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Physiology

Electrocardiogram 1: purpose, physiology and practicalities – Nursing Times

An electrocardiogram monitors the hearts electrical activity and is used in many clinical settings. This article explores how the technique works and is undertaken

An electrocardiogram assesses the hearts electrical activity; it is commonly used as a non-invasive monitoring device in many different healthcare settings. This article, the first in a three-part series, discusses cardiac electrophysiology, indications for an electrocardiogram, monitoring and troubleshooting.

Citation: Jarvis S (2021) Electrocardiogram 1: purpose, physiology and practicalities. Nursing Times [online]; 117: 6, 22-26.

Author: Selina Jarvis is research nurse, Guys and St Thomas NHS Foundation Trust.

An electrocardiogram (ECG) is a quick bedside investigation that assesses the electrical activity of the heart. It is a non-invasive, cheap technique that provides critical information about heart rate and rhythm, and helps assess for cardiac disease. ECG monitoring is used often in many different healthcare settings, including acute care, cardiac care and preoperative assessment.

This article, the first in a three-part series, discusses cardiac electrophysiology, indications for an ECG, monitoring and troubleshooting. Part2 of the series will take a methodical approach to interpretation, with a focus on cardiac ischaemia; part3 will explore cardiac rhythm and conduction abnormalities.

The heart is an organ that acts as a mechanical pump; it consists of four chambers (right and left atria, and right and left ventricles) that contract sequentially during the cardiac cycle and are regulated by an electrical conducting system. To understand the basics of an ECG, it is important to consider the normal electrophysiology of the heart, in which a cardiac electrical impulse is generated and transmitted to the heart muscle, leading to contractions (the heartbeat).

There are two main cell types in the heart:

Cardiomyocytes contract and relax in response to an electrical stimulus. During their resting state, inside the cells there are high internal levels of potassium ions (K+), compared with outside the cells; along with negatively charged proteins, which creates a chemical gradient. Outside the cardiomyocytes there are more sodium ions (Na+) and calcium ions (Ca2+) compared with inside the cell. Overall, this means there is a voltage difference across the cell membrane, called transmembrane potential (TMP). When there is net movement of Na+ and Ca2+ into the cell, TMP becomes more positive; when there is net movement of positive ions out of it, TMP becomes more negative.

In response to an electrical stimulus, cardiomyocytes become depolarised and fast Na+ channels open on the cell membrane, allowing Na+ into the cell; because this is positively charged, the TMP becomes more positive, increasing to -70millivolts (mV) (resting potential is -90mV). This is the point at which enough Na+ fast channels have opened to generate an inward Na+ current, and is known as the threshold potential. When the charge becomes greater than -40mV, L-type calcium channels open and allow an inward flux of Ca2+. This results in excitation-contraction coupling, which leads to the contraction of muscles in the heart. Following this, repolarisation occurs; the cardiac membrane potential returns to the resting state and no muscle contraction occurs.

The hearts electrical conducting system (Fig1) regulates its overall electrical activity and includes the following components:

Each heartbeat is initiated by an electrical impulse generated by the SAN; this impulse passes through the atria to the AVN, then through the right and left ventricles, the bundle of His, subsequent bundle branches and the Purkinje fibres. As a result, the atria and ventricles contract sequentially as the impulse is conducted through the different regions of the heart. In normal circumstances, the SAN is the hearts pacemaker; however, if there is a problem with the SAN, another conducting region centre such as the AVN, bundle of His or bundle branches can assume the role of the pacemaker in an occurrence known as an escape rhythm (Jarvis and Saman, 2018; Newby and Grubb, 2018).

In healthy individuals, the chambers of the heart contract and relax in a coordinated manner, referred to as systole and diastole respectively. The right and left atria synchronise during atrial systole and diastole, while the right and left ventricles synchronise during ventricular systole and diastole. One complete cycle of these events is called the cardiac cycle, during which the pressure in the cardiac chambers rises and falls, causing the opening and closure of heart valves that regulates blood flow between the chambers.

Pressures on the left side of the heart are around five times higher than those on the right side, but the same volume of blood is pumped per cardiac beat. In the cardiac cycle, blood moves from high- to low-pressure areas (Marieb and Keller, 2018).

The ECGs origin dates back to the discovery of the heart muscles electric activity. In 1901, Willem Einthoven made a breakthrough that facilitated the first steps towards electrocardiography, for which he subsequently won a Nobel Prize in 1924 (Yang et al, 2015).

ECGs are used as a technique to diagnose cardiac disease and to detect abnormal heart rhythm. They may also be used as a general health assessment in certain occupations, including aviation, diving and the military (Chamley et al, 2019). According to professional societies, adequate education for medical staff is critical for ECG monitoring and developing skills in interpreting waveforms and ECG data (Sandau et al, 2017).

In routine clinical practice, there are four main approaches to monitoring cardiac rhythm:

The 12-lead ECG is a non-invasive method of monitoring the hearts electrical activity. This bedside test can provide important diagnostic information or be used as part of a baseline assessment; Box1 outlines some indications for using it.

If there is a concern that a patients acute symptoms may have a cardiac cause, continuous cardiac monitoring might be used in a hospital setting. This may help with:

Continuous cardiac monitoring is also an important component of non-invasive monitoring of vital signs, with clinical benefits in medical ward settings (Sun et al, 2020).

The ECG is a graphical representation of the hearts electrical activity, plotting its voltage on a vertical axis against time on a horizontal axis. It is recorded onto ECG paper, which runs at a speed of 25mm per second. Standard pink ECG paper is made up of 5x5mm squares, each containing 25 smaller 1x1mm squares. The 1mm width of each small square represents 40milliseconds. On the vertical axis, the height of an ECG wave or deflection represents its amplitude (Prutkin, 2020). Fig2 shows what a normal ECG looks like and its relationship with the stages of the cardiac cycle.

During the normal cardiac cycle, the atrial contraction that takes place is associated with a P-wave (atrial depolarisation) and is of low amplitude because the muscle is relatively thin in the atria. This contrasts with the QRS complex, which represents the electrical impulse as it spreads through the ventricles (ventricular depolarisation). The first deflection of the QRS complex is the Q-wave, which is a negative wave that begins septal depolarisation. The R-wave represents depolarisation of the left ventricular myocardium and the next negative deflection is the S-wave, which represents terminal depolarisation. The T-wave occurs after that and represents the repolarisation of the ventricles.

The ECG also records a number of other parameters:

It is important to know the normal ranges for the various ECG parameters (Table1): if any measurements are outside the normal range, thought and investigation are needed to ascertain why and decide on a course of action. Parts 2 and 3 of this series will discuss this in more detail.

It is important to remember that the electrical lead actually represents the differences in electrical potentials measured in two points in space. The conduction of electrical impulses between these two points in space can be detected via electrodes that are positioned at various points on the body; this is then displayed as a waveform on the ECG machine/monitor.

