501 research outputs found

    O<sub>2</sub> reduction at a DMSO/Cu(111) model battery interface

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    In order to develop a better understanding of electrochemical O2\mathrm{O_2}reduction in non-aqueous solvents, we apply two-photon photoelectronspectroscopy to probe the dynamics of O2\mathrm{O_2} reduction at aDMSO/Cu(111) model battery interface. By analyzing the temporal evolution ofthe photoemission signal, we observe the formation of O2\mathrm{O_2^-} from atrapped electron state at the DMSO/vacuum interface. We find the verticalbinding energy of O2\mathrm{O_2^-} to be 3.80 ±\pm 0.05 eV, in good agreementwith previous results from electrochemical measurements, but with improvedaccuracy, potentially serving as a basis for future calculations on thekinetics of electron transfer at electrode interfaces. Modelling theO2\mathrm{O_2} diffusion through the DMSO layer enables us to quantify theactivation energy of diffusion (31 ±\pm 6 meV), the diffusion constant (1±\pm 1108\cdot 10^{-8} cm2^2/s), and the reaction quenching distance forelectron transfer to O2\mathrm{O_2} in DMSO (12.4 ±\pm 0.4 \unicode{x212B}),a critical value for evaluating possible mechanisms for electrochemical sidereactions. These results ultimately will inform the development andoptimization of metal-air batteries in non-aqueous solvents.<br

    Clearance kinetics and matrix binding partners of the receptor for advanced glycation end products

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    Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE). Previous studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin. Soluble RAGE administered intratracheally, intravenously, or intraperitoneally, does not distribute in a specific fashion to any healthy mouse tissue, suggesting against the existence of accessible sRAGE sinks and receptors in the healthy mouse. Intratracheal administration is the only effective means of delivering exogenous sRAGE to the lung, the organ in which RAGE is most highly expressed; clearance of sRAGE from lung does not differ appreciably from that of albumin. Copyright: © 2014 Milutinovic et al

    Homeopathy for depression: a systematic review of the research evidence

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    Objective: To systematically review the research evidence on the effectiveness of homeopathy for the treatment of depression and depressive disorders. Methods: A comprehensive search of major biomedical databases including MEDLINE, EMBASE, ClNAHL, PsycINFO and the Cochrane Library was conducted. Specialist complementary and alternative medicine (CAM) databases including AMED, CISCOM and Hom-Inform were also searched. Additionally, efforts were made to identify unpublished and ongoing research using relevant sources and experts in the field. Relevant research was categorised by study type and appraised according to study design. Clinical commentaries were obtained for studies reporting clinical outcomes. Results: Only two randomised controlled trials (RCTs) were identified. One of these, a feasibility study, demonstrated problems with recruitment of patients in primary care. Several uncontrolled and observational studies have reported positive results including high levels of patient satisfaction but because of the lack of a control group, it is difficult to assess the extent to which any response is due to specific effects of homeopathy. Single case reports/studies were the most frequently encountered clinical study type. We also found surveys, but no relevant qualitative research studies were located. Adverse effects reported appear limited to 'remedy reactions' ('aggravations') including temporary worsening of symptoms, symptom shifts and reappearance of old symptoms. These remedy reactions were generally transient but in one study, aggravation of symptoms caused withdrawal of the treatment in one patient. Conclusions: A comprehensive search for published and unpublished studies has demonstrated that the evidence for the effectiveness of homeopathy in depression is limited due to lack of clinical trials of high quality. Further research is required, and should include well designed controlled studies with sufficient numbers of participants. Qualitative studies aimed at overcoming recruitment and other problems should precede further RCTs. Methodological options include the incorporation of preference arms or uncontrolled observational studies. The highly individualised nature of much homeopathic treatment and the specificity of response may require innovative methods of analysis of individual treatment response

    Release of insulin from PLGA-alginate dressing stimulates regenerative healing of burn wounds in rats

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    Burn wound healing involves a complex set of overlapping processes in an environment conducive to ischemia, inflammation, and infection costing $7.5 billion/year in the US alone, in addition to the morbidity and mortality that occur when the burns are extensive. We previously showed that insulin, when topically applied to skin excision wounds, accelerates re-epithelialization, and stimulates angiogenesis. More recently, we developed an alginate sponge dressing (ASD) containing insulin encapsulated in PLGA microparticles that provides a sustained release of bioactive insulin for >20days in a moist and protective environment. We hypothesized that insulin-containing ASD accelerates burn healing and stimulates a more regenerative, less scarring, healing. Using a heat-induced burn injury in rats, we show that burns treated with dressings containing 0.04mg insulin/cm2, every three days for 9 days, have faster closure, faster rate of disintegration of dead tissue, and decreased oxidative stress.In addition, in insulin-treated wounds the pattern of neutrophil inflammatory response suggests faster clearing of the burn dead tissue. We also observe faster resolution of the pro-inflammatory macrophages. We also found that insulin stimulates collagen deposition and maturation with the fibers organized more like a basket weave (normal skin) than aligned and crosslinked (scar tissue). In summary , application of ASD-containing insulin-loaded PLGA particles on burns every three days stimulates faster and more regenerative healing. These results suggest insulin as a potential therapeutic agent in burn healing and, because of its long history of safe use in humans, insulin could become one of the treatments of choice when repair and regeneration are critical for proper tissue function.This work was supported by the National Natural Science Fund of China [grant numbers 81170761 and 81270909 (to Y.L.)]; the Natural Sciences and Engineering Research Council of Canada [grant numbers 204794-2011 (to M.H.) and private donor (to M.M.-G.)]

