Tag Archives: physiology

Supporting breathing in muscular dystrophy

By David P Burns and Ken D O’Halloran, Department of Physiology, University College Cork, Ireland

The respiratory system plays a very important role in maintaining oxygen levels within our blood. The supply of oxygen to our body is necessary to allow the cells in our body to make and use energy (a process called metabolism).

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Respiratory muscle from mdx mice displays signs of muscle damage. When dystrophin is absent from muscle, muscle fibres become damaged during normal cycles of muscle contraction and relaxation. Over time, damaged muscle becomes replaced by fat cells and there is an accumulation of connective tissue resulting in further muscle weakness and hardening of the tissue.

The respiratory system is an integrated organ system that relies on input from our central nervous system (brain and spinal cord). Motor nerves project from our central nervous system and send electrical signals, called action potentials, to our respiratory muscles. These signals activate our respiratory muscles, including the diaphragm (the main pump muscle of breathing) and intercostal muscles, resulting in contraction of these important muscles. The diaphragm and external intercostal muscles contract during inspiration, allowing a negative pressure to be generated within the respiratory system. This negative inspiratory pressure draws air from the atmosphere into our lungs. In our lungs, oxygen that has entered from the atmosphere enters our blood and is transported around our body to our cells. The same system is crucial for the excretion of carbon dioxide, a by-product of cellular metabolism, during expiration.

Poor performance or weakness of our respiratory muscles can result in impaired respiratory function, limiting how much air enters and leaves our lungs. Respiratory muscle weakness can occur due to a loss of muscle mass, such as in cancer cachexia and age-related sarcopenia.

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Recording of the electrical activity of diaphragm muscle (electromyogram) in an anaesthetised mouse.

Breathing with neuromuscular disease

Researchers at University College Cork in Ireland are focusing on respiratory muscles and how they are controlled by the central nervous system in neuromuscular diseases such as muscular dystrophy. Duchenne muscular dystrophy (DMD) is a genetic disease that causes severe muscle weakness in boys. The diaphragm has reduced strength in DMD due to the absence of an important structural protein found in muscle, called dystrophin. As boys with DMD grow older they have difficulty with their breathing. Initially, this occurs during sleep with the development of sleep-disordered breathing and later problems also present during wakefulness.

Studies led by researchers David Burns and Ken O’Halloran aim to understand the effects of a weakened diaphragm (due to a lack of dystrophin) on respiratory system performance in animal models of muscular dystrophy. Currently, the group is trying to understand ways in which the body can compensate for a mechanically weakened diaphragm muscle, with the aim of enhancing or at least protecting these compensatory mechanisms that support normal breathing.

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Healthy diaphragm muscle is composed of a blend of different types of muscle fibres (shown above as blue, red, black and green muscle fibres). Each muscle fibre type has its own unique characteristics. The blue muscle fibres (Type I) can generate small amounts of force when they contract and are resistant to fatigue. The green fibres (Type IIB) can generate large forces such as those required during coughing or clearing of our airways. Type IIB are not resistant to fatigue. Top left traces show diaphragm electromyogram activity. Bottom right shows diaphragm muscle contractions in response to increasing stimulation frequency.

New research published by the group in The Journal of Physiology (1) has revealed that the capacity of the respiratory system to increase breathing when challenged is preserved in an animal model of muscular dystrophy, the mdx mouse. This is an interesting finding given the diaphragm muscle of mdx mice can generate only half the force of a non-diseased diaphragm.

Compensation to support breathing

To understand how mdx mice can breathe at levels similar to the control group of mice, the group measured the inspiratory pressure generated by the system during normal and near maximal breathing. In order to examine how the central nervous system controls weakened respiratory muscles, the group measured the electrical signals in the diaphragm and intercostal muscles (which were sent along motor nerves from the central nervous system). These unique studies have revealed that although the diaphragm muscle of mdx mice is weakened and displays less electrical activity than the control group of mice, the mdx mice can generate inspiratory pressures similar to control mice. These novel findings reveal a form of compensation that supports breathing in young mdx mice.

Retaining the capacity to generate peak inspiratory pressure during the course of aging and in disease states such as DMD is essential during periods of increased demand on our respiratory systems. Current studies by Burns and O’Halloran aim to understand the specific mechanisms responsible for this compensatory support in young mdx mice and to determine if this compensation is preserved or lost over the course of this progressive disease. Therapeutic and rehabilitative strategies that promote compensatory support of breathing in muscular dystrophy may provide support for maintaining respiratory function in patients as the disease progresses.

