Category Archives: Physiology

Physiology

The Physiology of the Finishing Kick | Outside Online – Outside

I used to see my finishing kick as a sign of toughness. Nobody passed me in the closing stages of a race, Id tell myself, because nobody wanted it more than me.

But as time went on, I began to see it from a different perspective. No matter how a race played out, whether it was fast or slow and whether I was way ahead or way behind, I would always manage to sprint the last quarter-mile or so. Why did I always have energy left for a sprint, even if Id been dropped by the leaders? Shouldnt I have used that energy to avoid being dropped in the first place? Eventually, my kick became a source of frustration. I tried to race hard enough that Id have nothing left for a kick, but I almost never managed it.

As a result, Ive always been fascinated by attempts to unravel the physiology and psychology of the finishing kick. The most recent addition: a study in Medicine & Science in Sports & Exercise, led by graduate student Rafael Azevedo at the University of Calgary under the direction of Juan Murias and Guillaume Millet, using an interesting new methodology to tease out levels of fatigue in the brain and body before and after the finishing kick.

Some important background: I always come back to a 2006 study by University Cape Town researchers Ross Tucker, Michael Lambert, and Tim Noakes that analyzed pacing patterns in a centurys worth of mens world record performances over distances between 800 and 10,000 meters. As I discussed in more detail here, they observed a remarkably consistentU-shaped pacing template for races longer than 800 meters, featuring a fast start, even-paced middle, and fast finish, as shown in this graph:

(Illustration: International Journal of Sports Physiology and Performance)

The presence of a finishing kick even in elite athletes running at world-record pace, they argued, reflected a hardwired tendency to maintain a physiological reserve during intense exercise. In other words, it was evolution rather than cowardice that made me hold back energy for a sprint.

This big-picture explanation makes intuitive sense, but actually unraveling whats going in your body at different stages in a race has turned out to be more complicated than expected. To that end, Azevedos new study involved 12 male volunteers performing a series of 4K cycling time trials. The trials lasted a little over six minutes on average, and as expected they followed a U-shaped pacing profile with a fast start, even-paced middle, and finishing sprint. On average, according to a mathematical analysis, the fast start lasted 827 meters, and the finishing kick started with 410 meters left.

After a couple of familiarization trials, the subjects completed three experimental trials in randomized order: one in which they were stopped after the fast start, a second in which they were stopped after the even-paced section, and a third in which they continued to the finish. As soon as they stopped, they underwent a battery of tests to assess fatigue in various ways. The measurements used force sensors mounted in the pedals of the bikea crucial detail, since fatigue starts dissipating within a few seconds. Previous experiments have involved getting subjects off the bike and then strapping them into a separate apparatus to measure fatigue, so this is a key technical innovation.

The simplest way of measuring muscle fatigue is with a maximal voluntary contraction: you ask the subject to contract the relevant muscle (in this case the quads) as hard as possible. Using more sophisticated techniques, you can also break it down into two subcomponents. Central fatigue is how much the signal from the brain to the muscles has decreased; peripheral fatigue is how much weaker the muscle fibers themselves are when you stimulate them with electricity. The researchers performed all three of these measurements.

The results showed a rapid increase in fatigue during the initial fast start: the max voluntary contraction dropped by 23 percent, central fatigue was 8 percent, and peripheral fatigue was 40 percent. Then things stabilized: by the end of the even-paced phase, which accounts for about 70 percent of the overall race, all three of the fatigue markers were essentially unchanged compared to just after the fast start. But after the finishing sprint, fatigue ramped up again, for example to 34 percent for max voluntary contraction.

In other words, muscle fatigue doesnt accumulate in a nice straight line. After the initial excitement of the start, we settle into a sustainable pace that seems to have very little impact on muscle function. The sensation that your jellied legs couldnt take another step after a race is produced almost entirely by the finishing sprint, not by the miles that preceded it. One way to understand this is in terms of critical speed (or, equivalently, critical power), a concept Ive written about in detail a few times recently. Your critical speed is essentially the threshold of whats metabolically sustainable. You can run above critical speed for a while, but youre using up your finite reserves of anaerobic capacityand once theyre done, youre cooked.

If you were to run a race at a perfectly even pace, youd use up your anaerobic capacity gradually, hitting zero as you cross the finish line if you judge it right. In contrast, what most of us tend to do is use up a chunk of anaerobic capacity at the start. (There may be good physiological reasons for that, since a fast start ramps up your oxygen-processing capacities more quickly.) Then we settle into a pace relatively close to critical power, where were only nibbling away very slowly at anaerobic capacity. Then, as we approach the finish, we use it all up with a glorious sprint.

Sure enough, in Azevedos data, the cyclists settled into a pace barely above critical power for the middle portion of the race, meaning that they used most of their anaerobic capacity at the beginning and end. The big question is whether this approach is suboptimal. Thats certainly my intuition. When Joshua Cheptegei broke the 5,000-meter world record last summer, I argued that the Wavelight pacing lights flashing around the perimeter of the track at a perfectly even pace helped Cheptegei by enabling him to run the most evenly paced world record ever. It must be more efficient, right?

But its perhaps not as obvious as I thought. Back in 2013, a study from Andy Joness lab at the University of Exeter compared different pacing strategies in three-minute cycling trials: the typical self-paced U-shape, an all-out-from-the-start effort, and an even-paced trial. Heres what those pacing patterns looked like, with the amount of work done above critical power (i.e. the anaerobic capacity) shaded in grey. Panel A is an incremental test to exhaustion, B is all-out from the start, C is even pacing, and D is self-paced.

