retire from the quarter final at Tokyo 2020 due to heatstroke, using a wheelchair to leave the court. Novak Djokovic and Daniil Medvedev have also complained about the heat and scheduling of matches during the day.

As a result, International Tennis Federation officials decided to schedule Olympic tennis matches later in the afternoon, starting at 3 p.m. local time.

Ira Jacobs, a professor of exercise physiology in the University of Toronto's Faculty of Kinesiology & Physical Education, spoke to U of T's Jelena Damjanovicabout the temperatures in Tokyo and what athletes can do to prepare for the heat.

How do heat and humidity affect athlete performance?

The healthy human body is very sensitive to changes in both internal body temperature as well as air temperature. For example, we have neurons sensitive to temperature changes throughout our bodies, many located close to the skin surface. They act as temperature sensors resulting in many physiological changes. One of the most rapid changes that occurs within seconds of the sensing of warm air is the vasodilation, or expansion of the diameter of blood vessels, particularly the smaller ones closer to the skin surface. That enables more blood to be shunted to the skin surface, facilitating a more rapid and effective transfer of heat from the blood to the skin surface and away from the body to the surrounding environment.

When it comes to physical performance and sports there is a downside to that shunting of blood to the skin surface. Because our bodies give a higher priority to trying to maintain body temperature within a critical range, the heart has to work all that much harder to both continue to shunt blood to the skin surface while also trying to provide oxygenated blood flow to the exercising muscles. The end result is that the cardiovascular strain during intense exercise is much higher when its hot. Therefore, that intensity cannot be sustained for as long as when its done at a comfortable temperature.

Another example of how our bodies try to regulate internal body temperature is sweating. The evaporation of sweat from the skin surface is one of the most important avenues of heat transfer out of human bodies when we are exercising. Anything that impedes sweat secretion or evaporation will have a negative effect on exercise or physical performance. How much and how quickly sweat can be evaporated is dramatically affected by air humidity. The higher the humidity, the lower is the capacity of that air to accept more moisture which means that less sweat will be evaporated. More sweat simply drips off our bodies without being evaporated, and without removing as much heat from our bodies.

Recent research has also suggested that there is a central nervous system component to the regulation of body temperature that senses and predicts the rate of body temperature increase, and will cause us to involuntarily reduce our internal heat production by making us feel more fatigued. One of the underlying theories is that this a protective mechanism whereby the fatigue will cause us to slow down and thereby reduce the rate of increase of body temperatures to critical levels associated with serious damage to vital organs.

What can athletes do to adapt to extreme heat?

Fortunately, healthy humans can quickly improve their ability to cope with exercise in the heat. A period of 10 to14 days of daily exposure to a combination of heat stress and exercise will significantly improve the ability to exercise in the heat. Sweat rate increases, the volume of blood pumped by the heart per heart beat increases, heart rate decreases, blood plasma volume increases, the perception of how hard exercise feels decreases.These are but a few of the adaptations that help to preserve and increase exercise performance in the heat after a period of adaptation to heat stress.

So, Olympic athletes hopefully either went through a heat acclimation process a couple of weeks before their competitions in Japan, or they moved to Japan in sufficient time to give them a couple of weeks of natural acclimatization to Japans heat and humidity.

Is there something the International Tennis Federation (ITF) can do to protect players' health? Perhaps schedule matcheswhen it's cooler?

Frankly, I was surprised to learn that the scheduling of outdoor events like tennis at the Olympics did not start off with matches being scheduled to times that corresponded with reduced environmental heat stress. I read that they have now done so.

Many industrial, military and sporting organizations have standards whereby no hard work, training or competitions can take place when the heat index (an index of the combined effects of air temperature and air humidity) exceeds certain limits.

Longer rest intervals between sets; a longer break when changing courts within a set; cooling stations courtside where players could insert the arms and hands into cold water while on a break these are all examples of simple strategies that are employed in many other occupational and sport settings to reduce the health risks of high intensity physical exertion in the heat.

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In the hot seat: U of T expert on Tokyo's weather and how athletes can beat the heat - News@UofT

Physiology

R. Barry Dale Named Chair of Physical Therapy for College of Health Professions – UTHSC News

R. Barry Dale, DPT, PhD, MBA, has been named chair of the Department of Physical Therapy for the College of Health Professions at the University of Tennessee Health Science Center. He will begin his role July 30.

