George E. Wahlen Department of VA Medical Center

Aging changes the lipidome and mitochondrial function in a sex-dependent manner, yet their associations remain poorly understood. Twenty-four younger (7M/17F) and forty-three older (21M/22F) adults underwent blood draws and skeletal muscle biopsies for this cross-sectional investigation. Plasma lipidomic profiling was performed via liquid chromatography-tandem mass spectrometry, while peak mitochondrial O2 utilization (OXPHOS) and hydrogen peroxide (H2O2) emission were assessed using high-resolution respirometry. Plasma lipidomic analysis annotated 535 lipid species across 28 different lipid classes. Lipid-age associations were identified in four lipid classes for both sexes with twelve lipid classes demonstrating sex-specific associations, including triglycerides (TG), carnitines (CAR), and fatty acids (FA). For lipid-OXPHOS interactions, the primary lipid class and species associated with higher OXPHOS exclusively in males were ceramides (CER) and dimethyl cholesterol esters (dimethyl-CE), while TG were the primary lipid species associated with impaired OXPHOS in females. For lipid-H2O2 interactions, the primary lipid class and species associated with higher H2O2 were methyl desmosteryl esters (methyl-DE), methyl cholesterol esters (methyl-CE), FA and TG in males whereas females exhibited 10 (CE, SM, LPC, dihexosylceramides (Hex2Cer), LPE, PI, HexCer, LPI, CAR, and hexosyl-N-acetylneuraminyl-ceramides (Hex2NeuAcCer)) lipid classes associated exclusively with H2O2 emission. These findings establish novel age- and sex-specific relationships between age-related changes in plasma lipids and skeletal muscle mitochondrial function, revealing distinct lipid signatures for respiration and H2O2 emission in males and females.

Nicotine is the main substance responsible for the development of tobacco addiction. The α3β4 nicotinic acetylcholine receptors (nAChRs) are a potential key target for mitigating nicotine reward. Preliminary studies in our laboratory suggest that α-conotoxin [S9K]TxID serves as a selective and potent antagonist targeting α3β4 nAChRs, which may be beneficial in addressing nicotine addiction. However, the mechanisms of [S9K]TxID treatment in nicotine addiction are still to be determined. This study aimed to identify the differential metabolic profiles of [S9K]TxID treatment in nicotine addiction using an untargeted metabolomic profiling method. As demonstrated by behavioral experiments, [S9K]TxID effectively attenuated nicotine-induced conditioned place preference (CPP) expression without exerting inhibitory effects on the central nervous system (CNS). The results of untargeted metabolomics revealed that eight metabolites were significantly altered after [S9K]TxID treatment, particularly phenylalanine. [S9K]TxID also attenuated nicotine-induced metabolic disorders by regulating phenylalanine, tyrosine and tryptophan biosynthesis. In conclusion, our findings suggest that [S9K]TxID could be a potential therapeutic compound for nicotine addiction.

The Osseointegrated Neural Interface (ONI) is an innovative peripheral nerve interface design that houses a transected nerve and coupled electrical components within the medullary canal of long bones for eventual prosthetic control. Before the ONI can enter clinical testing, it must demonstrate longitudinal durability in an animal model analogous to the human anatomy. Adult sheep, possessing comparable weight and bone structure to adult humans, serve as the standard model for osseointegration research, solidifying them as the ideal animal for the development of an ONI. In this paper, we introduce an Ovine ONI model with a wireless, dual capsule implantable peripheral nerve interface capable of remote stimulation and recording of our subject’s nervous system 8 weeks post-implantation. This study investigates the interface design, surgical methodology, radiological evidence, and electrophysiological data that substantiate the osseointegrated approach to interfacing with the peripheral nervous system. We also explore the functional specifications, 3D printing, and coating processing steps for the capsule. Furthermore, our exploration includes the post-processing data analysis methodology used to validate our interface. This methodological study not only contributes crucial insights but also establishes the essential foundation for future goals of the ONI project. Emphasizing real-world applicability through closed-loop interfacing and enhanced efficacy of recording devices.

Exercise is an essential part of the treatment of Parkinson's disease. However, certain symptoms can make exercise difficult. In this viewpoint, we describe an under recognized symptom called running-induced dystonia (RID), which can prevent people with Parkinson's from exercising in their preferred way. We summarize the existing literature and use three case studies to outline potential mechanisms, aggravating and relieving factors and both pharmacological and non-pharmacological therapies to get rid of RID.

BackgroundAdvancements in device design have reduced infectious complications following inflatable penile prosthesis (IPP) implantation. This study evaluated infection rates among two models of IPP devices available in the United States, AMS 700™ and Titan®, using real-world data.MethodsPatients aged ≥18 years from the Premier PINC AI™ Healthcare Database who underwent IPP insertion with either AMS 700 or Titan between 2016 and 2022 were included. Twelve published risk factors for IPP infection [age >75 years, smoking, human immunodeficiency virus (HIV), diabetes, pelvic radiation, urinary diversion, spinal cord injury, obesity, concomitant circumcision, and Peyronie’s disease] were used to characterize patients. The association between device model and infection rates was assessed with Cox proportional hazards regression.ResultsIn total, 3,636 AMS 700 and 2,830 Titan patients were identified; 26.9% of AMS 700 patients had ≥1 risk factor compared to 19.2% of Titan patients (P<0.001). Patients in the AMS 700 group had higher rates of type 2 diabetes (10.7% vs. 6.0%, P<0.001), obesity (5.6% vs. 2.9%, P<0.001), and Peyronie’s disease (2.3% vs. 1.6%, P=0.04). Infection rates were 1.8% (AMS 700) vs. 2.9% (Titan) at 180 days post-IPP and 2.5% (AMS 700) vs. 3.3% (Titan) at a median follow-up of 3 years (P=0.047).ConclusionsAMS 700 patients experienced significantly lower infection rates in both the short- and long-term period post IPP implantation compared to Titan patients, despite having a higher prevalence of known risk factors for IPP infection. These findings suggest that other factors, including device selection, may influence device infection beyond intrinsic patient characteristics.