(Illustration: Medicine & Science in Sports & Exercise)

The numbers indicate the total anaerobic capacity shown by the shaded areas, and there are no significant differences between them. Even pacing produced an anaerobic capacity of 12.9 kJ; self-pacing with a finishing kick produced 12.8 kJ. Theres a big difference in how these different strategies feel, though. The closer you are to emptying your anaerobic capacity, the worse you feel. My interpretation/hunch, Jones told me by email, is that athletes have learnt, or know intuitively, that a pacing strategy involving an end spurt results in the same performance outcome as other strategies, BUT that this same performance can be achieved with less pain for most of the race! The athletes will be just as knackered at the end but that middle section wont be quite so excruciatingly intolerable if they implement an end spurt strategy.

Its an interesting idea. And it would explain why U-shaped pacing patterns are so ubiquitous even among the greatest runners in the world. It has always puzzled me that a seemingly suboptimal pacing strategy could produce so many world records. Even if were wired to pace ourselves cautiously, youd still expect that world records would happen when athletes accidentally started too fast if having a finishing kick was really so bad for performance.

On the other hand, as Ross Tucker has noted, the pacing in world records does seem to be getting more and more even. The gains from smoothing out your pacing may be marginal, but at that level you have to look for every possible edge. Personally, though, I find Andy Joness argument very temptingbecause if U-shaped pacing doesnt cost you anything, then I can start thinking of my finishing kick as a badge of pride again, rather than a mark of shame.

For more Sweat Science, join me on Twitter and Facebook, sign up for the email newsletter, and check out my book Endure: Mind, Body, and the Curiously Elastic Limits of Human Performance.

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The Physiology of the Finishing Kick | Outside Online - Outside

Physiology

The Need for New Biological Targets for Therapeutic Intervention in COPD – Pulmonology Advisor

Chronic obstructive pulmonary disease (COPD) continues to be a major cause of disability and is one of the leading causes of mortality worldwide. While there are numerous treatment options for the lung disease, the available treatments focus on symptoms secondary to inflammation, and are not curative. In a review published in the American Journal of Physiology Lung Cellular and Molecular Physiology, experts focus on potential disease-relevant pathways and emphasize the important of developing new treatments for patients with COPD.1

The objective of the review was to summarize COPD pathology, available treatment options and additional potential pathways and targets for new therapeutic development.

Cigarette smoke contains thousands of injurious agents and is the key cause of COPD worldwide as these induce tissue damage and inflammatory process leading to destruction of alveolar tissue, loss of extracellular matrix and alveolar cells, along with airway remodeling.2 As COPD may progress in patients despite smoking cessation it was suggested that persistent airway inflammation in these patients is related to repair of smoke-induced tissue damage in the airways.3 Failure to achieve normal lung function in early adulthood followed by age-appropriate rates of decline causes up to half of COPD cases.4

The 2020 Global Initiative for Chronic Obstructive Lung Disease guidelines recommend that the management strategy of COPD should be based on the assessment of symptoms and future risk of exacerbations and the main goals of pharmacological therapy for COPD are to reduce symptoms and frequency and severity of exacerbations, as well as to improve exercise tolerance and health status. However, at this point there is no evidence that any of the available medications can modify the long-term decline in lung function.5

The commonly used maintenance medications in COPD are short- and long-acting beta-2 agonists and anti-cholinergics, methylxanthines, inhaled or systemic corticosteroids, phosphodiesterase (PDE)-4 inhibitors and mucolytic agents.5 As these medications are mainly focused on relieving symptoms and reducing the risk for exacerbations, more effective treatment strategies are needed. COPD is a complex disease and precision medicine strategy, that considers biologic and psychosocial factors, may improve disease outcomes.4

New Treatment Targets

There is a real need to uncover new biology in order to advance more precision-based therapeutic strategies for patients with COPD. New disease-specific strategies in development are focusing on inflammatory pathways, hoping this will help to address disease onset. Early reports suggest there are several promising targets that can address inflammatory complications, including oxidative stress, kinase-mediates pathways, phosphodiesterase inhibitors, interleukins and chemokines.

Oxidative Stress a common denominator for aging and cellular senescence, resulting in macromolecular damage and DNA damage.2 With cigarette smoke exposure there is an increased oxidative stress, associated with an increase in Nrf2 activity which declines with the progression of COPD.6 As several studies have implicated Nrf2 in COPD pathology, this pathway is a potential important therapeutic target. Several agents may change Nrf2 expression and activity in airway cell, including aspirin-triggered resolvin D1, crocin, sulforaphane, and schisandrin B.1,6

Kinase-mediated Pathways as various kinases, including MAPK, receptor-tyrosine kinases, phosphoinositide-3-kinases, JAK, and NF-B, may induce chronic inflammation, they may serve as new targets for COPD treatment. There are several drugs that target different kinases but these are not approved for clinical use. Drugs with a more specific action, such as RV568 that inhibits p38, was well tolerated in a 14-day clinical trial and showed promising results with potent anti-inflammatory effects on cell and animal models relevant to COPD, with evidence for improvement in lung function and anti-inflammatory effects on sputum biomarkers.7