Dr. Dale brings significant experience to our college, said Stephen E. Alway, PhD, FACSM, dean of the UTHSC College of Health Professions. He is passionate about students and taking the training of Physical Therapy students to higher levels of excellence at UTHSC. He will provide outstanding energy for reshaping the Department of Physical Therapy and elevate its national visibility, clinical impact, teaching prominence and research productivity. We are delighted to recruit a leader of the caliber of Dr. Dale to our college.

The UTHSC Department of Physical Therapy is a proud and storied program with excellent faculty, students, and staff, Dr. Dale said. It is humbling to be a part of it.I am really looking forward to working with the faculty, students, and staff to continue the quest for programmatic excellence.

A nationally recognized leader in physical therapy, Dr. Dale joins UTHSC from the University of South Alabama, where he served as professor,department chair, and program director of the Department of Physical Therapy with expertise in Orthopedics, Sports, and Kinesiology.

Dr. Dales clinical expertise and research focuses on experimental sports-related and orthopedic areas of tendinopathy,rotator cuff fatigue, kinematics and kinetic analysis pertaining to the lumbar spine and thermoregulation. He has contributed to multiple textbook chapters pertaining to orthopedic and sports rehabilitation, exercise physiology and motor control. An active researcher, Dr. Dale has published 33 peer reviewed publications and has presented his research nationally and internationally.

Dr. Dale is certified as a Myofascial Trigger Point Therapist (CMTPT), Orthopedic Certified Specialist (OCS), and as a Sports Certified Specialist (SCS). In addition, he is Athletic Trainer Certified (ATC) and is a Certified Strength and Conditioning Specialist (CSCS).

Dr. Dale earned his bachelors degree from the University of South Alabama and a masters in Education in Exercise Science from the University of Alabama, Birmingham. He earned his PhD in Kinesiology with a specialization in Exercise Physiology from the University of Alabama, Tuscaloosa; a Doctor of Physical Therapy degree from University of Tennessee, Chattanooga; and his MBA from the University of South Alabama.

One facet of my role will be supporting student and faculty growth so that we may lead PT education in Tennessee, the region, and the nation, Dr. Dale said. Our department has a strong reputation, and we will only be getting better with time.

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R. Barry Dale Named Chair of Physical Therapy for College of Health Professions - UTHSC News

Physiology

Laurel Hubbard will make Olympic history on Monday before winning a medal despite the naysayers – ABC News

This weekend one Olympic athlete is preparing to make history.

Whether she wins or not is irrelevant, because just by taking part she will become one of those rare few who will be described as "the first ever".

There's no certainty that her history-making effort will be widely celebrated.

Certainly, it is controversial and yet the athlete herself is playing entirely by the rules.

New Zealand weightlifter Laurel Hubbard will become the first openly transgender woman to compete at the Olympics when she joins nine other competitors in the women's 87+ kilogram event at the Tokyo International Forum on Monday evening.

AAP:Dean Lewins

That's about the only simple thing to say about the story because everything else is highly complex and emotive.

Even the science is divided.

In years gone by there used to be rooms full of men making decisions for women, without hearing from the women themselves.

Then it was rooms full of white people making decisions for people of colour, without hearing their voices.

Now there are also rooms full of cisgender people making decisions for transgender people.

Some of those with the loudest voices and most forthright opinions have never actually discussed their views with a transgender athlete.

The most common view against transgender women competing in the women's category is:"Sooner or later there'll be no women left." By that, they mean cisgender women.

That line has been around for the best part of a decade and there is still no evidence of it happening.

One expert who worksin the field described it this week as "vastly overblown".

Australian weightlifter Charisma Amoe-Tarrant voices her support for Laurel Hubbard following her inclusion in New Zealand's squad for the Tokyo Games.

Significant numbers of men are not going to wakeup in the morning and decide, for a laugh, they'll become women so they can win a sporting contest.

Overwhelmingly, transgender women speak of knowing at age three or four that their bodies did notmatch what they knew themselves to be on the inside.

They describe living in a parallel world where the way people saw them was not who they were.

That experience alone can be psychologically traumatic.

When a male transitions to female, under the current International Olympic Committee (IOC) consensus, athletes need to prove they have reduced their testosterone levels to under 10 nanomoles per litre and maintain those levels for a period of 12months prior to their first competition.

