Citations

AbstractIntroductionWe conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD).MethodsSeven participants received (−)‐epicatechin 50 mg twice per day for 8 weeks. Pre‐ and postprocedures included biceps brachii biopsy to assess muscle structure and growth‐relevant endpoints by western blotting, mitochondria volume measurement, and cristae abundance by electron microscopy, graded exercise testing, and muscle strength and function tests.ResultsWestern blotting showed significantly increased levels of enzymes modulating cellular bioenergetics (liver kinase B1 and 5′‐adenosine monophosphate–activated protein kinase). Peroxisome proliferator‐activated receptor gamma coactivator‐1alpha, a transcriptional coactivator of genes involved in mitochondrial biogenesis and cristae‐associated mitofilin levels, increased as did cristae abundance. Muscle and plasma follistatin increased significantly while myostatin decreased. Markers of skeletal muscle regeneration myogenin, myogenic regulatory factor‐5, myoblast determination protein 1, myocyte enhancer factor‐2, and structure‐associated proteins, including dysferlin, utrophin, and intracellular creatine kinase, also increased. Exercise testing demonstrated decreased heart rate, maximal oxygen consumption per kilogram, and plasma lactate levels at defined workloads. Tissue saturation index improved in resting and postexercise states.Discussion(−)‐Epicatechin, an exercise mimetic, appears to have short‐term positive effects on tissue biomarkers indicative of mitochondrial biogenesis and muscle regeneration, and produced improvements in graded exercise testing parameters in patients with BMD.

Objective Information on the associations among arterial stiffness, carotid intima-media thickness (cIMT) and carotid plaques as biomarkers of atherosclerosis is limited in diverse populations. We aimed to assess whether aortic pulse wave velocity (aPWV) – as a surrogate of arterial stiffness – is associated with increased cIMT and the presence of carotid plaques in a cohort of older adults of Amerindian ancestry. Methods Atahualpa residents aged ≥60 years ( n = 320) underwent aPWV determinations, and carotid ultrasounds for cIMT and plaque assessment. Multivariate models were fitted to assess the independent association between the aPWV, and cIMT and carotid plaques, after adjusting for relevant confounders. Differences in risk factors across these biomarkers were investigated. Results Mean values of aPWV were 10.3 ± 1.8 m/s, and those of cIMT were 0.91 ± 0.21 mm (24% had a cIMT >1 mm). Carotid plaques were observed in 118 (37%) subjects. In univariate analyses, risk factors associated with an increased aPWV included age, female gender, poor physical activity and high blood pressure. An increased cIMT was associated with age, male gender, a poor diet, high blood pressure and severe tooth loss. The presence of carotid plaques was associated with increasing age, poor physical activity and high blood pressure. Multivariate models showed a significant association between aPWV and cIMT (β: 0.028; 95% C.I.: 0.001–0.056; p = 0.047) but not between aPWV and carotid plaques (OR: 1.14; 95% C.I.: 0.83–1.56; p = 0.423). Conclusions This study shows an independent association between aPWV and cIMT but not with carotid plaques. These biomarkers may indicate distinct phenotypes for atherosclerosis.

There is limited information on participants’ adherence and reasons for declining consent in observational cohort studies conducted in remote rural communities. We aimed at sharing lessons learned during the Atahualpa Project, a population-based cohort study conducted in a rural Ecuadorian village. Atahualpa residents aged ≥40 years identified during door-to-door surveys who signed a consent form were enrolled. Annual surveys were conducted to assess the number of participants who moved out of the village, as well as those who died, declined consent, and newly entered the study. Reasons for declining consent were tabulated. Abstracted data included age, sex, education, disability, time between enrollment and declining consent, and reasons for withdrawal. We also counted participants who, despite expressing their willingness to continue in the study, refused specific procedures. After five years of follow-up, 54 (6.3%) of 863 enrolled individuals declined consent. Increasing age and disability had no impact on declining consent. In contrast, refusal was higher among relatives or neighbors of a given participant declining consent. Most people who declined consent did so after one or two years of enrollment. Less than 20% of enrolled individuals refused certain procedures. “Fear of the needle” was the most frequent reason for refusing blood tests, and common reasons for declining complimentary exams were lack of interest and time constraints. Cohort retention in the Atahualpa Project is high. Main reasons for this adherence include adequate selection of the village, detailed planning of procedures, assurance of sponsorship, and field personnel who continuously engage with study participants. This trial is registered with NCT01627600.

Purpose Compare the effect of personalized feedback (PF) vs. task demonstration (TD), both delivered via video, on laparoscopic knot-tying skills and perceived workload; and evaluate the effect of repeated practice. Method General surgery interns and research fellows completed four repetitions of a simulated laparoscopic knot-tying task at one-month intervals. Midway between repetitions, participants received via e-mail either a TD video (demonstration by an expert) or a PF video (video of their own performance with voiceover from a blinded senior surgeon). Each participant received at least one video per format, with sequence randomly assigned. Outcomes included performance scores and NASA Task Load Index (NASA-TLX) scores. To evaluate the effectiveness of repeated practice, scores from these trainees on a separate delayed retention test were compared against historical controls who did not have scheduled repetitions. Results Twenty-one trainees completed the randomized study. Mean change in performance scores was significantly greater for those receiving PF (difference = 23.1 of 150 [95% confidence interval (CI): 0, 46.2], P = .05). Perceived workload was also significantly reduced (difference = −3.0 of 20 [95% CI: −5.8, −0.3], P = .04). Compared with historical controls (N = 93), the 21 with scheduled repeated practice had higher scores on the laparoscopic knot-tying assessment two weeks after the final repetition (difference = 1.5 of 10 [95% CI: 0.2, 2.8], P = .02). Conclusions Personalized video feedback improves trainees’ procedural performance and perceived workload compared with a task demonstration video. Brief monthly practice sessions support skill acquisition and retention.

Purpose To characterize reporting of P values, confidence intervals (CIs), and statistical power in health professions education research (HPER) through manual and computerized analysis of published research reports. Method The authors searched PubMed, Embase, and CINAHL in May 2016, for comparative research studies. For manual analysis of abstracts and main texts, they randomly sampled 250 HPER reports published in 1985, 1995, 2005, and 2015, and 100 biomedical research reports published in 1985 and 2015. Automated computerized analysis of abstracts included all HPER reports published 1970–2015. Results In the 2015 HPER sample, P values were reported in 69/100 abstracts and 94 main texts. CIs were reported in 6 abstracts and 22 main texts. Most P values (≥77%) were ≤.05. Across all years, 60/164 two-group HPER studies had ≥80% power to detect a between-group difference of 0.5 standard deviations. From 1985 to 2015, the proportion of HPER abstracts reporting a CI did not change significantly (odds ratio [OR] 2.87; 95% CI 1.04, 7.88) whereas that of main texts reporting a CI increased (OR 1.96; 95% CI 1.39, 2.78). Comparison with biomedical studies revealed similar reporting of P values, but more frequent use of CIs in biomedicine. Automated analysis of 56,440 HPER abstracts found 14,867 (26.3%) reporting a P value, 3,024 (5.4%) reporting a CI, and increased reporting of P values and CIs from 1970 to 2015. Conclusions P values are ubiquitous in HPER, CIs are rarely reported, and most studies are underpowered. Most reported P values would be considered statistically significant.

Abstract Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.