Phosphodiesterase Inhibitors inhibiting PDE leads to an increase in intracellular cAMP levels that may have anti-inflammatory effects. Roflumilast is an oral PDE-4 inhibitor already in use for more severe cases of COPD, but more potent medications are being developed, including several inhaled formulations, such as CHF6001, which was reported to have significant anti-inflammatory properties in the lungs of patients with COPD already receiving triple inhaled therapy (8). Ensifentrine is a PDE3/PDE4 inhibitor with anti-inflammatory and bronchodilator properties and when combined with short-acting bronchodilators or tiotropium caused additional improvement in lung function, reduced gas trapping, and improved airway conductance.9

Inflammatory Mediators exposure to inhaled irritants and tobacco smoke results in an increase in various interleukins (IL) that increase the number of immune cells and induce inflammatory responses. Hence, treatment directed against these mediators may reduce inflammation.1 Mepolizumab, reslizumab, and benralizumab are antibodies directed against IL-5 and its receptor and reduced eosinophil-related inflammation. These medications are approved for use for asthma, and were not effective in COPD, but may be valuable for patients with COPD with eosinophilia. Dupilumab, a monoclonal antibody directed against IL-4 and IL-13 receptor, is another potential candidate for future use. microRNAs are also involved in inflammation regulation, and miR-155 expression was shown to be increased in COPD, but at this point there are no available miRNA-based therapeutics for COPD.10

Additional Potential Treatment Targets

While multiple medications under development for COPD are focusing on the inflammatory pathways, they are not expected to reverse the lung damage. For this reason, it is important to study the upstream pathways that may help to identify strategies to reverse exiting lung damage, including targets that can lead to lung repair and regeneration.

These potential breakthrough targets may include treatments directed against mitochondrial dysfunction; structural integrity of airway epithelium such as proteins that comprise tight junctions or the extracellular matrix; various ion channels that are responsible for airway hydration; and pro-regenerative strategies, including stem cell and tissue-engineering treatments to repair lung damage.1

Animal models and 3D human-based disease models have an important role in the efforts to better understand disease process and identify specific therapeutic targets and pathways.11,12 These models improve our knowledge about the basic mechanisms underlying COPD physiology, pathophysiology and treatment. Although they can only mimic some of the features of the disease, they are valuable for further investigation of mechanisms involved in human COPD.11

Several different types of 3D cell culture models have been developed in recent years, and these have gained increasing interest in drug discovery and tissue engineering due to their evident advantages in providing more physiologically relevant information and more predictive data. Ex vivo modeling using primary human material can improve translational research activities by fostering the mechanistic understanding of human lung diseases while reducing animal usage. It is believed that using new model organisms may allow exploring new avenues and treatments approached for human disease, and these are especially promising.12

COPD is a major public health concern, and as it continues to be a global burden, the importance of developing new treatments is apparent. Current treatments are not curative, and while new strategies and drugs are in the pipeline, they still address mostly secondary inflammatory pathways of the disease. An additional major complication in COPD drug development likely comes from the essential dependency on surrogate endpoints like FEV1 to assess the impact of a therapeutic strategy. Thus, any new therapeutic strategy will ultimately require long-term studies to confirm that the surrogate endpoints accurately reflect efficacy on disease outcome, concluded the researchers.

References

1.Nguyen JMK, Robinson DN, Sidhaye VK. Why new biology must be uncovered to advance therapeutic strategies for chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2021;320(1):L1-L11. doi:10.1152/ajplung.00367.2020

2.Tuder RM, Petrache I. Pathogenesis of chronic obstructive pulmonary disease. J Clin Invest. 2012;122(8):2749-55. doi:10.1172/JCI60324

3.Willemse BW, ten Hacken NH, Rutgers B, Lesman-Leegte IG, Postma DS, Timens W. Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers. Eur Respir J. 2005;26(5):835-45. doi:10.1183/09031936.05.00108904

4.Sidhaye VK, Nishida K, Martinez FJ. Precision medicine in COPD: where are we and where do we need to go? Eur Respir Rev. 2018;27(149):180022. doi:10.1183/16000617.0022-2018

5.Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2020 report [Online]. Global Initiative for Chronic Obstructive Lung Disease. https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.1wms.pdf. Accessed January 25, 2021.

6.Cuadrado A, Rojo AI, Wells G, et al. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov. 2019;18(4):295-317. doi:10.1038/s41573-018-0008-x

7.Charron CE, Russell P, Ito K, et al. RV568, a narrow-spectrum kinase inhibitor with p38 MAPK- and - selectivity, suppresses COPD inflammation. Eur Respir J. 2017;50(4):1700188. doi:10.1183/13993003.00188-2017

8.Singh D, Beeh KM, Colgan B, et al. Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. Respir Res. 2019;20(1):180. doi:10.1186/s12931-019-1142-7

9.Singh D, Abbott-Banner K, Bengtsson T, Newman K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur Respir J. 2018;52(5):1801074. doi:10.1183/13993003.01074-2018

10.Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2018;18(7):454-466. doi:10.1038/s41577-018-0006-6

11.Ghorani V, Boskabady MH, Khazdair MR, Kianmeher M. Experimental animal models for COPD: a methodological review. Tob Induc Dis. 2017;15:25. doi:10.1186/s12971-017-0130-2

12.Zscheppang K, Berg J, Hedtrich S, et al. Human pulmonary 3D models For translational research. Biotechnol J. 2018;13(1):1700341. doi:10.1002/biot.201700341

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The Need for New Biological Targets for Therapeutic Intervention in COPD - Pulmonology Advisor

Physiology

Males and females are evolutionarily programmed differently in terms of sex – Tech Explorist

Regardless of sharing a very similar genome and nervous system, males and females vary significantly in reproductive investments. They require different behavioral, morphological, and physiological adaptions, suggests a new study from Oxford, which found sex-specific signals affect behavior.