Examine potentially modifiable risk factors (MRFs) for female/woman/girl athletes' lower-extremity injuries. Systematic review with meta- or semiquantitative analyses and Grading of Recommendations, Assessment, Development and Evaluation. MEDLINE, CINAHL, APA PsycINFO, Cochrane Systematic Review Database, CENTRAL, SPORTDiscus, EMBASE, ERIC searched 30 October or 23 November 2023. Primary data studies with comparison group(s) assessing the association of MRFs for sport-related lower-extremity injury(s) with ≥1 female/woman/girl per study group. Across 195 studies (n=115; 58.9% female/woman/girl-specific estimates) including 1 525 662 participants (2.4% females/women/girls), eight injury outcomes were assessed (n=75 general lower-extremity, n=3 groin, n=6 hip, n=17 thigh, n=88 knee, n=17 lower-leg, n=27 ankle, n=9 foot). Sixty-six MRF categories were identified. Substantial heterogeneity in MRFs and injury outcomes exists, with high risk of bias present in 37.4% of studies. Considering female/woman/girl specific estimates, we performed meta-analyses for 10 MRFs (body mass, x (BMI), weekly training distance, muscle strength, artificial turf, off-season plyometric training, readiness to return-to-sport, single-leg hop asymmetry, vertical drop jump peak knee flexion angle and ground reaction force) and semiquantitative analyses for 26 MRFs for a variety of injuries. Meta-analyses suggest no association between any lower-extremity strength outcome (g=0.01, 95% CI -0.11 to 0.14; I2=37.3%; very low certainty evidence) or artificial turf (Incidence Rate Ratio=0.97, 95% CI 0.88 to 1.07; I2=2.4%; low certainty evidence) and various lower-extremity injuries. Higher body mass (g=0.19, 95% CI 0.00 to 0.38; I2=71.7%) and/or BMI (g=0.22, 95% CI 0.09 to 0.36; I2=37.0%) are associated with several lower-extremity injuries (very low certainty evidence). This review synthesises a large body of exploratory research, exposes important knowledge gaps and provides a foundation for understanding MRFs for female/woman/girl athlete lower-extremity injuries. PROSPERO CRD42024486715.

Background/Objectives: Multimorbidity, where patients have ≥2 comorbidities, is recognized as a major challenge for health systems worldwide, driving up morbidity and cost. The differences in multimorbidity burden between those with and without type-2 diabetes mellitus (T2DM) in the Veteran population are not well studied. This large retrospective cohort study fills the existing gap. Methods: Using a retrospective cohort of adult Veterans with and without T2DM, we examined 29 comorbidities defined by Elixhauser criteria for 10,499,394 Veterans from 1 January 2008 to 31 December 2009. We then ascertained diabetes status for 10 years of follow-up from 1 January 2010 to 31 December 2019. Multimorbidity status was categorized using the Elixhauser comorbidity index (0, 1, ≥2) and logistic regression was used to estimate the odds ratio (OR) for its association with risk of diabetes, adjusting for covariates. Results: Compared to those with zero comorbidities, the odds of having diabetes were more than doubled (2.53, CI: 2.51–2.54) for those with ≥2 comorbidities. Conclusions: The doubling of the odds of T2DM among those with more than one comorbidity is typical of Veterans with T2DM. In addition, the odds were significantly higher for Hispanics compared to other groups when adjusting for covariates. This calls for more attention to reduce the risk of T2DM through improved management and effective use of treatments informed by disparities that exist in the VHA.

High-intensity/sprint interval training (HIIT/SIT) improves aerobic and anaerobic performance, but it is unknown if HIIT/SIT increases strength, muscle mass/size, and muscle endurance (ME). We aimed to determine if HIIT/SIT increases strength, muscle mass/size, and ME. Databases (Ovid Medline, Sport Discus, EMBASE, and CINAHL) and the gray literature (Google Scholar) were searched for original research articles investigating the impact of HIIT/SIT on strength, muscle mass/size, and ME (23 March 2025). The risk of bias (ROB) was assessed via the Cochrane ROB 2 Tool. Meta-analyses were performed when three or more randomized controlled trials compared HIIT/SIT to a common comparator. Fifty-four studies were included (N = 1136). Twenty-five studies had a high ROB, while twenty-nine had some concerns. Standardized mean differences (SMD) (95% CI) of 0.16; (−0.09, 0.40), 0.33; (−0.21, 0.87) were observed for meta-analyses comparing the effect of HIIT/SIT to moderate intensity continuous training (MICT) and non-exercise controls (CON) on FFM, respectively. A meta-analysis comparing the effect of HIIT/SIT to resistance training (RT) on leg press strength yielded a SMD of −0.82; 95% CI: (−1.97, 0.33). HIIT/SIT may induce slightly greater gains than MICT and CON for FFM, while RT is likely superior to HIIT/SIT for improving leg press strength. However, the certainty of evidence is low, and 95% CIs intersect zero for all analyses.