References:

  1. Burns DP, Murphy KH, Lucking EF, O’Halloran KD (2019) Inspiratory pressure-generating capacity is preserved during ventilator and non-ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness. The Journal of Physiology 597(3):831-848.

Treating autism spectrum disorders by targeting connections in the brain

By David A. Menassa, @DavidMenassa1, University of Southampton, Neuroscience Theme Lead of The Physiological Society

The United Kingdom has seen a rise in the number of people diagnosed with autism spectrum disorders (ASDs). More recently, some trusts in Northern Ireland have reported a three-fold increase in diagnoses since 2011. Some cases of ASD are linked to a genetic mutation but most of the time, we do not actually know why they occur.

ASD is an umbrella term for disorders characterised by impairments in social interaction and language acquisition, sensory and motor problems and stereotypical behaviours of variable severity according to the Diagnostic and Statistical Manual of Mental Disorders.

Multiple studies report that the physiology and structure of synapses (the gaps between our neurons) are affected in ASDs (1, 2) and that addressing these changes could offer clues for therapy.

The genetic mutations giving rise to different ASDs are predominantly involved in synaptic function. A large-scale analysis of 2000 human brains from individuals with ASDs, schizophrenia and bipolar disorder showed that genes involved in controlling the release of neurotransmitters into the synapse are least active in ASDs (3, 4).

An attempt using the CRISPR/Cas9 gene editing method in a genetic form of ASD known as Fragile-X syndrome (FXS) showed some promise (5). When the researchers turned on a gene that is turned off in this condition, this changed the cells derived from affected individuals from diseased to normal.

Because the number of synapses in ASD post-mortem brains is altered (1), microglia (the brain’s resident immune cells) are thought to be directly involved (as these cells can determine whether synapses stick around) (6-8). Minocycline, which inhibits these microglia, has been used in trials on FXS individuals with promising outcomes including improvements in language, attention and focus as well as an alleviation of core symptoms (9, 10). Furthermore, novel approaches involving inducing microglia to self-destruct (11) or shielding synapses from microglia (12) are being explored. At least in terms of symptom alleviation, addressing synaptic dysfunction and microglia seem to be promising avenues for treatment.

Environmental factors such as changes during pregnancy could contribute to ASD such as the transfer of maternal antibodies against fetal synapses (13) or maternal immune activation (14) or lack of oxygen to the mum or the baby (15). Ways to reduce the risk of injury to the brain with low oxygen in the mum for example have involved delivering antioxidants to the placenta (16). Furthermore, in the early life of the newborn when low oxygen is detected, inhalation of xenon gas combined with cooling also seem to provide promising results that improve neurological outcome (17).

The impact of altered brain development extends beyond the individual influencing their family, carers and the healthcare system. More funding is needed to support this research in order to elucidate the underlying physiology and identify effective treatments.

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This figure illustrates how connections can occur in the ASD brain. Neurons in various colours (black, green and blue) make connections with each other through synapses and some connections are interrupted. Microglia (pink) are near the synapses which we can see in the highlighted squares: in a) a part of the neuron called a dendrite with very few dots on it means there are less synapses than in b) where there are more black dots on the dendrite which means more synapses. These changes represent what we tend to see in post-mortem brain tissue in ASD. Microglia are thought to be involved here by either not clearing away black dots in which case we get more synapses (e.g. typical autism) or by overclearing in which case we have less synapses (e.g. Rett’s syndrome). ASD is otherwise known as a disorder of how connections are established in the brain or a connectivity disorder.