As the study suggested, Males and females behave differently in terms of sex, but the reality is both are evolutionarily programmed to do so. They both have evolved profoundly different adaptations to suit their own reproductive needs.

In their study, scientists uncovered a novel circuit architecture principle that permits deployment of entirely behavioral repertoires in males and females, with minimal circuit changes.

Scientists found that the nervous system of vinegar flies, Drosophila melanogaster, produced differences in behavior by delivering different information to the sexes.

In the vinegar fly, males compete for a mate through courtship displays; thus, the ability to chase other flies is adaptive to males but of little use. A females investment is focused on the success of their offspring; thus, choosing the best sites to lay eggs is adaptive to females.

While discovering the different roles of only four neurons clustered in pairs in each hemisphere of the central brain of both male and female flies, scientists detected sex differences in their neuronal connectivity. This neuronal connectivity reconfigures circuit logic in a sex-specific manner.

In essence, males received visual inputs and females received primarily olfactory (odor) inputs. Notably, the team demonstrated that this dimorphism leads to sex-specific behavioral roles for these neurons: visually guided courtship pursuit in males and communal egg-laying in females.

Scientists noted, Ultimately, these circuit reconfigurations lead to the same resultan increase in reproductive success.

Our findings suggest a flexible strategy used to structure the nervous system, where relatively minor modifications in neuronal networks allow each sex to react to their surroundings in a sex-appropriate manner.

Professor Stephen Goodwin from the Department of Physiology, Anatomy, and Genetics said, Previous high-profile papers in the field have suggested that sex-specific differences in higher-order processing of sensory information could lead to sex-specific behaviors; however, those experiments remained exclusively at the level of differences in neuroanatomy and physiology without any demonstrable link to behavior. I think we have gone further as we have linked higher-order sexually dimorphic anatomical inputs, with sex-specific physiology and sex-specific behavioral roles.

Scientists noted, In this study, we have shown how a sex-specific switch between visual and olfactory inputs underlies adaptive sex differences in behavior and provides insight on how similar mechanisms may be implemented in the brains of other sexually-dimorphic species.

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Males and females are evolutionarily programmed differently in terms of sex - Tech Explorist

Physiology

Subadditivity begins to explain the mysteries of the circadian system’s response to light (MAGAZINE) – LEDs Magazine

FIG. 1. Example of how the biological clock perceives light signals differently than the visual system. (Image credits: All illustrations and tables courtesy of Allison Thayer, Lighting Research Center, except where expressly indicated.)

As discussed in the previous article of the circadian light series, Industry must move beyond CCT to articulate circadian metrics, a wide range of photopic illuminance levels at the eye may be required to reach a specific circadian stimulus (CS), even for light sources of the same correlated color temperature (CCT). Since we know the circadian system to be a blue-sky detector, it may be generally true that cooler light-source spectra (>4000K) require a lower illuminance at the eye than warm light-source spectra (

Consider a blue LED (max = 486 nm) that produces 17 lx at the eye this gives a CS = 0.3. If one were to add 100 lx of low-pressure sodium (LPS) to make the combined light appear white (CCT = 3241K), the total illuminance at the eye would obviously be 117 lx, but counterintuitively, the circadian effectiveness of the combined light would drop to CS = 0.27 (Fig. 1). This is known as subadditivity in other words, 1 + 1

For humans, color vision has three dimensions (Fig. 2), each defined by a different neural channel. The first channel is the achromatic (black-and-white) channel that simply adds all the flux incident on the retina the more flux on the retina, the brighter the light will be, if it has no apparent hue. Hue is handled by two chromatic channels one that responds to light as blue or yellow (or nothing if it is black or white), and one that responds to light as red or green (or nothing if it is black or white).

FIG. 2. Schematic of the achromatic and chromatic channels in the retina that enable color vision and brightness perception in humans.

The two chromatic channels blue versus yellow (b-y) and red versus green (r-g) are spectrally opponent, meaning that a greenish red or a bluish yellow cannot exist. All hues we see are combinations of these two spectrally-opponent channel outputs so we can see a greenish blue (turquoise) or a bluish red (purple), for example.

Brightness perception is determined by these two chromatic channels as well as an achromatic, black-and-white channel. When more light is added to the retina, the achromatic channel increases its response. If that light has a hue, it will appear brighter than a white light that produces the same response in the achromatic channel. For example, a red light of 100 lx will look brighter than a white light of 100 lx because its red hue contributes to brightness perception. Because the color channels are spectrally opponent, adding a green light to the red light can make the red light appear less bright even though the achromatic channel increases.

As a specific example, 100 lx of light emitted by a red LED will appear equally as bright as 150 lx from a green LED (Fig. 3). If these two lights are combined, the achromatic illuminance at the eye will be 250 lx and its hue will appear yellow. Remarkably, the resulting yellow light of 250 lx will actually appear less bright than either the red light alone at 100 lx or the green light alone at 150 lx. This is a clear example of subadditivity. The reason behind this surprising outcome is that perceived brightness of a light depends not only on its achromatic light level but also on its apparent hue. Red and green lights are more hueful than a yellow (or white) light. The same basic physiology contributes to circadian light.