There are several configurations of electrode positioning; continuous ECG monitoring uses a 3-lead configuration but the standard 12-lead ECG comprises:

To position the chest electrodes accurately, it is important to first identify the sternal angle (angle of Louis); this is done by feeling the bony prominence at the top of the sternum, which articulates with the second rib above the second intercostal space. By moving the fingers downwards, the fourth intercostal space can be felt: here, the electrodes for V1 and V2 should be placed to the right and left of the sternum respectively. By feeling the fifth intercostal space and moving the fingers to the middle of the clavicle, V4 can be placed on the midclavicular line. V3 should then be placed midway between V2 and V4. V5 is placed in the fifth intercostal space, more lateral to the anterior axillary line, and V6 is placed in the fifth intercostal space in the midaxillary line.

To record the limb leads (Fig3b), four electrodes are placed on the body. In the upper limbs, an electrode pad is placed below the right clavicle (arm), the next electrode pad is placed below the left clavicle (arm); in the lower limbs, a cable is connected to an electrode pad placed on the left hip/ankle (LL) and on the right hip/ankle (RL).

It is important to follow local policy. All of the limb electrodes are placed on bony areas, rather than muscle, to avoid motion artifact caused by muscle oscillation. Positioning electrodes in this formation allows the heart to be electrically mapped in three dimensions.

When undertaking any cardiac monitoring, the first step is to give the patient a simple explanation of the purpose of the test and what they should expect, as well as gaining their informed consent. It is important to ensure they are not allergic to the gel used on the ECG electrodes by asking if they have had any previous reactions.

It is critical that the health professional can accurately place the electrodes this will help avoid inaccurate diagnosis and treatment and it is important to have good contact between the electrode and the skin, which should be clean and dry. Excessive hair may need to be shaved and oily skin cleaned with alcohol or gauze. The electrodes are then attached to the patient in line with the machines instructions. The ECG is displayed on the machines monitor and should be checked for clarity, wave size and any interference.

Inadequate ECG monitoring can be dangerous; for example, misreading artifacts (electrocardiographic impulses unrelated to cardiac electrical activity) during ECG monitoring can be costly and cause delays to care. Other potential problems and how to resolve them are listed in Table 2.

An excellent ECG trace must be acquired to aid appropriate interpretation and provide the best care. The Society of Cardiological Science and Technologys (2020) ECG guidance has more information about the reporting standards used by professional societies.

ECG monitoring is standard for patients in a variety of settings. Understanding the basic physiology underpinning the electrical and mechanical events of the heart is crucial for ECG interpretation. Part 2 of this series will focus on this and present important ischaemic pathologies, while part 3 will cover cardiac rhythm disorders and conduction defects.

Selina Jarvis was a recipient of the Mary Seacole Development Award and is focused on improving care for patients with cardiac disease.

References

Chamley RR et al (2019) ECG interpretation. European Heart Journal; 40: 32, 2663-2666.

Jarvis S, Saman S (2018) Cardiac system 1: anatomy and physiology. Nursing Times [online]; 114: 2, 34-37.

Marieb EN, Keller S (2018) Essentials of Human Anatomy and Physiology. Pearson.

Newby DE, Grubb NR (2018) Cardiovascular disease. In: Ralston SH et al (eds) Davidsons Principles and Practice of Medicine. Elsevier.

Prutkin JM (2020) ECG Tutorial: Electrical Components of the ECG. uptodate.com

Sandau KE et al (2017) Update to practice standards for electrocardiographic monitoring in hospital settings: a scientific statement from the American Heart Association. Circulation; 136: 19, e273-e344.

Society of Cardiological Science and Technology (2020) Clinical Guidelines by Consensus: ECG Reporting Standards and Guidance. SCST.

Sun L et al (2020) Clinical impact of multi-parameter continuous non-invasive monitoring in hospital wards: a systematic review and meta-analysis. Journal of the Royal Society of Medicine; 113: 6, 217-224.

Yang XL et al (2015) The history, hotspots, and trends of electrocardiogram. Journal of Geriatric Cardiology; 12: 4, 448-456.

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Electrocardiogram 1: purpose, physiology and practicalities - Nursing Times

Physiology

Women and endurance running part one: how to train with your cycle – Canadian Running Magazine

Dr. Stacy Simsis a researcher, entrepreneur, recreational athlete and scientist whose area of expertise is exercise physiology and sports nutrition. Early in her career, she became frustrated by the fact that the vast majority of sports science treated women like small men most studies were conducted on men, and all the training, recovery and nutrition principles we learned from those studies were applied to women, despite the fact that female physiology is different from that of a man. We sat down with her to talk about these differences to determine how women runners can work with their bodies to become stronger, faster and healthier athletes.

RELATED: Why sports medicine research needs more women

Today, in Part One of this series, we will be diving into the female menstrual cycle and how it affects training. Part Two will cover nutrition strategies to boost performance throughout your cycle and how contraceptives affect training, and Part Three will look at puberty, perimenopause and menopause.

One of the most obvious differences between women and men, of course, is the female menstrual cycle. For years, a womans period was seen as being detrimental to her performance, but Sims says this is entirely false.

If you dont have a period, its detrimental [to your performance], she explains. Having a period means youre healthy, youre adapting and youre resilient to stress.

Sims explains that the reason having a period developed such a negative connotation in sports is because of the way sport developed. In the beginning, she says it acted as a male demonstration of aggression, with an emphasis on traditionally male qualities, like speed, strength, aggression and power. There has always been a taboo around the female menstrual cycle, so when you bring that into the sporting context, it came across as a weakness. Because of this, the idea that not having a period meant you were just as strong or trained just as hard as the men became endemic in sport.

This couldnt be farther from the truth. Having a period means youre getting enough nutrients to support your health and your training, your body is responding well to training adaptations and stress, your sleep patterns are good, your endocrine system is healthy and youre in an energy balance. No longer getting a regular period is the first red flag that something is amiss, and sets you up for health complications down the road, like loss of bone density, irregular sleep patterns and hormone dysfunction, among others.

Sims says that for so long, women have been told that when theyre on their periods, they should feel flat, tired, awful and that they should be hiding. Instead, she argues, we should be telling women the opposite that their periods are an opportunity to increase the intensity of their training sessions.

The more we get women to move during their periods, the better it is and the less symptomatology they have, she explains.

From a physiology standpoint, this also makes a lot of sense. The week that youre on your period (days one through seven of your cycle) is when your hormones are at their lowest point, and this makes your body more resilient to stress. This, then, is the time to do more high-intensity sessions, because you recover much better. The only caveat to this, says Sims, is women who experience heavy bleeding during the first couple of days of their period. In this case, you want to keep moving but shift the focus from high intensity to technical work like drills, or simply moving for movings sake. You can hit your training hard again once the heavy bleeding subsides.

The myths and perceptions around bleeding need to be extracted from the training conversation, says Sims.