Some experts argue 10nm is still too high, with most cisgender women registering levels between one and five nanomoles per litre.

Some are happy with the ratio but want the time period extended from one to two years or longer before being allowed to compete.

Transgender athletes have spoken of the impact testosterone reduction has.

Explained basically, the skeletal and muscular development of a male body that has gone through puberty requires a certain amount of hormonal "fuel"to sustain the speed and muscular strength to carry that body.

Reducing testosterone impacts the entire endocrine system, with flow-on effects formoods, metabolism and the way thebody's organs function.

Canadian cyclist and transgender woman Kristen Worley described the impact on her body as "spontaneous menopause".

Put another way, there was not enough fuel to continue to drive the vehicle andeverything steadily declined.

One of Australia's first transgender athletes was middle-distance runner Ricki Coughlan.

Speaking at a recent Association of International Sports Press (AIPS) e-College session, Coughlan said her experience was different.

"I experienced very little in the way of a full-blown puberty," she said.

"When I began my transition, the doctors didn't put me on a testosterone blocker because I didn't need one.

"My testosterone levels are lower than the average females.

"This points to the fact that all of our lives are different; where we start from and where we finish and where we go are very different."

Australian rugby player and sprinterCaroline Laytsaidbefore transitioning she was running 100 metres in "very low 11 seconds".

"Six years after surgery I was running 13.5 seconds, so I was about two and a half seconds slower over 100 metres," she said.

As part of a PhD thesis, Loughborough University's Joanna Harper has been collecting data on "changing athletic attributes as trans athletes transition".

Layt said she hadgiven all her statistical information to Harper, including how the amount she could bench press decreased from around 115 kilogramsto about 70kg.

Her data showed as a male athlete she was graded at around 85 per cent whileas a female she was graded at around 80 per cent. In other words, compared to most others in each category, she was more competitive as a manthan as a woman.

"But I'm only one person," Layt said.

"As we know, there are people that don't take hormones, there are people who are non-binary, so I think it's going to be a case-by-case basis.

"There's not one set rule for all."

The IOC will make a significant announcement in the coming months regarding a transgender framework which individual sports can use in devising their own policies.

It is expected to be a major shift, looking at the inclusion of transgender athletes through a multi-dimensional prism including human rights, legal, medical, social and scientific aspects.

The IOC's medical and scientific director, Richard Budgett, saidthere was still more science needed.

"There's quite a large amount of research being done at the moment to ascertain the residual advantage after going through male puberty, but you have to weigh that against all the other disadvantages of going through transition, and it's not something any individual would ever take lightly," he said.

"There are lots of aspects of physiology and anatomy, and the mental side, that can contribute to elite performance and it's very difficult to say, 'Yes, she has an advantage because she went through male puberty,' when there's so many other factors to be taken into account.

"It's not simple.I think each sport has to make their own assessment depending on the physiology of that sport so that they can ensure that there's fair competition but also inclusion of everyone, whether they're male or female able to take part in the sport that they so love."

He paid tribute to Hubbard's courage and tenacity in competing at the Olympic Games.

Hubbard rarely gives interviews but on Friday issued a message.

"I see the Olympic Games as a global celebration of our hopes, ideals and values and I would like to thank the IOC for its commitment to making sport inclusive and accessible," she said.

Come Monday, Hubbard will make history.

By Tuesday we'll know how widely that will be celebrated.

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Laurel Hubbard will make Olympic history on Monday before winning a medal despite the naysayers - ABC News

Physiology

Why some Olympians restrict their blood flow to train better – CNN

The origins of this practice go back to 1966, when -- while sitting on his heels during a Japanese temple ceremony -- Yoshiaki Sato noticed his calves felt tingly and pumped up. Sato wondered if his limited blood flow was the key to experiencing that sensation, said Steven Munatones, the CEO of KAATSU, an eponymous blood flow restriction product and education company. Munatones cofounded KAATSU Global -- which translates to "additional pressure" in English -- with Sato in 2014 after being mentored by him about the Kaatsu technique for 13 years in Japan.

Seven years after that initial tingly feeling, Sato "experimented with different kinds of bands placed on different locations on his body -- from his head to his torso to his lower legs," Munatones said via email. "In 1973, he experienced a broken ankle and rehabilitated himself using KAATSU."

