The Pillars of Prevention: Discover, Advocate, and Educate.
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ABSTRACT:
SUBMITTER: Montgomery B
PROVIDER: S-EPMC5813306 | biostudies-other | 2018 Feb
REPOSITORIES: biostudies-other
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Project description:Alcohol addiction often compromises vision by impairing the visual pathway, particularly the retina and optic nerve. Vision decline in alcoholics consists of a sequential transition from reversible functional deterioration of the visual pathway to irreversible clinical vision degeneration or vision loss. Thus, the control of alcoholic vision decline should focus on prevention before permanent damage occurs. Visual electrophysiology is a promising method for early detection of retinal dysfunction and optic neuropathy, including full-field electroretinography (ffERG) and pattern-reversal visual evoked potential (PR-VEP). So far, however, research studying the electrophysiological characteristics in the preclinical stage of vision decline caused by alcohol addiction is still lacking. Here we conducted a retrospective study with 11 alcoholics and 14 matched control individuals to address this need. We had performed comprehensive visual electrophysiological tests, including ffERG and PR-VEP. We next analyzed all electrophysiological parameters using multivariate statistical analyses and discovered some highly sensitive alterations to alcohol addiction. We found severely reduced amplitudes in scotopic ffERG oscillatory potentials (OPs) in alcohol addicts. These changes indicate the alcohol-induced disturbances of amacrine cells and retinal circulation. In subjects with alcohol addiction, the amplitudes of b-waves diminish significantly in scotopic but not photopic ffERG, implying the impaired function of the retinal rod system and the dysfunction of the inner retina. PR-VEPs elicited by checkerboard stimuli with large 1 degree (°) checks mainly reflect the state of the optic nerve and ganglion cells, and PR-VEPs provoked by small 0.25° checks mainly reflect the function of the macular. We performed both measurements and observed a robust amplitude reduction in all three peaks (N75-P100, P100-N135) and a significant peak time extension in P100. Our research provides an affordable and non-invasive tool to accurately evaluate visual pathway conditions in alcohol addicts and help clinicians take targeted treatment.
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Project description:AimsThis sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors.Methods and resultsIn this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II-III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥-8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models.ConclusionsSacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.
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Project description:This study used elemental and stable isotope composition to characterize Slovenian truffles and used multi-variate statistical analysis to classify truffles according to species and geographical origin. Despite the fact that the Slovenian truffles shared some similar characteristics with the samples originating from other countries, differences in the element concentrations suggest that respective truffle species may respond selectively to nutrients from a certain soil type under environmental and soil conditions. Cross-validation resulted in a 77% correct classification rate for determining the geographical origin and a 74% correct classification rate to discriminate between species. The critical parameters for geographical origin discriminations were Sr, Ba, V, Pb, Ni, Cr, Ba/Ca and Sr/Ca ratios, while from stable isotopes δ18O and δ13C values are the most important. The key variables that distinguish T.magnatum from other species are the levels of V and Zn and δ15N values. Tuberaestivum can be separated based on the levels of Ni, Cr, Mn, Mg, As, and Cu. This preliminary study indicates the possibility to differentiate truffles according to their variety and geographical origin and suggests widening the scope to include stable strontium isotopes.
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Project description:Aim of this project was the evaluation of the effect of flushing (intraportal and intraoperative) hepatic allografts with tacrolimus before transplantation. Group A was administered tacrolimus, 20ng/ml in 1500ml albumin solution; and Group B was administered only albumin solution. Wedge biopsie of the allograft were harvested after 15 min flushing time and the gene expression profile were determined. The primary study objective was to determine on a genome-wide basis whether intraoperative and intraportal treatment of the allograft with tacrolimus reduces inflammatory signature in the liver. The secondary objective was the causally test, whether suppression of genes belongong to the ontologies of inflammation and immune response by tacrolimus will lead to a better initial function of the liver. randomized double-blind, placebo-controlled trial
2012-04-12 | E-GEOD-25338 | biostudies-arrayexpress
Project description:DISCOVER-seq (discovery of in situ Cas off-targets and verification by sequencing) is a broadly applicable approach for unbiased CRISPR-Cas off-target identification in cells and tissues. It leverages the recruitment of DNA repair factors to double-strand breaks (DSBs) after genome editing with CRISPR nucleases. Here, we describe a detailed experimental protocol and analysis pipeline with which to perform DISCOVER-seq. The principle of this method is to track the precise recruitment of MRE11 to DSBs by chromatin immunoprecipitation followed by next-generation sequencing. A customized open-source bioinformatics pipeline, BLENDER (blunt end finder), then identifies off-target sequences genome wide. DISCOVER-seq is capable of finding and measuring off-targets in primary cells and in situ. The two main advantages of DISCOVER-seq are (i) low false-positive rates because DNA repair enzyme binding is required for genome edits to occur and (ii) its applicability to a wide variety of systems, including patient-derived cells and animal models. The whole protocol, including the analysis, can be completed within 2 weeks.
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Project description:Using multistable mechanical metamaterials to develop deployable structures, electrical devices, and mechanical memories raises two unanswered questions. First, can mechanical instability be programmed to design sensors and memory devices? Second, how can mechanical properties be tuned at the post-fabrication stage via external stimuli? Answering these questions requires a thorough understanding of the snapping sequences and variations of the elastic energy in multistable metamaterials. The mechanics of deformation sequences and continuous force/energy-displacement curves are comprehensively unveiled here. A 1D array, that is chain, of bistable cells is studied to explore instability-induced energy release and snapping sequences under one external mechanical stimulus. This method offers an insight into the programmability of multistable chains, which is exploited to fabricate a mechanical sensor/memory with sampling (analog to digital-A/D) and data reconstruction (digital to analog-D/A) functionalities operating based on the correlation between the deformation sequence and the mechanical input. The findings offer a new paradigm for developing programmable high-capacity read-write mechanical memories regardless of thei size scale. Furthermore, exotic mechanical properties can be tuned by harnessing the attained programmability of multistable chains. In this respect, a transversely multistable mechanical metamaterial with tensegrity-like bistable cells is designed to showcase the tunability of chirality.
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Project description:BackgroundWe sought to describe global patterns in achievement of risk factor control for primary prevention in patients with T2D and explore the association of country's GNI/capita with risk factor control.MethodsThe DISCOVER study is a prospective, observational study of patients with T2D from 38 countries enrolled at initiation of second-line glucose-lowering therapy. We examined achievement of risk factor control (glycosylated hemoglobin <7%, blood pressure <140/90 mmHg, prescription of a statin) at 3 years among those without optimal control at baseline. Countries were stratified by gross national income (GNI)/capita, from 2017). We examined the impact of country GNI/capita with achievement of risk factor control.FindingsOur cohort included 9613 patients with T2D and without baseline cardiovascular disease (mean age 57.2 ± 8.7 years, 47.9% women). At baseline, 6354/7646 patients (83.1%) had suboptimal glucose control, 3449/9200 patients (37.5%) had suboptimal BP control, and 2800/4221 patients (66.7%) were not on an appropriate statin (sample sizes differed due to missing covariate data). Optimal control at 3 years of follow-up was achieved in 41% (glucose), 56% (blood pressure), and 29% (statins) of patients. There was significant variability in achievement of risk factor control across countries but no association between country GNI/capita with achievement of risk factor control (p > 0.08 for all).InterpretationIn a global, prospective study of patients with T2D, we found that cardiovascular risk factor control achievement was suboptimal despite 3 years of follow-up in specialized health care systems. Neither country-level nor patient-level socioeconomic factors fully explained this finding.
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