Around ovulation, which is usually around day 14 of the cycle for most women, is another good time to schedule a hard training session. After that, as your levels of estrogen and progesterone begin to rise again, Sims suggests focusing more on steady-state runs. Finally, the five days before your period starts, which is when your body is most affected by hormones, should be treated more like a de-load or off-week. This is the time to back off the intensity and focus on other aspects of training like running drills, de-loading in the gym and working on technique. Every woman will be slightly different, so its important to track your cycle and take note of the days you feel better and the days you feel worse, and adjust your training plan accordingly. While there are many ways to do this, Sims is a big fan of the app, Wild AI.

If youre coaching a team of female athletes, Sims recommends coming up with a system that allows you to keep track of where each of your athletes are at, so that you can adjust their training accordingly (or, at the very least, adjust your expectations of individual athletes depending on the day).

This is where training is different than performance, says Sims. Train according to your menstrual cycle, but we know that the psychological aspect of performance supersedes the physiological.

If, for example, your race ends up falling on a day during your cycle that you typically dont feel your best, its easy to let that get to your head. Putting certain nutrition interventions in place and boosting yourself up mentally will help you overcome whatever physiological downfall you might be experiencing.

We have to separate out performance versus training, which hasnt been done well yet, explains Sims. When we talk about performance, theres never a negative point in the menstrual cycle. When we talk about training, there are ups and downs. We can get better training adaptations when our bodies are more resilient to stress, and then start to taper down to support that hard training. But for performance, just go, just hit it hard.

The key takeaway from this is that a womans period should not be seen as a detriment to performance, but rather as a tool to make her a better athlete. If women can learn to work with their physiology rather than against it, they will be healthier, happier and faster runners.

RELATED: Exercising and your period: changing the conversation

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Women and endurance running part one: how to train with your cycle - Canadian Running Magazine

Physiology

Quantifying stress & anxiety: Why corporate wellness programs will play a pivotal role in this paradigm shift – MedCity News

The past decade has seen us come on leaps and bounds as a society in our awareness and understanding of the scale and impact of mental health problems. In recent years, the focus has switched somewhat from reaction to prevention in parallel with the healthcare industry as a whole, in a bid to secure the sustainability of care services.

The economic impact of the mental health epidemic is a key driver behind governments and businesses move towards more preventive wellbeing initiatives. For instance, the World Health Organization (WHO) estimates that mental health problems in the workplace cost the global economy $1 trillion annually in lost productivity.

Stress and anxiety contribute heavily to this statistic. Stress is defined as the bodys reaction to feeling threatened or under pressure. Anxiety, which is often linked to stress, is defined as a feeling of unease, such as worry or fear, which can be mild or severe and is the main symptom of several mental disorders.

In the UK, for example, 57% of all working days lost to ill health were due to stress and anxiety in 2018. Its a similar story in the US, where its estimated that over half of all working days lost annually from absenteeism are stress-related, with the annual cost in 2013 alone equating to over $84 billion.

Stress and anxiety can also have a significant impact on an individuals physical health, affecting their work performance and productivity and causing further absenteeism. This form of poor mental health can impact physical health either directly through autonomic nervous system activity or indirectly as a result of unhealthy behaviors (e.g. poor diet, physical inactivity, alcohol abuse and smoking), increasing an individuals risk of developing cardiovascular problems.

It is therefore in an effort to break this chain, and in doing so save costs long-term, that employers are increasing their focus on establishing effective wellness programs, meaning any promotional activity or organizational policy that supports healthy behavior in the workplace and improves health outcomes. Corporate wellness programs nowadays include anything from healthy eating education, financial advice and access to weight loss and fitness programs, to more direct healthcare such as on-site medical screening, stress management, smoking cessation programs, and counseling services (in the form of employee assistance programs).

And this certainly can save costs long-term! Most famously, Johnson & Johnson leaders estimate that wellness programs have cumulatively saved the company $250 million on healthcare costs over the past decade; with a return of $2.71 for every dollar spent between 2002 and 2008. Its no surprise, then, that in 2020 the workplace wellness industry was estimated to be worth $48 billion globally.

Recent innovations in the space include the integration of wearable or smartphone technologies, used by employees to monitor and collect physical health data. These technologies provide employees with real-world physiological health insights to further incentivize participation in programs and increase and maintain their engagement. They simultaneously provide employers with an insight into the overall physical health of their workforce.

A golden opportunity to transform our relationship with mental health

However, with this most recent integration of digital health technologies comes a hitherto unrecognized opportunity to transform our understanding and treatment of mental health and wellbeing.

One of the primary barriers to delivering quality mental health care throughout history has been the difficulty in establishing accurate and objective methods to diagnose, assess and monitor treatment outcomes for psychological conditions. As was explained so eloquently by Washington University in November last year, if patients display symptoms of a heart attack, there are biological tests that can be run to look for diagnostic biomarkers that determine whether they are indeed suffering a heart attack or not. However, in the case of mental health disorders, the window by which we access the mind is still through psychological questioning, not biological parameters.

Mental health professionals screen, diagnose and monitor the symptoms and outcomes of patients through self-reported methods prone to excess subjectivity and therefore unreliability, such as diagnostic interviews and questionnaires. A patients self-reported symptoms are correlated with the ICD or DSM diagnostic manuals, yet challenges arise in the high heterogeneity of mental illnesses, low inter-rate reliability (i.e. poor agreement between clinicians diagnoses) and high comorbidity.

There is therefore a need to expand further than solely symptom-based to biology-based characterization of mental health conditions if we are to combat this unreliability and establish more evidence-based methods for diagnosis and monitoring, similar to our approach to physical illness.

So, how do we do this?

The National Institute for Mental Health for instance has already taken the first steps towards this with the RDoC (Research Domain Criteria). Advancements in MRI technology have also enabled research into understanding brain activity in certain depressive conditions.

But the most exciting development lies in the proliferation of wearable and smartphone health monitoring technologies. As the ability to collect vast amounts of physiological health data becomes more and more ubiquitous, the opportunity to utilize machine learning (ML) to extract new insights into the physiology of each individual grows larger.

With this comes the chance to uncover and establish personalized digital biomarkers for mental health conditions; described as indicators of mental state that can be derived through a patients use of a digital technology. These digital biomarkers can cover physiology (e.g. heart rate), cognition (e.g. eye movement on screens), behavioral (e.g. via GPS) and social (e.g. call frequency) factors. However, it is physiology that concerns us here.

Corporate wellness programs provide the perfect environment to explore the use of wearables and smartphone sensors in uncovering digital biomarkers which link physical health to mental wellbeing due to the huge potential benefits for all parties involved; employers and employees.

For example, by validating elements of cardiopulmonary functions as a digital biomarker for excess stress or anxiety disorders (a relationship for which some empirical evidence already exists), employers can not only identify stress and anxiety risks in the workplace and intervene earlier to protect employee mental wellbeing, but also establish an evidence-based approach for evaluating the effectiveness of workplace wellness initiatives. This is due to the fact that quantitative cardiopulmonary data would serve as a reliable measure of employee stress and/or mental wellbeing.

Employees, on the other hand, are empowered with insight into direct correlations between how they feel and their physical health. Therefore their increased engagement in wellness programs will improve their efficacy in preventing the deterioration of their mental health. For this reason, accessibility and ease-of-use must remain top of mind when choosing health monitoring technologies.

