Although most people survive a heart attackTrusted Source initially, the risk of death significantly increases over the following years. In fact, 65% of peopleTrusted Source who have a heart attack over the age of 65 die within eight years of the initial incident. This is at least partly because while a person may survive an initial heart attack, the heart attack itself, which leads to the heart tissue being deprived of oxygen and then dying, does not regenerate in adult humans. In a recent animal study, researchers identified a mechanism that allowed them to treat heart tissue and make healthy mice’s hearts more resilient before a heart attack. The study’s results appear in Nature Cardiovascular Research. Heart attack and muscle death Prof. James Leiper, Ph.D., Associate Medical Director at the British Heart Foundation and Professor of Molecular Medicine in the School of Cardiovascular and Metabolic Health at the University of Glasgow, U.K. told Medical News Today in an email: “Most heart attacks are caused by coronary artery disease which can cause your coronary arteries to become narrowed. The narrowing is due to a gradual buildup of fatty deposits called atheroma. If a piece of atheroma breaks off, a blood clot forms around this to try and repair the damage to the artery wall. This clot can then block your coronary arteries causing the heart muscle to be starved of blood, oxygen, and vital nutrients, leading to heart muscle death. The amount of damage to the heart muscle depends on the size of the area supplied by the blocked artery. As heart muscle is unable to regenerate it never fully repairs. Instead, scar tissue forms in place of healthy cardiac muscle.” Cardiomyocytes are a type of cell in the heart that is responsible for the contraction of the muscle. This contraction of the muscle is essential for the heart to be able to squeeze blood around the body, in response to electrical signaling that maintains the heartbeat. When these cells are damaged in a heart attack, the heart loses some of its ability to squeeze blood around the body as effectively. While cardiomyocytes are able to proliferate in human fetuses, this ability is lost in mature adult humans. It is believed this is partly due to an evolutionary trade-off that sees the ability of mature cardiomyocytes to proliferate decline with contractile strength. This means damage caused by events such as heart attacks can not be corrected. Healing challenges after heart attack The stages of maturation through which cardiomyocytes go from fetal to adult cells are the focus of much research. Because cardiomyocytes can not proliferate after the damage caused by a heart attack, research has been done on how cardiomyocytes can be dedifferentiated back a stage, to one where they are able to proliferate. Elucidating the mechanisms around this could provide information about how heart tissue damage could be reversed. However, previous research into dedifferentiated cardiomyocytes has shown that deleterious and lethal effects of irreversible dedifferentiation occur. This is most likely due to the fact that dedifferentiated cells could become proliferative in a way that is similar to cancer. It has been hoped that redifferentiation of cardiomyocytes back to the state they were in before differentiation, could avoid some of these complications. However, it has been unclear if the potential beneficial effects of previous differentiation to a more proliferative state would remain. Treating the heart before an attack Researchers in Dr. Eldad Tzahor’s lab in the Weizmann Institute of Science Molecular Cell Biology Department, previously identifiedTrusted Source that when a particular protein ERBB2, coded for by the ERBB2 gene was over-expressed, dedifferentiation, occurred. However, the cardiomyocytes in this dedifferentiated, more proliferative state had a limited ability to contract. Researchers then observed that when overexpression was stopped, the cardiomyocytes underwent redifferentiation and went back to their original contractile ability, and cardiac performance improved. In the lab’s latest research, led by Dr. Avraham Shakked, Ph.D., they sought to investigate the mechanism behind this gene and protein and the longevity of its effects. They showed that when a transgenic mouse that had its ERBB2 gene temporarily activated at 3 months old had a heart attack 5 months later, it recovered. This demonstrated that redifferentiated cardiomyocytes maintained some of their proliferative, and therefore healing capacity. This was the most exciting finding for the team, lead author Dr. Avraham Shakked told MNT in an interview: “Perhaps the most exciting is the cardioprotective effect of this whole sequence of events that we weren’t really expecting to find or see at all, and actually that has the most potential impact at some point in the future.” HEALTHLINE NEWSLETTER Get our weekly Heart Health email To help you take good care of your heart, we’ll send you guidance on managing high blood pressure, cholesterol, nutrition, and more. Enter your emailSIGN UP NOWAlso get our MNT Daily News newsletter Your privacy is important to us Future research on cardiac regeneration The next steps for the team would involve elucidating the mechanism further. “One of the things that we’ll do is we’ll actually try and look into the mechanism behind that protection. Because if you can isolate the