Category Archives: Physiology

Mike Marshall, 78, First Relief Pitcher to Win Cy Young Award, Dies – The New York Times

Mike Marshall, who became the first relief pitcher to win the Cy Young Award when he appeared in a major league season-record 106 games for the 1974 Los Angeles Dodgers, died on Tuesday at his home in Zephyrhills, Fla., near Tampa. He was 78.

His death was announced by the Dodgers, who said that his daughter Rebekah had told them, without providing further details, that he had been in hospice care.

Marshall developed extraordinary endurance through his knowledge of kinesiology, the mechanics of bodily movement, long before pitchers used high-tech equipment in hopes of improving their performance and warding off arm injuries.

He earned a doctorate in exercise physiology from Michigan State University in 1978, when he was pitching for the Minnesota Twins, and later taught there. His best pitch was a screwball, which breaks in the opposite direction from that of a curveball.

In addition to his single-season record for most games pitched, Marshall, a right-hander, pitched in 13 consecutive games in 1974, threw 208 relief innings and finished 83 games major league records as well.

Appearing solely in relief in 1974, his sideburns curling toward his mouth, Marshall was an all too familiar figure to batters in the late innings. He had a 15-12 record in 1974 with a 2.42 earned run average and 21 saves.

But he gained a reputation for being condescending when baseball writers sought to interview him.

I remember the sportswriters in Los Angeles come into the locker room and ask: How are you able to do this? Youre going to break down, Marshall was quoted as saying by The Los Angeles Times. I said: Hey, its simple. Its kinesiology, and all you have to understand is what the latissimus dorsi muscle can do for you. And then you get to use the triceps brachii and the inner teres. Its right there. And theyd walk away.

During the 1974 World Series, the sports columnist Dave Anderson of The New York Times wrote of how Marshall had declined to provide more than perfunctory answers to reporters postgame questions. Privately, he noted, many of his teammates dislike his aloof, impersonal manner, but they tolerate it because of his durability and talent.

Indeed, there was no disputing Marshalls impact on his fellow Dodger pitchers. Im a better student of hitters since Mike joined this year, said Andy Messersmith, who won 20 games in 1974. Marshall had been traded to the Dodgers by the Montreal Expos.

In winning the National League Cy Young Award, the major leagues most coveted prize for a pitcher, Marshall beat out Messersmith for the honor, collecting 17 of 24 possible first place votes. Eight relief pitchers from both leagues have since won the award.

In his only postseason appearances, Marshall pitched in two National League Championship Series games against the Pittsburgh Pirates in 1974 and in every game of the World Series, when the Dodgers lost to the Oakland As, 4 games to 1. In the Dodgers only victory, he picked off Oaklands Herb Washington, their world-class sprinter, when Washington, representing the potential tying run, was taking a lead off first base in what became the Dodgers 3-2 victory in Game 2.

Marshall was an All-Star with the Dodgers in 1974 and 1975. He holds the still-standing American League record for games pitched in a season with 90 for the 1979 Twins.

Michael Grant Marshall was born on Jan. 15, 1943, in Adrian, Mich., about 70 miles southwest of Detroit. He was signed by the Philadelphia Phillies organization in September 1960 but didnt make his major league debut until 1967, with the Detroit Tigers.

After developing a sore arm in his rookie season, Marshall studied ways to reduce stress on his arm by changing the dynamics of his pitching motion.

The Seattle Pilots obtained him in baseballs expansion draft as they stocked their inaugural team of 1969, after he had returned to the minors for one season. He later pitched for the Houston Astros and the Expos, who traded him to the Dodgers for outfielder Willie Davis. The Dodgers traded him to the Atlanta Braves in midseason 1976, and he later pitched for the Texas Rangers, the Twins and then the 1981 Mets in his final major league season.

Marshall pitched in 724 games, all but 24 in relief, in his 14 major league seasons. He had a 97-112 record with 188 saves and an earned run average of 3.14.

In addition to his daughter Rebekah, his survivors include his second wife, Erica, and his daughters Kerry and Deborah. All three children were from his marriage to his first wife, Nancy Marshall, who died in April, The Associated Press reported.

Marshall left his posts as a physical education teacher and head baseball coach at West Texas A&M in 1994 and moved to Florida to found a baseball clinic in Zephyrhills.

He had his students throw hard every day, wind up with 30-pound weights around each wrist and heave 12-pound iron balls at a wooden backstop.

Nobody whos gone through this program has ever gotten hurt, he told Sports Illustrated in 2001. These kids are now injury-proof.

I was dismissed as a physical freak, he said. I did things nobody had ever done. For me not to be considered the best relief pitcher in the history of baseball is silly.

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Mike Marshall, 78, First Relief Pitcher to Win Cy Young Award, Dies - The New York Times

WGME, BDN cite UMaine discovery of invasive earthworm in Northern Maine – UMaine News – University of Maine – University of Maine

WGME (Channel 13 in Portland) and the Bangor Daily News cited a University of Maine study that discovered the invasive European earthworm in two forest sites in Northern Maine. The study by research associate Joshua Puhlick, professor of soil sciences and forest resources Ivan Fernandez and assistant professor of forest ecosystem physiology Jay Wason was published in the journal Forests. The County and Fiddlehead Focus advanced the BDN report.