FIG. 3. The accompanying chart is the 1931 CIE chromaticity chart with contour lines of chromaticities of equal perceived brightness (Guth et al., 1980). The chromaticities of a red and a green LED are plotted along with a specific combination of light from these two LEDs seen as yellow. For this example, the red LED provides an illuminance of 100 lx, delivering a perceived brightness of B(r) = 100 2.93 = 293; and the green LED provides an illuminance of 150 lx, delivering a brightness of B(g) = 150 2.15 = 322. The combined yellow light has a brightness of B(y) = 1.07 250 = 268. Image adapted from J. Optical Soc. of America, 70, 2, Vector model for normal and dichromatic color vision, by S. Lee Guth, Robert W. Massof, and Terry Benzschawel, 1980; http://bit.ly/3nXBEXr.

The intrinsically photosensitive retinal ganglion cells (ipRGCs) represent the lynchpin between the retina and the biological clock, linking the external 24-hour light dark cycle to our internal rhythms of behavior and physiology. As the name implies, ipRGCs contain the photopigment melanopsin that absorbs light and generates a neural signal for the biological clock. Without ipRGCs, our physiology and behavior would no longer be synchronized with sunrise and sunset. Experiments have shown that as long as the ipRGCs are intact, even without the photopigment melanopsin, light can still synchronize our biological clock to the daily light-dark cycle by neural signals from the rods and cones (photoreceptors responsible for vision). There is no direct connection between these photoreceptors and the ipRGCs rather, their signals are processed by a variety of neural circuits before reaching the ipRGCs. One of these neural circuits is a spectrally-opponent chromatic channel that also affects brightness perception. Specifically, the spectrally-opponent blue-yellow channel processes cone signals before reaching the ipRGC. This is why the blue LED delivering 17 lx at the eye becomes less effective for the circadian system when 100 lx of LPS is added the effectiveness of the blue LED for stimulating the ipRGC is reduced by adding yellow LPS.

As for creating metrics to quantify circadian response, the Lighting Research Center (LRC) uses circadian light (CLA) and circadian stimulus (CS; see the first installment in this series, which defines the terminology). Subsequently, the research team has developed a computational model that includes subadditivity. The spectral sensitivity of the modeled circadian circuit in the eye for one achromatic light level can be graphed with two curves (Fig. 4). It is a two-state model one for white light sources where the b-y channel balance tilts to signal blue or for another light source where it tilts to signal yellow. These white sources would appear cool or warm, respectively, but again the CCT designation will not necessarily be related to the actual appearance of the light.

FIG. 4. Warm and cool spectral response curves.

Recalling the summary from the previous article, the photopic illuminance level at the eye needs to reach a target CS of 0.3 for light sources categorized by their CCTs of 3000K, 4000K, and 5000K (Fig. 5, top).

The corresponding table in Fig. 5 indicates on which side of the b-y channel warm or cool a given light source falls. One 3000K light source has a cool spectral response unlike the others, and one 4000K light source has a warm spectral response. With regard to all warm sources, the spectral sensitivity of the circadian system (yellow dashed line in Fig. 4) is governed almost exclusively by melanopsin in the ipRGCs. For cool sources, however, subadditivity will come into play as illustrated by the positive and negative lobes of the solid blue line in Fig. 4. Again, adding a yellow light in the negative region to a blue light in the positive region will reduce the circadian effectiveness of the combined light relative to the blue light alone.

FIG. 5. Relating the previously-discussed chart of vertical illuminance values needed to reach 0.3 CS to which spectral response of the circadian system it falls on.

In Fig. 6, the spectral power distributions (SPDs) of a blue LED, a 3000K LED (Maximum), and a 5000K LED (Minimum) are indicated by the black curves, accompanied by the respective modeled spectral sensitivity responses indicated by the blue or yellow curves. Different combinations of spectra and vertical illuminance are required to reach the target CS of 0.3.

FIG. 6. Examples of illuminance at the eye required to achieve a CS of 0.3 using different light spectra.

This is fairly complicated! But the concepts are important to advancing the science behind applying circadian lighting principles. However, now that these complexities have been established, it should be relieving to know that a lighting manufacturer or designer does not need to know all of the intricacies of retinal neurophysiology to provide circadian light to building occupants. The final article of the series will go more into depth on the adaptation of the new language into application.

ALLISON THAYER, MS, BA, is a research specialist at the Lighting Research Center (LRC), formerly part of Rensselaer Polytechnic Institute. She holds a bachelors in architecture, and a masters of science with a concentration in lighting from Rensselaer. Thayer has played a main role in the development of the structure and content of the Healthy Living website.

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Subadditivity begins to explain the mysteries of the circadian system's response to light (MAGAZINE) - LEDs Magazine

Physiology

When Is Dead Really Dead? Results From the Largest International Study of Its Kind – SciTechDaily

A new international study, led by Dr. Sonny Dhanani of the CHEO Research Institute, and published in the January 28, 2021, issue of the New England Journal of Medicine, documents the physiology of the dying process. Working closely with the Canadian Donation and Transplantation Research Program, the research team asked over 600 families to allow their loved ones in the ICU to have their vital signs monitored during the dying process. This is the largest international study of its kind.

For families to choose organ donation when a loved one has died, they must be able to trust that death has really happened and that it is irreversible. Trust allows people to decide to donate at a time of grief and allows the medical community to feel comfortable opening a dialogue about donation. For donation after circulatory-determined death to be medically possible, death must be declared within a window of time after life sustaining measures are withdrawn. Yet, stories persist about people coming back to life following a declaration of death, and there was little evidence to inform the medical understanding of dying.

