Pilot Comparative Effectiveness Study of Surface Perturbation Treadmill Training to Prevent Falls in Older Adults

Falls are the leading cause of fatal and non-fatal injuries among older adults. Exercise programs appear to reduce fall risk, but the optimal type, frequency, and duration of exercise is unknown. External perturbations such as tripping and slipping are a major contributor to falls, and task-specific perturbation training to enhance dynamic stability has emerged as a promising approach to modifying fall risk. The purpose of this pilot study was 1) to determine the feasibility of conducting a large pragmatic randomized trial comparing a multidimensional exercise program inclusive of the surface perturbation treadmill training (SPTT) to multidimensional exercise alone (Standard PT); and 2) to assess fall outcomes between the two groups to determine whether an effect size large enough to warrant further study might be present

A Transient Sub-Eddington Black Hole X-ray Binary Candidate in the Dust Lanes of Centaurus A

We report the discovery of a bright X-ray transient, CXOU J132527.6-430023, in the nearby early-type galaxy NGC 5128. The source was first detected over the course of five Chandra observations in 2007, reaching an unabsorbed outburst luminosity of 1-2*10^38 erg/s in the 0.5-7.0 keV band before returning to quiescence. Such luminosities are possible for both stellar-mass black hole and neutron star X-ray binary transients. Here, we attempt to characterize the nature of the compact object. No counterpart has been detected in the optical or radio sky, but the proximity of the source to the dust lanes allows for the possibility of an obscured companion. The brightness of the source after a >100 fold increase in X-ray flux makes it either the first confirmed transient non-ULX black hole system in outburst to be subject to detailed spectral modeling outside the Local Group, or a bright (>10^38 erg/s) transient neutron star X-ray binary, which are very rare. Such a large increase in flux would appear to lend weight to the view that this is a black hole transient. X-ray spectral fitting of an absorbed power law yielded unphysical photon indices, while the parameters of the best-fit absorbed disc blackbody model are typical of an accreting ~10 Msol black hole in the thermally dominant state.Comment: 8 pages, 6 figures, accepted for publication in Ap

Trichuris muris infection drives cell-intrinsic IL4R alpha independent colonic RELMα+ macrophages

From PLOS via Jisc Publications RouterHistory: received 2021-02-23, accepted 2021-06-29, collection 2021-07, epub 2021-07-30Publication status: PublishedFunder: Medical Research Council; funder-id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/N022661/1Funder: wellcome trust; funder-id: http://dx.doi.org/10.13039/100004440; Grant(s): 106898/A/15/ZThe intestinal nematode parasite Trichuris muris dwells in the caecum and proximal colon driving an acute resolving intestinal inflammation dominated by the presence of macrophages. Notably, these macrophages are characterised by their expression of RELMα during the resolution phase of the infection. The RELMα+ macrophage phenotype associates with the presence of alternatively activated macrophages and work in other model systems has demonstrated that the balance of classically and alternatively activated macrophages is critically important in enabling the resolution of inflammation. Moreover, in the context of type 2 immunity, RELMα+ alternatively activated macrophages are associated with the activation of macrophages via the IL4Rα. Despite a breadth of inflammatory pathologies associated with the large intestine, including those that accompany parasitic infection, it is not known how colonic macrophages are activated towards an alternatively activated phenotype. Here, we address this important knowledge gap by using Trichuris muris infection, in combination with transgenic mice (IL4Rαfl/fl.CX3CR1Cre) and IL4Rα-deficient/wild-type mixed bone marrow chimaeras. We make the unexpected finding that education of colonic macrophages towards a RELMα+, alternatively activated macrophage phenotype during T. muris infection does not require IL4Rα expression on macrophages. Further, this independence is maintained even when the mice are treated with an anti-IFNγ antibody during infection to create a strongly polarised Th2 environment. In contrast to RELMα, PD-L2 expression on macrophages post infection was dependent on IL4Rα signalling in the macrophages. These novel data sets are important, revealing a surprising cell-intrinsic IL4R alpha independence of the colonic RELMα+ alternatively activated macrophage during Trichuris muris infection