    Development of a Modular Biosensor System for Rapid Pathogen Detection

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    Progress in the field of pathogen detection relies on at least one of the following three qualities: selectivity, speed, and cost-effectiveness. Here, we demonstrate a proof of concept for an optical biosensing system for the detection of the opportunistic human pathogen Pseudomonas aeruginosa while addressing the abovementioned traits through a modular design. The biosensor detects pathogen-specific quorum sensing molecules and generates a fluorescence signal via an intracellular amplifier. Using a tailored measurement device built from low-cost components, the image analysis software detected the presence of P. aeruginosa in 42 min of incubation. Due to its modular design, individual components can be optimized or modified to specifically detect a variety of different pathogens. This biosensor system represents a successful integration of synthetic biology with software and hardware engineering

    A High-Protein Diet With Resistance Exercise Training Improves Weight Loss and Body Composition in Overweight and Obese Patients With Type 2 Diabetes

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    OBJECTIVE: To evaluate the effects of two low-fat hypocaloric diets differing in the carbohydrate-to-protein ratio, with and without resistance exercise training (RT), on weight loss, body composition, and cardiovascular disease (CVD) risk outcomes in overweight/obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 83 men and women with type 2 diabetes (aged 56.1 ± 7.5 years, BMI 35.4 ± 4.6 kg/m2) were randomly assigned to an isocaloric, energy-restricted diet (female subjects 6 MJ/day, male subjects 7 MJ/day) of either standard carbohydrate (CON; carbohydrate:protein:fat 53:19:26) or high protein (HP; 43:33:22), with or without supervised RT (3 days/week) for 16 weeks. Body weight and composition, waist circumference (WC), and cardiometabolic risk markers were assessed. RESULTS: Fifty-nine participants completed the study. There was a significant group effect (P ≤ 0.04) for body weight, fat mass, and WC with the greatest reductions occuring in HP+RT (weight [CON: −8.6 ± 4.6 kg, HP: −9.0 ± 4.8 kg, CON+RT: −10.5 ± 5.1 kg, HP+RT: −13.8 ± 6.0 kg], fat mass [CON: −6.4 ± 3.4 kg, HP: −6.7 ± 4.0 kg, CON+RT: −7.9 ± 3.7 kg, HP+RT: −11.1 ± 3.7 kg], and WC [CON: −8.2 ± 4.6 cm, HP: −8.9 ± 3.9 cm, CON+RT: −11.3 ± 4.6 cm, HP+RT: −13.7 ± 4.6 cm]). There was an overall reduction (P < 0.001) in fat-free mass (−2.0 ± 2.3 kg), blood pressure (−15/8 ± 10/6 mmHg), glucose (−2.1 ± 2.2 mmol/l), insulin (−4.7 ± 5.4 mU/l), A1C (−1.25 ± 0.94%), triglycerides (−0.47 ± 0.81 mmol/l), total cholesterol (−0.67 ± 0.69 mmol/l), and LDL cholesterol (−0.37 ± 0.53 mmol/l), with no difference between groups (P ≥ 0.17). CONCLUSIONS: An energy-restricted HP diet combined with RT achieved greater weight loss and more favorable changes in body composition. All treatments had similar improvements in glycemic control and CVD risk markers.Thomas P. Wycherley, Manny Noakes, Peter M. Clifton, Xenia Cleanthous, Jennifer B. Keogh and Grant D. Brinkwort

    Amyloid associated with elastin-staining laminar aggregates in the lungs of patients diagnosed with acute respiratory distress syndrome

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    BACKGROUND: The heterogeneity of conditions underlying respiratory distress, whether classified clinically as acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS), has hampered efforts to identify and more successfully treat these patients. Examination of postmortem lungs among cases clinically diagnosed as ARDS identified a cohort that showed a consistent morphology at the light and electron microscope levels, and featured pathognomonic structures which we termed elastin-staining laminar structures (ELS). METHODS: Postmortem tissues were stained using the Verhoeff-Van Gieson procedure for elastic fibers, and with Congo red for examination under a polarizing microscope. Similar samples were examined by transmission EM. RESULTS: The pathognomonic ELS presented as ordered molecular aggregates when stained using the Verhoeff-van Gieson technique for elastic fibers. In several postmortem lungs, the ELS also displayed apple-green birefringence after staining with Congo red, suggesting the presence of amyloid. Remarkably, most of the postmortem lungs with ELS exhibited no significant acute inflammatory cellular response such as neutrophilic reaction, and little evidence of widespread edema except for focal intra-alveolar hemorrhage. CONCLUSIONS: Postmortem lungs that exhibit the ELS constitute a morphologically-identifiable subgroup of ARDS cases. The ordered nature of the ELS, as indicated by both elastin and amyloid stains, together with little morphological evidence of inflammation or edema, suggests that this cohort of ARDS may represent another form of conformational disease. If this hypothesis is confirmed, it will require a new approach in the diagnosis and treatment of patients who exhibit this form of acute lung injury
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