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WGME, BDN cite UMaine discovery of invasive earthworm in Northern Maine - UMaine News - University of Maine - University of Maine

MLB Injury Report: Zac Gallens Path Back to the Mound – fantraxhq.com

Nic Civale is a Doctor of Physical Therapy and former NCAA Division I Baseball player. He combines his knowledge of anatomy and physiology with that of baseball mechanics to provide expectations for injured players. Utilize The MLB Injury Report to make the most of your fantasy season. Today he looks into the recent injury woes of talented right-hander Zac Gallen.

Diagnosed with a UCL sprain in early May, Zac Gallen has begun his return to throwing bullpens. He is a staple of many fantasy managers rotations and one of the best young pitchers in MLB.

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The Ulnar Collateral Ligament (UCL) is a small, yet strong ligament that connects the humerus, or upper arm, to the proximal end of the ulna. The ulna is one of two bones that make up the forearm. The job of the UCL is to maintain stability in the elbow joint as it experiences massive rotational and translational forces during the throwing motion. As you may have heard from coaches or baseball analysts, the overhead throwing motion is not necessarily one that our bodies were designed for. To tolerate the repetitive nature of overhead throwing, the baseball athlete effectively reshapes their body and muscular identity to accommodate for the unnatural motion.

To most physical therapists, a baseball player is easy to spot without the need for an interview because they will almost certainly exhibit more shoulder external rotation and less internal rotation in their throwing arm. Also commonly seen is a greater allowance for trunk rotation to one side (unless they are a switch hitter or thrower). Additionally, there is almost always some degree of wear and tear on the UCL. Yes, many, if not most, ballplayers will end their careers with micro-tears, inflammation, and even scar tissue build-up in or around their UCL. If you took an MRI of all MLB pitchers, it wouldnt surprise me to learn that 90% of them had evidence of some type of UCL sprain. Which brings us to the hero of this story, Zac Gallen.

Diagnosed with a stress fracture in the radial head of his throwing arm earlier this year, Zac Gallen has more recently learned of a UCL sprain in the same arm. He has been resting his arm since experiencing discomfort back in early May. The last start he completed was May 7, where he completed six frames of 1 run ball. After about 3 weeks of rest and therapy, his pain had diminished, the swelling had abated and subsequent imaging and testing showed appropriate healing.

On Tuesday, June 1, Gallen threw a 30 pitch bullpen, with the entire arsenal on the table. There have not been any reports of setbacks or discomfort and it appears he is ready to progress in intensity and volume. If he was to progress with his pitch count by about 15 pitches per 5-day rotation, he would theoretically be available by late June or early July. There is a heavy dose of optimism in that projection, for sure, but it is possible.

Gallens scenario is a very fitting example of the dangers of giving up on a player too early if you dont completely understand the injury and its implications. Many fantasy managers were hastily selling low on Gallen, assuming Tommy John surgery (TJS) was imminent. Ultimately, it is still possible that Gallen has a setback and receives the surgery. After all, hes not in the clear after a successful 30-pitch pen. But deeming a player as doomed after any type of injury pops up in the throwing elbow is something fantasy managers are too hasty in resorting to. As previously mentioned, youd likely be hard-pressed to find an MLB pitcher who hasnt undergone some sort of UCL injury or damage; a sprain isnt a ticket to the operating room.

Additionally, we know Gallen was recovering from a separate and unrelated arm injury in the radial stress fracture. This was essentially a crack, but not a displacement, of the other forearm bone, with no isolated long-term implications, whatsoever. The only long-term effect this may have indirectly had on Gallen is that it disrupted his throwing program and routine. It is possible that this alteration of scheduling may have influenced the ultimate sprain of the UCL. There is no way we could ever know for sure, but it is reasonable to connect the two.

This makes me think the UCL sprain was not something that was inevitable and slowly approaching. Theres nothing glaringly abnormal about his mechanics, he has not experienced a dramatic velocity gain or a significant arsenal change. His control has been characteristically good. Nothing about his game draws a red flag. I think the UCL sprain was more likely to be related to the abnormal year he had had so far.

Pitchers are generally an extremely regimented and schedule-based species. And Gallen has not had any normalcy to his year. A month-long alteration is his throwing program and daily routine coupled with a nearby fracture certainly seem more responsible than anything else.

So what does this mean going forward? My only option is to look at this as a physical therapist would. I could see it being an exam question in a biomechanics final

You are evaluating a 25-year-old, otherwise healthy, professional baseball pitcher. He has experienced a UCL sprain as evidenced by MRI. There are no concrete indications that this was a progressive injury, linked to increased load, or arsenal change. There has been no other recent UCL injury. The athlete recently experienced a nearby stress fracture that altered his throwing program and caused a month-long progression in workload to return to his baseline. The athlete was able to return from this stress fracture and perform to his standards for over 1 month until he experienced discomfort in the medial elbow. He is currently progressing his pitch count and has successfully built up to a 30-pitch bullpen without symptoms. How do you approach the remaining rehabilitation program?

A) Contact surgeon for additional consultation. Suggest TJS due to previous sprain.

B) Aggressively progress patient though throwing program up to his previous norms. He is ready for increased intensity.

C) Incrementally increase workload and complexity of throwing sessions, with constant evaluation of symptoms, while checking patient range of motion and strength.

D) Tell your fantasy baseball friends to trade him for cents on the dollar; hes toast.

Yes, the answer is C! Its always C!