Finally, establishing digital biomarkers which correlate physiological parameters with mental health and wellbeing not only has the potential to provide more reliable tools for guiding diagnosis and evaluating patient outcomes but will also improve our understanding of the pathophysiology of mental disorders, in turn allowing for more effective preventive measures.

Photo: Creativeye99, Getty Images

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Quantifying stress & anxiety: Why corporate wellness programs will play a pivotal role in this paradigm shift - MedCity News

Physiology

Is riding an electric bike good exercise, or just convenient transportation? – The Irish Times

Does riding an electric bike to work count as exercise, and not just a mode of transportation?

It can, if you ride right, according to a pragmatic new study comparing the physiological effects of e-bikes and standard road bicycles during a simulated commute. The study, which involved riders new to e-cycling, found that most could complete their commutes faster and with less effort on e-bikes than standard bicycles, while elevating their breathing and heart rates enough to get a meaningful workout.

But the benefits varied and depended, to some extent, on how peoples bikes were adjusted and how they adjusted to the bikes. The findings have particular relevance at the moment, as pandemic restrictions loosen and offices reopen, and many of us consider options other than packed trains to move ourselves from our homes to elsewhere.

Few people bike to work. Asked why, many tell researchers that bike commuting requires too much time, perspiration and accident risk. Simultaneously, though, people report a growing interest in improving their health and reducing their ecological impact by driving less.

In theory, both these hopes and concerns could be met or minimised with e-bikes. An alluring technological compromise between a standard, self-powered bicycle and a scooter, e-bikes look almost like regular bikes but are fitted with battery-powered electric motors that assist pedalling, slightly juicing each stroke.

With most e-bikes, this assistance is small, similar to riding with a placid tailwind, and ceases once you reach a maximum speed of about 30km/h or stop pedalling. The motor will not turn the pedals for you.

Essentially, e-bikes are designed to make riding less taxing, which means commuters should arrive at their destinations more swiftly and with less sweat. They can also provide a psychological boost, helping riders feel capable of tackling hills they might otherwise avoid. But whether they also complete a workout while e-riding has been less clear.

So, for the new study, which was published in March in the Translational Journal of the American College of Sports Medicine, researchers at Miami University in Oxford, Ohio decided to ask inexperienced cyclists to faux-commute. To do so, they recruited 30 local men and women, aged 19 to 61, and invited them to the physiology lab to check their fitness levels, along with their current attitudes about e-bikes and commuting.

Then, they equipped each volunteer with a standard road bike and an e-bike and asked them to commute on each bike at their preferred pace for approximately 5km. The cyclists pedalled around a flat loop course, once on the road bikes and twice with the e-bike. On one of these rides, their bike was set to a low level of pedal assistance, and on the other, the oomph was upped until the motor sent more than 200 watts of power to the pedals. Throughout, the commuters wore timers, heart rate monitors and facial masks to measure their oxygen consumption.

Afterward, to no ones surprise, the scientists found that the motorised bikes were zippy. On e-bikes, at either assistance level, riders covered the 5km several minutes faster than on the standard bike about 11 or 12 minutes on an e-bike, on average, compared to about 14 minutes on a regular bike. They also reported that riding the e-bike felt easier. Even so, their heart rates and respiration generally rose enough for those commutes to qualify as moderate exercise, based on standard physiological benchmarks, the scientists decided, and should, over time, contribute to health and fitness.

But the cyclists results were not all uniform or constructive. A few riders efforts, especially when they used the higher assistance setting on the e-bikes, were too physiologically mild to count as moderate exercise. Almost everyone also burned about 30 per cent fewer calories while e-biking than while road riding 344 to 422 calories on average on an e-bike versus 505 calories on a regular bike which may be a consideration if someone is hoping to use bike commuting to help lose weight.

And several riders told the researchers they worried about safety and control on the e-bikes, although most, after the two rides, reported greater confidence in their bike-handling skills, and found the e-commutes, compared to the road biking, more fun.

This study, though, was obviously small-scale and short-term, involving only three brief pseudo-commutes. Still, the findings suggest that riding an e-bike, like other forms of active transport, can be as good for the person doing it as for the environment, says Helaine Alessio, the chair of the department of kinesiology at Miami University, who led the new study with her colleague Kyle Timmerman and others.

But to increase your potential health benefits the most, she says, keep the pedal assistance level set as low as is comfortable for you. Also, for the sake of safety, practice riding a new e-bike or any standard bike on a lightly trafficked route until you feel poised and secure with bike handling.

Wear bright, visible clothing, too, and choose your commuting route wisely, Dr Alessio says. Look for bike paths and bike lanes whenever possible, even if you need to go a little bit out of your way. New York Times

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Is riding an electric bike good exercise, or just convenient transportation? - The Irish Times

Physiology

Why we find the sound of our voice cringeworthy – Scroll.in

As a surgeon who specialises in treating patients with voice problems, I routinely record my patients speaking. For me, these recordings are incredibly valuable. They allow me to track slight changes in their voices from visit to visit, and it helps confirm whether surgery or voice therapy led to improvements.

Yet I am surprised by how difficult these sessions can be for my patients. Many become visibly uncomfortable upon hearing their voice played back to them.

Do I really sound like that? they wonder, wincing.

(Yes, you do.)

Some become so unsettled they refuse outright to listen to the recording much less go over the subtle changes I want to highlight.

The discomfort we have over hearing our voices in audio recordings is probably due to a mix of physiology and psychology.

For one, the sound from an audio recording is transmitted differently to your brain than the sound generated when you speak.

When listening to a recording of your voice, the sound travels through the air and into your ears what is referred to as air conduction. The sound energy vibrates the ear drum and small ear bones. These bones then transmit the sound vibrations to the cochlea, which stimulates nerve axons that send the auditory signal to the brain.

However, when you speak, the sound from your voice reaches the inner ear in a different way. While some of the sound is transmitted through air conduction, much of the sound is internally conducted directly through your skull bones. When you hear your own voice when you speak, it is due to a blend of both external and internal conduction and internal bone conduction appears to boost the lower frequencies.

For this reason, people generally perceive their voice as deeper and richer when they speak. The recorded voice, in comparison, can sound thinner and higher-pitched, which many find cringeworthy.

There is a second reason hearing a recording of your voice can be so disconcerting. It really is a new voice one that exposes a difference between your self-perception and reality. Because your voice is unique and an important component of self-identity, this mismatch can be jarring. Suddenly you realise other people have been hearing something else all along.

Even though we may actually sound more like our recorded voice to others, I think the reason so many of us squirm upon hearing it is not that the recorded voice is necessarily worse than our perceived voice. Instead, we are simply more used to hearing ourselves sound a certain way.

A study published in 2005 had patients with voice problems rate their own voices when presented with recordings of them. They also had clinicians rate the voices. The researchers found that patients, across the board, tended to more negatively rate the quality of their recorded voice compared with the objective assessments of clinicians.

