Mid-Atlantic States Raccoon Rabies Outbreak

In the mid-1950s, an outbreak of raccoon rabies was recognized in South Florida and marked the beginning of epizootic/enzootic rabies in raccoons in this country. It spread at a rate of about 25 miles per year and currently includes eastern Alabama and most of Georgia and South Carolina. Up until the recent mid-Atlantic outbreak, the southern focus accounted for about 85 to 90% of the approximately 400 confirmed rabid raccoons reported in the United States each year

Pyridoxamine, an Inhibitor of Advanced Glycation Reactions, Also Inhibits Advanced Lipoxidation Reactions: Mechanism of Action of Pyridoxamine

Maillard or browning reactions lead to formation of advanced glycation end products (AGEs) on protein and contribute to the increase in chemical modification of proteins during aging and in diabetes. AGE inhibitors such as aminoguanidine and pyridoxamine (PM) have proven effective in animal model and clinical studies as inhibitors of AGE formation and development of diabetic complications. We report here that PM also inhibits the chemical modification of proteins during lipid peroxidation (lipoxidation) reactions in vitro, and we show that it traps reactive intermediates formed during lipid peroxidation. In reactions of arachidonate with the model protein RNase, PM prevented modification of lysine residues and formation of the advanced lipoxidation end products (ALEs) N(epsilon)-(carboxymethyl)lysine, N(epsilon)-(carboxyethyl)lysine, malondialdehyde-lysine, and 4-hydroxynonenal-lysine. PM also inhibited lysine modification and formation of ALEs during copper-catalyzed oxidation of low density lipoprotein. Hexanoic acid amide and nonanedioic acid monoamide derivatives of PM were identified as major products formed during oxidation of linoleic acid in the presence of PM. We propose a mechanism for formation of these products from the 9- and 13-oxo-decadienoic acid intermediates formed during peroxidation of linoleic acid. PM, as a potent inhibitor of both AGE and ALE formation, may prove useful for limiting the increased chemical modification of tissue proteins and associated pathology in aging and chronic diseases, including both diabetes and atherosclerosis

The Advanced Glycation End Product, N\u3csup\u3eE\u3c/sup\u3e-(Carboxymethyl)lysine, Is a Product of Both Lipid Peroxidation and Glycoxidation Reactions

Nepsilon-(Carboxymethyl)lysine (CML) is an advanced glycation end product formed on protein by combined nonenzymatic glycation and oxidation (glycoxidation) reactions. We now report that CML is also formed during metal-catalyzed oxidation of polyunsaturated fatty acids in the presence of protein. During copper-catalyzed oxidation in vitro, the CML content of low density lipoprotein increased in concert with conjugated dienes but was independent of the presence of the Amadori compound, fructoselysine, on the protein. CML was also formed in a time-dependent manner in RNase incubated under aerobic conditions in phosphate buffer containing arachidonate or linoleate; only trace amounts of CML were formed from oleate. After 6 days of incubation the yield of CML in RNase from arachidonate was approximately 0.7 mmol/mol lysine compared with only 0.03 mmol/mol lysine for protein incubated under the same conditions with glucose. Glyoxal, a known precursor of CML, was also formed during incubation of RNase with arachidonate. These results suggest that lipid peroxidation, as well as glycoxidation, may be an important source of CML in tissue proteins in vivo and that CML may be a general marker of oxidative stress and long term damage to protein in aging, atherosclerosis, and diabetes

Acceptance of Simulated Oral Rabies Vaccine Baits by Urban Raccoons

In summer 1986, a study was conducted to evaluate raccoon (Procyon lotor) acceptance of oral baits that could be used for rabies vaccination, One thousand wax-coated sponge bait cubes were filled with 5 mg of a seromarker (iophenoxic acid), placed in polyethylene bags, and hand-distributed in an 80 ha area within an urban National Park in Washington, D.C. (USA), After 3 wk, target and nontarget animals were trapped and blood samples collected to evaluate bait uptake. Thirty-three of 52 (63%) raccoons had elevated blood iodine levels indicating they had eaten at least one bait, 13 (25%) were negative, and six (12%) had marginal values, These results indicate that sponge baits hand-placed at a density of 12,4/ha can reach a significant proportion of an urban raccoon population. Implications for oral rabies vaccination of raccoons are discussed

Using the Galactic Dynamics of M7 Dwarfs to Infer the Evolution of Their Magnetic Activity

We present a spectroscopic study and dynamical analysis of ~2600 M7 dwarfs. We confirm our previous finding that the fraction of magnetically active stars decreases with vertical distance from the Galactic plane. We also show that the mean luminosity of the H-alpha emission has a small but statistically significant decrease with distance. Using space motions for ~1300 stars and a simple one-dimensional dynamical simulation, we demonstrate that the drop in the activity fraction of M7 dwarfs can be explained by thin disk dynamical heating and a rapid decrease of magnetic activity at a mean stellar age of ~6-7 Gyr.Comment: 6 pages, accepted for publication in A

Peer support for the maintenance of physical activity and health in cancer survivors: the PEER trial - a study protocol of a randomised controlled trial