References

  1. Penzes P, Cahill ME, Jones KA, Van Leeuwen JE, Woolfrey KM. Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci. 2011;14(3):285-93.
  2. Lima Caldeira G, Peça J, Carvalho AL. New insights on synaptic dysfunction in neuropsychiatric disorders. Curr Opin Neurobiol. 2019;57:62-70.
  3. Zhu Y, Sousa AMM, Gao T, Skarica M, Li M, Santpere G, et al. Spatiotemporal transcriptomic divergence across human and macaque brain development. Science. 2018;362(6420).
  4. Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C, Liu S, et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science. 2018;362(6420).
  5. Liu XS, Wu H, Krzisch M, Wu X, Graef J, Muffat J, et al. Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene. Cell. 2018;172(5):979-92.e6.
  6. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012;74(4):691-705.
  7. Schafer DP, Heller CT, Gunner G, Heller M, Gordon C, Hammond T, et al. Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression. Elife. 2016;5.
  8. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, et al. Synaptic pruning by microglia is necessary for normal brain development. Science. 2011;333(6048):1456-8.
  9. Utari A, Chonchaiya W, Rivera SM, Schneider A, Hagerman RJ, Faradz SM, et al. Side effects of minocycline treatment in patients with fragile X syndrome and exploration of outcome measures. Am J Intellect Dev Disabil. 2010;115(5):433-43.
  10. Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, et al. Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol. 2010;10:91.
  11. Kim HJ, Cho MH, Shim WH, Kim JK, Jeon EY, Kim DH, et al. Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. Mol Psychiatry. 2017;22(11):1576-84.
  12. Lehrman EK, Wilton DK, Litvina EY, Welsh CA, Chang ST, Frouin A, et al. CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development. Neuron. 2018;100(1):120-34.e6.
  13. Coutinho E, Menassa DA, Jacobson L, West SJ, Domingos J, Moloney TC, et al. Persistent microglial activation and synaptic loss with behavioral abnormalities in mouse offspring exposed to CASPR2-antibodies in utero. Acta Neuropathol. 2017;134(4):567-83.
  14. Careaga M, Murai T, Bauman MD. Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates. Biol Psychiatry. 2017;81(5):391-401.
  15. Kolevzon A, Gross R, Reichenberg A. Prenatal and perinatal risk factors for autism: a review and integration of findings. Arch Pediatr Adolesc Med. 2007;161(4):326-33.
  16. Phillips TJ, Scott H, Menassa DA, Bignell AL, Sood A, Morton JS, et al. Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development. Sci Rep. 2017;7(1):9079.
  17. Mayor S. Xenon shows promise to prevent brain injury from lack of oxygen in newborns. BMJ. 2010;340:c2005.

Blended learning in physiology – merging new technologies with traditional approaches

By Louise Robson, @LouisescicommDepartment of Biomedical Science, University of Sheffield, United Kingdom

Learning and teaching in physiology has undergone something of a revolution over the last 30 years, and as someone who had their very first teaching experience back in 1989 (running tutorials as a PhD student) I speak from experience! One of the biggest changes has been around digital technologies, bringing benefits and challenges to both students and staff. However, while there are challenges (e.g. information overload), for me the benefits far outweigh any challenges digital technologies generate.

I teach ion channel physiology, and aim for students to not only understand the ideas and concepts in this area, but also be able to apply these to novel experimental data. For this reason, I use data handling and interpretation exercises in my modules, i.e. students utilise mathematical approaches, interpret their data and draw on data from other sources. One thing that certainly hasn’t changed is that students struggle with mathematics, and I suspect I am not the only academic to observe a sea of white faces when I have equations on my slides!  However, my modules are very popular, despite the complex mathematics. The reason for this is my blended learning approach to teaching, matching traditional teaching with digital technologies.

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Figure 1:  Top tips for students on using lecture capture. Click here for more details: https://osf.io/edmzf/ (E, Nordmann et al, 2018).

In this approach, recorded lectures introduce calculations underpinning physiological mechanisms,  so that students can revisit to help their understanding. I have been using lecture capture for several years, and my experience is that it enhances learning. I have observed an increase in academic performance in my final year modules, and the types of questions students ask are more insightful. They utilise the captures to get to grips with the lecture content and their higher level questions are then often about the published literature. Of course if you are providing captures it is really important that students understand how to use these. Work by a cross-institutional group of academics, of which I am a member, has recently provided top tips for students and staff on using lecture capture, also presenting these in a student-friendly infographic format, Figure 1 (E, Nordmann et al 2018). his work highlights an important but often forgotten aspect of learning and teaching, share your ideas and experiences and collaborate with others.  

The best way to learn is to do, and my students complete formative data handling workbooks that reinforce lectures and provide additional guidance. This allows students to develop skills in a low risk environment, and feed-forward and improve for the assessments. Problem solving classes require students to apply their knowledge and skills, providing an opportunity for personal feedback. I also provide dynamic maths videos for them to view. Using a variety of approaches allows students to work in the way they find most beneficial (one size does not fit all in education). The final module session tests knowledge and understanding using the interactive Lecture Tools platform, allowing students to test knowledge and understanding. This blended approach provides an enhanced learning experience for the students, and is clearly appreciated by them, as they have voted me best Biomedical Science Lecturer at Sheffield several years in a row.  

