Clanton

This first of a 2-part series of articles recounts the key points presented in a collaborative symposium sponsored jointly by the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society with the intent to survey the state of scientific knowledge related to incidence, diagnosis, pathologic mechanisms, and injection treatment options for osteoarthritis (OA) of the foot and ankle. A meeting was held virtually on December 3, 2021. A group of experts were invited to present brief synopses of the current state of knowledge and research in this area...

INTRODUCTION: The capability of male mice to exercise in hot environments without succumbing to exertional heat stroke (EHS) is markedly blunted compared to females. Epidemiological evidence in humans and other mammals also suggests some degree of greater vulnerability to heat stroke in males compared to females. The origins of these differences are unknown, but testosterone has previously been shown to induce faster elevations in core temperature during acute, passive heat exposure. In this study, we tested the hypothesis that loss of testosterone and related sex hormones through castration would improve the performance and heat tolerance of male mice during EHS exposure...

Evidence from human epidemiological studies suggests that exertional heat stroke (EHS) results in elevated risk of long-term cardiovascular and systemic disease. Previous results using a preclinical mouse model of EHS demonstrated severe metabolic imbalances in ventricular myocardium developing at 9-14 d of recovery. Whether this resolves over time is unknown. We hypothesized that long-term effects of EHS on the heart reflect retained maladaptive epigenetic responses. In this study, we evaluated genome-wide DNA methylation, RNA-Seq and metabolomic profiles of the left ventricular myocardium in female C57BL/6 mice, 30 d after EHS (exercise in 37...

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Epidemiological studies indicate that exposure to exertional heat stroke (EHS) can increase the risk of all-cause cardiovascular and systemic disease and promote early mortality. Using a preclinical mouse model of EHS, we previously characterized profound DNA methylation changes in immune cells at 30 d of recovery and severe cardiometabolic disturbances in the ventricular myocardium (VM) at 9-14 d. These observations indicate that a single exposure to EHS can result in long-term epigenetic and metabolic alterations...

Exertional heat stroke (EHS) is a life threating condition that has grown in prevalence with rising global temperatures. Development and use of new preclinical models are necessary to understand the pathophysiology. In our previous model of EHS, a metabolic disorder occurred in the ventricular myocardium (VM) after 14 days of recovery only in female mice. However, females were able to achieve much higher levels of exercise than males. In this study we developed a new model, specific for male mice, that prolonged exercise time and intensity but at a lower environmental temperature (Te )...

INTRODUCTION: Previous work has demonstrated large sex differences in the response to sepsis when various components of immune signaling are knocked out of muscle fibers. Skeletal muscle is a heterogeneous organ that holds many phenotypes, including resident immune cells such as resident myeloid-derived immune cells. Skeletal muscle fibers are functional contributors to the inflammatory pathway, however, the contribution of these fibers to secrete cytokines relative to resident myeloid cells remains unknown...

NEW FINDINGS: What is the topic of this review? This review outlines the history of research on epigenetic adaptations to heat exposure. The perspective taken is that adaptations reflect properties of hormesis, whereby low, repeated doses of heat induce adaptation (acclimation/acclimatization); whereas brief, life-threatening exposures can induce maladaptive responses. What advances does it highlight? The epigenetic mechanisms underlying acclimation/acclimatization comprise specific molecular programmes on histones that regulate heat shock proteins transcriptionally and protect the organism from subsequent heat exposures, even after long delays...

BACKGROUND: The best operative construct and technique for treatment of isolated syndesmotic injuries is highly debated. The purpose of this study was to determine whether the addition of anterior inferior tibiofibular ligament (AITFL) suture repair or suture tape (ST) augmentation provides any biomechanical advantage to the operative repair of an isolated syndesmotic injury. METHODS: Twelve lower leg specimens underwent biomechanical testing in 6 states: (1) intact, (2) AITFL suture repair, (3) AITFL suture repair + transsyndesmotic suture button (SB), (4) AITFL suture repair + ST augmentation + SB, (5) AITFL suture repair + ST augmentation, and (6) complete syndesmotic injury...