This was the first experimentation with KAATSU cycle mode, Munatones added, which is when bands with internal "air bladders" are inflated for 30 seconds as the bands compress around upper limbs, then deflate for five seconds before repeating the cycle. This rhythmic compression slows the blood flow back to the heart and therefore allows the veins and capillaries in the treated areas to engorge with blood -- visible as the skin gradually reddens -- while you're exercising, Munatones said.

"Individuals exercise during the application of BFR to improve muscle mass, muscle strength, reduce pain, improve recovery, increase cardiovascular capacity and augment sports performance," said physical therapist Nicholas Rolnick via email.

How it works

When someone exercises while practicing Kaatsu or blood flow restriction, blood and metabolic byproducts are "stuck in the muscle, unable to leave," Rolnick said.

"The metabolites increase muscle fatigue, causing the muscle to work much harder than it normally would to produce a contraction at light loads," he added. "We have to work very hard to keep up with the exercise and that extra effort, paired with the fatigue produced through the BFR, accelerates muscle mass and strength gains."

Muscle fibers required to perform high-intensity actions -- such as jumping, throwing, lifting weights or kicking -- are recruited at lower intensities than usually required, said Stephen Patterson, a professor in applied exercise physiology and performance at St Mary's University, London, via email. That means someone could lift 20% to 30% of their maximum weight instead of the usual 70% or greater, and still experience a response like that of training with heavier loads, he added.

Need-to-knows before attempting BFR

People these experts have sold related products to, treated or studied include athletes of nearly all levels of ability, people who lead sedentary lifestyles, and those recovering from injuries, and range from 18 years old to 104.

The ability to use much lower loads when blood flow restriction training to build muscle and increase strength "is especially beneficial for those who are injured or have other conditions that do not allow them to either lift heavy or perform high intensity aerobic exercise," Patterson said. This includes people who have recently had surgery or are paraplegic or quadriplegic.

"Major problems in the rehabilitation setting are the inability for patients to effectively strength train due to an injury or post-surgical precautions as well as pain," Rolnick said. "The growth of BFR training allows those individuals who would be unable to challenge their bodies under normal circumstances a chance to build more strength and muscle mass during times where it would be near impossible."

If you have just had surgery and have large incisions with stitches and you want to practice Kaatsu immediately, talk to your doctor first, Munatones said. "The reason why is because the incision will dramatically heal much, much faster than normal and their skin can grow very quickly over their stitches - which usually surprises orthopedic surgeons how quickly the body recovers using KAATSU."

Groups for whom blood flow restriction might not be appropriate include people with hypertension, uncontrolled diabetes, obesity, kidney disease, arterial calcification, a history of blood clots and medications or conditions causing higher risk of clotting, venous thromboembolism, vascular diseases, sickle cell anemia, cancer, poor circulatory systems or open fracture, these experts said.

Potential side effects have included lightheadedness, tiny red spots on arms, bruising near the equipment, feelings of pins and needles, and nerve damage, some of which can be avoided by properly practicing blood flow restriction.

Contact your doctor before trying this type of training, or if you experience these or other negative side effects.

How to practice the technique

Regarding equipment, Patterson recommended using medical grade-type products that will give you a reading to ensure the pressures advertised are true. "Exercise bands and other material etc. may be able to restrict blood flow but from a safety perspective there is no idea what level of restriction you are applying," he wrote via email. That could limit adaptations and responses or cause injury.

"There are many cuffs on the market but my line in the sand is a pneumatic cuff that can be inflated either automatically or manually (like a blood pressure cuff)," Rolnick said. "Each of these types of cuffs can carefully measure the amount of blood is restricted to increase safety profile. This is very important because as BFR continues to grow, more cuffs are going to enter the marketplace that may not be adequate or appropriate."

Rolnick and Patterson advised anyone starting out with blood flow restriction to work and train with trusted practitioners to determine what cuffs would be consistent with your goals -- and to understand how and when to use this type of training. Otherwise, Rolnick added, you could be at higher risk of experiencing a negative outcome -- especially since an ordinary exercise band can't measure how much pressure you're applying.

You can expect burning sensations or soreness during or after the first couple of sessions, but these generally subside by the third session, said Hunter Bennett, a lecturer in exercise science at the University of South Australia, via email.

