Part 1: potential dangers of extreme endurance exercise: how much is too much? Part 2: screening of school-age athletes

The question is not whether exercise is or isn’t one of the very best strategies for improving quality of life, cardiovascular (CV) health and longevity—it is. And there is no debate as to whether or not strenuous high-intensity endurance training produces an amazingly efficient, compliant, and powerful pump—it does. The essence of the controversy centers on what exactly is the ideal pattern of long-term physical activity (PA) for conferring robust and enduring CV health, while also optimizing life expectancy. With that goal in mind, this review will focus on the question: “Is more always better when it comes to exercise?” And if a dose–response curve exists for the therapeutic effects of PA, where is the upper threshold at which point further training begins to detract from the health and longevity benefits noted with moderate exercise? The emerging picture from the cumulative data on this hotly debated topic is that moderate exercise appears to be the sweet spot for bestowing lasting CV health and longevity. However, the specific definition of moderate in this context is not clear yet

Sodium restriction and insulin resistance: A review of 23 clinical trials

Background: Many clinicians recommend low-salt diets for lowering blood pressure but there may be unintended consequences such as worsening insulin resistance. Aim: This paper aimed to find human clinical studies looking at low-salt diets on markers of glucose and insulin. Methods: We reviewed PubMed using the search terms ‘sodium’, ‘insulin’ and ‘insulin resistance’ and found 23 human clinical studies testing low-salt diets showing negative harms on insulin or glucose. Results: Twenty-three human clinical trials have shown that low-salt diets lead to systemic or vascular insulin resistance, glucose intolerance, elevated fasting insulin and/or elevations in glucose and/or insulin levels after an oral glucose tolerance test. Conclusion: We discovered 23 human clinical studies showing that low-salt diets worsen markers of insulin and glucose. Caution is advised when recommending salt restriction for blood pressure control as this may lead to worsening insulin resistance. Contribution: This review has revealed that low salt diets can induce insulin resistance

Alcohol and CV health: Jekyll and Hyde J-curves

A routine of light or moderate alcohol consumption (≤1 drink/day for women and 1 to 2 drinks/day for men) were associated with a lower risk for all-cause mortality, coronary artery disease (CAD), type 2 diabetes mellitus (T2D), heart failure (HF), and stroke. Conversely, heavy drinking, (>4 drinks/day) is associated with an increased risk for death and cardiovascular (CV) disease (CVD). Excessive alcohol intake trails behind only smoking and obesity among the 3 leading causes of premature deaths in the United States (US). Heavy alcohol use is a common cause of reversible hypertension (HTN), nonischemic dilated cardiomyopathy, atrial fibrillation (AF), and stroke (both ischemic and hemorrhagic). Among males aged 15 to 59 years, alcohol abuse is perhaps the leading cause of premature death. As such, the risk-to-benefit ratio of drinking is less favorable in younger individuals. A daily habit of light to moderate drinking is ideal for those who choose to consume alcohol regularly. Red wine in particular before or during the evening meal is linked with the best long-term CV outcomes. Most of the studies on alcohol and health are observational, and correlation does not prove causation. Health care professionals should not advise nondrinkers to begin drinking because of the paucity of randomized outcome data coupled with the potential for alcohol abuse even among seemingly low risk individuals

Statins, ezetimibe, and proprotein convertase subtilisin–kexin type 9 inhibitors to reduce low-density lipoprotein cholesterol and cardiovascular events

Multiple lines of evidence suggest that the physiologically normal levels of low-density lipoprotein cholesterol (LDL-C) and the thresholds for development of atherosclerosis and adverse coronary events are in the 30- to 70-mg/dl range. More patients have been studied in randomized controlled trials assessing the effects of statins on outcomes than any other drug class in the history of medicine. This cumulative body of evidence documents that atherosclerosis progression is halted and coronary heart disease events are minimized when statin therapy with or without ezetimibe, and possibly proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors, is used to drive down the LDL-C to a range of about 30 to 50\ua0mg/dl. Thus far, these agents appear to be safe even when LDL-C is lowered to about 50\ua0mg/dl, although more robust outcome and safety data are required, particularly for the PCSK9 inhibitors and very low LDL-C levels (e.g., down to 25\ua0mg/dl). In conclusion, the current national guidelines specifying only the use of a high-potency statin without specific LDL-C goals may lead to substantial undertreatment of high-risk patients, leaving them vulnerable to future adverse cardiovascular events

Coffee for Cardioprotection and Longevity

Coffee, a complex brew containing hundreds of biologically active compounds, exerts potent effects on long-term human health. Recently, a plethora of studies have been published focusing on health outcomes associated with coffee intake. An inverse association between coffee consumption and all-cause mortality has been seen consistently in large prospective studies. Habitual coffee consumption is also associated with lower risks for cardiovascular (CV) death and a variety of adverse CV outcomes, including coronary heart disease (CHD), congestive heart failure (HF), and stroke; coffee's effects on arrhythmias and hypertension are neutral. Coffee consumption is associated with improvements in some CV risk factors, including type 2 diabetes (T2D), depression, and obesity. Chronic coffee consumption also appears to protect against some neurodegenerative diseases, and is associated with improved asthma control, and lower risks for liver disease and cancer. Habitual intake of 3 to 4 cups of coffee appears to be safe and is associated with the most robust beneficial effects. However, most of the studies regarding coffee's health effects are based on observational data, with very few randomized controlled trials. Furthermore, the possible benefits of coffee drinking must be weighed against potential risks, which are generally due to its high caffeine content, including anxiety, insomnia, headaches, tremulousness, and palpitations. Coffee may also increase risk of fracture in women, and when consumed in pregnancy coffee increases risk for low birth weight and preterm labor. Abbreviations and Acronyms

Oligosaccharide and Glycoprotein Microarrays as Tools in HIV Glycobiology Glycan-Dependent gp120/Protein Interactions

AbstractDefining HIV envelope glycoprotein interactions with host factors or binding partners advances our understanding of the infectious process and provides a basis for the design of vaccines and agents that interfere with HIV entry. Here we employ carbohydrate and glycoprotein microarrays to analyze glycan-dependent gp120-protein interactions. In concert with new linking chemistries and synthetic methods, the carbohydrate arrays combine the advantages of microarray technology with the flexibility and precision afforded by organic synthesis. With these microarrays, we individually and competitively determined the binding profiles of five gp120 binding proteins, established the carbohydrate structural requirements for these interactions, and identified a potential strategy for HIV vaccine development