So if the voice in your head castigates the voice coming out of a recording device, it is probably your inner critic overreacting and you are judging yourself a bit too harshly.

Neel Bhatt is an Assistant Professor of Otolaryngology, UW Medicine at the University of Washington.

This article first appeared on The Conversation.

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Why we find the sound of our voice cringeworthy - Scroll.in

Physiology

Compound may prevent risk of form of arrhythmia from common medications – Washington University in St. Louis Newsroom

Dozens of commonly used drugs, including antibiotics, anti-nausea and anticancer medications, have a potential side effect of lengthening the electrical event that triggers contraction, creating an irregular heartbeat, or cardiac arrhythmia called acquired Long QT syndrome. While safe in their current dosages, some of these drugs may have a more therapeutic benefit at higher doses, but are limited by the risk of arrhythmia.

Through both computational and experimental validation, a multi-institutional team of researchers has identified a compound that prevents the lengthening of the hearts electrical event, or action potential, resulting in a major step toward safer use and expanded therapeutic efficacy of these medications when taken in combination.

The team found that the compound, named C28, not only prevents or reverses the negative physiological effects on the action potential, but also does not cause any change on the normal action potential when used alone at the same concentrations. The results, found through rational drug design, were published online in Proceedings of the National Academy of Sciences (PNAS) on May 14.

The research team was led by Jianmin Cui, professor of biomedical engineering in the McKelvey School of Engineering at Washington University in St. Louis; Ira Cohen, MD, PhD, Distinguished Professor of Physiology and Biophysics, professor of medicine and director of the Institute for Molecular Cardiology at the Renaissance School of Medicine at Stony Brook University; and Xiaoqin Zou, professor of physics, biochemistry and a member of the Dalton Cardiovascular Research Center and Institute for Data Science and Informatics at the University of Missouri.

The drugs in question, as well as several that have been pulled from the market, cause a prolongation of the QT interval of the heartbeat, known as acquired Long QT Syndrome, that predisposes patients to cardiac arrhythmia and sudden death. In rare cases, Long QT also can be caused by specific mutations in genes that code for ion channel proteins, which conduct the ionic currents to generate the action potential.

Although there are several types of ion channels in the heart, a change in one or more of them may lead to this arrhythmia, which contributes to about 200,000 to 300,000 sudden deaths a year, more deaths than from stroke, lung cancer or breast cancer.

The team selected a specific target, IKs, for this work because it is one of the two potassium channels that are activated during the action potential: IKr (rapid) and IKs (slow).

The rapid one plays a major role in the action potential, said Cohen, one of the worlds top electrophysiologists. If you block it, Long QT results, and you get a long action potential. IKs is very slow and contributes much less to the normal action potential duration.

It was this difference in roles that suggested that increasing IKs might not significantly affect normal electrical activity but could shorten a prolonged action potential.

Cui, an internationally renowned expert on ion channels, and the team wanted to determine if the prolongation of the QT interval could be prevented by compensating for the change in current and inducing the Long QT Syndrome by enhancing IKs. They identified a site on the voltage-sensing domain of the IKs potassium ion channel that could be accessed by small molecules.

Zou, an internationally recognized expert who specializes in developing new and efficient algorithms for predicting protein interactions, and the team used the atomic structure of the KCNQ1 unit of the IKs channel protein to computationally screen a library of a quarter of a million small compounds that targeted this voltage-sensing domain of the KCNQ1 protein unit. To do this, they developed software called MDock to test the interaction of small compounds with a specific protein in silico, or computationally.

By identifying the geometric and chemical traits of the small compounds, they can find the one that fits into the protein sort of a high-tech, 3D jigsaw puzzle. While it sounds simple, the process is quite complicated as it involves charge interactions, hydrogen bonding and other physicochemical interactions of both the protein and the small compound.

We know the problems, and the way to make great progress is to identify the weaknesses and challenges and fix them, Zou said. We know the functional and structural details of the protein, so we can use an algorithm to dock each molecule onto the protein at the atomic level.

One by one, Zou and her lab docked the potential compounds with the protein KCNQ1 and compared the binding energy of each one. They selected about 50 candidates with very negative, or tight, binding energies.

Cui and his lab then identified C28 using experiments out of the 50 candidates identified in silico by Zous lab. They validated the docking results by measuring the shift of voltage-dependent activation of the IKs channel at various concentrations of C28 to confirm that C28 indeed enhances the IKs channel function. They also studied a series of genetically modified IKs channels to reveal the binding of C28 to the site for the in silico screening.

Cohen and his lab tested the C28 compound in ventricular myocytes from a small mammal model that expresses the same IKs channel as humans. They found that C28 could prevent or reverse the drug-induced prolongation of the electrical signals across the cardiac cell membrane and minimally affected the normal action potentials at the same dosage. They also determined that there were no significant effects on atrial muscle cells, an important control for the drugs potential use.

We are very excited about this, Cohen said. In many of these medications, there is a concentration of the drug that is acceptable, and at higher doses, it becomes dangerous. If C28 can eliminate the danger of inducing Q-T prolongation, then these drugs can be used at higher concentrations, and in many cases, they can become more therapeutic.

While the compound needs additional verification and testing, the researchers say there is tremendous potential for this compound or others like it and could help to convert second-line drugs into first-line drugs and return others to the market. With assistance from the Washington University Office of Technology Management, they have patented the compound, and Cui has founded a startup company, VivoCor, to continue to work on the compound and others like it as potential drug candidates.

The work was accelerated by a Leadership and Entrepreneurial Acceleration Program (LEAP) Inventor Challenge grant Washington University in St. Louis in 2018 funded by the Office of Technology Management, the Institute of Clinical and Translational Sciences, the Center for Drug Discovery, the Center for Research Innovation in Biotechnology, and the Skandalaris Center for Interdisciplinary Innovation and Entrepreneurship.

This work was done by an effective drug design approach: identifying a critical site in the ion channel based on understanding of structure-function relation, using insilico dockingto identify compounds that interact with the critical site in the ion channel, validating functional modulation of the ion channel by the compound, and demonstrating therapeutic potential in cardiac myocytes, Zou said. Our three labs form a great team, and without any of them, this would not be possible.

The McKelvey School of Engineering at Washington University in St. Louis promotes independent inquiry and education with an emphasis on scientific excellence, innovation and collaboration without boundaries. McKelvey Engineering has top-ranked research and graduate programs across departments, particularly in biomedical engineering, environmental engineering and computing, and has one of the most selective undergraduate programs in the country. With 140 full-time faculty, 1,387 undergraduate students, 1,448 graduate students and 21,000 living alumni, we are working to solve some of societys greatest challenges; to prepare students to become leaders and innovate throughout their careers; and to be a catalyst of economic development for the St. Louis region and beyond.

Lin Y, Grinter S, Lu Z, Xu X, Wang H Z, Liang H, Hou P, Gao J, Clausen C, Shi J, Zhao W, Ma Z, Liu Y, White, K M, Zhao L, Kang P W, Zhang G, Cohen I, Zou X, Cui J. Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects. Proceedings of the National Academy of Sciences (PNAS), date, DOI.

