The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Self-reported quality of life in children with ventricular assist devices

BackgroundWe sought to describe QOL in children with VAD and to identify factors associated with impaired QOL.MethodsThere were 82 children (6–19 years) in the Pediatric Interagency Registry for Mechanical Circulatory Support who completed the PedsQL +/− a VAD-specific QOL assessment pre-VAD implant (n = 18), 3 months post-VAD (n = 63), and/or 6 months post-VAD (n = 38). Significantly impaired QOL is a score >1 SD below norms.ResultsStudy patients were 59% male, 67% Caucasian, with cardiomyopathy diagnosis in 82%, and median age at implant of 14 y (IQR 11–17). PedsQL scores were lower than norms for physical (p 2 weeks/ongoing post-VAD (p = .04).ConclusionPhysical QOL is significantly impaired in most children pre- and post-VAD. However, psychosocial QOL is not significantly impaired in most children post-VAD suggesting VAD implantation may improve psychosocial QOL in children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172804/1/petr14237_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172804/2/petr14237.pd

The Effects of a Fat Loss Supplement on Resting Metabolic Rate and Hemodynamic Variables in Resistance Trained Males: A Randomized, Double-blind, Placebo-controlled, Cross-over Trial

Background: While it is known that dietary supplements containing a combination of thermogenic ingredients can increase resting metabolic rate (RMR), the magnitude can vary based on the active ingredient and/or combination of active ingredients. The purpose of this study was to examine the effects of a commercially available thermogenic fat loss supplement on RMR and hemodynamic variables in healthy, resistance trained males. Methods: Ten resistance-trained male participants (29 ± 9 years; 178 ± 4 cm; 85.7 ± 11 kg, and BMI = 26.8 ± 3.7) volunteered to participate in this randomized, double-blind, placebo controlled cross-over study. Participants underwent two testing sessions separated by at least 24 h. On their first visit, participants arrived to the laboratory after an overnight fast and a 24-h avoidance of exercise, and underwent a baseline RMR, HR, and BP assessment. Next, each participant ingested a thermogenic fat loss supplement (TFLS) or a placebo (PLA) and repeated the RMR, HR, and BP assessments at 60, 120, and 180 min post-ingestion. During the second visit the alternative supplement was ingested and the assessments were repeated in the exact same manner. Data were analyzed via a 2-factor [2x4] within-subjects repeated measures analysis of variance (ANOVA). Post-hoc tests were analyzed via paired samples t-tests. The criterion for significance was set at p ≤ 0.05. Results: A significant main effect for time relative to raw RMR data (p = 0.014) was observed. Post-hoc analysis revealed that the TFLS significantly increased RMR at 60-min, 120-min, and 180-min post ingestion (p \u3c 0.05) as compared to baseline RMR values. No significant changes in RMR were observed for the PLA treatment (p \u3e 0.05). Specifically, RMR was increased by 7.8 % (from 1,906 to 2,057 kcal), 6.9 % (from 1,906 to 2,037 kcal), and 9.1 % (from 1,906 to 2,081 kcal) in the TFLS, while the PLA treatment increased RMR by 3.3 % (from 1,919 to 1,981 kcal), 3.1 % (from 1,919 to 1,978 kcal), and 2.1 % (from 1,919 to 1,959 kcal) above baseline at 60, 120, and 180-min post ingestion, respectively. Additionally, the TFLS significantly elevated RMR at the 3-h time point as compared to the PLA treatment (2,081 vs 1,959 kcal, p = 0.034). A main effect for groups was observed for systolic blood pressure, and a significant interaction and main effect for time were observed for diastolic blood pressure. It should be noted that although changes in diastolic blood pressure were significant, all values stayed within normal clinical ranges ( \u3c 80 mmHg). Conclusions: The TFLS led to significant elevations in RMR as compared to baseline. These elevations came with no adverse effect relative to resting heart rate, but a slight increase in blood pressure values. Taken on a daily basis, this TFLS may increase an individual’s overall energy expenditure, however; future studies should investigate if this leads to a reduction in fat mass loss over time

The Effects of a Fat Loss Supplement on Resting Metabolic Rate and Hemodynamic Variables in Resistance Trained Males: A Randomized, Double-blind, Placebo-controlled, Cross-over Trial

Background: While it is known that dietary supplements containing a combination of thermogenic ingredients can increase resting metabolic rate (RMR), the magnitude can vary based on the active ingredient and/or combination of active ingredients. The purpose of this study was to examine the effects of a commercially available thermogenic fat loss supplement on RMR and hemodynamic variables in healthy, resistance trained males. Methods: Ten resistance-trained male participants (29 ± 9 years; 178 ± 4 cm; 85.7 ± 11 kg, and BMI = 26.8 ± 3.7) volunteered to participate in this randomized, double-blind, placebo controlled cross-over study. Participants underwent two testing sessions separated by at least 24 h. On their first visit, participants arrived to the laboratory after an overnight fast and a 24-h avoidance of exercise, and underwent a baseline RMR, HR, and BP assessment. Next, each participant ingested a thermogenic fat loss supplement (TFLS) or a placebo (PLA) and repeated the RMR, HR, and BP assessments at 60, 120, and 180 min post-ingestion. During the second visit the alternative supplement was ingested and the assessments were repeated in the exact same manner. Data were analyzed via a 2-factor [2x4] within-subjects repeated measures analysis of variance (ANOVA). Post-hoc tests were analyzed via paired samples t-tests. The criterion for significance was set at p ≤ 0.05. Results: A significant main effect for time relative to raw RMR data (p = 0.014) was observed. Post-hoc analysis revealed that the TFLS significantly increased RMR at 60-min, 120-min, and 180-min post ingestion (p \u3c 0.05) as compared to baseline RMR values. No significant changes in RMR were observed for the PLA treatment (p \u3e 0.05). Specifically, RMR was increased by 7.8 % (from 1,906 to 2,057 kcal), 6.9 % (from 1,906 to 2,037 kcal), and 9.1 % (from 1,906 to 2,081 kcal) in the TFLS, while the PLA treatment increased RMR by 3.3 % (from 1,919 to 1,981 kcal), 3.1 % (from 1,919 to 1,978 kcal), and 2.1 % (from 1,919 to 1,959 kcal) above baseline at 60, 120, and 180-min post ingestion, respectively. Additionally, the TFLS significantly elevated RMR at the 3-h time point as compared to the PLA treatment (2,081 vs 1,959 kcal, p = 0.034). A main effect for groups was observed for systolic blood pressure, and a significant interaction and main effect for time were observed for diastolic blood pressure. It should be noted that although changes in diastolic blood pressure were significant, all values stayed within normal clinical ranges ( \u3c 80 mmHg). Conclusions: The TFLS led to significant elevations in RMR as compared to baseline. These elevations came with no adverse effect relative to resting heart rate, but a slight increase in blood pressure values. Taken on a daily basis, this TFLS may increase an individual’s overall energy expenditure, however; future studies should investigate if this leads to a reduction in fat mass loss over time