Ideal cardiovascular health, handgrip strength, and muscle mass among college students: The fuprecol adults study

The American Heart Association established the 2020 Strategic Impact Goals to define the concept of ideal cardiovascular health (CVH) and the metrics needed to monitor it across populations. The purpose of this study was to investigate the relationship between handgrip strength, muscle mass, and ideal CVH among Colombian college students. Data from 1,835 college students were analyzed (1,128 female). Muscular strength was estimated using a hand-held dynamometer and normalized to body mass (normalized grip strength [NGS]). The percentage of body fat was determined for bioelectrical impedance analysis using tetrapolar whole-body impedance. Ideal CVH was defined as meeting the ideal levels of 4 behaviors (smoking, body mass index, physical activity, and diet adherence) and 3 factors (total cholesterol, fasting glucose, and blood pressure). Higher levels of NGS and muscle mass (relative to body mass) were associated with a higher number of ideal CVH metrics in both sexes (p for trend less than 0.001). For the total ideal CVH metrics scored on a continuous scale from 0 (all 7 poor) to 7 (all 7 ideal), a 1-metric increase was associated with reduced odds of weak NGS (33 and 36%) and low-medium muscle mass (28 and 34%) mass in men and women, respectively (all p less than 0.001). This study indicates that in Colombian college students, both handgrip strength and muscle mass are positively associated with the ideal CVH metrics. To reduce the possible future public health burden of muscular weakness, health professionals need to encourage the public to optimize lifestyle-related risk factors during the young adult stage. © 2019 National Strength and Conditioning Association

New alkaloid antibiotics that target the DNA topoisomerase I of Streptococcus pneumoniae

Streptococcus pneumoniae has two type II DNA-topoisomerases (DNA-gyrase and DNA topoisomerase IV) and a single type I enzyme (DNA-topoisomerase I, TopA), as demonstrated here. Although fluoroquinolones target type II enzymes, antibiotics efficiently targeting TopA have not yet been reported. Eighteen alkaloids (seven aporphine and 11 phenanthrenes) were semisynthesized from boldine and used to test inhibition both of TopA activity and of cell growth. Two phenanthrenes (seconeolitsine and N-methyl-seconeolitsine) effectively inhibited both TopA activity and cell growth at equivalent concentrations (∼17 μM). Evidence for in vivo TopA targeting by seconeolitsine was provided by the protection of growth inhibition in a S. pneumoniae culture in which the enzyme was overproduced. Additionally, hypernegative supercoiling was observed in an internal plasmid after drug treatment. Furthermore, a model of pneumococcal TopA was made based on the crystal structure of Escherichia coli TopA. Docking calculations indicated strong interactions of the alkaloids with the nucleotide-binding site in the closed protein conformation, which correlated with their inhibitory effect. Finally, although seconeolitsine and N-methyl-seconeolitsine inhibited TopA and bacterial growth, they did not affect human cell viability. Therefore, these new alkaloids can be envisaged as new therapeutic candidates for the treatment of S. pneumoniae infections resistant to other antibiotics.The work was supported by Comunidad de Madrid Grant CM-BIO0260-2006, COMBACT (to J. H. and A. G. C.); Spanish Ministry of Science and Innovation Grants BIO2008-02154 (to A. G. C.), BFU2008-01711 (to J. A. H.), and SAF2008-03477 (to M. J. S.); and Spanish Ministry of Health, Carlos III Health Institute Grants RIER, RD08/0075/0016 (to M. J. S.).S

Role of sleep duration and sleep-related problems in the metabolic syndrome among children and adolescents

Background: There is increasing recognition that sleep is a risk factor for metabolic syndrome (MetS). The aim of the present study was to analyze the relationship between self-reported sleep duration, sleep-related problems and the presence of MetS in children and adolescents from Bogotá, D.C., Colombia. Methods: This is a cross-sectional analysis from the FUPRECOL study (2014-15). Participants included 2779 (54.2% girls) youth from Bogota (Colombia). MetS was defined as the presence of ≥3 of the metabolic abnormalities (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol [HDL-c], hypertension, and increased waist circumference) according to the criteria of de Ferranti/Magge and colleges. Self-reported sleep duration and sleep-related problems were assessed with the BEARS questionnaire. Results: Logistic regression analysis showed that boys who meet recommended duration of sleep had a decreased risk of elevated blood glucose levels (Odds Ratio [OR] = 0.71, 95%CI [0.40-0.94]; p = 0.031) compared to boys who have short-long sleep duration. Also, compared to young without sleep problems, excessive sleepiness during the day was related to low HDL-c levels in boys (OR = 1.36, 95%CI [1.02-1.83] ; p = 0.036) and high triglyceride levels in girls (OR = 1.28, 95%CI [1.01-1.63]; p = 0.045). Girls with irregular sleep patterns had decreased HDL-c levels (OR = 0.71, 95%CI [0.55-0.91] ; p = 0.009). Conclusions: Recommended sleep duration was associated with a decreased risk of elevated fasting glucose levels in boys, and sleep problems was related to lower HDL-c in girls and higher triglyceride levels in boys. These findings suggested the clinical importance of improving sleep hygiene to reduce metabolic risk factors in children and adolescents