This research was supported by grants from the National Institutes of Health (R01 HL126774, R01 DK108989, R01 GM109980, R35GM136409; the American Heart Association (13GRNT16990076). The computations were performed on the high-performance computing infrastructure supported by NSF CNS-1429294 and the HPC resources supported by the University of Missouri Bioinformatics Consortium (UMBC).

Authors Jianmin Cui and Jingyi Shi are cofounders of a startup company, VivoCor LLC, which is targeting IKs for the treatment of cardiac arrhythmia.

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Compound may prevent risk of form of arrhythmia from common medications - Washington University in St. Louis Newsroom

Physiology

Life on Earth may be carbon-based, but another element matters, too > News > USC Dornsife – USC Dornsife College of Letters, Arts and Sciences

Marine microbiologist Doug Capone details the current understanding of the role nitrogen-fixing marine microbes play in the nitrogen cycle in his latest book. [5 min read]

Middle school students learn in science class about the carbon cycle the flow of carbon among the atmosphere, living organisms, soil and the oceans. But another, less familiar cycle also plays a crucial role in the balance of nature: the nitrogen cycle.

Nitrogen constitutes about 78% of the Earths atmosphere, where it exists mainly in its most stable form, a gas called dinitrogen, or N2. A significant amount also resides in the oceans as dissolved gas.

Most animals and plants cant use N2; they first need it turned into a more reactive form, such as ammonia, through a process called nitrogen fixation. But only certain microorganisms can fix nitrogen, and many of those live in marine environments. They draw the N2from the water and, using a specialized enzyme, break the bond between the two nitrogen atoms and attach other atoms to each, making new molecules that other living organisms can use.

The process is crucial to life on Earth and directly affects humans.

The oceans are becoming an ever-increasing source of food for humanity, and nitrogen fixation is critical in maintaining many marine food webs, saidDoug Capone, professor ofbiological sciencesat the USC Dornsife College of Letters, Arts and Sciences. His research focuses on understanding how ocean microbes affect the movement of important elements, including carbon and nitrogen, through plants and animals and from land to sea to air and back.

Getting a fix on global fixation

Capone has studied diverse ecological systems throughout the world, including the tropical open ocean, coral reefs, mangroves, temperate estuaries, groundwater aquifers and Antarctic snows.

A thorough understanding of the factors involved in nitrogen fixation in the oceans could help future generations safely and sustainably farm the oceans, he said.

Capone, collaborating with Jonathan Zehr of the University of California, Santa Cruz, recently publishedMarine Nitrogen Fixation(Springer, 2021), which summarizes the extensive research and current understanding of marine nitrogen fixation. The book builds onan articlethe pair wrote and published last year at the request of the journalScience.

Capone, who holds the William and Julie Wrigley Chair in Environmental Studies, and Zehr, a Distinguished Professor at UC Santa Cruz, are widely respected authorities on marine nitrogen fixation.

Ive been working on aspects of marine N2fixation since my days as a Ph.D. student, Capone said. His dissertation focused on the importance of N2fixation in the tropical seagrassThalassia, also known as turtle grass.

In shallow tropical waters, turtle grass forms dense meadows that many sea-going species from microbes to mollusks to manatees call home. Nitrogen-fixing microbes, known scientifically as diazotrophs, live on the plants leaves and its roots, providing a critical source of nitrogen in the nutrient-depleted tropical waters, Capone said.

Combined expertise in a vital field of study

After landing his first faculty position at New Yorks Stony Brook University in the late 70s, Capone turned his attention to the open ocean, and in the decades since, he has led many research cruises to locations throughout the globe and conducted extensive research on the physiology, ecology and biogeochemical impact of open ocean diazotrophs.

Hes also spent a large share of his career mentoring young scientists and brought many others into this field.

Ive trained a gaggle of researches in this area undergrads, grad students and postdocs as well as having entrained researchers from diverse fields into the area of marine nitrogen fixation, he said.

Zehr is among those researchers, having joined Capones Stony Brook University Lab as a postdoctoral fellow in 1980.

His postdoc with me was not on N2fixation, but he subsequently joined me on many of the cruises I led to study this process in the tropical ocean, said Capone.

Zehr has gone on to establish one of the best model systems for studying functional genes in the environment, according to Capone. Major advances in uncovering the vast biodiversity of microbes in the environment have generally relied upon analyzing the ribosomal genes genes involved in creating ribosomes that are common to all life to establish relationships and diversity. Zehr has instead used the genes directly involved with nitrogen fixation to find and characterize previously unknown microbes capable of fixing N2in the ocean and to track the expression of these genes.

Well-known for his work among the tiniest marine plankton, Zehr discovered a biological partnership, or symbiosis, of two microorganisms found throughout much of the worlds upper ocean.

One partner, the host alga, is eukaryotic meaning it has a nucleus and is autotrophic, able to use light energy and fix carbon; that is, take up carbon dioxide to feed itself and produce new organic molecules.

The other partner is a small, unicellular cyanobacterium, or blue-green alga, that can also derive energy from light but is unable to fix carbon. However, it does fix N2.

The two exchange metabolites in their symbiosis, and the cyanobacterium is a major player in fixing N2in the oceans, says Capone, who also hints that his and Zehrs combined expertise is a kind of symbiosis in its own right, making them particularly well-suited to put togetherMarine Nitrogen Fixation.

In many ways, we complement each other Jon on the molecular biology, physiology and biogeography of nitrogen fixation, myself focusing on ecology and biogeochemistry, Capone says.

In the book, which is primarily intended for scientists, graduate students and upper division undergraduates, he and Zehr give a detailed overview of the current understanding of global marine nitrogen fixation. Topics include which marine microorganisms are fixing nitrogen, where they live and what environmental factors including human-caused changes such as ocean warming and acidification impact microbial activity. And they point out that much about the physiology and regulation of N2fixation remains to be uncovered.

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Life on Earth may be carbon-based, but another element matters, too > News > USC Dornsife - USC Dornsife College of Letters, Arts and Sciences

Physiology

Honoring the Class of 2021 – Daily Sentinel

REEDSVILLE Members of the Eastern High School Class of 2021 were recognized for their athletic and academic achievement during an awards ceremony on Thursday at Eastern High School.

Jenna Chadwell was announced as the Class of 2021 Valedictorian, with Layna Catlett announced as the Class of 2021 Salutatorian.

The remainder of the Top 10 of the Class of 2021 includes Jonna Epple, Olivia Barber, Skylar Honaker, Alysa Howard, Kelsey Roberts, Whitney Durst, Tessa Rockhold and Alisa Ord.

Class of 2021 graduates to receive an Honors Diploma include: Jake Barber, Olivia Barber, Layna Catlett, Jenna Chadwell, Whitney Durst, Jonna Epple, Ashton Guthrie, Skylar Honaker, Alysa Howard, McKenzie Long, Brianna Nutter, Alisa Ord, Kelsey Roberts, Kennadi Rockhold, Tessa Rockhold, and KayCee Schreckengost.