Low-Mass X-ray Binaries and Globular Clusters in Centaurus A

We present results of Hubble Space Telescope and Chandra X-ray Observatory observations of globular clusters (GCs) and low-mass X-ray binaries (LMXBs) in the central regions of Centaurus A. Out of 440 GC candidates we find that 41 host X-ray point sources that are most likely LMXBs. We fit King models to our GC candidates in order to measure their structural parameters. We find that GCs that host LMXBs are denser and more compact, and have higher encounter rates and concentrations than the GC population as a whole. We show that the higher concentrations and masses are a consequence of the dependence of LMXB incidence on central density and size plus the general trend for denser GCs to have higher masses and concentrations. We conclude that neither concentration nor mass are fundamental variables in determining the presence of LMXBs in GCs, and that the more fundamental parameters relate to central density and size.Comment: 4 pages, 2 figures. Accepted for publication in ApJ Letter

Implication for Functions of the Ectopic Adipocyte Copper Amine Oxidase (AOC3) from Purified Enzyme and Cell-Based Kinetic Studies

AOC3 is highly expressed in adipocytes and smooth muscle cells, but its function in these cells is currently unknown. The in vivo substrate(s) of AOC3 is/are also unknown, but could provide an invaluable clue to the enzyme's function. Expression of untagged, soluble human AOC3 in insect cells provides a relatively simple means of obtaining pure enzyme. Characterization of enzyme indicates a 6% titer for the active site 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor and corrected kcat values as high as 7 s−1. Substrate kinetic profiling shows that the enzyme accepts a variety of primary amines with different chemical features, including nonphysiological branched-chain and aliphatic amines, with measured kcat/Km values between 102 and 104 M−1 s−1. Km(O2) approximates the partial pressure of oxygen found in the interstitial space. Comparison of the properties of purified murine to human enzyme indicates kcat/Km values that are within 3 to 4-fold, with the exception of methylamine and aminoacetone that are ca. 10-fold more active with human AOC3. With drug development efforts investigating AOC3 as an anti-inflammatory target, these studies suggest that caution is called for when screening the efficacy of inhibitors designed against human enzymes in non-transgenic mouse models. Differentiated murine 3T3-L1 adipocytes show a uniform distribution of AOC3 on the cell surface and whole cell Km values that are reasonably close to values measured using purified enzymes. The latter studies support a relevance of the kinetic parameters measured with isolated AOC3 variants to adipocyte function. From our studies, a number of possible substrates with relatively high kcat/Km have been discovered, including dopamine and cysteamine, which may implicate a role for adipocyte AOC3 in insulin-signaling and fatty acid metabolism, respectively. Finally, the demonstrated AOC3 turnover of primary amines that are non-native to human tissue suggests possible roles for the adipocyte enzyme in subcutaneous bacterial infiltration and obesity

Home-Based Cardiac Rehabilitation

Cardiac rehabilitation (CR) is an evidence-based intervention that uses patient education, health behavior modification, and exercise training to improve secondary prevention outcomes in patients with cardiovascular disease. CR programs reduce morbidity and mortality rates in adults with ischemic heart disease, heart failure, or cardiac surgery but are significantly underused, with only a minority of eligible patients participating in CR in the United States. New delivery strategies are urgently needed to improve participation. One potential strategy is home-based CR (HBCR). In contrast to center-based CR services, which are provided in a medically supervised facility, HBCR relies on remote coaching with indirect exercise supervision and is provided mostly or entirely outside of the traditional center-based setting. Although HBCR has been successfully deployed in the United Kingdom, Canada, and other countries, most US healthcare organizations have little to no experience with such programs. The purpose of this scientific statement is to identify the core components, efficacy, strengths, limitations, evidence gaps, and research necessary to guide the future delivery of HBCR in the United States. Previous randomized trials have generated low- to moderate-strength evidence that HBCR and center-based CR can achieve similar improvements in 3- to 12-month clinical outcomes. Although HBCR appears to hold promise in expanding the use of CR to eligible patients, additional research and demonstration projects are needed to clarify, strengthen, and extend the HBCR evidence base for key subgroups, including older adults, women, underrepresented minority groups, and other higher-risk and understudied groups. In the interim, we conclude that HBCR may be a reasonable option for selected clinically stable low- to moderate-risk patients who are eligible for CR but cannot attend a traditional center-based CR program