Citations

Aging disrupts multiple homeostatic processes, including autophagy, a cellular process for the recycling and degradation of defective cytoplasmic structures. Acute treatment with the autophagy inhibitor chloroquine blunts the maximal forces generated by the diaphragm muscle, but the mechanisms underlying neuromuscular dysfunction in old age remain poorly understood. We hypothesized that chloroquine treatment increases the presynaptic retention of the styryl dye FM 4-64 following high-frequency nerve stimulation, consistent with the accumulation of unprocessed bulk endosomes. Diaphragm-phrenic nerve preparations from 24-month-old male and female C57BL/6 × 129 J mice were incubated with FM 4-64 (5 µM) and either chloroquine (50 µM) or vehicle during 80 Hz phrenic nerve stimulation. Acute chloroquine treatment significantly decreased FM 4-64 intensity at diaphragm neuromuscular junctions following 80 Hz phrenic nerve stimulation, consistent with disrupted synaptic vesicle recycling. A similar reduction was evident in regions with the greatest FM 4-64 fluorescence intensity, which most likely surround synaptic vesicle release sites. In the absence of nerve stimulation, chloroquine treatment significantly increased FM 4-64 intensity at diaphragm neuromuscular junctions. These findings highlight the importance of autophagy in regulating presynaptic vesicle retrieval (including vesicle recycling and endosomal processing) and support the role of autophagy impairments in age-related neuromuscular dysfunction.

Objective: To retrospectively analyze publicly available elbow ulnar collateral ligament reconstruction (UCLR) injury data for professional baseball players. Design: Descriptive epidemiology study. Setting: A retrospective analysis using an open-source database was performed. The database contained all known UCLR surgeries among Major League Baseball (MLB) and Minor League Baseball (MiLB) players. Participants: In total, 1801 professional male professional baseball pitchers (age: 24.5 ± 3.9 years) who have undergone UCLR between 1974 and 2024. Main Outcome Measures: The number of UCLR procedures each year. Independent Variables: Change-point analysis was used to identify changes in the number of UCLR surgeries over time among MLB and MiLB players. For MLB players, number of UCLR surgeries from 1974 to 2023 was analyzed, while for MiLB players, data starting from 1981 to 2024 were analyzed. Results: For MLB players, 3 change points were identified, occurring around 1989 (95% confidence interval [CI], 1988–1990), 2000 (95% CI, 2000–2000), and 2012 (95% CI, 2011–2017). For MiLB players, 3 change points were identified occurring around 2001 (95% CI, 2001–2001), 2009 (95% CI, 2008–2010), and 2013 (95% CI, 2013–2015). Conclusions: Overall, there has been a rise in the number of UCLR surgeries per year for the past 50 years in professional baseball, with distinct time points identified, representing increases in the number of UCLR surgeries each year. A higher number of UCLR surgeries are performed per year in the MiLB than in the MLB.

Abstract With the advent of anti‐amyloid monoclonal antibody (AAMA) therapy, precision diagnosis is necessary for identifying appropriate patients with cognitive disorders due to Alzheimer's disease. Therapy with AAMAs requires that candidates be diagnosed with mild cognitive impairment or mild dementia, have elevated brain amyloid‐β, have good physical, psychiatric, and medical health, and lack clinical or biomarker evidence of potentially impactful non‐Alzheimer brain disorders. The first three diagnostic activities are the core of the Clinical Practice Guidelines, but the last element of the precision diagnosis requires new decision‐making tools for recognizing multi‐etiology cognitive impairment. Within the context of shared decision‐making between clinician, patient, and family, proper diagnosis is essential. In addition to discussing the benefits and risks of AAMA therapy, the experienced clinician must empathetically assist in bridging the gap between expectations of benefit and the patient's overall diagnostic suitability for AAMA therapy. Highlights In order to prescribe an anti‐amyloid monoclonal antibody (AAMA) to the right patients, those selected for treatment should be diagnosed with mild cognitive impairment or mild dementia, have elevated brain amyloid‐β (Aβ), and have good physical, psychiatric, or medical health. Persons with Alzheimer's biology as the primary etiology are the ideal AAMA treatment recipients. A novel activity necessary to optimize therapeutic response is to exclude persons with clinical or biomarker evidence of alternative contributory brain disorders. While mild clinical severity and elevated brain amyloid‐β are essential elements for selecting patients for AAMA treatment, clinical judgment is required to weigh the implications of more advanced disease severity, other medical co‐morbidities, and the presence of other contributory neuropathologies.