Many of you reading this article may be in the early years of your academic careers, and while there is lots of advice on developing your research profile, there is often less structured support on developing learning and teaching. So here are my top tips:

  1. Get experience early on.  I started as a PhD student and continued to gain experience as a postdoctoral researcher.  
  2. Seek advice from experienced individuals.
  3. Identify the key developments in learning and teaching, and give them a go.
  4. Evaluate what you do.  Some things will work (but not everything).  Don’t forget ethical approval if you want to publish.
  5. Document innovation as you go.  In research, outputs are easy to define.  In learning and teaching, it’s not so easy!
  6. Always think about what is best for your students (note, it’s not always what they want).
  7. Share your ideas and collaborate as much as possible.  

I hope you have found this article useful, and that you have been able to identify some ideas for your learning and teaching development (if you want more information, just ask)!    

References

E, Nordmann, CE, Kuepper-Tetzel, L, Robson, S, Phillipson, GI, Lipan, P, McGeorge (2018). Lecture capture: Practical recommendations for students and lecturers (pre-publication): 10.31234/osf.io/sd7u4

Obesity: hamsters may hold the clue to beating it

Apply by 28 February for our Research Grants of up to £10,000 (over a 12 to 18-month period). This scheme supports physiologists in their first permanent academic position or returning to a permanent position after a career break, to provide support for their research or to provide seed-funding to start a new project. Gisela Helfer was a 2017 awardee of this grant, and you can read about her research below:

The global obesity crisis shows no signs of abating, and we urgently need new ways to tackle it. Consuming fewer calories and burning more energy through physical activity is a proven way to lose weight, but it’s clearly easier said than done. The problem with eating less and moving more is that people feel hungry after exercise and they have to fight the biologically programmed urge to eat. To develop effective ways to lose weight, we need a better understanding of how these biological urges work. We believe hamsters hold some clues.

Hamsters and other seasonal animals change their body and behaviour according to the time of year, such as growing a thick coat in winter or only giving birth in spring. Some seasonal animals can also adjust their appetite so that they aren’t hungry when less food is available. For example, the Siberian hamster loses almost half its body weight in time for winter, so they don’t need to eat as much to survive the winter months. Understanding the underlying physiological processes that drive this change may help us to understand our own physiology and may help us develop new treatments.

How hungry we feel is controlled by a part of the brain called the hypothalamus. The hypothalamus helps to regulate appetite and body weight, not only in seasonal animals but also in humans.

Tanycytes (meaning “long cells”) are the key cells in the hypothalamus and, amazingly, they can change size and shape depending on the season. In summer, when there is a lot of daylight and animals eat more, tanycytes are long and they reach into areas of the brain that control appetite. In winter, when days are shorter, the cells are very short and few.

These cells are important because they regulate hormones in the brain that change the seasonal physiology of animals, such as hamsters and seasonal rats.

Growth signals

We don’t fully understand how all these hormones in the hypothalamus interact to change appetite and weight loss, but our recent research has shown that growth signals could be important.

One way that growth signals are increased in the brain is through exercise. Siberian hamsters don’t hibernate; they stay active during the winter months. If hamsters have access to a running wheel, they will exercise more than usual. When they are exercising on their wheel, they gain weight and eat more. This is true especially during a time when they would normally be small and adapted for winter. Importantly, the increased body weight in exercising hamsters is not just made up of increased muscle, but also increased fat.

We know that the hamsters interpret the length of day properly in winter, or, at least, in a simulated winter day (the lights being on for a shorter duration), because they still have a white winter coat despite being overweight. We now understand that in hamsters the exercise-stimulated weight gain has to do with hormones that usually regulate growth, because when we block these hormones the weight gain can be reversed.

When people take up exercise, they sometimes gain weight, and this may be similar to what happens in hamsters when appetite is increased to make up for the increased energy being burned during exercise. This doesn’t mean that people shouldn’t exercise during the winter, because we don’t naturally lose weight like Siberian hamsters, but it does explain why, for some people, taking up exercise might make them feel hungrier and so they might need extra help to lose weight.