This will be a closely observed and slow process, but everything that is occurring points to a return in 2021, even if it means waiting until the All-Star break. The Diamondbacks would be very smart to be extremely cautious with their young ace, and heed any warnings based off of negative symptoms. But I am all in on Gallen, as I have been for years. He is a special pitcher, who has a great understanding of what he needs to get out of his body to be a successful pitcher. It isnt a coincidence he has had such success in the league without elite velocity or stuff. If he continues to increase his workload without setback, Im not going to be worried about any long-term implications here. You shouldnt either.

Did you know Eric Cross has recently updated his Dynasty Rankings? Check them out here for all the best info on the long-term values of the top MLB and MiLB players.

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MLB Injury Report: Zac Gallens Path Back to the Mound - fantraxhq.com

LifeQ, Preeminent Provider of Biometrics and Health Information, Partners with 1Life on New COVID-19 Screening Application – BioSpace

ATLANTA, June 2, 2021 /PRNewswire/ --LifeQ, the preeminent independent provider of biometrics and health information derived from wearable devices and used in world-leading health management solutions, announced it has partnered with South Africa-based insurance leader 1Life on a new version of its COVID-19 screening application. This announcement comes at a time when COVID is still a serious threat across the globe, and the importance of early detection and spread prevention remains critical.

1Life's new LifeQ-powered health management solutiontracking and providing insights derived from users' LifeQ enabled wearable deviceswill now flag potential COVID-19 onset in policy holders before symptoms are experienced. This is in addition to providing a wealth of health information that improves users' lives.

The LifeQ COVID-19 app aims to reduce and prevent transmission of the virus by alerting individuals to possible infection prior to symptom onset through a combination of physiological monitoring and user feedback. Individuals are alerted to changes in physiology, including heart rate, breathing rate and other factors detected via their wearable device, and are prompted to provide contextual feedback via the app.

Utilizing biometric data to give users an indication of changes in their health, LifeQ already has a proven track record with early-adopter employers of flagging COVID onset in an employee ahead of the dangerous 48-hour period of viral shedding, avoiding costly office sterilization and imposing quarantine on fellow-employees.

"One of the biggest problems with COVID-19 is the period in which the individual has the disease and doesn't know it, making transmission to loved ones, work colleagues or the general public more likely," said Laurence Olivier, CEO of LifeQ. "While the screening app is not an official diagnostic tool, and all medical and testing protocols must be followed according to local government guidelines, LifeQ's COVID application utilizes state-of-the-art technology to give people the information they need to be proactive, slow the rate of infection, and avoid illness."

The LifeQ COVID-19 app ensures users can monitor their status to receive any indication of changes in health and possible COVID infection. A green status signals that you are doing well; a yellow status signals that that you should be exercising caution and monitor yourself for symptoms within the next 1-2 days; and a red status signals that you are unwell since you have either reported symptoms or a positive COVID test within the app. The app also gives users a pre-infection risk score that provides an indication of their risk of getting seriously ill if they were to contract the virus.

About LifeQ

LifeQ is the leading independent provider of biometrics and health insights derived from wearable devices, helping people live healthier lives. By providing a 24/7 lens into the body, LifeQ's solutions go beyond an everyday smart watch, generating business-grade biometrics for consumers, athletes, and the acutely and chronically ill to detect health problems earlier, manage their existing problems, and prevent illness. Consumers, wearable device companies, insurers and reinsurers, health-tech companies, clinicians, researchers and analytics companies all benefit from LifeQ's powerful capabilitiesrepresenting the future of healthcare. For more information, please visit http://www.lifeq.com.

Contact: Deborah Geiger, deborah@geigercommunications.com

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LifeQ, Preeminent Provider of Biometrics and Health Information, Partners with 1Life on New COVID-19 Screening Application - BioSpace

Should You Avoid All Alcohol? Here’s What the Experts Think – Healthline

Is alcohol good for you or bad? Does it depend on the quantity?

According to a recent study by a group of scientists at Oxford University in England, theres no safe dose for alcohol consumption.

The observational study looked at data from more than 25,000 middle-aged adults. The study found that moderate consumption is more closely associated with adverse effects on the brain than was previously known. They found that alcohol was negatively associated with global brain gray matter volume. Also, individuals with comorbidities like high blood pressure and a high BMI, or those who binge drink, may be more susceptible to these adverse effects.

For decades, doctors have described moderate drinking a maximum of one drink per day for women and two a day for men as low risk and perhaps even good for health.

But that view appears to be shifting. Last year, an expert advisory committee for the 2020 Dietary Guidelines for Americans recommended that the daily limit be lowered to one drink for men. One drink is said to be equivalent to 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of liquor.

Experts are mixed on the benefits of alcohol, but they are clear on the harm of too much drinking. Binge drinking can increase the risk for high blood pressure, stroke, and congestive heart failure. Experts also agree that alcohol is a proven cause of several kinds of cancer, including breast and liver cancer.

Alcohol is associated with dementia. Even moderate intake can affect brain dementia, said Kenechukwu Mazue, a nuclear cardiology fellow at Massachusetts General Hospital in Boston. Theres really no safe level.

While Mazue has seen studies that suggest that wine may have health benefits, he counsels patients to stay within limits set by the U.S. Department of Health and Human Services.

For those who dont drink, I dont ask them to start because of the potential for alcohol dependency.

Shivendra Shukla, PhD, the Margaret Proctor Mulligan Professor of medical pharmacology and physiology at the University of Missouri in Columbia, warns even a small amount of alcohol can be damaging.

Shukla has researched binge drinking and chronic drinking over the last 25 years.