To do this, we had to go into ICUs and monitor people as they were dying. This is a very personal experience. And here we were collecting data, sending it to a server, downloading it and having people review the vital signs how things stopped and if they restarted. People were worried. Some physicians didnt want to do it. Some researchers felt uncomfortable. But we knew we should keep going when we met Heather.

Dr. Sonny Dhanani, MDDePPaRT Study LeadInvestigator, CHEO Research InstituteChief Critical Care, Childrens Hospital of Eastern OntarioAssociate Professor, University of Ottawa

Dr. Dhanani and his team found that the classic flatline of death is not so straightforward. The study showed that cardiac activity often stops and re-starts several times during the dying process before it finally stops completely but no one regained sustained circulation or consciousness. The study provides evidence to support the current standard to wait for 5 minutes after the heart stops before determining death and proceeding to organ donation.

How do you ask a family whose loved one is dying in the ICU to participate in a research study on organ donation? DePPaRT was empowered by the support and perspectives of a family partner, Ms. Heather Talbot, a woman whose son became a donor after dying in a car accident. The Canadian Donation and Transplantation Research Programs Patient, Family and Donor Partnership Platform connected Heather with the DePPaRT team in 2015, and she took on the emotional challenges of joining as a consultant. Heather provided feedback from a familys perspective, contributing ideas on how to appropriately approach families of dying patients. Her ability to reflect on her experiences and apply them to the study was pivotal for the projects success. Her contributions helped achieve a family consent rate of 93% and dampened the teams fears of overstepping boundaries. Her sons gift of organ donation saved at least four lives and her involvement in DePPaRT is multiplying those gifts.

This is an outstanding example of the powerful impact that a national framework for collaborative team science can achieve. Through the Canadian Donation and Transplantation Research Program, we have brought together different research communities, patient, family and donor partners, stakeholder organizations, and health care professionals who take non-traditional paths to doing research. This has created new synergies and new knowledge that will help more Canadians become donors and more patients receive transplants.

Dr. Lori West, MD, DPhilCanada Research Chair in Cardiac Transplantation, University of AlbertaDirector, Canadian Donation and Transplantation Research ProgramOfficer of the Order of Canada (2020)

Families and health care teams can trust that when death is determined, it is safe to begin the organ donation process. DePPaRT study data can now be used to inform policy and guidelines for determining death for organ donation both nationally and internationally. Further work using the study data will allow donation and transplant teams to predict how long it will take patients to die after removing life-sustaining measures. Predicting a time of death would be immensely useful to coordinate a donation and improve how organs are allocated.

On behalf of the Canadian Institutes of Health Research (CIHR), I would like to congratulate CDTRP and the DePPaRT team on the publication of this important study. CIHR is very pleased to be supporting a national network like CDTRP that has been able to bring together multiple stakeholders in the transplant area. This study is an example of the impactful work collaborations such as this one can achieve that will lead to improved outcomes for Canadians waiting for transplants.

Dr. Charu Kaushic, MSc, PhDScientific Director, CIHR Institute of Infection and Immunity

Reference: Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures by Sonny Dhanani, M.D., Laura Hornby, M.Sc., Amanda van Beinum, M.Sc., Nathan B. Scales, Ph.D., Melanie Hogue, M.Sc., Andrew Baker, M.D., Stephen Beed, M.D., J. Gordon Boyd, M.D., Ph.D., Jennifer A. Chandler, L.L.B., L.L.M., Michal Chass, M.D., Ph.D., Frederick DAragon, M.D., Ph.D., Cameron Dezfulian, M.D., Christopher J. Doig, M.D., Frantisek Duska, M.D., Ph.D., Jan O. Friedrich, M.D., D.Phil., Dale Gardiner, M.D., Teneille Gofton, M.D., Dan Harvey, M.D., Christophe Herry, Ph.D., George Isac, M.D., Andreas H. Kramer, M.D., Demetrios J. Kutsogiannis, M.D., David M. Maslove, M.D., Maureen Meade, M.D., Sangeeta Mehta, M.D., Laveena Munshi, M.D., Loretta Norton, Ph.D., Giuseppe Pagliarello, M.D., Tim Ramsay, Ph.D., Katerina Rusinova, M.D., Ph.D., Damon Scales, M.D., Ph.D., Matous Schmidt, M.D., Andrew Seely, M.D., Ph.D., Jason Shahin, M.D., C.M., Marat Slessarev, M.D., Derek So, M.D., Heather Talbot, B.Ed., Walther N.K.A. van Mook, M.D., Ph.D., Petr Waldauf, M.D., Matthew Weiss, M.D., Jentina T. Wind, R.N., Ph.D. and Sam D. Shemie, M.D. for the Canadian Critical Care Trials Group and the Canadian Donation and Transplantation Research Program, 27 January 2021, New England Journal of Medicine.DOI: 10.1056/NEJMoa2022713

This research was supported by the Canadian Institutes of Health Research as part of the Canadian Donation and Transplantation Research Program, the CHEO Research Institute, and Karel Pavlk Foundation.