Jenna Chadwell was the WSAZ Best of the Class representative.

Class of 2021 National Honor Society members were Jake Barber, Matthew Blanchard, Natalie Browning, Layna Catlett, Whitney Durst, Jonna Epple, Ashton Guthrie, Skylar Honaker, Alysa Howard, Blake Newland, Brianna Nutter and Kelsey Roberts.

Hunter Corwin-Cline, a member of the Class of 2021 who passed away earlier this year, was recognized with the OHSAAs Courageous Student Award. Athletic Director Josh Fogle stated that the award recognized the strength, courage, and ability to overcome challenges which Hunter had shown during his life. The award was accepted by his mother Michelle Cline.

Athletic Awards

Steven Fitzgerald was recognized as the Ivan B. Walker Male Athlete of the Year. Sydney Sanders was recognized as the Ivan B. Walker Female Athlete of the Year.

Steven Fitzgerald and Ashton Guthrie received the OHSAA Archie Griffin Sportsmanship Award.

Matthew Blanchard and Jenna Chadwell received the OHSAA Scholar-Athlete Award.

Jake Barber and KayCee Schrekengost received the NFHS Award of Excellence.

US Army Reserve National Scholar-Athlete Awards were presented to Blake Newland and Whitney Durst.

Senior Athlete Awards were presented to Jake Barber, Olivia Barber, Matthew Blanchard, Layna Catlett, Jenna Chadwell, Whitney Durst, Jonna Epple, Steven Fitzgerald, Ashton Guthrie, Brad Hawk, Bruce Hawley, Alysa Howard, Derrisa Johnson, Owen Johnson, Jacey Martin, Blake Newland, William Oldaker, Alisa Ord, Conner Ridenour, Kelsey Roberts, Kennadi Rockhold, Tessa Rockhold, Sydney Sanders, KayCee Schrekengost, Faith Smeeks, Hunter Sisson and Preston Thorla.

Jim Barber was recognized with the Community Member Award.

Scholarships and additional awards

Eastern Athletic Boosters Scholarship Kelsey Roberts and Jake Barber, $1,000 each;

Emeri Connery Flying Eagle Scholarship Ashton Guthrie, $1,000;

Kevin Fick Scholarship Skylar Honaker, $1,000;

University of Rio Grande Jake Bapst Scholarship Whitney Durst, two years tuition approximately $10,000;

University of Rio Grande Robert S. Wood Scholarship Tessa Rockhold, $1,000;

4-H Cords Whitney Durst, Steven Fitzgerald, and McKenzie Long;

Jordan Hardwick Memorial Scholarship Tessa Rockhold;

Justin Hill Memorial Scholarship Jenna Chadwell and Tessa Rockhold, $500 each;

Eagles Scout Award Jake Barber;

Eastern Music Booster Scholarship Blake Newland and Matthew Blanchard;

Eastern Music Booster Awards Blake Newland, Matthew Blanchard, Derrisa Brewer-Johnson, Brogan Holter, Kelsey Reed, Katlyn Lawson, William Oldaker, Conner Ridenour, and Hunter Sisson.

ELEA Schoalrship Brad Hawk, Blake Newland and Nicole Bean (Athens High School), $500 each;

Board of Education Scholarships Valedictorian Scholarship, Jenna Chadwell, $550 (four years); Salutatorian Scholarship, Layna Catlett, $450 (four years); Green Scholarship, Jonna Epple, $425 (four years); White Scholarship, Skylar Honaker, $350 (two years);

William and Wilma Williams Scholarship Sydney Sanders and Whitney Durst, $750 each for four years;

Bill Call Scholarship Blake Newland, $2,100;

Lewis Parker Scholarship Alysa Howard, $1,000;

OVEC Kyger Creek Science Scholarship Jonna Epple, $450;

Eichinger Family Scholarship Layna Catlett and Alysa Howard, $2,500 each;

Hills Classic Cars Cruisin Saturday Night Car Show Scholarship Blake Newland, $1,000;

Washington State Community College Presidential Scholarship Skylar Honaker and Alisa Ord, $2,000 each per year;

Marshall University Opportunity Grant Alysa Howard, $2,000 per year;

Holzer Science Award Jonna Epple, $450;

Anatomy and Physiology Award Jonna Epple;

Calculus Kelsey Roberts;

Trigonometry Olivia Barber;

Transition to College Math Natalie Browning.

2021 Ohio Valley Publishing, all rights reserved.

Sydney Sanders receives the Ivan B. Walker Female Athlete of the Year award from Athletic Director Josh Fogle.

Steven Fitzgerald receives the Ivan B. Walker Male Athlete of the Year award from Athletic Director Josh Fogle.

Hunter Corwin-Cline, a member of the Class of 2021 who passed away earlier this year, was honored with the Courageous Student Award.

Skylar Honaker receives the Board of Education White Scholarship from board member Jessica Staley.

Michelle Cline, the mother of Hunter Corwin-Cline, accepts the Courageous Student Award from Athletic Director Josh Fogle in memory of her son Hunter.

Jake Barber was presented the Eagle Scout award and cords by Floyd Ridenour.

Jonna Epple receives the anatomy and physiology award and Holzer Science Award from Ginger Wills.

Members of the Eastern National Honor Society received their gold cords.

Whitney Durst, Steven Fitzgerald and McKenzie Long, 4-H members, received green cords to be worn at graduation from Carolyn Kesterson.

Tessa Rockhold receives the Jordan Hardwick Memorial Scholarship from Rebecca Birt.

Tessa Rockhold receives the University of Rio Grande Robert S. Wood Scholarship from Michelle Kennedy.

Kelsey Roberts receives the Eastern Athletic Booster Scholarship from Josh Fogle.

Eagles receive scholarships, awards

Sarah Hawley is the managing editor of The Daily Sentinel.

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Honoring the Class of 2021 - Daily Sentinel

Physiology

Bizarre ‘stomach’ case put Plattsburgh on the map – Plattsburgh Press Republican

PLATTBURGH -- French-Canadian Alexis St. Martin returned several times to the United States, where hundreds of physiological experiments were conducted on him by Dr. William Beaumont,The Father of Gastric Physiology.

CUTTING-EDGE RESEARCH

In 1833, Beaumont's notes and drawings were consolidated in a book, Experiments and Observations of the Gastric Juice and the Physiology of Digestion published by by F. P. Allen, a local newspaper publisher in Plattsburgh.

The book was later published in Great Britain, France, Germany and Scotland.

Dr. Paolo Fedi of Beaumont Gastroenterology Services was able to secure a first-edition copy of the rare tome.

The book was poorly published because this was a newspaper, Fedi said.

It was not a publication that was done in a bound book. Beaumont never used any of the important universities at that time. He never connected with them. So this book, a few copies remained.

Medical interest surged in Beaumont's research and his study of St. Martin.

Everybody wanted him to come to their place, but this guy refused to connect further, Fedi said.