Abstract Background A passive dosimeter framework for the measurement of dose in carbon ion beams has yet to be characterized or implemented for regular use. Purpose This work determined the dose calculation correction factors for absorbed dose in thermoluminescent dosimeters (TLDs) in a therapeutic carbon ion beam. TLD could be a useful tool for remote audits, particularly in the context of clinical trials as new protocols are developed for carbon ion radiotherapy. Methods TLD‐100 were irradiated in a carbon ion beam at the Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia, Italy. The dose correction factors for linearity, fading, and beam quality were characterized. Fading was characterized from 5 to 100 days post‐irradiation. For linearity, the TLDs were irradiated to absorbed doses ranging from 1 to 15 Gy in both the entrance of a high‐energy pristine carbon ion peak and the center of a 2 cm spread‐out Bragg peak. For beam quality, the TLD was irradiated to the same absorbed dose (3 Gy) in several pristine carbon ion Bragg peaks, as well as in several spread‐out Bragg peaks. Each correction factor was calculated and compared to photon correction factors. The correction factors were also compared between high and low dose‐averaged linear energy transfer (LET D ) in the carbon ion beams. The absorbed dose was compared between ion chamber and TLD‐100 in the several tissue substitute phantom materials, applying the carbon ion TLD correction factors. Results There was no statistically significant difference in the TLD fading correction factor between photons, low LET D carbon ion beams, or high LET D carbon ion beams. The TLD linearity correction factor did differ between photons, low LET D carbon ions, and high LET D carbon ions. The beam quality correction factor was large and changed linearly with LET D . The overall uncertainty of the carbon ion absorbed dose calculation was 3.9% at the one‐sigma level, driven largely by a 3.5% uncertainty in the beam quality correction. TLD measurements were within 1.2% of ion chamber measurements in the phantom material for polyethylene, solid water (Gammex and Sun Nuclear), acrylic, blue water, and techtron HPV. TLD measurements in balsa wood were within 3.0% and cork was 6.6% low compared to ion chamber. Conclusion TLD‐100 can be used for passive dosimetry in a therapeutic carbon ion beam. Importantly, the linearity and beam quality correction factors are both different from photon therapy, and dependent on LET D of the carbon ion beam. This opens the possibility of TLD use for carbon ion output audits, phantom audits, and in vivo dose measurements, but may be subject to more complicated management and slightly larger uncertainties than are achieved in photon beams.

ABSTRACTBackgroundAnemia is frequently observed as a comorbidity in atrial fibrillation (AF), especially in elderly patients and in those on anticoagulation. This has been associated with poor clinical outcomes. We aim to investigate the impact of anemia on clinical outcomes in patients with AF on oral anticoagulation.MethodsWe comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through March 2024 and conducted a prognostic systematic review and meta‐analysis. All analyses were performed using R V. 4.3.1. This meta‐analysis was registered at PROSPERO (CRD42024556023).ResultsWe included 23 studies comprising 286,781 patients for analysis. Anemia had a significant association with an 84% increase in risk of major bleeding (HR: 1.84 with 95% CI [1.59, 2.13], p < 0.01), a 32% increase in the risk of intracranial hemorrhage (HR: 1.32 with 95% CI [1.10, 1.58], p < 0.01), a 98% increase in the risk of gastrointestinal bleeding (HR: 1.98 with 95% CI [1.67, 2.35], p < 0.01), and a 91% increase in the risk of all‐cause mortality (HR: 1.91 with 95% CI [1.46, 2.51], p < 0.01). However, the impact of anemia did not significantly affect the risk of stroke, transient ischemic stroke (TIA), or systemic embolism (HR: 1.07 with 95% CI [0.93, 1.22], p = 0.36).ConclusionAnemia was significantly associated with an increased risk of major bleeding, intracranial hemorrhage, gastrointestinal bleeding, and all‐cause mortality. However, anemia did not significantly impact stroke, TIA, or systemic embolism.

Background: Sarcomas are a rare, complex group of malignancies characterized by numerous clinical and pathological features. Sarcomas originate from various tissues such as fat, muscle, bone, nerves, blood vessels and connective tissues. Typically, the treatment of sarcomas consists of surgery, chemotherapy, and radiation therapy. The location, type, stage, and treatment of sarcomas contribute to the development of physical impairments affecting joint and limb function, peripheral nerves, strength, and mobility, diminishing physical function and quality of life. Traditionally, rehabilitative therapy has been implemented after cancer treatment to help improve physical impairments imparted from cancer therapy. Recent work in rehabilitative medicine has explored the implementation of rehabilitative therapy prior to beginning cancer treatment (pre-habilitation) to help mitigate the detrimental physical consequences seen in sarcoma patients. Objective: The objective of this narrative review is to examine the physical impairments affecting sarcoma patients after cancer therapy and the impact of rehabilitative medicine on physical function and quality of life when implemented before and after cancer treatment.

