Clinical management of patients with genetic obesity during COVID-19 pandemic: position paper of the ESE Growth & Genetic Obesity COVID-19 Study Group and Rare Endo-ERN main thematic group on Growth and Obesity

This article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated.Transplantation and immunomodulatio

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Metabolically Healthy Obesity: Criteria, Epidemiology, Controversies, and Consequences

PURPOSE OF REVIEW: To present a comprehensive overview regarding criteria, epidemiology, and controversies that have arisen in the literature about the existence and the natural course of the metabolic healthy phenotype. RECENT FINDINGS: The concept of metabolically healthy obesity (MHO) implies that a subgroup of obese individuals may be free of the cardio-metabolic risk factors that commonly accompany obese subjects with adipose tissue dysfunction and insulin resistance, known as having metabolic syndrome or the metabolically unhealthy obesity (MUO) phenotype. Individuals with MHO appear to have a better adipose tissue function, and are more insulin sensitive, emphasizing the central role of adipose tissue function in metabolic health. The reported prevalence of MHO varies widely, and this is likely due the lack of universally accepted criteria for the definition of metabolic health and obesity. Also, the natural course and the prognostic value of MHO is hotly debated but it appears that it likely evolves towards MUO, carrying an increased risk for cardiovascular disease and mortality over time. Understanding the pathophysiology and the determinants of metabolic health in obesity will allow a better definition of the MHO phenotype. Furthermore, stratification of obese subjects, based on metabolic health status, will be useful to identify high-risk individuals or subgroups and to optimize prevention and treatment strategies to compact cardio-metabolic diseases

The role of nicotinamide in cancer chemoprevention and therapy

Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Glucose metabolism disorders in patients with adrenal gland disorders: pathophysiology and management

The aim of this review is to explore and discuss disorders of glucose metabolism that can arise in individuals with adrenal gland disorders, as well as to enumerate the available therapeutic treatments for these while considering their benefits and drawbacks. Hyperfunctioning adrenal glands, as in hypercortisolism, hyperaldosteronism, and malignancy, or hypofunctioning of adrenal glands, as in adrenal insufficiency, can lead to carbohydrate metabolism dysregulation with subsequent glucometabolic repercussions, either hyperglycemia or hypoglycemia. Glycemic disorders further affect patients’ quality of life and represent a therapeutic dilemma for physicians. Current management strategies for glycemic dysregulation in individuals with adrenal gland disorders are fighting the underlying causes, as well as utilizing antidiabetic therapies that aid in maintaining euglycemia. Further research focused on discovering drug preparations of greater accuracy and effectiveness tailored to patients with adrenal problems as well as studies investigating optimal lifestyle management models for these individuals will assist towards achieving optimal regulation of glucose metabolism. © 2019, Hellenic Endocrine Society