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When Is Dead Really Dead? Results From the Largest International Study of Its Kind - SciTechDaily

Physiology

Impact of Obesity and Its Associated Comorbid Conditions on COVID-19 P | DMSO – Dove Medical Press

Osama Mehanna,1,2 Ahmad El Askary,3,4 Ebtesam Ali,5 Basem El Esawy,3,6 Tamer FathAlla,7 Amal F Gharib3,8

1Department of Medical Physiology, College of Medicine, Taif University, Taif 21944, Saudi Arabia; 2Department of Medical Physiology, Faculty of Medicine, Al-Azhar University, New Damietta, Egypt; 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia; 4Department of Medical Biochemistry, Faculty of Medicine, Al-Azhar University, New Damietta, Egypt; 5Directorate of Health Affairs, Gharbia Governorate, Ministry of Health and Population, Cairo, Egypt; 6Department of Pathology, Faculty of Medicine, Mansoura University, Al Mansurah, Egypt; 7Department of Anaesthesia and ICU, Faculty of Medicine, Al-Azhar University, New Damietta, Egypt; 8Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Correspondence: Osama Mehanna Email dr587@yahoo.com

Background: There is great variability in clinical presentation of COVID-19 worldwide. The current study evaluated the impact of obesity and its related complications on the course of COVID-19 in Egyptian patients.Methods: We included 230 COVID-19 Egyptian patients from Tanta City. According to their body-mass index (BMI), patient were divided into three groups: normal weight (BMI < 25 kg/m2), overweight (BMI > 25< 30 kg/m2), and obese (BMI 30 kg/m2). Patients glycemic status, lipid profile, and serum levels of acute-phase reactants were assessed. The number of patients receiving intensive care and the number of deaths in each group were counted.Results: Mean values of random blood sugar, serum cholesterol, triglycerides, serum ferritin, erythrocyte-sedimentation rate, LDH, CRP, D-dimer levels, and blood pressure were significantly higher in obese patients (165.6, 129.5, 105, 1,873, 26, 403, 56.45, 977.16 and 142/87, respectively) than in normal-weight (97.2, 103.5, 70.4, 479, 17.4, 252, 23.2, 612.4, and 118.6/76.8, respectively) and overweight patients (111.4, 106.3, 78.13, 491.3, 19.8, 269.27, 25.42, 618.4, and 120.3/79.3, respectively). Lymphopenia was also significantly predominant in the obese group. Multivariate logistic regression analysis revealed that elevated serum triglycerides, total cholesterol, low densitylipoprotein cholesterol, blood pressure, ferritin, CRP, and low relative lymphocyte count were significant risk factors in obese COVID-19 patients.Conclusion: Obesity and its related complications increase the risk of presenting a more severe form of COVID-19 in Egyptian patients.

Keywords: obesity, COVID-19, Egyptian

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Impact of Obesity and Its Associated Comorbid Conditions on COVID-19 P | DMSO - Dove Medical Press

Physiology

Insecticide on flowers can stop bees and flies from getting sleep – THE WEEK

Pesticides used on plant can make flies, like bees, mad without sleep, say researchers who studed the impact of common pesticides on the insect brain.

Just like us, many insects need a decent night's sleep to function properly, but this might not be possible if they have been exposed to neonicotinoid insecticides, the most common form of insecticide used worldwide, suggests research by academics at the University of Bristol.

Two studies by scientists at Bristol's Schools of Physiology, Pharmacology and Neuroscience and Biological Sciences have shown these insecticides affect the amount of sleep taken by both bumblebees and fruit flies, which may help us understand why insect pollinators are vanishing from the wild.

Dr Kiah Tasman, Teaching Associate in the School of Physiology, Pharmacology and Neuroscience and lead author of the studies, said: "The neonicotinoids we tested had a big effect on the amount of sleep taken by both flies and bees. If an insect was exposed to a similar amount as it might experience on a farm where the pesticide had been applied, it slept less, and its daily behavioural rhythms were knocked out of synch with the normal 24-hour cycle of day and night."

The fruit fly study has been published in Scientific Reports.

As well as finding that typical agricultural concentrations of neonicotinoids ruined the flies' ability to remember, the researchers also saw changes in the clock in the fly brain which controls its 24-hour cycle of day and night.

"Being able to tell time is important for knowing when to be awake and forage, and it looked like these drugged insects were unable to sleep. We know quality sleep is important for insects, just as it is for humans, for their health and forming lasting memories," said Dr James Hodge, Associate Professor in Neuroscience in the School of Physiology, Pharmacology and Neuroscience and senior author for the study.

"Bees and flies have similar structures in their brains, and this suggests one reason why these drugs are so bad for bees is they stop the bees from sleeping properly and then being able to learn where food is in their environment, explained Dr Sean Rands, Senior Lecturer in the School of Biological Sciences and co-author.

"Neonicotinoids are currently banned in the EU, and we hope that this continues in the UK as we leave EU legislation."

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Insecticide on flowers can stop bees and flies from getting sleep - THE WEEK

Physiology

Physiology: What it takes to run a two-hour marathon – AW – Athletics Weekly

Study highlights the physiological demands linked to breaking the fabled barrier

Elite marathon runners need a specific blend of physiological traits to stand a chance of breaking two hours in the marathon, according to a study from the University of Exeter published in the Journal of Applied Physiology.

Eliud Kipchoge was one of the athletes tested by Andy Jones, professor of applied physiology at Exeter and the study author, along with 16 others who took part in the selection stage of the ambitious Nike Breaking2 project of 2017. Kipchoge was to record 1:59:40.2 in the INEOS 1:59 challenge after the trial had finished.