Alcoholic consumption in any amount is bad, Shukla said. Alcohol has a domino effect. Alcohol is a very mysterious chemical. Once in the body, it has multiple pathways by which it can exert damaging effects. Its just like a cluster bomb. The consequences can be very injurious.

Dr. Jeanette Tetrault, a professor of medicine and addiction specialist at the Yale School of Medicine, takes a more measured view of alcohol consumption.

We know that there are negative health effects related to alcohol consumption, she said. We know there are situations where any drinking can have negative health effects, including for populations such as pregnant women, adolescents. Our messaging as providers needs to be to look at individual circumstances and assess the risk and health effects of individuals. Abstinence-only does not work. Weve seen public health campaigns like that fail in the past.

A message that alcohol is bad and should be avoided at all costs could lead to the loss of a clinical relationship between providers and patients, she said.

Dr. Patricia Molina, professor and head of the Department of Physiology at the Louisiana State University School of Medicine in New Orleans, shares a similar view. Yes, alcohol use in certain populations such as those with chronic diseases should be discouraged, said Molina, a physician and past president of the American Physiological Society.

The message should be alcohol consumption in moderation, said Molina. The pattern of consumption can have a significant impact on health. Talk with a physician if you have a chronic disease.

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Should You Avoid All Alcohol? Here's What the Experts Think - Healthline

Naval aviation bridges medicine, engineering to advance aerospace tech – The Southern Maryland Chronicle

NAVAL AIR WARFARE CENTER AIRCRAFT DIVISION, (Patuxent River, Md.) The Naval Air Warfare Center Aircraft Division (NAWCAD) is advancing its human systems technology by combining best practices from the medical and engineering communities.

The warfare center recently stood up the Aeromedical Monitoring and Analysis branch comprised of licensed medical military officers bridging their perspective with engineering disciplines to improve operational capabilities like night vision technology, hearing protection, mission planning software, and more.

Medicine and engineering seldom wholly come together, said NAWCAD Aeromedical Monitoring and Analysis branch head Cmdr. Matthew Doubrava, a Navy Flight Surgeon board certified in Aerospace Medicine and Occupational Medicine. Our team of biomedical scientists looks forward to bringing human oriented science and a medical perspective to enhance our Navys advanced technology.

The uniformed medical specialists have a broad range of academic expertise including aerospace and occupation medicine, optometry and vision science, audiology, research and aviation physiology, and experimental psychology. With these skillsets, they will work directly alongside NAWCAD engineers, testers, and aviators to enhance their research, development, tests, and evaluation to advance aerospace technology. Adding this expertise will help create technology more relevant to human capability, and fill knowledge gaps where technical professionals typically hold little experience.

The Navys challenge with physiological episodes showed us how critically important a medical perspective can be, said Doubrava. Were working to stay ahead of the curve what is the next physiological episode on the horizon and how can we prevent it?

NAWCADs lineup of clinical scientists completed health care professional and graduate school, and entered the Navy to receive specialized training as aeromedical and research professionals. Most attended the six-month Aeromedical Officer Course that consists of a specialized flight school syllabus and clinical training in Pensacola, Florida. As an aeromedical officer, they hold a Navy aeronautical rating that requires a monthly minimum of aircrew flight time making them uniquely qualified as aeromedical professionals. While their primary mission is medical research, they are required to accrue flight time with fleet aviators for continued understanding of naval aviations evolving systems.

NAWCAD advances capability and operational readiness for naval aviation and our warfighters. The warfare center is where naval aviation takes flight through research, development, test, evaluation, and sustainment of both fielded and not-yet fielded naval platforms and technologies that ensure Americas Sailors and Marines always go into conflict with significant advantage. With sites in Patuxent River, Maryland, Lakehurst, New Jersey, and Orlando, Florida, the command is the Navys largest warfare center with a diverse force of military, civilians, and contractors building the Navy of today, the Navy of tomorrow, and the Navy after next.

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Naval aviation bridges medicine, engineering to advance aerospace tech - The Southern Maryland Chronicle

Gene therapy for overactive bladder | TCRM – Dove Medical Press

Introduction

Overactive bladder (OAB) is a disorder characterized by urgency and frequency with and without urinary incontinence. It affects 15% to 25% of the general population older than 40 years of age.15 Current guidelines recommend non-subtypeselective oral antimuscarinics or 3-adrenergic receptor agonists as primary pharmacotherapy.68 Although these agents modulate the neurotransmitter-mediated signals that cause OAB-related symptoms,9 some, such as anticholinergics, are associated with challenging adverse effects that limit compliance, and they may not be effective in all patients.611 Chemodenervation agents may improve symptoms with similar or even greater efficacy compared with oral agents; however, treatment with botulinum toxin may result in unwanted post-procedural outcomes such as urinary retention and urinary tract infections. Other treatments for OAB are limited by cost and invasiveness, require general anesthesia (eg, sacral neuromodulation), or have limited efficacy and require inconvenient weekly treatment sessions (eg, percutaneous tibial nerve stimulation).12 Thus, while bladder-targeted treatments are available, there remains an unmet need for locally administered interventions to treat OAB.

The large-conductance, voltage- and calcium-activated K+ channel, known as the big potassium (BK) or Maxi-K channel, is highly expressed on urinary bladder smooth muscle cells and regulates bladder detrusor muscle function.13 BK channel activation reduces smooth muscle cell excitability, and therefore modulation of this channels activity by the introduction of a locally instilled plasmid expressing the BK channel is a potential novel approach to OAB treatment. This article reviews the physiological importance and regulation of the BK channel in the bladder, as well as the potential of BK channel modulation with gene therapy in the management of OAB.