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We need to find ways to overcome appetite. Lucky Business/Shutterstock.com

What we have learned from studying hamsters so far has already given us plenty of ideas about which cells and systems we need to look at in humans to understand how weight regulation works. This will create new opportunities to identify possible targets for anti-obesity drugs and maybe even tell us how to avoid obesity in the first place.

By Gisela Helfer@gi_helfer and Rebecca Dumbell

(This blog was originally published on The Conversation.)

Life at the Limits: Register now for our extreme environmental physiology conference

By Mike Tipton, @ProfMikeTiptonExtreme Environments Laboratory, Department of Sport and Exercise Science, Portsmouth University

“Ecology”, from the Greek “oikos” meaning home or place to live, is the branch of biology that deals with the relationships of organisms and their physical surroundings. It encompasses the impact of animals on their environment, and the environment on animals. Both sides of the ecology coin are becoming increasingly important and linked.

On one side we are careering, largely unfettered, towards the man-made abyss of the end game of global warming; we are threatening our direct descendants, but at a rate and distance that doesn’t provoke us to action.

On the other side, only 15% of the surface of our planet is not water, desert, ice or mountain. For a tropical, low altitude, air-breathing human, this means most of planet Earth represents an extreme environment, defined as a place where it is difficult to survive. The link between the two is, of course, that global warming will make our planet even more extreme with flooding, erosion, heat waves, cold snaps and desertification.

group of climbers on rope on glacier

Perhaps, therefore, there is no better time for The Physiological Society to plan a specialist conference on Extreme Environmental Physiology (EEP) on 2-4 September.

From origins where EEP research was largely undertaken for occupational groups such as miners and the military, as well as those attempting expeditions to remote parts of the globe, EEP has now become much more “mainstream.” The greatest number of submissions and publications in the journals of The Physiological Society come from the areas of “environmental” and “exercise” physiology; both of which have extreme environmental components.

EEP research continues to examine the responses of humans to environmental stressors such as heat, cold and altitude; these remain important areas in themselves with, for example, at least 1000 people dying from drowning every day around the planet. But EEP research is now also providing insights into a wide range of other conditions such as: responses to hypoxia on intensive care (“survivor phenotypes”); ageing; peripheral vascular disease; osteoporosis; and debilitation caused in critical care patients by bed rest.

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In addition, as we take greater and greater control of our environment through technology, it is becoming increasingly apparent that we need to challenge our homeostatic mechanisms in order to remain functional. At one time we did this naturally by exercise and exposure to the natural world, now we have to employ thermal therapies for a wide range of physiological and mental health pathologies, from microvascular function through autonomic function to depression.

The specialist conference at Portsmouth in September will reflect all of the above, with sessions on cold, heat, hypo- and hyperbaric physiology, micro-gravity and cross-adaptation. To remind us what an eclectic discipline physiology is, each session will include short keynotes on physiology, pathophysiology and comparative physiology, as well as plenty of time for free communications. Finally, it seems appropriate that we should “flip the coin” and spend some time on what the environment might have in store for us if we continue to damage it.

Our exciting keynote speakers include:

References

  1. Martin & McKenna (2017). High Altitude Research and its Relevance to Critical Illness. ICU Management & Practice 17(2): 103-105.
  2. Tipton MJ (2015). GL Brown Lecture: “Extreme Threats” Environmental extremes: origins, consequences and amelioration. Experimental Physiology. doi: 10.1113/EP085362.
  3. Tipton, M. J. (2018) Humans: a homeothermic animal that needs perturbation? Experimental Physiology. https://doi.org/10.1113/EP087450.

Early Career Conference: Join us in December!

Want to run a two-day early career physiology conference? This valuable experience will give you leadership experience and boost your CV! Any Affiliate and/or Undergraduate Members of The Society may apply. Read testimonials from our first Future Physiology conference in 2017 below. 

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Jose L. Areta, Norwegian School of Sport Sciences, Oslo, Norway:

Attending the Future Physiology meeting in Leeds in December 2017, coming all the way from Oslo, Norway, was a privilege I had thanks to a Physiological Society travel grant. I am a post-doctoral researcher in the early stages of what, I think, might turn into a long academic career. I signed up for this conference specifically to get a better overview and insights on what a researcher at my stage could do to make the right choices for his future career. The conference did not fail to provide valuable food for thought.