BackgroundObjective, controlled eye‐tracking measurement of gaze patterns during layperson evaluation of facial attractiveness is currently lacking.ObjectivesTo objectively investigate (1) where on the face laypeople direct their attention when assessing attractiveness compared with a control group, and (2) whether increased fixation on certain facial regions is associated with high attractiveness ratings.MethodsLay observers viewed a cohort of 40 faces with a diverse age, sex, and racial distribution. Observers were either allowed to free‐gaze without a specific task or rate facial attractiveness for 10 seconds per face while their gaze was recorded by an eye‐tracking system.ResultsForty‐seven observers assessed facial attractiveness (mean age 35.1 years (range 21–76), 62% female) and 57 observers free‐gazed at the facial photos without a specific task (mean age 35.5 years (range 22–66), 54% female). Preliminary analysis showed that sex of both the face and observer substantially influence gaze‐attractiveness associations (p < 0.05). Mixed effects analysis suggests that when males assessed female facial attractiveness, increased fixation time at the mouth correlated most strongly with high attractiveness (p = 0.001), whereas when females assessed male faces, increased fixation at the eyes (p < 0.001) and hair (p = 0.002) were most strongly associated with high ratings of attractiveness.ConclusionsIncreased gaze at the mouth in females and eyes and hair in males is associated with significantly higher ratings of attractiveness by observers of the opposite sex. Practitioners may want to pay special attention to these areas when designing an evidence‐based aesthetic treatment plan.Level of EvidenceNA Laryngoscope, 135:1995–2002, 2025

Abstract Aims Sodium–glucose co-transporter-2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR). Methods and Results We conducted a pooled participant-level analysis of two double-blind, randomized trials, DEFINE-HF (n = 236) and PRESERVED-HF (n = 324), which evaluated dapagliflozin versus placebo. Both multicentre studies enrolled adults with HF, New York Heart Association Class II or higher, elevated natriuretic peptides, and an EF &lt; 40% in DEFINE-HF or &gt;45% in PRESERVED-HF. The primary exposure was eGFR. The main outcome was the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at 12 weeks. Across both trials, there were 583 (99.3%) participants with a baseline eGFR. The median (25th, 75th) eGFR was 59 (46, 77) mL/min/1.73 m2. Dapagliflozin improved KCCQ-CSS at 12 weeks [placebo-adjusted difference, +5.0 points, 95% confidence interval (CI) 2.6–7.5; P &lt; 0.001], and this was consistent in participants with an eGFR ≥ 60 (+6.0 points, 95% CI 2.4–9.7; P = 0.001) and eGFR &lt; 60 (+4.1 points, 95% CI 0.5–7.7; P = 0.025) (P interaction = 0.46). The benefits of dapagliflozin on KCCQ-CSS remained robust across eGFR when modelled as a continuous variable (P interaction = 0.48). Conclusions Dapagliflozin led to early and clinically meaningful improvements in health status in HF patients, regardless of EF or baseline eGFR.

Sex differences in sports performances continue to attract considerable scientific and public attention, driven in part by high profile cases of: 1) biological male (XY) athletes who seek to compete in the female category after gender transition, and 2) XY athletes with medical syndromes collectively known as disorders or differences of sex development (DSDs). In this perspective, we highlight scientific evidence that informs eligibility criteria and applicable regulations for sex categories in sports. There are profound sex differences in human performance in athletic events determined by strength, speed, power, endurance, and body size such that males outperform females. These sex differences in athletic performance exist before puberty and increase dramatically as puberty progresses. The profound sex differences in sports performance are primarily attributable to the direct and indirect effects of sex-steroid hormones and provide a compelling framework to consider for policy decisions to safeguard fairness and inclusion in sports.

Objective Patients with heart failure (HF) perform a variety of self-care activities to control symptoms and minimise the risk of HF decompensations. The objective of this study was to understand how patients build capacity and manage the work of living with HF. Design A qualitative study using semi-structured telephone interviews. The interview guide was informed by the Cumulative Complexity Model, a conceptual framework that focuses on a patient’s workload and their capacity to manage that work. Interview transcripts were analysed using a mixed inductive and deductive coding approach with organisation into larger thematic categories. Setting Southeastern Minnesota USA (11 counties) with capture of data from local community healthcare providers under the auspices of the Rochester Epidemiology Project. Participants Intentional sampling of local patients with HF (n=24, median age 69.5 years, 54% women, 63% rural, 54% preserved ejection fraction) who reported high treatment burden and/ or poor health status on a questionnaire. Results Three major themes emerged: using capacity to manage workload, disruptions resulting in workload exceeding capacity and regaining workload-capacity balance. Participants described routinising the daily tasks associated with living with HF to minimise the associated burden and identified disruptions to their routines, including hospitalisations, emergency room visits, worsening health status and changes in healthcare access. To accommodate disruptions and regain workload-capacity balance, participants decreased workload and/or transferred tasks to others to maximise capacity. Conclusions Participants with HF described managing patient workload in times of stable health, but they sometimes struggled to accommodate disruptions and worsening health status. These findings can inform the design of interventions to minimise workload, maximise capacity and improve quality of life for patients with HF.