When functioning normally, the bladder has a change in internal volume from nearly zero to >400 mL during its filling cycle.14 During voluntary or involuntary voiding, the detrusor smooth muscle cells go from a state of low tension to a rapid contraction in order to empty the bladder. Detrusor smooth muscle is organized in contractile units in a syncytium connected by gap junctions that facilitate the spread of contractile function throughout the detrusor muscle tissue.15 These contractile units show spontaneous depolarizations leading to uncoordinated contractile activity that has little effect on intravesical pressure but is essential for maintaining tone of the bladder wall.16 The spontaneous activity in turn generates afferent nerve activity and the sensation of bladder filling.17,18 Increases in the spontaneous activity leading to increased afferent nerve activity have been considered important in the generation of OAB symptoms.

In order to produce an emptying contraction, coordination of the activity of the muscle units is necessary, and this is provided by excitatory input from the parasympathetic system.17 Bladder emptying contraction is initiated by a massive release of acetylcholine from the pelvic nerve, which stimulates muscarinic (M3) receptors on the detrusor smooth muscle cell, and triggers an intracellular signaling cascade that leads to simultaneous membrane depolarization of all detrusor muscle cells. This results in the opening of voltage-dependent Ca2+ channels at the cell surface and a massive influx of extracellular calcium. High intracellular Ca2+ is sensed by calmodulin, an intracellular messenger protein, which leads to the activation of myosin light chain kinase and muscle contraction.17

Relaxation of detrusor smooth muscle cells is mediated, at least in part, when K+ channels open to allow the efflux of K+ ions, and hyperpolarization of the cell membrane is produced, leading to diminished intracellular calcium levels and reduction of the spontaneous activity and thus reduced detrusor muscle tone.13 This mechanism operates during the filling phase, when OAB symptoms are experienced, and has no effect on the emptying contraction. Thus, restoration/maintenance of the endogenous ionic mechanisms that govern smooth muscle cell tone, through targeted gene therapy, is an attractive approach to the treatment of any disease or disorder characterized by altered smooth muscle cell physiologyincluding OAB. The BK or Maxi-K channel is the K channel subtype most responsible for creating and maintaining the cells resting membrane potential.

Gene therapy can be used to treat diseases and conditions such as OAB. Specifically, we suggest that tissue or organ-specific overexpression of key modulators of smooth muscle function can mitigate pathophysiological features of diseases as diverse as hypertension, asthma, irritable bowel, erectile dysfunction, and OAB. The explicit scientific rationale, in the case of the bladder, is driven by the supposition that targeted, locally delivered, gene therapy can address the pathophysiological changes in molecular and biochemical pathways that result in dysfunctional control of detrusor smooth muscle tone, which in turn, manifests as OAB.

In this scenario, gene therapy can be used to restore, reduce, or enhance the expression of the normal gene products that control key cellular actions.19 Aging and disease can modify normal gene expression, for example, by elaboration of splice variants whose downstream products alter normal cellular physiology to result in dysfunctional bladder control. The introduction of carefully selected genes into a significant fraction of affected cells can return the cells and organs to more normal physiology and function.

The bladder is notably amenable to such an approach for 3 main reasons. First, the bladder is readily accessible via the urethra for delivery of therapeutic genes to the urothelium, neural network, and/or underlying detrusor myocytes.20,21 Second, therapeutic administration is local, and thus the main part of the corresponding activity should be confined to the bladder. In fact, these 2 points have recently been demonstrated in pilot clinical studies of naked DNA gene therapies for OAB, which have produced no evidence of systemic effects.22 Third, relatively modest transfection efficiency can be therapeutically tolerated, as the bladders myocytes communicate with each other through intercellular channels, referred to as gap junctions. This latter mechanism leverages the important role that gap junctions play in the coordinated contractile responses mediated by the extant syncytial smooth muscle cell network to ensure complete bladder emptying upon appropriate parasympathetic activation.15,20 More specifically, although only a small proportion of myocytes might incorporate and express the therapeutic naked DNA gene, the presence of an intercellular network of gap junctions allows corrective changes in gene expression to facilitate passage of current-carrying ions and secondary messenger molecules from cell to cell throughout the bladder wall.23

Again, it appears that the large-conductance, voltage- and calcium-activated BK (Maxi-K) channel is the K channel subtype most responsible for creating and maintaining the cells resting membrane potential.13 The BK channel consists of a tetramer of pore-forming -subunits that are typically surrounded by modulatory -subunits.24,25 The -subunit is encoded by a single gene called Slo or KCNMA1 that is located on the long arm of chromosome 10.26 Activation by either membrane depolarization or increased intracellular Ca2+ increases the permeability of the BK channel permitting outward K+ efflux across the cell membrane down the electrochemical gradient, resulting in hyperpolarization and reduced cellular excitability (Figure 1). Since increased myogenic activity may contribute to bladder overactivity, increasing the number of BK channels (via gene transfer) has a rational scientific basis.

Figure 1 Schematic depiction of the central role of the BK channel in regulation of myogenic tone in bladder smooth muscle. As shown, detrusor smooth muscle exhibits spontaneous myogenic contractile activity (spikes) associated with depolarizations. The depolarizations are associated with Ca2+ influx via voltage-dependent calcium channels (VDCCs). Ca2+-induced Ca2+ release from the sarcoplasmic reticulum activates BK channels via sparks, but BK channels are also activated via more global increases in intracellular calcium, and eventually the cell is repolarized. The repolarization closes (temporarily) the VDCC, and spike activity is reduced.