BACKGROUND: Despite an overwhelming body of evidence showing the benefits of physical activity (PA) and exercise for cancer survivors, few survivors meet the exercise oncology guidelines. Moreover, initiating, let alone maintaining exercise programs with cancer survivors continues to have limited success. The aim of this trial is to evaluate the influence of peer support on moderate-to-vigorous PA (MVPA) and various markers of health 12 months following a brief supervised exercise intervention in cancer survivors. METHODS: Men and women previously diagnosed with histologically-confirmed breast, colorectal or prostate cancer (n = 226), who are \u3e1-month post-treatment, will be invited to participate in this trial. Once enrolled, participants will complete 4 weeks (12 sessions) of supervised high intensity interval training (HIIT). On completion of the supervised phase, both groups will be provided with written recommendations and verbally encouraged to achieve three HIIT sessions per week, or equivalent exercise that meets the exercise oncology guidelines. Participants will be randomly assigned to receive 12 months of peer support, or no peer support (control). Primary and secondary outcomes will be assessed at baseline, after the 4-week supervised HIIT phase and at 3-, 6- and 12-months. Primary outcomes will include accelerometry-derived MVPA and prescribed HIIT session adherence; whilst secondary outcomes will include cardiorespiratory fitness ([Formula: see text]), body composition, quality of life and select cytokines, myokines and inflammatory markers. Random effects mixed modelling will be used to compare mean changes in outcomes between groups at each time point. A group x time interaction will be used to formally test for differences between groups (alpha =0.05); utilising intention-to-treat analyses. DISCUSSION: If successful, peer support may be proposed, adopted and implemented as a strategy to encourage cancer survivors to maintain exercise beyond the duration of a short-term, supervised intervention. A peer support-exercise model has the long-term potential to reduce comorbidities, improve physical and mental wellbeing, and significantly reduce the burden of disease in cancer survivors. ETHICS: Human Research Ethics Committee of Bellberry Ltd. (#2015-12-840). TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry 12618001855213 . Retrospectively registered 14 November 2018. Trial registration includes all components of the WHO Trial Registration Data Set, as recommended by the ICMJE

ECM crosslinking enhances fibroblast growth and protects against matrix proteolysis in lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of extra cellular matrix (ECM) proteins and fibroblast proliferation. ECM cross-linking enzymes have been implicated in fibrotic diseases and we hypothesised that the ECM in IPF is abnormally cross-linked which enhances fibroblast growth and resistance to normal ECM turnover. We used a combination of in vitro ECM preparations and in vivo assays to examine the expression of cross-linking enzymes and the effect of their inhibitors on fibroblast growth and ECM turnover. Lysyl oxidase like 1, 2, 3 and 4 were expressed equally in control and IPF derived fibroblasts. Transglutaminase 2 was more strongly expressed in IPF fibroblasts. Lysyl oxidase like 2, transglutaminase 2 and transglutaminase generated cross-links were strongly expressed in IPF lung tissue. Fibroblasts grown on IPF ECM had higher LOXL3 protein expression and transglutaminase activity compared with those grown on control ECM. IPF derived ECM also enhanced fibroblast adhesion and proliferation compared with control ECM. Inhibition of lysyl oxidase and transglutaminse activity during ECM formation affected ECM structure as visualised by electron microscopy and reduced the enhanced fibroblast adhesion and proliferation of IPF ECM to control levels. Inhibition of transglutaminase, but not lysyl oxidase activity, enhanced the turnover of ECM in vitro. In bleomycin treated mice, during the post-inflammatory fibrotic phase, inhibition of transglutaminases was associated with a reduction in whole lung collagen. Our findings suggest that the ECM in IPF may enhance pathological cross-linking which contributes to increased fibroblast growth, resistance to normal ECM turnover to drive lung fibrosis

International challenges without borders: a descriptive study of family physicians' educational needs in the field of diabetes

<p>Abstract</p> <p>Background</p> <p>The optimal care of persons with diabetes by general practitioners and family physicians (GP/FP) is complex and requires multiple competencies. This is a fairly unrecognized key challenge in the healthcare systems. In some cases, local and national Continuous Professional Development (CPD) initiatives target these challenges; however there have been few international initiatives, possibly because challenges emerging from different studies have not been linked across national boundaries. In this context, the authors have compiled data about gaps and/or barriers inherent to GP/FP care of persons with type 2 diabetes from Austria, Canada, Germany and the United Kingdom.</p> <p>Methods</p> <p>Secondary analyzes of pre-existing studies were conducted to identify challenges in the care of patients with type 2 diabetes as faced by GPs/FPs. Two sources of data were reviewed: unpublished research data from collaborating organizations and articles from a literature search (in English and German). Articles retrieved were scanned by the research team for relevance to the study objectives and to extract existing gaps and barriers. The identified challenges were then categorized along three major axes: (1) phase of the continuum of care {from screening to management}; (2) learning domain {knowledge, skills, attitudes, behavior, context}; and (3) by country/region. Compilation and categorization were performed by qualitative researchers and discrepancies were resolved through discussion until concordance was achieved.</p> <p>Results and discussion</p> <p>Thirteen challenges faced by GPs/FPs in the care for patients with type 2 diabetes were common in at least 3 of the 4 targeted countries/regions. These issues were found across the entire continuum of care and included: pathophysiology of diabetes, diagnostic criteria, treatment targets assessment, drugs' modes of action, decision-making in therapies, treatment guidelines, insulin therapy, adherence, management of complications, lifestyle changes, team integration, bureaucracy and third-party payers. The issues reported were not restricted to the physicians' knowledge, but also related to their skills, attitudes, behaviours and context.</p> <p>Conclusions</p> <p>This study revealed challenges faced by GPs/FPs when caring for patients with diabetes, which were similar across international and health system borders. Common issues might be addressed more efficiently through international educational designs, adapted to each country's healthcare system, helping develop and maintain physicians' competencies.</p