Once you inflate the cuff, you could practice blood flow restriction by alternating repetitions and rest while training your preferred muscle group, Bennett said.

The consensus among these experts is that using blood flow restriction two to four times a week is required for results to occur.

Read more here:
Why some Olympians restrict their blood flow to train better - CNN

Physiology

The secrets of the Alps’ strange red snow – BBC News

The secrets of the Alps' strange red snow

(Image credit: Bob Gibbons/Alamy)

Growing patches of coloured snow in the French Alps could be a sign of the impact climate change is having in the mountains.

I

It is a shocking, garish sight to come across on a peaceful mountainside. Hike high enough in the French alps during the late spring and early summer, and there is a good chance thatyou will come across some rather strange patches of snow among the grey limestone and stunted clumps of vegetation. This snow isn't white it's blood red.

The peculiar phenomenon sometimes known as blood snow is the result of a defence mechanism produced by microscopic algae that grow in the Alpine snow. Normally these microalgae have a green colour as they contain chlorophyll, the family of pigments produced by most plants to help them absorb energy from sunlight.However, when the snow algae grow prolifically and are exposed to strong solar radiation, they produce red-coloured pigment molecules known as carotenoids, which act as a sunshield to protect their chlorophyll.

While red snow algaehas been known for a long time (it is mentioned in a book published in 1819 as having been discovered during an expedition to the Arctic in 1818) it is still steeped in mysteries that scientists are attempting to unravel.

Just two years ago, botanists at Charles University, Prague, in the Czech Republic, identified an entirely new genus of microalgae that is responsible for causing red and orange snow in different parts of the world, which they named "Sanguina" in reference to the blood-red colour they produce. The researchers found forms of Sanguina algae that cause red snow samples from Europe, North America, South America along with both polar regions. A species of Sanguina that causes an unusual orange snow was also found in Svalbard.

Researchers discovered a new genus of algae called Sanguina that is responsible for the red snow in the French Alps above 2,400 metres (7,874ft) (Credit: ALPALGA)

It isn't the only type of microalgae responsible for red snow though. Several other types, such as Chlamydomonasnivalis and an algae found growing close to Antarctic penguin colonies called Chloromonas polyptera, also produce pigments to create red and pink stained snow.

But understanding more about red snow algae carries a significance far greater than simply explaining the existence of strange-coloured patches in the Alps and near the poles. Its appearance and disappearance are important markers of climate change and how it is affecting the delicate ecosystems where the algae are found.

According to Liane G Benning, professor of interface geochemistry at the German Research Centre for Geosciences in Potsdam, red snow is becoming more common due to global warming. "The rise in the atmospheric carbon dioxide levels increases the temperature, which leads to more snow melting," she says. "The moment there is liquid water on the snow, the algae start growing."

This increasing abundance of red snow algae may also be contributing to climate change too. The red pigment turns the snow surface dark, reducing the amount of light and heat it reflects back into space something known as the albedo effect. By trapping more of the Sun's heat, the snow melts even faster, allowing the algae to proliferate further. "There is a runaway effect in which the algae melt their preferred habitat," says Benning. "Its as if they are destroying their own house."

On a wider scale, the extra heat absorbed by the tinted snow can alter the temperature in the wider environment, speeding up the melting of snow packs and glaciers. One study estimated that over a single melt season, red pigmented algal blooms could reduce the snow albedo by 13%, suggesting it plays an important role in how the effects of climate change can be amplified within mountain environments.

Studies have shown red algal blooms occur on glaciers all over the world, from Antarctica to the Himalayas and in the Arctic. So one question that scientists like Benning and Eric Marchal, director of the Cell and Plant Physiology Laboratory in Grenoble, France, are keen to answer is whether red snow algal blooms are becoming more widespread and occurring more often.

One way of doing this would be to use satellite imagery to study the albedo-reducing effect of the red snow. A study using satellite imagery of snow fields on Fildes Peninsula on King George Island, off the coast of Antarctica, revealed that in January 2017, 26% of the snow was darkened by algae.

Although there is little widespread data to show if red algae are becoming more common globally, both Benning and Marchal believe they will occur more often as our planet warms, and this will need to be taken into account as scientists try to estimate what the impacts will be.

But even laying aside their role in climate change, scientists are unpicking other mysteries surrounding red snow.

