High intensity interval training exercise-induced physiological changes and their potential influence on metabolic syndrome clinical biomarkers: a meta-analysis

Abstract: Background: Despite the current debate about the effects of high intensity interval training (HIIT), HIIT elicits big morpho-physiological benefit on Metabolic Syndrome (MetS) treatment. However, no review or meta-analysis has compared the effects of HIIT to non-exercising controls in MetS variables. The aim of this study was to determine through a systematic review, the effectiveness of HIIT on MetS clinical variables in adults. Methods: Studies had to be randomised controlled trials, lasting at least 3 weeks, and compare the effects of HIIT on at least one of the MetS clinical variables [fasting blood glucose (BG), high-density lipoprotein (HDL-C) triglyceride (TG), systolic (SBP) or diastolic blood pressure (DBP) and waist circumference (WC)] compared to a control group. The methodological quality of the studies selected was evaluated using the PEDro scale. Results: Ten articles fulfilled the selection criteria, with a mean quality score on the PEDro scale of 6.7. Compared with controls, HIIT groups showed significant and relevant reductions in BG (− 0.11 mmol/L), SBP (− 4.44 mmHg), DBP (− 3.60 mmHg), and WC (− 2.26 cm). Otherwise, a slight increase was observed in HDL-C (+ 0.02 mmol/L). HIIT did not produce any significant changes in TG (− 1.29 mmol/L). Conclusions: HIIT improves certain clinical aspects in people with MetS (BG, SBP, DBP and WC) compared to people with MetS who do not perform physical exercise. Plausible physiological changes of HIIT interventions might be related with large skeletal muscle mass implication, improvements in the vasomotor control, better baroreflex control, reduction of the total peripheral resistance, increases in excess post-exercise oxygen consumption, and changes in appetite and satiety mechanisms

Caracterización y potencial aplicación industrial de extractos enzimáticos de pacú (Piaractus mesopotamicus)

Fish production can generate considerable amounts of waste, whose inadequate final disposition could cause environmental damage. The use of these wastes to obtain high value-added products of industrial relevance is an alternative for sustainable aquaculture production. In this study, acidic extracts rich in pepsin-like enzymes (EP) and alkaline extracts rich in trypsin-like enzymes (ET) were obtained and characterized from the viscera of pacu (Piaractus mesopotamicus), evaluating their potential biotechnological applications. EP and ET showed maximum catalytic activity at pH 2 - 45°C and pH 7 - 45°C, respectively. They were stable in pH ranges of 1.0 to 3.5 and 7.5 to 10.5 and temperature ranges of 0 to 37°C and 0 to 45°C, respectively. The activity of EP was inhibited by pepstatin A, but not by PMSF and SBTI. EDTA and SDS caused partial inhibition, confirming the presence of pepsin-like enzymes. ET was inactivated in the presence of SBTI but not by SDS. PMSF and EDTA decreased the activity by 50%, confirming the presence of trypsin-like enzymes. Divalent ions (Ca2+ and Mg2+) did not alter the proteolytic capacity of the extracts, but it decreased with increasing NaCl concentration. Moreover, ET and EP were effective in hydrolyzing the silver-impregnated gelatin coating of discarded x-ray films and generating F(ab’)2 fragments from equine IgG degradation, respectively. In conclusion, these extracts could be applicable in processes requiring maximum activity at moderate temperatures and low NaCl concentrations, in the recovery of metallic silver and PET sheet from used x-ray films and in the production of biological products. These results open up new perspectives for the circular economy of pacú aquaculture farms.La producción pesquera puede generar cantidades considerables de residuos cuya disposición final inadecuada puede causar daños ambientales. La utilización de estos desechos para la obtención de productos con alto valor agregado y de interés industrial, es una alternativa para la producción acuícola sostenible. En este trabajo se obtuvieron y caracterizaron extractos ácidos ricos en enzimas tipo pepsina (EP) y alcalinos ricos en enzimas tipo tripsina (ET) a partir de vísceras de pacú (Piaractus mesopotamicus) evaluando sus potenciales aplicaciones biotecnológicas. EP y ET exhibieron máxima actividad catalítica a pH 2 - 45°C y pH 7 - 45°C; mostraron ser estables en los rangos de pH 1,0 a 3,5 y 7,5 a 10,5 y de temperatura 0 a 37°C y 0 a 45°C, respectivamente. La actividad de EP fue inhibida por pepstatina A pero no por PMSF y SBTI; EDTA y SDS provocaron inhibición parcial, confirmando la presencia de enzimas de tipo pepsina. ET se inactivó en presencia de SBTI pero no por SDS; PMSF y EDTA disminuyeron en un 50% su actividad, confirmando la existencia de enzimas tipo tripsina. Los iones divalentes (Ca2+ y Mg2+) no modificaron la capacidad proteolítica de los extractos, en cambio se redujo a concentraciones crecientes de NaCl. Por otra parte, ET y EP fueron eficaces para hidrolizar el recubrimiento de gelatina impregnado con plata de placas radiográficas usadas y generar fragmentos F(ab’)2 a partir de la degradación de IgG equinas, respectivamente. En conclusión, estos extractos podrían ser aplicables en procesos donde se requiera máxima actividad a temperatura moderada y baja concentración de NaCl; en la recuperación de plata metálica y celuloide de placas radiográficas reveladas como así también la obtención de productos biológicos. Estos resultados abren nuevas perspectivas para la economía circular de las explotaciones acuícolas del pacú