The attendees included a wide range of representatives of the academic career continuum, from undergraduates to professors. A majority of these were, seemingly, early career researchers (ECRs) and they belonged to a reasonably wide range of areas within the field of physiology. This showed that the purpose of the conference was to go beyond delving into their specific areas of expertise. A dominant topic of interest seemed to be commonalities irrespective of the specific area of expertise, meaning the ins and outs of working in and growing through academia.

Several of the sessions provided examples of more established researchers showcasing how they built their own academic careers in the context of research in physiology. The take-home message for me was that there is no one way to become an established researcher in any given area. The impression that I got is that love for the work you do followed by dedication and a solid network play a key role, immediately followed by serendipity. This seemed to provide some support to the saying ‘the harder you work, the luckier you get’, that I sometimes remind myself of.

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On that note, it was also nice to feel supported by other researchers going through similar difficulties in a research system that seems to very often put high-pressure on individuals and can lead to sub-optimal life quality and, in many cases, burnout. Uncertainty seems to be a common denominator for many researchers in different stages of their careers (more so ECRs). Making this explicit is important to find a solution for it. I think this conference was a good first step to bridge the gap between ECRs who have a lot of questions on how to progress through the ranks, while making meaningful contributions to science and more experienced researchers talking about their specific experiences or professionals providing advice.

Personally, one of my favourite events was a small grant-writing workshop I had the chance to attend that also turned into a bit of a career advice workshop. Transitioning towards being an independent researcher is very significant milestone for anyone in research, I think. Gathering some tools to do so in the context finding one’s place in the field was a nice addition to the experience of the conference.

In conclusion, I think this conference was a good first step to put the uncertainties that ECRs face throughout their development as researchers in the spotlight, and provide them (us!) with tools and networks for better tackling these.

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Dan Brayson, King’s College London, London, UK:

As a member of the Affiliate Working Group of The Society, I was privileged to have the opportunity to help with the planning and execution of the Future Physiology meeting, an early career researcher (ECR) focussed meeting held at the University of Leeds last month. The meeting was ‘by ECRs for ECRs’. This meant that the Affiliate Working Group was placed at forefront of the brainstorming process to come up with a plan for a meeting which facilitated an engaging experience for early career scientists.

What we hoped for was an opportunity for ECR’s to shed their inferiority complex baggage (we all have it), and to feel invigorated by the conference experience rather than being overwhelmed. To this end 20 ECRs were selected for oral presentations whilst five talks were given by senior scientists (for balance, of course). Of these, three were young PIs and shining examples that we don’t have to wait around for professors to retire in order to make significant progress in our careers. We hoped that this would add a motivational slant for attendees. If they can do it, why can’t we?

On a personal note it was a red letter day. I was charged with sharing the chairing and presentation-marking duties with my fellow Affiliate Working Group members, a first for me, and with this, I got to experience the joy of facilitating meeting proceedings rather than merely taking part. At least this was my perception of it, and I would definitely do it again.

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Reflecting now on the meeting I feel that it was a good first crack at a meeting for ECRs. However, I also feel that there is further scope to create the most engaging and immersive experience for young scientists. One idea would be to have facilitated debate workshops on general topics (neuroscience, cardiovascular physiology, gastrointestinal physiology etc.). This would engage people in a relaxed environment to talk more generally about the big issues/questions facing their chosen fields.

Friends in high places: Researchers go global for answers at high altitude (Part 1)

By Alexandra Williams, @AlexM_Williams

Global Research Expedition on Altitude Related Chronic Health (or Global REACH) is an international collaboration of academics and physicians from 14 institutions across Canada, the UK, the US, Peru and Nepal. While the “Global REACH” title is relatively new, its leaders have conducted a multitude of expeditions over the last decade to Nepal’s Himalaya, California’s White Mountains and now Peru’s Andes. With a collective interest in heart, lung and vascular health and altitude medicine, Global REACH’s collaborations ultimately aim to understand how the human body adapts, or maladapts, chronically to the low oxygen environments of earth’s highest altitudes.

I am writing this from 4,300 m, at the Laboratorio de Cerro de Pasco and Institutio de Investigaciones de la Altura in Peru. Our team of over 40 researchers, trainees, principal investigators and physicians are currently conducting approximately 20 studies examining heart, lung and brain physiology in lowlanders (us) and Andean highlanders with and without chronic mountain sickness.

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Example of a centrifuged blood sample from an Andean participant with chronic mountain sickness. A normal, healthy lowlander’s hematocrit (i.e. fraction of red cells in the blood) is ~40%; several Andean participants including this one had hematocrit values of 75-80%.