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Marchal and his colleagues recently found that red snow algae appear to only grow at elevations above 2,000m (6,562ft) in the French Alps, and particularly flourish at around 2,400m (7,874ft). According to Marchal, the Sanguina algae is found at high elevations because of the quantity, quality and longevity of the snowpacks present at these heights.

Puzzlingly, scientists have so far failed to grow these algae on real snow in a laboratory.

"It is for this reason that researchers need to collect as many samples as possible for a more refined study," Marchal says.

Algae that grow close to penguin colonies near Antartica produce vivid red pigments (Credit: Robert Harding/Alamy)

During a recent two-day expeditionto the Lautaret pass in Hautes-Alpes, southeastern France, in June this year Marchal and his colleagues in the ALPALGA consortium of five French institutes dedicated to the study of mountain algae, collected their first samples of 2021. Unlike previous years, however, the snow didn't have its typical red hue. Instead, it was dominated by ochre yellow.

The yellow tinge, they believe, was due to the presence of sand on the snow that interfered with the colour imparted by the algae. While not an unusual phenomenon, this year was exceptional as strong winds carried plenty of Saharan sand to the Alpine heights.

"This has provided us a great opportunity to evaluate the relationship between sand and the growth of snow algae," says Marchal. "By analysing these particles, we will try to determine if sand provides nutrients, metals or any specific elements that may interfere, positively or negatively, with the algae growth."

The team hopes to increase the ambit of their understanding to see how iron levels in the snow and acidity levels affect the red algae growth. They are also studying whether other microorganisms and animals living alongside the snow algae may play a role.

Glaciologists fear that if the algae spreads it will decrease the albedo of the snow and drive further melting of snowpacks in mountain ranges around the world (Credit: ALPALGA)

According to Marchal, the first tests on the new samples collected in June have revealed the presence of unicellular animals, called zooplankton, with the algae cells. Although more normally associated with oceans and lakes, where they form a key element of the food chain, zooplankton can also survive in the meltwaters from glaciers and snow packs.

Their research is helping to build a picture that although snow might appear to be inert, it is in fact teeming with life.

"As snow falls, quite often it traps minerals and elements like nitrogen and phosphorus, both anthropogenic and naturally occurring," Benning says. The snow algae can then feed on these while bacteria in the snow also form a trophic relationship with the algae.

"In this ecosystem, the snow algae are primary producers," says Benning. "When they bloom, they photosynthesise, consume nutrients while producing waste products such as sugars and other components, which serve as possible food for bacteria and other microorganisms."

In some places the algae can produce a faint pink colour to the snow while in others it can be blood red (Credit: Ashley Cooper Pics/Alamy)

According to Marchal, the algae, which need just carbon dioxide and light, appear to form the basis of a more complex and mature ecosystem that involves bacteria, fungi and unicellular animal cells such as the zooplankton.

But while these patches of coloured snow flourish with life they are also short lived, appearing only for a few weeks of the year. When the weather turns cold again, the colour disappears and the snow returns to its usual white colour.

It raises an intriguing question what actually happens to the red algae over the winter?

"One theory is that they go dormant and become almost transparent as they freeze in," says Benning. "When it's no longer needed, they lose the pigmentation as it is an energy consuming process."

While the red pigment returns each year with the sunshine and heat of the late spring and early summer, Benning and her fellow scientists will be watching the stains in the snow closely for what else they can teach us.

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The secrets of the Alps' strange red snow - BBC News

Physiology

Study paves the way for development of new therapeutics for C. difficile infection – News-Medical.Net

A new study paves the way for the development of next generation therapeutics for the prevention and treatment of Clostridioides difficile infection (CDI), the most frequent cause of healthcare-acquired gastrointestinal infections and death in developed countries.

Published today in Nature Communications, the study reveals the first 3D structure of the Clostridioides difficile toxin B (TcdB) in complex with chondroitin sulfate proteoglycan 4 (CSPG4), a human receptor. The study was co-led by senior author Rongsheng Jin, PhD, a professor in the Department of Physiology & Biophysics at the University of California, Irvine, School of Medicine, and Min Dong, PhD, an associate professor at Harvard Medical School.

TcdB is one of two homologous C. difficile exotoxins, which are major virulence factors responsible for the spread of C. difficile infections. TcdB alone is capable of causing the full-spectrum of diseases associated with CDI in humans."

