Genetic context modulates aging and degeneration in the murine retina.

Background: Age is the principal risk factor for neurodegeneration in both the retina and brain. The retina and brain share many biological properties; thus, insights into retinal aging and degeneration may shed light onto similar processes in the brain. Genetic makeup strongly influences susceptibility to age-related retinal disease.

Individual Patient Data Meta-Analysis of 10-Year Follow-Up after Endovascular and Open Repair for Ruptured Abdominal AorticAneurysms.

Background: Endovascular aortic repair (EVAR) has conferred an early survival advantage compared to an open surgical repair (OSR) in patients with ruptured abdominal aortic aneurysms (rAAA). However, the long-term survival benefit after EVAR was not displayed among randomized controlled trials (RCTs), whereas many non-RCTs have provided conflicting results. We conducted a time-to-event individual patient data (IPD) meta-analysis on long-term rAAA data.

Assessment of the reporting quality of randomised controlled trials for vitamin D supplementation in autoimmune thyroid disorders based on the CONSORT statement.

Background-purpose: Randomized controlled trials (RCTs) are the cornerstone of evidence-based medicine, yet their quality is often suboptimal. The Consolidated Standards of Reporting Trials (CONSORT) statement is a list of advice to upgrade the quality of RCTs. The aim of this study was the assessment of the quality of RCTs for vitamin D supplements in thyroid autoimmunity according to the revised CONSORT 2010 checklist.

Perspectives on Cognitive Phenotypes and Models of Vascular Disease.

Clinical investigations have established that vascular-associated medical conditions are significant risk factors for various kinds of dementia. And yet, we are unable to associate certain types of vascular deficiencies with specific cognitive impairments. The reasons for this are many, not the least of which are that most vascular disorders are multi-factorial and the development of vascular dementia in humans is often a multi-year or multi-decade progression.

A novel adiponectin receptor agonist (AdipoAI) ameliorates type 2 diabetes-associated periodontitis by enhancing autophagy in osteoclasts.

Background And Objective: Type 2 diabetes (T2D)-associated periodontitis is severe and refractory in many cases. Considered an inflammatory disease, T2D predisposes to periodontitis by increasing whole-body inflammation. One mechanism of increased inflammation is thatT2D is mediated by loss of production or function of the anti-inflammatory hormone adiponectin.

Cellular reprogramming of diabetic foot ulcer fibroblasts triggers pro-healing miRNA-mediated epigenetic signature.

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes, constitute a major medical challenge with a critical need for development of cell-based therapies. We previously generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts derived from the DFU patients, location-matched skin of diabetic patients and normal healthy donors and re-differentiated them into fibroblasts. To assess the epigenetic microRNA (miR) regulated changes triggered by cellular reprogramming, we performed miRs expression profiling.

Tissue Imaging and Quantification Relying on Endogenous Contrast.

Cell-matrix interactions play an important role in regulating a variety of essential processes in multicellular organisms, and are closely associated with numerous diseases. Modified interactions have major effects upon key features of both cells and extracellular matrix (ECM), and a thorough understanding of changes in these features can lead to critically important insights of diseases as well as the identification of effective therapeutic targets. Here, we summarize recent advances in quantitative, optical imaging of cellular metabolism and ECM spatial organization using endogenous sources of contrast.

Blocking Borrelia burgdorferi transmission from infected ticks to nonhuman primates with a human monoclonal antibody.

Disrupting transmission of Borrelia burgdorferi sensu lato complex (B. burgdorferi) from infected ticks to humans is one strategy to prevent the significant morbidity from Lyme disease. We have previously shown that an anti-OspA human mAb, 2217, prevents transmission of B.

Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease.