Overall, the BK channels in bladder smooth muscle act to promote detrusor relaxation and limit the amplitude and duration of spontaneous or nerve-induced detrusor contraction.13 Several lines of evidence suggest the importance of BK channels for modulating and sustaining the bladders resting state. In normal detrusor smooth muscle, the BK channel is expressed at high levels.27,28 In fact, the conductance of the BK channelthat is, the rate of K+ ions passing through the channelis an order of magnitude greater than the conductance of other K+ channels.29 The BK channel is therefore unique among K+ channels in its responsiveness either to membrane depolarization or a rise in intracellular calcium, enabling it to integrate these contraction-governing signals.13 Consistent with these electrophysiological properties, in mice, for example, knockout of BK channel -subunits is associated with increased detrusor contractility and urination frequency.30 In mouse bladder myocytes, deletion of the BK -subunit or pharmacologic blockade of transient BK currents is sufficient to depolarize the cell membrane.31,32

Ion channel dysfunction, often referred to as channelopathy, is often associated with disorders of smooth muscle.33 In the case of the BK channel, mutations, splice variants, or low levels of channel expression in bladder myocytes would be expected to lead to increased intracellular Ca2+ levels and abnormal responsiveness to cholinergic signaling.13,34 Using detrusor smooth muscle tissue samples obtained from 33 patients during open bladder surgeries, neurogenic detrusor overactivity was associated with decreased BK channel expression and function, leading to increased detrusor smooth muscle excitability and contractility.35 BK channel dysfunction may also heighten the responsiveness of the central nervous system to sensory signals from the bladder, a phenomenon called central sensitization, which appears to occur in illnesses such as irritable bowel syndrome and fibromyalgia.36 High levels of gap junction expression would likewise be expected to make the bladder smooth muscle cells hypersensitive to cholinergic stimulation, presumably due to excessive diffusion of Ca2+ ions among detrusor coupled myocytes.15,3739 Indeed, upregulation of connexin 43, a predominant connexin protein expressed in human bladder gap junctions, has been identified in patients with urgency incontinence.32

The use of gene therapy to treat bladder dysfunction may have intrinsic advantages over conventional pharmacotherapies when the therapeutic target is subject to epigenetic modification. It was recently demonstrated that diabetes results in epigenetic changes in the methylation pattern of the detrusor genome which are mostly, but not entirely, normalized with glycemic control.40 This phenomenon is known as hyperglycemic memory and would likely contribute to the persistence of bladder dysfunction even in diabetic patients that achieve glycemic control. The KCNMA1 gene (encoding the BK channel, -subunit) was identified in the subset of genes encoded by genomic loci that had modulated methylation patterns with diabetes that were not reversed with glycemic control. The changes in methylation pattern correlated with expression of the BK channel -subunit protein; its expression was downregulated with diabetes that was not reversed with insulin treatment. Although decreased expression and activity of KCNMA1 in the diabetic bladder has been reported (and used to support targeting BK channel activity to treat diabetic bladder dysfunction), expression was previously not known to be subject to hyperglycemic memory. Gene therapy overcomes hyperglycemic memory by introducing exogenous DNA into the bladder that has not been subject to epigenetic modification, restoring BK channel activity. In contrast, pharmacologic approaches to increase BK channel activity in the bladder of diabetic patients, even patients who have achieved glycemic control, would have no target to act on, or have such low levels of expression that activation is insufficient for physiological effect. Therefore, the strategy of increasing BK channel activity to treat patients with bladder dysfunction involving epigenetic modification will be more effective using gene therapy (which overexpress the KCNMA1 gene) than the use of pharmacologic agents (which may have no or little target to activate).

Gene therapies are often designed for the purpose of gene augmentation or the introduction of a functional gene into a cell with deficient expression of the desired gene product.19 To ensure sufficient expression, the gene delivery system must permit uptake by the targeted cells, protect the exogenous nucleic acid from degradation by host-cell nuclease enzymes, and ensure intracellular transport of the gene to the cell nucleus. To these ends, viral vectors have often been used. However, viral-based gene therapy has been associated with severe adverse events and risk of mortality, leading to increased investigations of non-viral vectors.19,41,42

Naked plasmid DNA (pDNA) is one such non-viral vector option. Naked pDNA is significantly less immunogenic relative to viral and retroviral vectors.43 Further, naked pDNA has less potential for integration into the host cells genome, thereby reducing the risk of adverse events associated with insertional mutagenesis, position-effect variegation, or inflammatory immune responses.41,44 However, gene transfer via naked pDNA is also limited by low transfection efficiency and transient expression of the transgene, necessitating the administration of large quantities of the vector.41 Organs and systems successfully targeted by naked pDNA in preclinical and clinical studies have included the heart, central nervous system, pancreas, penis, and skeletal muscle.41,4547

URO-902 is a 6880-base-pair naked pDNA incorporating a DNA sequence synthesized from the messenger RNA (mRNA) that encodes the human BK channel -subunit (Figure 2).21,48 To ensure robust expression of the encoded protein in eukaryotic cells, the -subunit code is flanked at its upstream end by a CMV promoter (from cytomegalovirus) to initiate DNA transcription and at its downstream end by a polyadenylation signal (from the bovine growth hormone gene) to terminate transcription and protect the transcript from enzymatic degradation. In addition, the plasmid incorporates sequences that are frequently used in plasmid construction to facilitate its selection and replication in Escherichia coli cultures. None of the modules enable the plasmid to replicate in eukaryotic cells, thereby confining the treatment to targeted cells transfected with the plasmid.