Rongsheng Jin, PhD, Professor, Department of Physiology & Biophysics, University of California, Irvine, School of Medicine

Previous studies had identified CSPG4 as a potential receptor for TcdB, however the pathophysiological relevance and molecular details were unknown. Results from this new study reveal a unique binding site involving TcdB and CSPG4, and also show that CSPG4-binding residues are highly conserved across most TcdB variants known to date.

CDI has become the most common cause of antibiotic-associated diarrhea and gastroenteritis-associated death in developed countries, accounting for approximately 223,900 infections, 12,800 deaths, and $1 billion in healthcare costs in the United States in 2017. It is classified as one of the top five "urgent threats" by CDC. There is also growing global concern surrounding the emergence of rapidly spreading hypervirulent C. difficile strains, reminiscent of the current COVID pandemic.

"What these new findings tell us is that a rationally designed CSPG4-mimicking decoy could neutralize major TcdB variants, providing a unique therapeutic avenue for combating some of the hypervirulent C. difficile strains," said Jin. In contrast, researchers also revealed that the therapeutic mechanism for bezlotoxumab, the only FDA approved anti-TcdB antibody, is sensitive to escaping mutations in some bacterial strains.

The current standard of care for CDI involves treatments using broad spectrum antibiotics, which often lead to frequent disease recurrence. While bezlotoxumab could reduce the recurrence rate of CDI in some patients, results from this and some earlier studies indicate it has weaker potency against some TcdB variants.

"We have designed a CSPG4-mimicking decoy based on the 3D structure we observed, which could neutralize major TcdB variants and is superior to bezlotoxumab on a major TcdB variant from a hypervirulent strain (TcdB2) in our studies. As a highly conserved cellular receptor of TcdB, a CSPG4 decoy molecule would be difficult for TcdB to escape, since any mutations that disrupt toxin binding to the decoy would also disrupt binding to its native receptors," said Jin.

The team of researchers has also developed a family of recombinant protein therapeutics based on these new findings, as well as on an earlier discovery on how TcdB recognizes another human receptor Frizzled (FZD).

"We are now examining the therapeutic features of these novel antitoxin molecules, and we believe they could provide broad-spectrum protection and neutralization against most known TcdB variants, thus improving existing antibody therapeutics for CDI," said Jin, whose team has filed a patent on these neutralizing molecules.

Source:

Journal reference:

Chen, P., et al. (2021) Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection. Nature Communications. doi.org/10.1038/s41467-021-23878-3.

Read more from the original source:
Study paves the way for development of new therapeutics for C. difficile infection - News-Medical.Net

Physiology

Switching from face-to-face to an online teaching strategy: how anatomy and physiology teaching transformed post-COVID-19 for a university…

This article was originally published here

Adv Physiol Educ. 2021 Sep 1;45(3):481-485. doi: 10.1152/advan.00233.2020.

ABSTRACT

The College of Science and Health Professions offers a university preprofessional program. Like most medical schools in Saudi Arabia, the teaching delivery strategy in the university preprofessional program is on campus and face-to-face. During the month of March 2020, teaching activities of the spring semester were proceeding as normal; however, the sudden emergence of COVID-19 disturbed routine activities and compelled authorities to switch all teaching activities from face-to-face to online. Training sessions and workshops for all stakeholders on online delivery methods were arranged. Blackboard and other online facilities were utilized. All teaching materials, including newly made video clips for anatomy and physiology practicals, were uploaded on Blackboard and discussed online with students. Students anxiety related to the exam was reassured by giving them the option of open book quizzes during summative continuous assessment. All scheduled teaching sessions, lectures, and practicals were conducted proficiently. Revision sessions and assessment quizzes were conducted with students satisfaction. At the end of the semester, a final exam was conducted online as an open book exam. Students with technical issues while attempting the exam were given an opportunity to make up for it. After a successful final exam, the cumulative block grades showed students secured higher grades in the open book exam. Following that, the King Saud bin Abdulaziz University for Health Sciences has managed to conduct on-campus close book exams that abide by self-distancing and standard operating procedure policies.

PMID:34142877 | DOI:10.1152/advan.00233.2020

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Switching from face-to-face to an online teaching strategy: how anatomy and physiology teaching transformed post-COVID-19 for a university...