This series of blogs, however, does not intend to outline our experiments or specific scientific findings (which was described in a recent issue of Physiology News). Instead, you will get a raw, behind-the-scenes look at what transpires on these expeditions: the challenges we face, the experiences we gain, and most importantly the team values that drive the success of these international collaborations.

30 June 2018: Day 1 at altitude

Yesterday, the last of three groups of the Global REACH team drove from sea level in Lima up to 4,300 m in Cerro de Pasco, Peru. Amongst the team, some individuals are feeling “okay” (say, a rating of 7/10), while others have been in bed with splitting headaches for more than 24 hours. We would later discover that one, in fact, had a bout of pneumonia. Nevertheless, one thing remains constant across the team – the excitement. It is palpable. Seven lab bays are set up, participants are being scheduled in, the equipment is (mostly) accounted for and working. Data collection has already begun today, and our first Andean participants are coming in tomorrow morning. This is what we came for, and we’re ready for the fun to begin.

For those who haven’t experienced the thin air of Earth’s highest mountain ranges, a 7-hour jump from sea level to over 4,300 m altitude is significant, one which often leaves individuals feeling much worse than “not great.” Yet, with advanced knowledge of the side effects of altitude and hypoxic exposure, Global REACH members have joined forces to answer a plethora of physiological questions. For many, this will mark more than four expeditions to high altitude, a select few even in the double digits. In the first few days, most – including our team leaders – will have headaches, nausea, sleep disturbances and apnoeas. The inter-individual variability of these symptoms is quite high, as a select few may feel fine, most will feel some magnitude and combination of the list, and others will be periodically out of commission.

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Performing a carbon monoxide rebeathe test to measure red cell volume and total blood volume with an Andean participant in Cerro de Pasco. This method is technically challenging, and is made more difficult with a significant language barrier.

So, why do we do it? Why do we involve ourselves with the potential suffering at altitude and any additional risks (i.e. transport, illness) kindred to these trips? From my experience, three fundamental elements outweigh the risks and define the success of expeditions and collaborations like Global REACH: the science, the experience, and the team.

Science

1 July 2018: Day 2 at altitude

“MAS FUERTE, MAS FUERTE, yeah Johnny!” Johnny, our first Andean participant is laying on the bed of testing Bay 1, currently practising a handgrip protocol for a vascular study. Johnny already has a venous catheter placed in his forearm and will be shuttled through a screening circuit: ultrasound imaging (cardiac, ocular and vascular), a maximal exercise test and assessment of total blood volume. Our Spanish skills are currently dismal, but we’re managing to compliment the amazing work of our translators to collect a large cardiovascular dataset on approximately 50 Andean participants.

3 July 2018: Day 4 at altitude

Four of us are working in the bloods room to measure total blood volume, hematocrit and viscosity. We knew from previous reports that Andeans would have augmented total blood volumes and hematocrit levels compared to us lowlanders but seeing those bloods ourselves was staggering. ‘A hematocrit of SEVENTY-EIGHT per cent!’ a colleague yelled, astounded. For reference, a lowlander’s normal hematocrit is ~40%. (Fig. 1) An undeniable passion for physiology underpins collaborations like Global REACH.

The energy amongst the group drives impressive productivity and allows us to complete multiple studies in relatively restricted time periods. During the 2016 Nepal Expedition our team conducted 18 major studies, including a total of 335 study sessions in just three weeks at 5,050 m (further to multiple sea level and ascent testing sessions). This high-density data collection is relatively uncommon outside of field work and is only made possible by the vast breadth of technical fluency, specific expertise and research experience amongst the team. The expeditions allow us to not only answer our current questions but further breed a multitude of ideas for future study.

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‘We could answer that one next, Ethiopia 2020? Another Nepal expedition?’ Of course, these expeditions allow us as trainees and investigators to be productive, and to present and publish high-quality data and exciting findings. They strongly contribute to our development and career progression in academia. But what is undoubtedly most important is the greater aim of Global REACH: to understand altitude health on a ‘global’ scale. This collaboration and research ultimately aims to understand why chronic mountain sickness occurs, how different high-altitude communities have adapted (or maladapted) to low oxygen, and what might ultimately be done to improve the health of individuals exposed to acute or chronic hypoxia.

Stay tuned for Part 2 next week, or read the full article in its original version in Physiology News magazine.