READ MORE: Eliud Kipchoge runs sub-two-hour marathon

Jones reported that a perfect balance of a high VO2 max (maximal oxygen uptake) and high lactate turn point (the percentage of someones VO2 max that can be sustained before anaerobic respiration, and fatigue, set in) were also necessary attributes of potential sub-two-hour runners.

His findings showed that a 59kg runner would need to take in about four litres of oxygen per minute (or 67ml per kg of weight per minute) to maintain two-hour marathon pace (21.1km/hr) meaning they take in oxygen during a marathon at double the speed a normal person of the same age would while sprinting flat out.

Some of the results particularly the VO2 max were not actually as high as we expected, Jones says. But these runners possess a perfect balance of characteristics for marathon performance.

Supreme efficiency of movement or an effective running action were also a requirement, to enable the body to use oxygen efficiently.

Of the athletes studied, 15 were from East Africa and, says Jones, seemed to know intuitively how to run just below their critical speed, close to the lactate turn point but never exceeding it.

Across the board, they displayed remarkable fatigue resistance.

Jones says: The requirements of a two-hour marathon have been extensively debated, but the actual physiological demands have never been reported before now.

This article was first published in the November 2020 edition of AW magazine, which is available to order online in print hereandread digitally here

See AW magazine each month for the latest performance news

For more on the latest athletics news, athletics events coverage and athletics updates, check out theAW homepageand our social media channels onTwitter,FacebookandInstagram

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Physiology: What it takes to run a two-hour marathon - AW - Athletics Weekly

Physiology

Senior Lecturer in Physiology job with ULSTER UNIVERSITY | 242508 – Times Higher Education (THE)

Faculty of Life and Health SciencesSchool of MedicineSenior Lecturer in Physiology Salary 52,590 - 60,939 pa Closing date: 31 January 202Campus: Magee Ref 003402

As Northern Irelands civic University, Ulster is grounded in the heart of the community and strives to make a lasting contribution to society. Renowned for its world-class teaching, Ulster aims to transform lives, stretch minds and develop the skills required by a growing economy.

This is an exciting time for the University as we develop our new School of Medicine: our aim is to deliver Graduate Entry Medical Education as a means of widening access to medicine in Northern Ireland, seeking to produce doctors who are locally focussed, globally ambitious change agents who will work in and lead teams to improve the health of their patients and the wider community.

The creation of the new School offers a unique opportunity for the successful candidate to join a team of like-minded medical educators. The post is a key early appointment to the School allowing the successful applicant to play a pivotal part in shaping our educational delivery. We are seeking capable team players who are willing to explore new ways of delivery and who are enthused by the prospect of being involved in establishing a new School.

The successful candidate will work closely with the Foundation Dean and Director of Education to design, develop and deliver an imaginative and integrated approach to the learning of Physiology for medical students.

The focus of the School is educational excellence and, as such, will require partnership working with colleagues throughout the University and with a wide range of clinical stakeholders. The University has a global research profile to complement its strong educational achievements and maintenance of research activity is also supported and encouraged.

We prefer to issue and receive applications via our on-line recruitment website by clicking Apply.

Hard copy applications can be obtained by telephoning 028 7012 4072

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.Appointment will be made on merit.

Ulster University holds a Bronze Athena SWAN award in recognition of our commitment to advancing gender equality in higher education. Read more on our website https://www.ulster.ac.uk/peopleandculture/employee-benefits/equality-diversity/athena-swan. The University has a range of initiatives to support a family friendly working environment, including flexible working.

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Senior Lecturer in Physiology job with ULSTER UNIVERSITY | 242508 - Times Higher Education (THE)

Physiology

Application of Nanotechnology in the COVID-19 Pandemic | IJN – Dove Medical Press

Dongki Yang

Department of Physiology, College of Medicine, Gachon University, Incheon, 21999, South Korea

Correspondence: Dongki YangDepartment of Physiology, College of Medicine, Gachon University, Incheon 21999, South KoreaTel +82-32-899-6072Fax +82-32-899-6588Email dkyang@gachon.ac.kr

Abstract: COVID-19, caused by SARS-CoV-2 infection, has been prevalent worldwide for almost a year. In early 2000, there was an outbreak of SARS-CoV, and in early 2010, a similar dissemination of infection by MERS-CoV occurred. However, no clear explanation for the spread of SARS-CoV-2 and a massive increase in the number of infections has yet been proposed. The best solution to overcome this pandemic is the development of suitable and effective vaccines and therapeutics. Fortunately, for SARS-CoV-2, the genome sequence and protein structure have been published in a short period, making research and development for prevention and treatment relatively easy. In addition, intranasal drug delivery has proven to be an effective method of administration for treating viral lung diseases. In recent years, nanotechnology-based drug delivery systems have been applied to intranasal drug delivery to overcome various limitations that occur during mucosal administration, and advances have been made to the stage where effective drug delivery is possible. This review describes the accumulated knowledge of the previous SARS-CoV and MERS-CoV infections and aims to help understand the newly emerged SARS-CoV-2 infection. Furthermore, it elucidates the achievements in developing COVID-19 vaccines and therapeutics to date through existing approaches. Finally, the applicable nanotechnology approach is described in detail, and vaccines and therapeutic drugs developed based on nanomedicine, which are currently undergoing clinical trials, have presented the potential to become innovative alternatives for overcoming COVID-19.

Keywords: COVID-19, SARS-CoV-2, antiviral drug, vaccines, nanoparticles, nanotechnology

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Application of Nanotechnology in the COVID-19 Pandemic | IJN - Dove Medical Press