TMEM106B Fibrils from FTLD Patients and Healthy Controls.

Recent studies involving four research teams have revealed that amyloid fibrils in FTLD-TDP patients and cognitively healthy individuals primarily consist of TMEM106B, a protein previously identified as a risk factor for FTLD-TDP. Through cryogenic electron microscopy, the studies identified various protofilament structures of TMEM106B fibrils from individuals with several neurodegenerative diseases. These findings raise new questions and opportunities for future research, as they suggest that TMEM106B plays a central role in FTLD pathology. These discoveries also prompt the need for the development of specific antibodies for fibrillar TMEM106B and necessitate further investigation of the potential mechanistic link between TMEM106B and other filamentous aggregates. The power of cryo-EM techniques is underscored in these unexpected findings and may be a vital tool for gaining further molecular insights into neurodegenerative diseases characterized by amyloid deposits.

Gender Bias in Clinical Trial Enrollment: Female Authorship Matters.

BACKGROUND: Despite initiatives to promote equal enrollment of human subjects in clinical trials, females continue to be underrepresented. The goal of this work is to determine if female enrollment in human clinical trials published in 3 high-impact journals from 2015 to 2019 is correlated with gender of first and/or senior authors. METHODS: Clinical trials published in the Journal of the American Medical Association (JAMA), The Lancet, and the New England Journal of Medicine (NEJM) from January 1, 2015, to December 31, 2019, were reviewed. Trials were excluded for ongoing enrollment, sex-specific disease research, or author name without gender assignment. One-sample χ2 pairwise comparisons and two-tailed proportion tests on the proportion of females between gender author pairings were done overall and for each subset analysis. RESULTS: In total, 1,427 articles enrolled a total of 2,104,509 females and 2,616,981 males (44.6% vs. 55.4%, P ≤ 0.0001) in clinical trials. Overall, more females were enrolled if both first and senior authors were female (51.7% vs. 48.3%, P ≤ 0.0001). Proportion of females enrolled decreased with the following first and senior author pairings: female-male (48.9%), male-female (48.6%), and male-male (40.5%, P ≤ 0.0001 compared to female-female authorship). Greater female enrollment in clinical trials with female-female compared to male-male authorship persisted in subset analyses by funding source, phase, randomization for study participants, drug and/or device trial, and geographic location. Female enrollment was higher in 3 surgical specialties: neurosurgery (all authors: 52%, P ≤ 0.01), ophthalmology (all authors: 53.6%, P ≤ 0.0001), and surgery (all authors: 54.4%, P ≤ 0.0001). The majority of surgical specialties did not publish trials with female-female authorship but when stratifying by author gender pairing, surgical oncology had the highest female enrollment with female-female authorship (98.4%, P ≤ 0.0001). CONCLUSIONS: Female authorship of clinical trial publications, specifically having both first and senior authors as female, was correlated with higher female enrollment in clinical trials when compared to male authorship and endured with multiple subset analyses.

Intensity of exercise recovery, blood lactate disappearance, and subsequent swimming performance.

The aim of this study was to examine the effects of active versus passive recovery on blood lactate disappearance and subsequent maximal performance in competitive swimmers. Fourteen male swimmers from the University of Virginia swim team (mean age 20.3 years, s= 4.1; stature 1.85 m, s= 2.2; body mass 81.1 kg, s= 5.6) completed a lactate profiling session during which the speed at the lactate threshold (V(LT)), the speed at 50% of the lactate threshold (V(LT.5)), and the speed at 150% of the lactate threshold (V(LT1.5)) were determined. Participants also completed four randomly assigned experimental sessions that consisted of a 200-yard maximal-effort swim followed by 10 min of recovery (passive, V(LT.5), V(LT), V(LT1.5)) and a subsequent 200-yard maximal effort swim. All active recovery sessions resulted in greater lactate disappearance than passive recovery (P < 0.0001 for all comparisons), with the greatest lactate disappearance associated with recovery at V(LT) (P= 0.006 and 0.007 vs. V(LT.5) and V(LT1.5) respectively) [blood lactate disappearance was 2.1 mmol l(-1) (s= 2.0), 6.0 mmol l(-1) (s=2.6), 8.5 mmol l(-1) (s= 1.8), and 6.1 mmol l(-1) (s= 2.5) for passive, V(LT.5), V(LT), and V(LT1.5) respectively]. Active recovery at VLT and V(LT1.5) resulted in faster performance on time trial 2 than passive recovery (P=0.005 and 0.03 respectively); however, only active recovery at V(LT) resulted in improved performance on time trial 2 (TT2) relative to time trial 1 (TT1) [TT2- TT1: passive +1.32 s (s= 0.64), V(LT.5) +1.01 s (s= 0.53), V(LT) -1.67 s (s= 0.26), V(LT1.5) -0.07 s (s = 0.51); P < 0.0001 for V(LT)). In conclusion, active recovery at the speed associated with the lactate threshold resulted in the greatest lactate disappearance and in improved subsequent performance in all 14 swimmers. Our results suggest that coaches should consider incorporating recovery at the speed at the lactate threshold during competition and perhaps during hard training sessions.