He went into Canada and disappeared from any public venue. He didn't want to have anything anymore.

SUCCESSFUL PRACTICE

St. Martin would not meet in St. Louis with Beaumont, whowas stationed there in 1830 and was appointed Surgeon at Jefferson Barrack and later the Arsenal.

About 1835, he took up his residence in St. Louis and two or three years later he resigned from the Army and took up private practice, according to his obituary.

Beaumont lived in St. Louis 19 years, where he was appointed Professor of Surgery at Saint Louis University's Medical Department.

He died (April 25, 1853) after a slip on the ice while he was going to see a patient, Fedi said.

Beaumont is buried in Bellefontaine Cemetery in St. Louis as his wife, Deborah Greene Beaumont (1799-1870) and their daughter, Sarah Beaumont Keim (1825-1913).

Their son, Israel Greene Beaumont (1829-1901 is buried in the Woodlawn Cemetery in Green Bay, Wisconsin.

Living in Plattsburgh here, he had an office where the store that is now called Ashley Furniture is, Fedi said.

He had an office and practice there. There is a plaque there that was placed by the Medical Society, I think in the '70s.

After his publication, he was able to determine that the stomach is able to digest food because it produces acid. They called it at the time muratic acid. Now, it's what is called hydrochloric acid. Before that we did not know the stomach was producing acid. The science at the time held food sat or putrefied in the stomach.

Beaumont's experiments with St. Martin proved and demonstrated otherwise.

That made an explosion of research everywhere, Fedi said.

His work was really fundamental to the understanding of the digestion of the GI tract.

He was a great observer. He was able to kind of look at the stomach and he realized that the weather, the stress of different things was able to affect the stomach of the GI tract, illnesses.

So when Alexis was drinking too much, they were able to see that his stomach wasn't really healthy, and it was taking much longer to digest than what was normal.

The pioneering medical researcher also noticed similar outcomes for the effects of tobacco on the stomach.

Beaumont put Plattsburgh on the map for medical history because at that time there was not really major hospital or any other things here, Fedi said.

Because of the Army base and him, it became an important site.

PARTED WAYS

St. Martin, born April 8, 1802 in Berthierville, Quebec, died June 24, 1880 in Saint-Thomas de Joilette in Quebec.

The wood chopper fathered 22 children, and his burial site remained secret until 1962.

He was so worried that somebody would come and get even when he was dead, he left a will that stated his body should be left to decompose for four or five days before he was put in the ground and one should know where the body would be, Fedi said.

Alexis Bidagan dit St-Martin is buried at St. Thomas Parish Cemetery in Joliette, Quebec.

A great-niece of his made it public that he was actually buried in the cemetery of a specific church, so they were able to put a tombstone with his name and other things," Fedi said.

"It is just outside of Montreal.

Beaumont name's graces the Beaumont Hall Science Building at SUNY Plattsburgh, the William Beaumont Army Medical Center in El Paso, Texas, and the largest health care system in Michigan.

It's still amazing that many people do not know anything about this history, Fedi said.

I have medical practice called Beaumont. Many people are like 'You're Italian, why do you use this French name?'

I love history. I'm fascinated with the idea that I can use his name for a practice of the GI tract.

Email Robin Caudell:

rcaudell@pressrepublican.com

Twitter:@Robin Caudell

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Bizarre 'stomach' case put Plattsburgh on the map - Plattsburgh Press Republican

Physiology

New method shows that tau forms small aggregates as part of the body’s normal physiology – News-Medical.Net

It turns out that not all build-ups of tau protein are bad, and a team of researchers from the Perelman School of Medicine at the University of Pennsylvania developed a method to show that. Using mammalian cell models, the researchers combined extremely high-resolution microscopy with machine learning to show that tau actually forms small aggregates as a part of the body's normal physiology.

Through this, they could distinguish between the aggregates occurring under healthy conditions from the ones associated with neurological diseases, potentially opening the door to screening for treatments that might break apart harmful aggregates. This research was published in the Proceedings of the National Academy of Sciences of the United States of America.

"There aren't many tools that can visualize small, pathological protein aggregates within cells," said the study's senior author, Melike Lakadamyali, PhD, an associate professor of Physiology. "But through machine learning informed by super-resolution microscopy, we believe we've been able to show that tau forms both normal physiological aggregates and distinct pathological aggregates. In doing so, we created a useful method that could be the basis for new research into the appropriate treatments for tau-related pathologies."

Tau is a protein that attaches to the microtubule structure of axons - which act much like highways in nerve cells. Previously, tau aggregates had been thought to only form once tau falls off the microtubules. These have been associated with some neurological diseases, including Alzheimer's and other types of dementia. However, it turns out that small tau aggregates can also form outside disease conditions.

Intrinsically, there is value in being able to tell which tau aggregates are a part of a healthy person's nervous system, and which have formed harmful aggregates. Unfortunately, there has not been a process sensitive enough to make that distinction yet inside cells. So we set out to create one using mammalian cell models."

Melina Theoni Gyparaki, Study Lead Author adn Doctoral Student in Lakadamyali's Lab

First, the researchers used extremely high resolution microscopes capable of looking at single molecules to differentiate physiological and pathological oligomers (molecular formations). Monomers, dimers and trimers, which are oligomers made up of one, two, and three tau molecules, respectively, were most likely to end up associated with healthy physiological conditions because they were associated with microtubules and regular function.

When the team looked at tau structures associated with a mammalian cell model approximating frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) - a disease associated with tau aggregation - the structures were larger and more complex. These appeared to be the pathological tau aggregates that broke off.

With the differences in configuration established, the researchers created a machine learning algorithm to classify the pathological tau aggregates by shape alone. Additionally, they used antibodies that can detect and differentiate when the tau aggregates become "hyper-phosphorylated" - when they pick up a lot of phosphate groups and tend to harmfully break off. Combining these methods showed that tau containing phosphate groups on certain amino-acids was more likely to form linear fibrils, a thin structure, as opposed to other shapes of tau aggregates.

"The method we developed to identify tau aggregates is not yet a diagnostic tool, but we think it would be a useful research tool for anyone interested in studying the mechanisms that lead to pathological protein oligomerization in neurodegenerative disease," Lakadamyali said.

Tau aggregates aren't the only ones that this method could be used to classify, either. There's an opportunity to use it on other potentially pathological protein build-ups, such as alpha-synuclein, which is associated with Parkinson's disease, or huntingtin, related to Huntington's disease. It could also be used to screen for potential treatments for these conditions that don't harm the body's regular protein complexes.

The team is now studying potential mechanisms for clearing tau aggregates and determining what other pathways could be helpful in this regard.

"We are also further using the method we devised to visualize tau aggregates in human postmortem brain tissue slices from Alzheimer's disease to determine the role of tau's post-translational modifications in aggregation," Lakadamyali said.

Source:

Journal reference:

Gyparaki, M. T., et al. (2021) Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2021461118.

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New method shows that tau forms small aggregates as part of the body's normal physiology - News-Medical.Net