Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults

Impaired glucose tolerant (IGT) adults are at elevated risk for cardiovascular disease (CVD). Exercise or metformin reduce CVD risk, but the efficacy of combining treatments is unclear. To determine the effects of exercise training plus metformin, compared to each treatment alone, on CVD risk factors in IGT adults. Subjects were assigned to: placebo (P), metformin (M), exercise plus placebo (EP), or exercise plus metformin (EM) (8/group). In a double-blind design, P or 2000mg/d of M were administered for 12 weeks and half performed aerobic and resistance training 3 days/week for approximately 60 minutes/day at 70% pre-training heart rate peak. Outcomes included: adiposity, blood pressure (BP), lipids and high sensitivity C-reactive protein (hs-CRP). Z-scores were calculated to determine metabolic syndrome severity. M and EM, but not EP, decreased body weight compared to P (p \u3c0.05). M and EP lowered systolic BP by 6% (p \u3c 0.05), diastolic BP by 6% (p \u3c 0.05), and hs-CRP by 20% (M: trend p = 0.06; EP: p \u3c 0.05) compared to P. Treatments raised HDL-cholesterol (p \u3c 0.05; EM: trend p = 0.06) compared to P and lowered triacyglycerol (p \u3c 0.05) and metabolic syndrome Z-score compared to baseline (EP; trend p = 0.07 and EM or M; p \u3c 0.05). Although exercise and/or metformin improve some CVD risk factors, only training or metformin alone lowered hs-CRP and BP. Thus, metformin may attenuate the effects of training on some CVD risk factors and metabolic syndrome severity in IGT adults

Obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer’s disease risk allele

IntroductionExcess body weight and Alzheimer’s disease (AD) disproportionately affect older African Americans. While mid-life obesity increases risk for AD, few data exist on the relationship between late-life obesity and AD, or how obesity-based and genetic risk for AD interact. Although the APOE-ε4 allele confers a strong genetic risk for AD, it is unclear if late-life obesity poses a greater risk for APOE-ε4 carriers compared to non-carriers. Here we assessed: (1) the influence of body mass index (BMI) (normal; overweight; class 1 obese; ≥ class 2 obese) on cognitive and structural MRI measures of AD risk; and (2) the interaction between BMI and APOE-ε4 in older African Americans.MethodsSeventy cognitively normal older African American participants (Mage = 69.50 years; MBMI = 31.01 kg/m2; 39% APOE-ε4 allele carriers; 86% female) completed anthropometric measurements, physical assessments, saliva collection for APOE-ε4 genotyping, cognitive testing, health and lifestyle questionnaires, and structural neuroimaging [volume/surface area (SA) for medial temporal lobe subregions and hippocampal subfields]. Covariates included age, sex, education, literacy, depressive symptomology, and estimated aerobic fitness.ResultsUsing ANCOVAs, we observed that individuals who were overweight demonstrated better hippocampal cognitive function (generalization of learning: a sensitive marker of preclinical AD) than individuals with normal BMI, p = 0.016, ηp2 = 0.18. However, individuals in the obese categories who were APOE-ε4 non-carriers had larger hippocampal subfield cornu Ammonis region 1 (CA1) volumes, while those who were APOE-ε4 carriers had smaller CA1 volumes, p = 0.003, ηp2 = 0.23.DiscussionThus, being overweight by BMI standards may preserve hippocampal function, but obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer’s disease risk allele

Examining the efficacy of a cardio-dance intervention on brain health and the moderating role of ABCA7 in older African Americans: a protocol for a randomized controlled trial

IntroductionAfrican Americans are two to three times more likely to be diagnosed with Alzheimer’s disease (AD) compared to White Americans. Exercise is a lifestyle behavior associated with neuroprotection and decreased AD risk, although most African Americans, especially older adults, perform less than the recommended 150 min/week of moderate-to-vigorous intensity exercise. This article describes the protocol for a Phase III randomized controlled trial that will examine the effects of cardio-dance aerobic exercise on novel AD cognitive and neural markers of hippocampal-dependent function (Aims #1 and #2) and whether exercise-induced neuroprotective benefits may be modulated by an AD genetic risk factor, ABCA7 rs3764650 (Aim #3). We will also explore the effects of exercise on blood-based biomarkers for AD.Methods and analysisThis 6-month trial will include 280 African Americans (≥ 60 years), who will be randomly assigned to 3 days/week of either: (1) a moderate-to-vigorous cardio-dance fitness condition or (2) a low-intensity strength, flexibility, and balance condition for 60 min/session. Participants will complete health and behavioral surveys, neuropsychological testing, saliva and venipuncture, aerobic fitness, anthropometrics and resting-state structural and functional neuroimaging at study entry and 6 months.DiscussionResults from this investigation will inform future exercise trials and the development of prescribed interventions that aim to reduce the risk of AD in African Americans

Galaxy and Mass Assembly (GAMA): Variation in Galaxy Structure Across the Green Valley

Using a sample of 472 local Universe (z < 0.06) galaxies in the stellar mass range 10.25 < log M*/MG < 10.75, we explore the variation in galaxy structure as a function of morphology and galaxy colour. Our sample of galaxies is sub-divided into red, green and blue colour groups and into elliptical and non-elliptical (disk-type) morphologies. Using KiDS and VIKING derived postage stamp images, a group of eight volunteers visually classified bars, rings, morphological lenses, tidal streams, shells and signs of merger activity for all systems. We find a significant surplus of rings (2.3σ) and lenses (2.9σ) in disk-type galaxies as they transition across the green valley. Combined, this implies a joint ring/lens green valley surplus significance of 3.3σ relative to equivalent disk-types within either the blue cloud or the red sequence. We recover a bar fraction of ∼ 44% which remains flat with colour, however, we find that the presence of a bar acts to modulate the incidence of rings and (to a lesser extent) lenses, with rings in barred disk-type galaxies more common by ∼ 20 − 30 percentage points relative to their unbarred counterparts, regardless of colour. Additionally, green valley disk-type galaxies with a bar exhibit a significant 3.0σ surplus of lenses relative to their blue/red analogues. The existence of such structures rules out violent transformative events as the primary end-of-life evolutionary mechanism, with a more passive scenario the favoured candidate for the majority of galaxies rapidly transitioning across the green valley. Key words: galaxies: elliptical and lenticular, cD – galaxies: spiral – galaxies: evo- lution – galaxies: star formation – galaxies: statistics – galaxies: structur

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer

Background Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P Conclusion Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.Peer reviewe

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene