Boston University

About: Boston University is a education organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 48688 authors who have published 119622 publications receiving 6276020 citations. The organization is also known as: BU & Boston U.

New loci associated with kidney function and chronic kidney disease

Abstract: Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.

Endothelial Function A Barometer for Cardiovascular Risk

Abstract: The endothelium regulates vascular homeostasis by elaborating a variety of paracrine factors that act locally in the blood vessel wall and lumen.1 Under normal conditions, the sum total effect of these endothelial factors is to maintain normal vascular tone, blood fluidity, and limit vascular inflammation and smooth muscle cell proliferation. However, when coronary risk factors are present, the endothelium may adopt a phenotype that facilitates inflammation, thrombosis, vasoconstriction, and atherosclerotic lesion formation.2 In human subjects, this maladaptive endothelial phenotype manifests itself prior to the development of frank atherosclerosis and is associated with traditional risk factors such as hypercholesterolemia, hypertension, and diabetes mellitus and with emerging risk factors such as hyperhomocystinemia, obesity, and systemic inflammation.1 See p 653 In addition to its role in early atherosclerosis, there is growing recognition that endothelial dysfunction also contributes to the later stages of the disease when patients develop clinical symptoms. Cross-sectional studies have demonstrated the most severe impairment of endothelial function in arteries containing a culprit lesion that precipitates unstable angina or myocardial infarction.3,4⇓ Furthermore, endothelial dysfunction promotes pathological vasoconstrictor responses in situations known to provoke ischemia, including physical and emotional stress.5 Another line of evidence supporting the pathophysiological role of endothelial dysfunction is provided by intervention studies.6 The ability to improve endothelial function is a common feature of many otherwise diverse interventions proven to reduce cardiovascular risk. For example, lipid-lowering therapy, angiotensin-converting enzyme inhibitors, smoking cessation, and physical exercise have all been shown to reduce cardiovascular risk and to improve endothelium-dependent vasodilation in the coronary and peripheral circulations.1 In the past, most of the evidence suggesting a causal relation between endothelial dysfunction and clinical events from atherosclerosis was circumstantial. Recently, this evidence has been strengthened by a series of outcome studies showing that endothelial dysfunction …

Reliability of DSM-IV Anxiety and Mood Disorders: Implications for the Classification of Emotional Disorders

Abstract: The reliability of current and lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) anxiety and mood disorders was examined in 362 outpatients who underwent 2 independent administrations of the Anxiety Disorders Interview Schedule for DSM-IV: Lifetime version (ADIS-IV-L). Good to excellent reliability was obtained for the majority of DSM-IV categories. For many disorders, a common source of unreliability was disagreements on whether constituent symptoms were sufficient in number, severity, or duration to meet. DSM-IV diagnostic criteria. These analyses also highlighted potential boundary problems for some disorders (e.g., generalized anxiety disorder and major depressive disorder). Analyses of ADIS-IV-L clinical ratings (0-8 scales) indicated favorable interrater agreement for the dimensional features of DSM-IV anxiety and mood disorders. The findings are discussed in regard to their implications for the classification of emotional disorders.

Nascent Focal Adhesions Are Responsible for the Generation of Strong Propulsive Forces in Migrating Fibroblasts

Abstract: Fibroblast migration involves complex mechanical interactions with the underlying substrate. Although tight substrate contact at focal adhesions has been studied for decades, the role of focal adhesions in force transduction remains unclear. To address this question, we have mapped traction stress generated by fibroblasts expressing green fluorescent protein (GFP)-zyxin. Surprisingly, the overall distribution of focal adhesions only partially resembles the distribution of traction stress. In addition, detailed analysis reveals that the faint, small adhesions near the leading edge transmit strong propulsive tractions, whereas large, bright, mature focal adhesions exert weaker forces. This inverse relationship is unique to the leading edge of motile cells, and is not observed in the trailing edge or in stationary cells. Furthermore, time-lapse analysis indicates that traction forces decrease soon after the appearance of focal adhesions, whereas the size and zyxin concentration increase. As focal adhesions mature, changes in structure, protein content, or phosphorylation may cause the focal adhesion to change its function from the transmission of strong propulsive forces, to a passive anchorage device for maintaining a spread cell morphology.

The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism.

Abstract: Importance Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several decades. Objective To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy. Evidence Review A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Findings Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise. Conclusions and Relevance Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.