Figure 2 The URO-902 plasmid construct. For further construct details, see Melman et al.48 BGH, bovine growth hormone; CMV, cytomegalovirus.

Within targeted cells, URO-902 enters the cell presumably via endocytosis and then transits the cell nucleus through a nuclear pore. The type of plasmid promoter driving BK expression determines which cells will express the protein. URO-902 uses a CMV promoter, which is a nonspecific promoter that is active in all cells. Smooth muscle cellspecific promoters, such as the smooth muscle -actin (SMAA) promoter, also have been incorporated into the plasmid backbone and were shown to be physiologically active.49,50 In the nucleus, pDNA for the BK -subunit is transcribed by the host cell into an mRNA, which is translated into protein in the cytoplasm. The expressed BK -subunit channels are then inserted into the cell membrane via the cells endogenous machinery. Reverse transcription polymerase chain reaction (RT-PCR) measures show that the gene is expressed in erectile smooth muscle for up to 6 months.51 The hypothesis underlying the development of URO-902 as a gene therapy for OAB is that increased expression of BK channels in bladder myocytes may enhance the cellular capacity to expel K+ ions, promoting membrane hyperpolarization and reducing excitability (Figure 1). The resulting smooth muscle relaxation would be expected to reduce the symptoms associated with OAB.

Transfer of DNA encoding the BK channel -subunit was first tested as a potential treatment for erectile dysfunction.21 In 2 rat models, intracavernosal injection of a plasmid incorporating the -subunit gene yielded improvement in the ratio of intracavernous pressure to systemic arterial blood pressure.5153 A dose-dependent effect on erectile response to cavernous nerve stimulation was seen for up to 6 months. Improvement in erectile function also was identified in atherosclerotic male cynomolgus monkeys, where intracorporal BK channel gene transfer also enhanced sexual behaviorimplying that erectile function per se may lead to increased sexual function.49

In a phase 1 safety study, 11 men with severe erectile dysfunction who were unresponsive to pharmacotherapy but otherwise in good health were treated with open-label URO-902 administered as a single dose by intracavernosal injection.47,48 The tested dose levels were 0.5, 1, 5, and 7.5 mg. Patients were monitored for 6 months with annual follow-up for 2 years. The therapy was well tolerated, with no adverse events considered to be gene-transfer-related and no clinically significant changes in physical, laboratory, or electrocardiographic parameters. Semen samples obtained up to 4 weeks after URO-902 dosing showed no evidence of the plasmid. At the 2 highest doses, a clinical response persisted throughout the 6-month study period. A phase 2 study in 26 men confirmed the tolerability of URO-902, with all events being mild and considered not related to study drug.54

To evaluate potential use in OAB, preclinical research established the ability of bladder instillation of pDNA encoding the BK -subunit to ameliorate the bladder overactivity observed in rats following partial urethral obstruction.55 These studies were followed by phase 1 safety studies of female patients with OAB.22 In each of 2 such trials, the participants were otherwise healthy, non-fertile women with non-neurogenic (idiopathic) OAB and associated detrusor overactivity of at least 6-month duration (Table 1). Moreover, study participants were required to document at least 8 micturitions per day and at least 5 urgency urinary incontinence episodes per week at baseline, without clinically significant stress incontinence. Each woman received a single double-blind dose of URO-902 or placebo administered by intravesical instillation in one trial (ION-02 [NCT00495053]) and by direct detrusor injection in another trial (ION-03 [NCT01870037]). For instilled URO-902, the tested dose levels were 5 and 10 mg. For injected URO-902, dose levels were 16 and 24 mg divided among 20 to 30 injection sites. Patients were assessed and monitored for 6 months with periodic follow-up for an additional 18 months.

Table 1 Baseline Characteristics by Study Drug Treatment in Women Participating in Phase 1 URO-902 Trials

In ION-02 (intravesical installation), the 90-mL dose of URO-902 was instilled through a small-diameter catheter into the lumen of the bladder, and patients were requested to retain the solution in the bladder for at least 2 hours.22 In ION-03 (direct injection), URO-902 was injected approximately 2 mm into the detrusor muscle with a BoNee needle through a rigid cystoscope, without general or regional anesthesia, and 20 injections of either 0.2 mL (16-mg dose) or 30 injections of 0.2 mL (24-mg dose) each were spaced approximately 1 cm apart.22 Prior to direct injection, 40 mL of 2% lidocaine was instilled into the bladder, and 10 mL of 2% xylocaine gel was instilled into the urethra.