causative agent with a causative effect, then you don’t necessarily have to undergo a [dedifferentiation and redifferentiation] DR cycle, which could be quite invasive, or quite dramatic. “If you know exactly what it was then you could probably be a lot more precise in achieving the same result,” he said. The team had several hypotheses about what could be behind this mechanism and wanted to test them one by one, he said. Seeing if the findings could be replicated in non-transgenic mice or larger mammals, such as pigs, would be necessary before considering clinical applications in humans, he explained. Prof. Mauro Giacca, Professor of Cardiovascular Sciences at King’s College London told MNT in an email: “The issue of understanding whether cardiomyocytes return to a physiological, differentiated state after being pushed to proliferate is a key question for clinical cardiac regeneration, and the results obtained by the Tzahor group in their elegant model are quite comforting in this respect. What was less expected is the issue of

In today’s society, stress and change often are thought of as the same thing. Stress is a physiological and psychological response to a change in a situation the body and mind find to be overwhelming. With the fast pace of work and home, being constantly inundated with technology and still wanting to have time to connect with those around you, life can feel overwhelming and stressful at times. You may often ask yourself how you should manage stress. Try these five tips to manage stress and reduce the overall stress of day-to-day activities: 1. Use guided meditation. Guided meditation is a great way to distract yourself from the stress of day-to-day life. There are many guided meditations available online that can help you find five minutes of centered relaxation. 2. Practice deep breathing. Deep breathing is a great way to reduce the activation of your sympathetic nervous system, which controls the body’s response of fight or flight to a perceived threat. Deep breaths taken in for a count of five seconds, held for two seconds and released for a count of five seconds, can help activate your parasympathetic nervous system to rest and digest, which helps reduce the overall stress and anxiety you may be experiencing. 3. Maintain physical exercise and good nutrition. Physical exercise and nutrition are two important components in how you respond to stress. When your body is healthy, your mind can be healthy and vice versa. Physical exercise is proven to be a great stress reliever and also helps to improve your overall quality of life. Nutrition is important because stress can deplete certain vitamins, such as A, B complex, C and E. Maintaining proper nutrition not only helps your body feel better, but your mind as well, which allows you to better combat stress. 4. Manage social media time. Spending time on social media sites can become stressful, not only by what you might see on them, but also because the time might best be spent enjoying visiting with friends, being outside enjoying the weather or reading a great book. In addition, many people use social media at night, which may worsen sleep due to increased stress at the exact time people are trying to wind down for the evening, resulting in fewer overall hours of quality sleep. 5. Connect with others. Humans are social beings. You need to have connections with people to feel supported. Finding a sense of community, whether at work, with a religious organization or through shared activities, such as organized sports, is important to your well-being. Enjoying a shared activity allows you to find support and foster relationships that can be supportive in difficult times. Brian Hesler, M.D., is a psychiatrist in Psychiatry & Psychology in Albert Lea, Minnesota.

Background:  Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials. Areas of uncertainty:  We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID-19 infection. Data sources:  We searched bibliographic databases up to April 25, 2021. Two review authors sifted for studies, extracted data, and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using the GRADE approach and additionally in trial sequential analyses for mortality. Twenty-four randomized controlled trials involving 3406 participants met review inclusion. Therapeutic Advances:  Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19–0.73; n = 2438; I2 = 49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis using the same DerSimonian–Laird method that underpinned the unadjusted analysis. This was also robust against a trial sequential analysis using the Biggerstaff–Tweedie method. Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%–91%). Secondary outcomes provided less certain evidence. Low-certainty evidence suggested that there may be no benefit with ivermectin for “need for mechanical ventilation,” whereas effect estimates for “improvement” and “deterioration” clearly favored ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty. Conclusions:  Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally. INTRODUCTION To date, very few treatments have been demonstrated to reduce the burden of morbidity and mortality from COVID-19. Although corticosteroids have been proven to reduce mortality in severe disease,1 there has been little convincing evidence on interventions that may prevent disease, reduce hospitalizations, and reduce the numbers of people progressing to critical disease and death. Ivermectin is a well-known medicine that is approved as an antiparasitic by the World Health Organization and the US Food and Drug Administration. It is widely used in low- and middle-income countries (LMICs) to treat worm infections.2,3 Also used for the treatment of scabies and lice, it is one of the World Health Organization’s Essential Medicines.4 With total doses of ivermectin distributed apparently equaling one-third of the present world population,5 ivermectin at the usual doses (0.2–0.4 mg/kg) is considered extremely safe for use in humans.6,7 In addition to its antiparasitic activity, it has been noted to have antiviral and anti-inflammatory properties, leading to an increasing list of therapeutic indications.8 Since the start of the SARS-CoV-2 pandemic, both observational and randomized studies have evaluated ivermectin as a treatment for, and as prophylaxis against, COVID-19 infection. A review by the Front Line COVID-19 Critical Care Alliance summarized findings from 27 studies on the effects of ivermectin for the prevention and treatment of COVID-19 infection, concluding that ivermectin “demonstrates a strong signal of therapeutic efficacy” against COVID-19.9 Another recent review found that ivermectin reduced deaths by 75%.10 Despite these findings, the National Institutes of Health in the United States recently stated that “there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19,”11 and the World Health Organization recommends against its use outside of clinical trials.12 Ivermectin has exhibited antiviral activity against a wide range of RNA and some DNA viruses, for example, Zika, dengue, yellow fever, and others.13 Caly et al14 demonstrated specific action against SARS-CoV-2 in vitro with a suggested host-directed mechanism of action being the blocking of the nuclear import of viral proteins14,15 that suppress normal immune responses. However, the necessary cell culture EC50 may not be achievable in vivo.16 Other conjectured mechanisms include inhibition of SARS-CoV-2 3CLPro activity17,18 (a protease essential for viral replication), a variety of anti-inflammatory effects,19 and competitive binding of ivermectin with the viral S protein as shown in multiple in silico studies.20 The latter would inhibit viral binding to ACE-2 receptors suppressing infection. Hemagglutination via viral binding to sialic acid receptors on erythrocytes is a recently proposed pathologic mechanism21 that would be similarly disrupted. Both host-directed and virus-directed mechanisms have thus been proposed, the clinical mechanism may be multimodal, possibly dependent on disease stage, and a comprehensive review of mechanisms of action is warranted. Developing new medications can take years; therefore, identifying existing drugs that can be repurposed against COVID-19 that already have an established safety profile through decades of use could play a critical role in suppressing or even ending the SARS-CoV-2 pandemic. Using repurposed medications may be especially important because it could take months, possibly years, for much of the world’s population to get vaccinated, particularly among LMIC populations. Currently, ivermectin is commercially available and affordable in many countries globally.6 A 2018 application for ivermectin use for scabies gives a direct cost of $2.90 for 100 12-mg tablets.22 A recent estimate from Bangladesh23 reports a cost of US$0.60—US$1.80 for a 5-day course of ivermectin. For these reasons, the exploration of ivermectin’s potential effectiveness against SARS-CoV-2 may be of particular importance for settings with limited resources.24 If demonstrated to be effective as a treatment for COVID-19, the cost-effectiveness of ivermectin should be considered against existing treatments and prophylaxes. The aim of this review was to assess the efficacy of ivermectin treatment among people with COVID-19 infection and as a prophylaxis among people at higher risk of COVID-19 infection. In addition, we aimed to prepare a brief economic commentary (BEC) of ivermectin as treatment and as prophylaxis for COVID-19.25 METHODS The conduct of this review was guided by a protocol that was initially written using Cochrane’s rapid review template and subsequently expanded to a full protocol for a comprehensive review.26 Search strategy and selection criteria Two reviewers independently searched the electronic databases of Medline, Embase, CENTRAL, Cochrane COVID-19 Study Register, and Chinese databases for randomized controlled trials (RCTs) up to April 25, 2021 (see Appendix 1–3, Supplemental digital content 1, https://links.lww.com/AJT/A95); current guidance25 for the BEC was followed for a supplementary search of economic evaluations. There were no language restrictions, and translations were planned to be performed when necessary. We searched the reference list of included studies, and of two other 2021 literature reviews on ivermectin,9 as well as the recent WHO report, which included analyses of ivermectin.12 We contacted experts in the field (Drs. Andrew Hill, Pierre Kory, and Paul Marik) for information on new and emerging trial data. In addition, all trials registered on clinical trial registries were checked, and trialists of 39 ongoing trials or unclassified studies were contacted to request information on trial status and data