Muscle mass to visceral fat ratio is an important predictor of the metabolic syndrome in college students

This study aimed to evaluate the associations between the muscle mass to visceral fat (MVF) ratio and cardiometabolic risk factors in a large population of college students in Colombia and to propose cut-off points of this index for the metabolic syndrome (MetS). A total of 1464 young adults recruited from the FUPRECOL (Asociación de la Fuerza Prensil con Manifestaciones Tempranas de Riesgo Cardiovascular en Jóvenes y Adultos Colombianos) study were categorised into four groups based on their MVF ratio. Muscle mass and visceral fat level of the participants were measured using a bioelectrical impedance analysis. Cardiometabolic risk factors including lifestyle characteristics, anthropometry, blood pressure and biochemical parameters were assessed. The prevalence of moderate to severe obesity, hypertension and the MetS was higher in subjects in quartile (Q)1 (lower MVF ratio) (P less than 0·001). ANCOVA revealed that the subjects in Q1 had higher cardiometabolic disturbances, including altered anthropometry, blood pressure, muscle strength and biochemical parameters after adjusting for age and sex compared with young adults in higher MVF ratio quartiles (P less than 0·001). Muscular mass and physical activity levels were significantly lower in subjects with a lower MVF ratio (P less than 0·001). The receiver operating characteristic curve analyses indicated that in men the best MVF ratio cut-off point for detecting the MetS was 18·0 (AUC 0·83, sensitivity 78 % and specificity 77 %) and for women, the MVF ratio cut-off point was 13·7 (AUC 0·85, sensitivity 76 % and specificity 87 %). A lower MVF ratio is associated with a higher risk cardiometabolic profile in early adulthood, supporting that the MVF ratio could be used as a complementary screening tool that may help clinicians identify young adults at high cardiometabolic risk. © The Authors 2018

Physiological and public health basis for assessing micronutrient requirements in children and adolescents. The EURRECA network

This paper provides an overview of the current knowledge relating to the nutritional requirements and corresponding recommended nutrient intake values of children and adolescents for micronutrients and specificities related to these requirements in the course of childhood and adolescence in Europe. Aspects that can influence micronutrient requirements, such as physiological requirements and bioavailability of the nutrients in the organism, are discussed. The methodology used to obtain the data and also the main knowledge gaps regarding these concepts are emphasized. Methodological critical points in achieving the data and physiological aspects of children and adolescents are important in order to standardize the reference values for micronutrients among Europe for these stages of life

Patterns of healthy lifestyle behaviours in older adults: findings from the Chilean National Health Survey 2009–2010

The purpose of this study was to investigate healthy lifestyle behaviours across age categories in the older population in Chile. Data from 1390 older adults (≥60 years), in the 2009–2010 Chilean National Health Survey were analyzed. We derived the following age categories: 60–65, 66–70, 71–75, 76–80 and >80 years. The association between age and compliance with healthy lifestyle behaviours (smoking, sitting time, physical activity, sleep duration and intake of salt, alcohol, fruit and vegetables) were investigated using logistic regression. The probability of meeting the guidelines for alcohol intake (OR trend: 1.35 [95% CI: 1.11; 1.64], p = 0.001) and smoking (OR trend: 1.23 [95% CI: 1.13; 1.33], p < 0.0001) increased with age, whereas spending <4 h per day sitting time or engaging in at least 150 min of physical activity per week or sleep on average between 7 and 9 h per day were less likely to be met with increasing age (OR trend: 0.77 [95% CI: 0.71; 0.83], p < 0.000; OR trend: 0.73 [95% CI: 0.67; 0.79], p < 0.0001, and OR trend: 0.89 [95% CI: 0.82; 0.96], p = 0.002, respectively). No significant trend across age categories was observed for fruit and vegetables, and salt intake. The probability of meeting at least 3 out of 7 healthy lifestyle behaviours across the age categories was also lower in older age categories compared to those aged 60 to 65 years. Overall, in older adults the probability of having the healthy lifestyle behaviours of physical activity, sitting time and sleeping behaviours was low but not for smoking or alcohol consumption. With an increasingly ageing population, these findings could inform stakeholders on which lifestyle behaviours could be targeted in the older adults and therefore which interventions should take place to promote healthy ageing

Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies

The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death. CM-272 significantly prolongs survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series as a promising therapeutic tool for unmet needs in haematological tumours.We particularly acknowledge the Biobank of the University of Navarra for its collaboration. We thank Dr Edorta Martínez de Marigorta and Dr Francisco Palacios from Departamento de Química Orgánica I, Facultad de Farmacia, Universidad del Pais Vasco for 13C NMR determination and Angel Irigoyen Barrio and Dr Ana Romo Hualde, from University of Navarra, for HRMS determination. Dr. Irene de Miguel Turrullols from Small Molecule Discovery Platform, CIMA, University of Navarra is acknowledged for NMR data interpretation. This work was funded by grants from Instituto de Salud Carlos III (ISCIII) PI10/01691, PI13/01469, PI14/01867, PI10/2983, TRASCAN (EPICA), CIBERONC, cofinanciacion FEDER, RTICC RD12/0036/0068, Fundació La Marató de TV3 (20132130-31-32) and ‘Fundación Fuentes Dutor’. B.P. is supported by a Sara Borrell fellowship CD13/00340 and X.A. is a Marie Curie researcher under contract ‘LincMHeM-330598’.S

Proposed nomenclature for Pseudallescheria, Scedosporium and related genera

As a result of fundamental changes in the International Code of Nomenclature on the use of separate names for sexual and asexual stages of fungi, generic names of many groups should be reconsidered. Members of the ECMM/ISHAM working group on Pseudallescheria/Scedosporium infections herein advocate a novel nomenclature for genera and species in Pseudallescheria, Scedosporium and allied taxa. The generic names Parascedosporium, Lomentospora, Petriella, Petriellopsis, and Scedosporium are proposed for a lineage within Microascaceae with mostly Scedosporium anamorphs producing slimy, annellidic conidia. Considering that Scedosporium has priority over Pseudallescheria and that Scedosporium prolificans is phylogenetically distinct from the other Scedosporium species, some name changes are proposed. Pseudallescheria minutispora and Petriellidium desertorum are renamed as Scedosporium minutisporum and S. desertorum, respectively. Scedosporium prolificans is renamed as Lomentospora prolificans

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent

Genotypic Diversity Is Associated with Clinical Outcome and Phenotype in Cryptococcal Meningitis across Southern Africa.

Cryptococcal meningitis is a major cause of mortality throughout the developing world, yet little is known about the genetic markers underlying Cryptococcal virulence and patient outcome. We studied a cohort of 230 Cryptococcus neoformans (Cn) isolates from HIV-positive South African clinical trial patients with detailed clinical follow-up using multi-locus sequence typing and in vitro phenotypic virulence assays, correlating these data with clinical and fungal markers of disease in the patient. South African Cn displayed high levels of genetic diversity and locus variability compared to globally distributed types, and we identified 50 sequence types grouped within the main molecular types VNI, VNII and VNB, with 72% of isolates typed into one of seven 'high frequency' sequence types. Spatial analysis of patients' cryptococcal genotype was not shown to be clustered geographically, which might argue against recent local acquisition and in favour of reactivation of latent infection. Through comparison of MLST genotyping data with clinical parameters, we found a relationship between genetic lineage and clinical outcome, with patients infected with the VNB lineage having significantly worse survival (n=8, HR 3.35, CI 1.51-7.20, p=0.003), and this was maintained even after adjustment for known prognostic indicators and treatment regimen. Comparison of fungal genotype with in vitro phenotype (phagocytosis, laccase activity and CSF survival) performed on a subset of 89 isolates revealed evidence of lineage-associated virulence phenotype, with the VNII lineage displaying increased laccase activity (p=0.001) and ex vivo CSF survival (p=0.0001). These findings show that Cryptococcus neoformans is a phenotypically heterogeneous pathogen, and that lineage plays an important role in cryptococcal virulence during human infection. Furthermore, a detailed understanding of the genetic diversity in Southern Africa will support further investigation into how genetic diversity is structured across African environments, allowing assessment of the risks different ecotypes pose to infection