Quantitative Analysis of Protein-Protein Equilibrium Constants in Cellular Environments Using Single-Molecule Localization Microscopy.

Current methods for determining equilibrium constants often operate in three-dimensional environments, which may not accurately reflect interactions with membrane-bound proteins. With our technique, based on single-molecule localization microscopy (SMLM), we directly determine protein-protein association () and dissociation () constants in cellular environments by quantifying associated and isolated molecules and their interaction area. We introduce Kernel Surface Density (ks-density,) a novel method for determining the accessible area for interacting molecules, eliminating the need for user-defined parameters.

Quantitative single molecule analysis of podoplanin clustering in fibroblastic reticular cells uncovers CD44 function.

Upon initial immune challenge, dendritic cells (DCs) migrate to lymph nodes and interact with fibroblastic reticular cells (FRCs) via C-type lectin-like receptor 2 (CLEC-2). CLEC-2 binds to the membrane glycoprotein podoplanin (PDPN) on FRCs, inhibiting actomyosin contractility through the FRC network and permitting lymph node expansion. The hyaluronic acid receptor CD44 is known to be required for FRCs to respond to DCs but the mechanism of action is not fully elucidated.

Purinergic GPCR-integrin interactions drive pancreatic cancer cell invasion.

Pancreatic ductal adenocarcinoma (PDAC) continues to show no improvement in survival rates. One aspect of PDAC is elevated ATP levels, pointing to the purinergic axis as a potential attractive therapeutic target. Mediated in part by highly druggable extracellular proteins, this axis plays essential roles in fibrosis, inflammation response, and immune function.

Inflammatory and thrombotic valvulopathies in autoimmune disease.

Rheumatologic diseases are characterised by loss of immune tolerance, resulting in systemic inflammation. Inflammation and scarring of the endocardium, which lines the inner surface of the heart chambers and valves, can result in valvular thickening and dysfunction. Estimates of prevalence vary depending on the sensitivity of the screening methodology used and range from 30%-50% in systemic lupus and rheumatoid arthritis to 10%-30% in ankylosing spondylitis.

Quantitative Super-Resolution Imaging for the Analysis of GPCR Oligomerization.

G-protein coupled receptors (GPCRs) are known to form homo- and hetero- oligomers which are considered critical to modulate their function. However, studying the existence and functional implication of these complexes is not straightforward as controversial results are obtained depending on the method of analysis employed. Here, we use a quantitative single molecule super-resolution imaging technique named qPAINT to quantify complex formation within an example GPCR.

Right Ventricular Dysfunction and Adverse Outcomes after Renal Transplantation.

Introduction: Pulmonary hypertension is common among patients with end-stage renal disease, although data regarding the impact of right ventricular (RV) failure on postoperative outcomes remain limited. We hypothesized that echocardiographic findings of RV dilation and dysfunction are associated with adverse clinical outcomes after renal transplant.

Methods: A retrospective review of adult renal transplant recipients at a single institution from January 2008 to June 2010 was conducted.

Management of heart failure in patients with end-stage kidney disease on maintenance dialysis: a practical guide.

End-stage kidney disease (ESKD) and heart failure (HF) often coexist and must be managed simultaneously. Multidisciplinary collaboration between nephrology and cardiology is critical when treating patients with such complicated physiology. There is no "one-size-fits-all" approach to the evaluation of patients with new left ventricular systolic dysfunction, and diagnostic testing should be adapted to an individual's risk factors.

The Impact Of Structured Exercise Programs On Metabolic Syndrome And Its Components: A Systematic Review.

Background: The metabolic syndrome (MetS) is highly prevalent and associated with higher risk of diabetes and cardiovascular events. Exercise programs have been shown to improve components of MetS, but the optimal design of a structured exercise program for treatment of the MetS remains unclear.

Purpose: To assess the impact of different exercise programs on the MetS and its components.

Effects of Race on Statin Prescribing for Primary Prevention With High Atherosclerotic Cardiovascular Disease Risk in a Large Healthcare System.

Background Although guidelines recommend statins with a high level of evidence for 4 primary prevention benefit groups, prescribing disparities still exist. The objective of this study was to evaluate the effects of race on statin prescribing for primary prevention. Methods and Results A retrospective cohort analysis of patients within a large academic health system was performed to investigate statin prescribing among primary prevention groups.

Clinical Decision Making in Patients with Stroke-Related Dysphagia.

This article aims to highlight stroke considerations in the evaluation and management of dysphagia. Although dysphagia was previously thought to occur only following brainstem or bilateral cortical strokes, the development of brain imaging and dynamic swallowing studies has revealed small, unilateral supratentorial strokes can produce dysphagia. In this article, screening, evaluation, and management of dysphagia are outlined, as well as the clinical decision making that occurs when taking into account cognitive and communication deficits that may be present.

Impact of a structured lifestyle programme on patients with metabolic syndrome complicated by non-alcoholic fatty liver disease.

Background: Lifestyle interventions are first-line therapy for non-alcoholic fatty liver disease (NAFLD).

Aims: To examine the prevalence of NAFLD among participants of the University of Michigan Metabolic Fitness (MetFit) Programme and to assess the impact of this programme on weight, metabolic and liver-related parameters among patients with and without NAFLD.

Methods: Adults who completed the programme between 2008 and 2016 were included.

Long-term outcomes following completion of a structured nutrition and exercise lifestyle intervention program for patients with metabolic syndrome.

Introduction: Metabolic syndrome is associated with an increased risk of cardiovascular disease and multiple other chronic health conditions. Studies have demonstrated the effectiveness of structured diet and exercise programs to improve the components of metabolic syndrome. The durability of these benefits after program completion is unclear.

An Emerging Theoretical Model of Music Therapy Student Development.

Background: Music therapy students negotiate a complex relationship with music and its use in clinical work throughout their education and training. This distinct, pervasive, and evolving relationship suggests a developmental process unique to music therapy.

Objective: The purpose of this grounded theory study was to create a theoretical model of music therapy students' developmental process, beginning with a study within one large Midwestern university.

Antidepressant-coincident mania in children and adolescents treated with selective serotonin reuptake inhibitors.

Several factors have amplified concern about the possibility that antidepressant medication may contribute to induction of pediatric mania. These include the high rate of antidepressant medication prescription, the recent surge in the rate of diagnosis of pediatric bipolar disorder in the USA, and a growing number of case reports and clinical studies showing coincidence of manic symptoms with antidepressant pharmacotherapy in both youths and adults. However, the question of how medications and manic symptoms might be related is complicated, and decisive research studies with rigorous designs for evaluating the issues have not been published.

A quantitative and qualitative review of neurocognitive performance in pediatric bipolar disorder.

Bipolar disorder (BD) is an increasingly prevalent diagnosis in youth. As a result, there has been a corresponding increase in interest about neuropsychological and cognitive profiles in children and adolescents diagnosed with BD. Meta-analysis of the existing literature comparing individuals with BD to healthy controls indicated that the largest differences are observed for measures of verbal memory (d = 0.

Comparing the psychometric properties of multiple teacher report instruments as predictors of bipolar disorder in children and adolescents.

The psychometric properties of four teacher report measures and their utility for accurate diagnosis of pediatric bipolar spectrum disorders (BPSDs) were examined. Participants were 191 youth (65% male; 62% African-American; 23% diagnosed with a BPSD), age 5-18 (M=10.16, SD=3.

Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.

Objective: Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors' knowledge.

Method: The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003.