In both studies, few treatment-related adverse events were noted. Of 34 participants in both studies, only 3 had treatment-related adverse events, and 1 of those patients received placebo. Furthermore, there were no adverse events leading to an early withdrawal from the study (Tables 2 and 3).22 One serious adverse event was reported in ION-03: exacerbation of pre-existing asthma in a patient treated with 16 mg URO-902. This event was not considered related to the investigational agent. Across both trials, no patients experienced urinary retention as a reported adverse event.22

Table 2 Reported Adverse Events by Study Drug Treatment Among Women Participating in the Phase 1 ION-02 URO-902 Trial

Table 3 Reported Adverse Events by Study Drug Treatment Among Women Participating in the Phase 1 ION-03 URO-902 Trial

Among the 16 women receiving URO-902 by instillation, post-dose urine samples showed no evidence of the plasmid.22 Among the 9 women receiving URO-902 by injection, post-dose samples obtained after dosing detected the plasmid in the urine of 4 patients and in the blood of 1 patient 15 minutes after dosing. There was no evidence of the plasmid in later samples.22

In both ION-02 and ION-03, the efficacy of URO-902 for the treatment of OAB was assessed by several endpoints.22 In ION-02, patients receiving URO-902 by intravesical instillation exhibited no significant changes in the mean number of voids or urgency incontinence episodes at either dose. Nevertheless, several efficacy signals were detected. Across URO-902 recipients, the mean reduction in detrusor contractions from baseline to week 24 was trending toward significance (P<0.0508). At week 8, the 5-mg subgroup showed a >40% mean reduction in urgency incontinence episodes.22

In ION-03, URO-902 administered by direct detrusor injection showed greater efficacy compared with results of ION-02.22 Improvement of OAB manifestations included a dose-dependent reduction in the mean number of micturitions and urgency episodes per day, with statistical significance versus placebo for the 24-mg dose at post-dose time points including weeks 12 and 24 (Figure 3A and B). These improvements were accompanied by a decrease in urgency incontinence episodes per day, with dose dependence observed at week 24 (Figure 3C). For micturitions per day and urgency episodes per day, the mean improvement at both URO-902 doses was statistically significant versus placebo at week 1, whereas placebo recipients showed no improvement throughout the trial. In future trials, these higher doses of URO-902 may lead to further improved response. URO-902 recipients also reported improvements versus baseline in quality of life (QoL) as measured by the Kings Health Questionnaire, a healthrelated QoL instrument specific for urinary incontinence. At multiple post-dose visits, statistically significant improvements were reported in domain scores measuring impact on life, physical limitations, role limitations, social limitations, and sleep/energy.22

Figure 3 Mean changes from baseline in (A) micturitions, (B) urgency episodes, and (C) UUI episodes by treatment group during the ION-03 study of URO-902.22 Data on file from Dr. Melman. *P<0.05 versus placebo. P values are derived from a linear mixed model with the number of urgency episodes or number of voids as dependent variables, treatments, time point, and interaction of time and treatment.

Abbreviations: BL, baseline; SE, standard error; UUI, urge urinary incontinence.

It has been demonstrated that large molecular weight proteins, such as nerve growth factor, botulinum toxin,56 and wheat germ agglutinin conjugated to horseradish peroxidase,57 are capable of retrograde transport to dorsal root ganglia from intradetrusor injection sites. A similar transport of the injected plasmid in ION-03 is possible, and, provided that this is the case, a contribution to the lack of dose dependence in toxicity and in efficacy cannot be excluded. However, in a recently published study,58 it was the absence of the BK channel and not increased expression that resulted in decreased neuromuscular transmission. Additionally, because URO-902 uses a nonspecific promoter, it is possible that there may be an effect on neurons in the bladder.

As different injection techniques and doses were used for delivery of URO-902 in ION-02 and ION-03, results from these studies cannot be compared. At present, it is not known whether direct detrusor injection or intravesical instillation will yield the best gene expression in patients with OAB, nor is it established which technique may ultimately be more effective at reducing the symptoms of OAB. As long-term animal studies may pose challenges with multiple survival surgeries, further in-human studies are required to optimize and refine the use of URO-902.

Among transmembrane ion channels in bladder smooth muscle cells, the BK channel has a particularly crucial role in modulating smooth muscle excitability and thus detrusor tone and contraction. The rationale for URO-902 as a gene therapy for OAB is that enhanced expression of BK channel -subunits in bladder myocytes may decrease detrusor smooth muscle cell excitability leading to decreased afferent activity. In turn, this leads to decreased urgency, urinary frequency, and urge urinary incontinence. In preclinical research, gene transfer via naked pDNA encoding the BK channel -subunit led to improvement in animal models of detrusor overactivity. In adult female patients with OAB, secondary analyses of efficacy endpoints suggested sustained benefits through 24 weeks of post-dose monitoring, especially with direct detrusor injection of the gene therapy, which were accompanied by improvements in QoL. These findings warrant continued investigation of URO-902 in larger-scale clinical studies.

Medical writing and editorial support was provided to the authors by The Curry Rockefeller Group, LLC, Tarrytown, NY, and was funded by Urovant Sciences.

ION-03 was supported in part by National Institute on Aging grant R44DK093279. Urovant Sciences provided funding for medical writing and editorial support, which was provided by The Curry Rockefeller Group, LLC.

K-EA has nothing to disclose. GJC is co-founder, director, and shareholder of Ion Channel Innovations, LLC, and has a US Patent Application Appl. No. 16/612286; 371(c) Date: November 8, 2019 (US National Phase of Intl Appl. No. PCT/US2018/032574; Intl Filing Date: May 14, 2018) For: Compositions And Methods For Treating Idiopathic Overactive Bladder Syndrome And Detrusor Overactivity, pending to Urovant. KD is a shareholder of Ion Channel Innovations, LLC, and received research funds from Urovant. ER reports relationships with Ion Channel Innovations, LLC, during the conduct of the study and with Urovant in the form of consulting honoraria. AM reports an NIH grant for Ion Channel Innovations, LLC, and consultant relationship with Urovant; he was co-founder of Ion Channel Innovations, LLC.

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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

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