Sex-Linked Discrepancies in C57BL6/J Mouse Osteoarthritis are Associated With the Gut Microbiome and are Transferrable by Microbiome Transplantation.

Objective: Females have reduced osteoarthritis (OA) in surgical models. The objective of the current study was to evaluate a sex-linked gut microbiome in the pathogenesis of OA.

Methods: We induced OA via destabilization of the medial meniscus surgery in adult male and female C57BL6/J mice with and without opposite-sex microbiome transplantation.

Interstitial lung disease: the diagnostic role of bronchoscopy.

Interstitial lung diseases (ILDs) form one of the most fascinating fields in pulmonary medicine. They also pose one of the greatest challenges for accurate diagnosis and proper treatment. Even within the recommended and warranted multidisciplinary approach, differentiating between one disease and another may lead to frustration, especially when proper lung tissue is not available for adequate pathological review.

Comparison of Whole Body SOD1 Knockout with Muscle-Specific SOD1 Knockout Mice Reveals a Role for Nerve Redox Signaling in Regulation of Degenerative Pathways in Skeletal Muscle.

Aims: Lack of Cu,Zn-superoxide dismutase (CuZnSOD) in homozygous knockout mice (Sod1) leads to accelerated age-related muscle loss and weakness, but specific deletion of CuZnSOD in skeletal muscle (mSod1KO mice) or neurons (nSod1KO mice) resulted in only mild muscle functional deficits and failed to recapitulate the loss of mass and function observed in Sod1 mice. To dissect any underlying cross-talk between motor neurons and skeletal muscle in the degeneration in Sod1 mice, we characterized neuromuscular changes in the Sod1 model compared with mSod1KO mice and examined degenerative molecular mechanisms and pathways in peripheral nerve and skeletal muscle.

Results: In contrast to mSod1KO mice, myofiber atrophy in Sod1 mice was associated with increased muscle oxidative damage, neuromuscular junction degeneration, denervation, nerve demyelination, and upregulation of proteins involved in maintenance of myelin sheaths.

Effects of transgenic methionine sulfoxide reductase A (MsrA) expression on lifespan and age-dependent changes in metabolic function in mice.

Mechanisms that preserve and maintain the cellular proteome are associated with long life and healthy aging. Oxidative damage is a significant contributor to perturbation of proteostasis and is dealt with by the cell through regulation of antioxidants, protein degradation, and repair of oxidized amino acids. Methionine sulfoxide reductase A (MsrA) repairs oxidation of free- and protein-bound methionine residues through enzymatic reduction and is found in both the cytosol and the mitochondria.

Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer's disease.

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice.

STOP-BANG questionnaire as a screening tool for diagnosis of obstructive sleep apnea by unattended portable monitoring sleep study.

The Snoring, Tiredness, Observed apnea, high blood Pressure (STOP)-Body mass index (BMI), Age, Neck circumference, and Gender (BANG) questionnaire is a well validated screening tool for diagnosis of Obstructive sleep apnea (OSA) by an in- lab sleep study. However, performance of STOP-BANG as a screening tool for diagnosis of OSA in patients undergoing portable monitoring (PM) sleep study has not been well validated. We conducted a retrospective chart review of patients older than 18 years who had unattended portable monitoring sleep study done at a VA medical center between June 2012 and October 2014.

MsrA Overexpression Targeted to the Mitochondria, but Not Cytosol, Preserves Insulin Sensitivity in Diet-Induced Obese Mice.

There is growing evidence that oxidative stress plays an integral role in the processes by which obesity causes type 2 diabetes. We previously identified that mice lacking the protein oxidation repair enzyme methionine sulfoxide reductase A (MsrA) are particularly prone to obesity-induced insulin resistance suggesting an unrecognized role for this protein in metabolic regulation. The goals of this study were to test whether increasing the expression of MsrA in mice can protect against obesity-induced metabolic dysfunction and to elucidate the potential underlying mechanisms.

Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype.

Our previous studies showed that adult (8 month) mice lacking CuZn-superoxide dismutase (CuZnSOD, Sod1KO mice) have neuromuscular changes resulting in dramatic accelerated muscle atrophy and weakness that mimics age-related sarcopenia. We have further shown that loss of CuZnSOD targeted to skeletal muscle alone results in only mild weakness and no muscle atrophy. In this study, we targeted deletion of CuZnSOD specifically to neurons (nSod1KO mice) and determined the effect on muscle mass and weakness.

Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging.

Rapamycin-induced metabolic defects are reversible in both lean and obese mice.

The inhibition of mTOR (mechanistic target of rapamycin) by the macrolide rapamycin has many beneficial effects in mice, including extension of lifespan and reduction or prevention of several age-related diseases. At the same time, chronic rapamycin treatment causes impairments in glucose metabolism including hyperglycemia, glucose intolerance and insulin resistance. It is unknown whether these metabolic effects of rapamycin are permanent or whether they can be alleviated.

Antibody-secreting cell specificity in labial salivary glands reflects the clinical presentation and serology in patients with Sjögren's syndrome.

Objective: The serologic hallmark of primary Sjögren's syndrome (SS) is the presence of IgG antibodies specific for Ro (SSA) and La (SSB). The molecular characteristics of gland-derived B cells at the site of primary SS inflammation have been described previously; however, parallels between glandular antibody-secreting cells (ASCs) and serologic antibody specificities have not been evaluated. We used recombinant monoclonal antibody (mAb) technology to study the specificities of salivary gland (SG)-derived ASCs, evaluate their molecular characteristics, and identify IgG antibody specificity.

Rapamycin and dietary restriction induce metabolically distinctive changes in mouse liver.

Dietary restriction (DR) is the gold standard intervention used to delay aging, and much recent research has focused on the identification of possible DR mimetics. Energy sensing pathways, including insulin/IGF1 signaling, sirtuins, and mammalian Target of Rapamycin (mTOR), have been proposed as pathways involved in the antiaging actions of DR, and compounds that affect these pathways have been suggested to act as DR mimetics, including metformin (insulin/IGF1 signaling), resveratrol (sirtuins), and rapamycin (mTOR). Rapamycin is a promising DR mimetic because it significantly increases both health span and life span in mice.

Sustained-release fampridine (4-aminopyridine) in multiple sclerosis: efficacy and impact on motor function.

Objective: The aim of this study was to determine the efficacy of sustained-release fampridine (4-aminopyridine) in veterans with multiple sclerosis (MS) with limited ambulatory ability, and its impact on motor function in an outpatient setting.

Design: Retrospective.

Setting: Tertiary referral center [Veterans Affairs (VA) Medical Center].

Inhibition of epidermal growth factor receptor activation enhances in vivo histamine-stimulated gastric acid secretion in the rat.

Epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) have been shown to inhibit gastric acid secretion through stimulation of the EGF receptor (EGFR). In this study we examined in vivo the effects of inhibition of the EGFR on histamine-stimulated acid secretion in the rat. Submaximal (1.