We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 ( Aath5 ), on mouse chromosome 10 by three-way QTL analyses between Apoe -/- mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 ( Stab2 ), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown...

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BACKGROUND: This investigation's purpose was to perform a systematic review of the literature examining the biomechanics of the ligaments comprising the distal tibiofibular syndesmosis with specific attention to their resistance to translational and rotational forces. Although current syndesmosis repair techniques can achieve an anatomic reduction, they may not reapproximate native ankle biomechanics, resulting in loss of reduction, joint overconstraint, or lack of external rotation resistance...

Molecular Imaging is entering the most fruitful, exciting period in its history with many new agents under development, and several reaching the clinic in recent years. While it is unusual for just one laboratory to take an agent from initial discovery through to full clinical approval the steps along the way are important to understand for all interested participants even if one is not involved in the entire process. Here, we provide an overview of these processes beginning at discovery and preclinical validation of a new molecular imaging agent and using as an exemplar a low molecular weight disease-specific targeted positron emission tomography (PET) agent...

Skeletal muscles play important roles in innate immunity. However, in vitro, their sensitivity to LPS is low. In other tissues, LPS sensing is facilitated by the presence of plasma, LPS binding protein (LBP), or soluble CD14 (sCD14). This study addressed whether these are critical for LPS sensitivity in skeletal muscle and whether LPS responsiveness is different between slow versus fast muscle. Soleus (SOL) or extensor digitorum longus (EDL) muscles from adult male C57bl/6 mice were mounted in 1 mL oxygenated baths containing: buffer only; buffer+1% mouse plasma; buffer+1 μg/mL LBP; or buffer+1% plasma from sCD14-/- mice...

To evaluate the diagnostic yield of the first 8 hours of video-EEG (vEEG) monitoring in detecting Psychogenic Non-Epileptic Seizures (PNES) during the Epilepsy Monitoring Unit (EMU) admission. We performed a retrospective chart review of patients ages ≥4 years who were admitted to the EMU between 2011 and 2018 (n = 616). We calculated the proportion of patients diagnosed with PNES within the first 8 hours of EEG recording and studied the associated risk factors for patients diagnosed with PNES and patients with epileptic seizures (ES)...

PURPOSE: During magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for refractory tremor, high temperatures must be achieved and sustained for tissue necrosis. We assessed the impact of both patient-specific as well as procedure-related factors on the efficiency of acoustic energy transfer, or heating efficiency (HE). METHODS: Retrospective analysis of 92 consecutive patients (857 sonications) with essential tremor or tremor-dominant Parkinson's disease treated at a single institution...

Sepsis induces a myopathy characterized by loss of muscle mass and weakness. Septic patients undergo prolonged periods of limb muscle disuse due to bed rest. The contribution of limb muscle disuse to the myopathy phenotype remains poorly described. To characterize sepsis-induced myopathy with hindlimb disuse, we combined the classic sepsis model via cecal ligation and puncture (CLP) with the disuse model of hindlimb suspension (HLS) in mice. Male C57bl/6j mice underwent CLP or SHAM surgeries. Four days after surgeries, mice underwent HLS or normal ambulation (NA) for 7 days...

Heat stroke is the most severe manifestation of heat-related illnesses. Classic heat stroke (CHS), also known as passive heat stroke, occurs at rest, whereas exertional heat stroke (EHS) occurs during physical activity. EHS differs from CHS in etiology, clinical presentation, and sequelae of multi-organ dysfunction. Until recently, only models of CHS have been well established. This protocol aims to provide guidelines for a refined preclinical mouse model of EHS that is free from major limiting factors such as the use of anesthesia, restraint, rectal probes, or electric shock...

BACKGROUND: The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research. METHODS: We conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021...

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