Genetic and genome-wide association studies suggest a central role for microglia in Alzheimer's disease (AD). However, single-cell RNA sequencing (scRNA-seq) of microglia in mice, a key preclinical model, has shown mixed results regarding translatability to human studies. To address this, scRNA-seq of microglia from C57BL/6J (B6) and wild-derived strains (WSB/EiJ, CAST/EiJ, and PWK/PhJ) with and without APP/PS1 demonstrates that genetic diversity significantly alters features and dynamics of microglia in baseline neuroimmune functions and in response to amyloidosis.

Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction.

Ischemic stroke, a major cause of mortality in the United States, often contributes to disruption of the blood-brain barrier (BBB). The BBB along with its supportive cells, collectively referred to as the "neurovascular unit," is the brain's multicellular microvasculature that bi-directionally regulates the transport of blood, ions, oxygen, and cells from the circulation into the brain. It is thus vital for the maintenance of central nervous system homeostasis.

Complement peptide C3a receptor 1 promotes optic nerve degeneration in DBA/2J mice.

Background: The risk of glaucoma increases significantly with age and exposure to elevated intraocular pressure, two factors linked with neuroinflammation. The complement cascade is a complex immune process with many bioactive end-products, including mediators of inflammation. Complement cascade activation has been shown in glaucoma patients and models of glaucoma.

Analysis of the quality of reporting of randomized controlled trials in anticoagulant versus antiplatelet medication for venous thromboembolism prophylaxis as governed by the CONSORT statement.

Randomized controlled trials (RCTs) are the gold standard research in evaluating healthcare interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement improves the quality of RCTs in an evidence-based approach. To evaluate the reporting quality of published RCTs concerning the use of anticoagulants versus antiplatelet agents for venous thromboembolism prophylaxis according to the CONSORT statement.

Long-term Clinical Outcomes Among Responders and Nonresponders to the In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems (ICH CAHPS) Survey.

Rationale & Objective: The In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems (ICH CAHPS) survey, introduced into the End-Stage Renal Disease Quality Incentive Program, is the only patient-reported outcome currently used for value-based reimbursement in dialysis. Current response rates are ∼30% and differences in long-term clinical outcomes between survey responders and nonresponders are unknown.

Study Design: Retrospective cohort study.

Precision Health Analytics With Predictive Analytics and Implementation Research: JACC State-of-the-Art Review.

Emerging data science techniques of predictive analytics expand the quality and quantity of complex data relevant to human health and provide opportunities for understanding and control of conditions such as heart, lung, blood, and sleep disorders. To realize these opportunities, the information sources, the data science tools that use the information, and the application of resulting analytics to health and health care issues will require implementation research methods to define benefits, harms, reach, and sustainability; and to understand related resource utilization implications to inform policymakers. This JACC State-of-the-Art Review is based on a workshop convened by the National Heart, Lung, and Blood Institute to explore predictive analytics in the context of implementation science.

Effect of Stress on Neuroimmune Processes.

Purpose: Psychological stress worsens many diseases, especially those with inflammatory components, such as atopic dermatitis (AD) and autism spectrum disorder (ASD), conditions that are significantly correlated in large epidemiologic studies. However, how stress contributes to these conditions is still poorly understood. This narrative review of the relevant literature advances the premise that stress affects inflammatory processes in AD and ASD via stimulation of mast cells (MCs).

Conformational changes in the Ebola virus membrane fusion machine induced by pH, Ca2+, and receptor binding.

The Ebola virus (EBOV) envelope glycoprotein (GP) is a membrane fusion machine required for virus entry into cells. Following endocytosis of EBOV, the GP1 domain is cleaved by cellular cathepsins in acidic endosomes, removing the glycan cap and exposing a binding site for the Niemann-Pick C1 (NPC1) receptor. NPC1 binding to cleaved GP1 is required for entry.

Epilepsy Benchmarks Area I: Understanding the Causes of the Epilepsies and Epilepsy-Related Neurologic, Psychiatric, and Somatic Conditions.