Skeletal maturation in relation to ethnic background in children of school age: The Generation R Study

Ethnicity is a well-established determinant of pediatric maturity, but the underlying genetic and environmental contributions to these ethnic differences are poorly comprehended. We aimed to evaluate the influence of ethnicity on skeletal age (SA), an assessment of pediatric maturation widely used in clinical settings. We included children from the Generation R Study, a multiethnic population-based pregnancy cohort, assessed at a mean age of 9.78 (±0.33) years. SA was evaluated by a trained observer on hand DXA scans using the Greulich and Pyle method. Ethnic background was defined as geographic ancestry (questionnaire-based assessment) (N = 5325) and genetic ancestry (based on admixture analysis) (N = 3413). Associations between the ethnic background and SA were investigated separately in boys and girls, using linear regression models adjusted for age, height and BMI. Based on geographic ancestry, 84% of the children were classified as European, 6% as Asian and 10% as African. Children of European background had on average younger SA than those of Asian or African descent. Asian boys had 0.46 (95% CI 0.26–0.66, p-value < 0.0001) and African boys 0.36 years (95% CI 0.20–0.53, p-value < 0.0001) older SA as compared to European boys. Similarly, Asian girls showed 0.64 (95% CI 0.51–0.77, p-value < 0.0001) and African girls 0.38 years (95% CI 0.27–0.48, p-value < 0.0001) older SA as compared to European girls. A similar pattern was observed in the analysis with genetically-defined ancestry. Furthermore, an increase in the proportion of Asian or African component was associated with older SA in both boys (log[Non-European/European]proportion = 0.10, 95% CI 0.06–0.13, p-value < 0.0001) and girls (log[Non-European/European]proportion = 0.06, 95% CI 0.04–0.08, p-value < 0.0001). In summary, children of Asian and African backgrounds have on average older SA as compared to children of European descent, partially explained by a genetic com

Adaptation, reliability and validity of a Brief Multicomponent AIDS Phobia Scale (MAPS) in Colombian adolescents

La fobia al sida consiste en un miedo persistente, anormal e injustificado a contraer el VIH. Uno de los instrumentos disponibles para evaluar la fobia al sida es la Multicomponent AIDS Phobia Scale (MAPS). El objetivo de este estudio fue adaptar y validar la MAPS en adolescentes colombianos. Participaron 859 estudiantes entre 14-19 años respondiendo a la MAPS y otros autoinformes para analizar su validez (conocimientos sobre las ITS, actitud hacia el VIH y ansiedad por la salud). El análisis factorial confirmó la estructura bifactorial (F1: miedo a la infección y F2: miedo a otros), de acuerdo con la versión original. Se obtuvo evidencias de fiabilidad y validez consistentes con la teoría. La aplicación de la MAPS es idónea para evaluar miedo al VIH/sida y estudiar su relación con factores de riesgo sexual (uso de condón, múltiples parejas sexuales) a nivel investigador y comunitario en Colombia. También puede ser útil para evaluar el impacto de campañas sociales para reducir el estigma hacia el VIH y programas de prevención dirigidos a promover una sexualidad saludable en adolescentes mediante la transmisión de conocimientos adecuados y actitudes más tolerantes hacia las personas que viven con VIH.The AIDS phobia is a persistent, abnormal and unjustified fear of contracting HIV. The objective of this study was to adapt and validate MAPS in Colombian adolescents. Participants included 856 students aged 14-19 years who responded to the MAPS and other self-reports to analyze its validity (including knowledge about STIs, attitude towards HIV and health anxiety). Factor analysis confirmed the bifactorial structure (F1: fear of infection and F2: fear of others), according to the original version. Evidence of reliability and validity was obtained consistently with the theory. The application of MAPS is appropriate for assessing fear of HIV/AIDS and to study its relationship with sexual risk factors (e.g. condom use, multiple sexual partners) at research and community levels in Colombia. It also can be useful for assessing the impact of social campaigns to reduce stigma towards HIV and prevention programs aimed at promoting healthy sexuality in adolescents through the transmission of adequate knowledge and more favorable attitudes toward people living with HI

Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification:The Rotterdam Study

BACKGROUND: Hyperphosphatemia has been associated with coronary artery calcification (CAC) mostly in chronic kidney dis-ease, but the association between phosphate levels within the normal phosphate range and CAC is unclear. Our objectives were to evaluate associations between phosphate levels and CAC among men and women from the general population and assess causality through Mendelian randomization. METHODS AND RESULTS: CAC, measured by electron-beam computed tomography, and serum phosphate levels were assessed in 1889 individuals from the RS (Rotterdam Study). Phenotypic associations were tested through linear models adjusted for age, body mass index, blood pressure, smoking, prevalent cardiovascular disease and diabetes, 25-hydroxyvitamin D, total calcium, C-reactive protein, glucose, and total cholesterol: high-density lipoprotein cholesterol ratio. Mendelian randomiza-tion was implemented through an allele score including 8 phosphate-related single-nucleotide polymorphisms. In phenotypic analyses, serum phosphate (per 1 SD) was associated with CAC with evidence for sex interaction (Pinteraction =0.003) (men β, 0.44 [95% CI, 0.30– 0.59]; P=3×10−9; n=878; women β, 0.24 [95% CI, 0.08– 0.40]; P=0.003; n=1011). Exclusion of hyperphos-phatemia, chronic kidney disease (estimated glomerular filtration rate &lt;60 mL/min per 1.73 m2) and prevalent cardiovascular disease yielded similar results. In Mendelian randomization analyses, instrumented phosphate was associated with CAC (total population β, 0.93 [95% CI: 0.07–1.79]; P=0.034; n=1693), even after exclusion of hyperphosphatemia, chronic kidney disease and prevalent cardiovascular disease (total population β, 1.23 [95% CI, 0.17– 2.28]; P=0.023; n=1224). CONCLUSIONS: Serum phosphate was associated with CAC in the general population with stronger effects in men. Mendelian randomization findings support a causal relation, also for serum phosphate and CAC in subjects without hyperphosphatemia, chronic kidney disease, and cardiovascular disease. Further research into underlying mechanisms of this association and sex differences is needed.</p

Towards Field Theory Amplitudes From the Cohomology of Pure Spinor Superspace

A simple BRST-closed expression for the color-ordered super-Yang-Mills 5-point amplitude at tree-level is proposed in pure spinor superspace and shown to be BRST-equivalent to the field theory limit of the open superstring 5-pt amplitude. It is manifestly cyclic invariant and each one of its five terms can be associated to the five Feynman diagrams which use only cubic vertices. Its form also suggests an empirical method to find superspace expressions in the cohomology of the pure spinor BRST operator for higher-point amplitudes based on their kinematic pole structure. Using this method, Ansaetze for the 6- and 7-point 10D super-Yang-Mills amplitudes which map to their 14 and 42 color-ordered diagrams are conjectured and their 6- and 7-gluon expansions are explicitly computed.Comment: 14 pages, harvmac, v4: trivial edits in the text to comply with JHEP refere

Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations

Background: Type 2 diabetes (T2D) is a heterogeneous and polygenic disease. Previous studies have leveraged the highly polygenic and pleiotropic nature of T2D variants to partition the heterogeneity of T2D, in order to stratify patient risk and gain mechanistic insight. We expanded on these approaches by performing colocalization across GWAS traits while assessing the causality and directionality of genetic associations. Methods: We applied colocalization between T2D and 20 related metabolic traits, across 243 loci, to obtain inferences of shared casual variants. Network-based unsupervised hierarchical clustering was performed on variant-trait associations. Partitioned polygenic risk scores (PRSs) were generated for each cluster using T2D summary statistics and validated in 21,742 individuals with T2D from 3 cohorts. Inferences of directionality and causality were obtained by applying Mendelian randomization Steiger’s Z-test and further validated in a pediatric cohort without diabetes (aged 9–12 years old, n = 3866). Results: We identified 146 T2D loci that colocalized with at least one metabolic trait locus. T2D variants within these loci were grouped into 5 clusters. The clusters corresponded to the following pathways: obesity, lipodystrophic insulin resistance, liver and lipid metabolism, hepatic glucose metabolism, and beta-cell dysfunction. We observed heterogeneity in associations between PRSs and metabolic measures across clusters. For instance, the lipodystrophic insulin resistance (Beta − 0.08 SD, 95% CI [− 0.10–0.07], p = 6.50 × 10−32) and beta-cell dysfunction (Beta − 0.10 SD, 95% CI [− 0.12, − 0.08], p = 1.46 × 10−47) PRSs were associated to lower BMI. Mendelian randomization Steiger analysis indicated that increased T2D risk in these pathways was causally associated to lower BMI. However, the obesity PRS was conversely associated with increased BMI (Beta 0.08 SD, 95% CI 0.06–0.10, p = 8.0 × 10−33). Analyses within a pediatric cohort supported this finding. Additionally, the lipodystrophic insulin resistance PRS was associated with a higher odds of chronic kidney disease (OR 1.29, 95% CI 1.02–1.62, p = 0.03). Conclusions: We successfully partitioned T2D genetic variants into phenotypic pathways using a colocalization first approach. Partitioned PRSs were associated to unique metabolic and clinical outcomes indicating successful partitioning of disease heterogeneity. Our work expands on previous approaches by providing stronger inferences of shared causal variants, causality, and directionality of GWAS variant-trait associations.</p

Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations

Background: Type 2 diabetes (T2D) is a heterogeneous and polygenic disease. Previous studies have leveraged the highly polygenic and pleiotropic nature of T2D variants to partition the heterogeneity of T2D, in order to stratify patient risk and gain mechanistic insight. We expanded on these approaches by performing colocalization across GWAS traits while assessing the causality and directionality of genetic associations. Methods: We applied colocalization between T2D and 20 related metabolic traits, across 243 loci, to obtain inferences of shared casual variants. Network-based unsupervised hierarchical clustering was performed on variant-trait associations. Partitioned polygenic risk scores (PRSs) were generated for each cluster using T2D summary statistics and validated in 21,742 individuals with T2D from 3 cohorts. Inferences of directionality and causality were obtained by applying Mendelian randomization Steiger’s Z-test and further validated in a pediatric cohort without diabetes (aged 9–12 years old, n = 3866). Results: We identified 146 T2D loci that colocalized with at least one metabolic trait locus. T2D variants within these loci were grouped into 5 clusters. The clusters corresponded to the following pathways: obesity, lipodystrophic insulin resistance, liver and lipid metabolism, hepatic glucose metabolism, and beta-cell dysfunction. We observed heterogeneity in associations between PRSs and metabolic measures across clusters. For instance, the lipodystrophic insulin resistance (Beta − 0.08 SD, 95% CI [− 0.10–0.07], p = 6.50 × 10−32) and beta-cell dysfunction (Beta − 0.10 SD, 95% CI [− 0.12, − 0.08], p = 1.46 × 10−47) PRSs were associated to lower BMI. Mendelian randomization Steiger analysis indicated that increased T2D risk in these pathways was causally associated to lower BMI. However, the obesity PRS was conversely associated with increased BMI (Beta 0.08 SD, 95% CI 0.06–0.10, p = 8.0 × 10−33). Analyses within a pediatric cohort supported this finding. Additionally, the lipodystrophic insulin resistance PRS was associated with a higher odds of chronic kidney disease (OR 1.29, 95% CI 1.02–1.62, p = 0.03). Conclusions: We successfully partitioned T2D genetic variants into phenotypic pathways using a colocalization first approach. Partitioned PRSs were associated to unique metabolic and clinical outcomes indicating successful partitioning of disease heterogeneity. Our work expands on previous approaches by providing stronger inferences of shared causal variants, causality, and directionality of GWAS variant-trait associations.</p

A Brief Review on the Regulatory Roles of MicroRNAs in Cystic Diseases and Their Use as Potential Biomarkers

miRNAs are small endogenous conserved non-coding RNA molecules that regulate post-transcriptional gene expression through mRNA degradation or translational inhibition, modulating nearly 60% of human genes. Cystic diseases are characterized by the presence of abnormal fluid-filled sacs in the body, and though most cysts are benign, they can grow inside tumors and turn malignant. Recent evidence has revealed that the aberrant expression of a number of miRNAs present in extracellular fluids, including plasma or serum, urine, saliva, follicular fluid, and semen, contribute to different cystic pathologies. This review aims to describe the role of different miRNAs in three worldwide relevant cystic diseases: polycystic ovarian syndrome (PCOS), polycystic kidney disease (PKD), and pancreatic cyst tumors (PCTs), as well as their potential use as novel biomarkers.publishedVersio