The 2014 NINDS Benchmarks for Epilepsy Research included area I: Understand the causes of the epilepsies and epilepsy-related neurologic, psychiatric, and somatic conditions. In preparation for the 2020 Curing Epilepsies Conference, where the Benchmarks will be revised, this review will cover scientific progress toward that Benchmark, with emphasize on studies since 2016.

Real-Time Analysis of Individual Ebola Virus Glycoproteins Reveals Pre-Fusion, Entry-Relevant Conformational Dynamics.

The Ebola virus (EBOV) envelope glycoprotein (GP) mediates the fusion of the virion membrane with the membrane of susceptible target cells during infection. While proteolytic cleavage of GP by endosomal cathepsins and binding of the cellular receptor Niemann-Pick C1 protein (NPC1) are essential steps for virus entry, the detailed mechanisms by which these events promote membrane fusion remain unknown. Here, we applied single-molecule Förster resonance energy transfer (smFRET) imaging to investigate the structural dynamics of the EBOV GP trimeric ectodomain, and the functional transmembrane protein on the surface of pseudovirions.

Staging Alzheimer's Disease in the Brain and Retina of B6.APP/PS1 Mice by Transcriptional Profiling.

Alzheimer's disease (AD) is a common form of dementia characterized by amyloid plaque deposition, tau pathology, neuroinflammation, and neurodegeneration. Mouse models recapitulate some key features of AD. For instance, the B6.

Factors adversely influencing neurodevelopment.

Neurodevelopment has been studied extensively, especially in respect to abuse, anoxia, nutritional status and prematurity/low birth weight. However, less attention has been paid to innate and environmental factors, as well as to inflammatory conditions that may adversely affect neurodevelopment and learning in children. These include heavy metals, herbicides and polyvinyl chlorides (PVCs), mycotoxins, viral infections and Lyme disease-associated pathogens, as well as number of conditions such as chronic inflammatory response syndrome (CIRS) and Mast cell activation syndrome (MCAS).

Genetic perturbations of disease risk genes in mice capture transcriptomic signatures of late-onset Alzheimer's disease.

Background: New genetic and genomic resources have identified multiple genetic risk factors for late-onset Alzheimer's disease (LOAD) and characterized this common dementia at the molecular level. Experimental studies in model organisms can validate these associations and elucidate the links between specific genetic factors and transcriptomic signatures. Animal models based on LOAD-associated genes can potentially connect common genetic variation with LOAD transcriptomes, thereby providing novel insights into basic biological mechanisms underlying the disease.

Vascular Landmark-Based Method for Highly Reproducible Measurement of Left Atrial Appendage Volume in Computed Tomography.

Background: Modern computed tomographic scanning can produce 4-dimensional images of the left atrial appendage (LAA). LAA function and morphology can then be measured, to plan interventions such as occlusion and to evaluate LAA flow for thrombogenic risk analysis. A current problem here is defining a reproducible boundary between the LAA and the left atrium.

AdipoRon promotes diabetic fracture repair through endochondral ossification-based bone repair by enhancing survival and differentiation of chondrocytes.

Diabetic bone defects may exhibit impaired endochondral ossification (ECO) leading to delayed bone repair. AdipoRon, a receptor agonist of adiponectin polymers, can ameliorate diabetes and related complications, as well as overcome the disadvantages of the unstable structure of artificial adiponectin polymers. Here, the effects of AdipoRon on the survival and differentiation of chondrocytes in a diabetic environment were explored focusing on related mechanisms in gene and protein levels.

TRANSLATOR Database-A Vision for a Multi-Institutional Research Network.

The formation of the CTSI One Health Alliance (COHA) network has generated the infrastructure necessary to support "Big Data" collaborative comparative and translational research in veterinary medicine. We describe the first step in the design, implementation, and dissemination of a collaborative information technology infrastructure that will serve the public and clinicians (COHA public/member based web site at https://ctsaonehealthalliance.org/) and its research focused COHA Research Workbench application.