Immunohistochemical localization of somatostatin receptor sst2A in human rheumatoid synovium

OBJECTIVE: To identify the somatostatin receptor-expressing cells in rheumatoid synovium using a recently developed antiserum directed against the somatostatin receptor subtype 2A (sst2A). METHODS: We carried out immunohistochemical studies of synovial biopsies from 7 patients with rheumatoid arthritis (RA) and one non-RA patient, using a rabbit polyclonal antiserum directed against sst2A and monoclonal antibodies directed against phenotypic markers. RESULTS: SSt2A was expressed by the endothelial cells of the synovial venules but also by a subset of synovial macrophages. CONCLUSION: The identification of somatostatin receptors on macrophages, which are thought to be important effector cells in RA, may offer mechanistic insights into the potential therapeutic effect of somatostatin (analogs) in RA.     

Glucose tolerance and B cell function in chronic alcoholism: its relation to hepatic histology and exocrine pancreatic function

Glucose tolerance and B cell function were assessed in 30 consecutive chronic alcoholic patients without overt diabetes mellitus. Plasma glucose, insulin, and C peptide concentrations were measured during an oral glucose tolerance test. All patients underwent a liver biopsy and an exocrine pancreatic function test (Lundh test). Compared with the controls, the three groups of alcoholic patients (those with histologically normal livers, n = 12; those with steatosis, n = 10; and those with cirrhosis, n = 8) all had a two-fold increase in plasma concentrations of insulin as well as C peptide in the fasting state, despite normal fasting levels of glucose. After oral glucose all groups of patients had elevated plasma levels of glucose, insulin, and C peptide compared with the controls. The C peptide/insulin ratio was similar to that in the controls in all groups of alcoholics. Patients with decreased exocrine pancreatic function (n = 7) had a significantly lower insulin and C peptide response to glucose than the patients with normal exocrine pancreatic function. It is concluded that (1) chronic alcoholics even with histologically normal livers have endogenous insulin resistance, and (2) associated damage to the exocrine pancreas is more common than previously recognized and decompensation of B cell function could be demonstrated in patients with decreased exocrine pancreatic secretion.     

Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole,Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species

We compared EUCAST and CLSI antifungal susceptibility testing (AFST) methods for triazoles and amphotericin B against 124 clinical Mucorales isolates. The EUCAST method yielded MIC values 1- to 3-fold dilutions higher than those of the CLSI method for amphotericin B. The essential agreements between the two methods for triazoles were high, i.e., 99.1% (voriconazole), 98.3% (isavuconazole), and 87% (posaconazole), whereas it was significantly lower for amphotericin B (66.1%). Strategies for harmonization of the two methods for Mucorales AFST are warranted.     

Schizophrenia and Metacognition: An Investigation of Course of Illness and Metacognitive Beliefs Within a First Episode Psychosis

Cognitive Therapy and Research - The Self Regulatory Executive Function (S-REF) model implicates maladaptive metacognitive beliefs and processes in the predisposition and/or maintenance of positive...     

Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group

Annals of Surgical Oncology - Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades....     

High intraepithelial eosinophil counts in esophageal squamous epithelium are not specific for eosinophilic esophagitis in adults

OBJECTIVES: The histologic criterion of >20 eosinophils per high power field (hpf) is presently believed to establish the diagnosis of idiopathic eosinophilic esophagitis (IEE). This is based on data that the number of intraepithelial eosinophils in gastroesophageal reflux disease (GERD) is less than 20/hpf. This study tests this belief. METHODS: Pathology records were searched for patients who had an eosinophil count >20/hpf in an esophageal biopsy. This patient population was biased toward adults with GERD who had routine multilevel biopsies of the esophagus. The clinical, radiological, and manometric data and biopsies were studied. RESULTS: Forty patients out of a total of 3,648 reports examined had an eosinophil count >20/hpf in squamous epithelium of an esophageal biopsy. Analysis of these 40 cases indicated that 6 (15%) patients had IEE, 2 (5%) had coincident IEE and GERD, 28 (70%) had GERD, and 2 (5%) each had achalasia and diverticulum. There was no significant difference among these groups in terms of maximum eosinophil number, biopsy levels with >20 esoinophils/hpf, presence of eosinophilic microabscesses, involvement of surface layers by eosinophils, and severity of basal cell hyperplasia and dilated intercellular spaces. CONCLUSION: All histologic features presently ascribed to IEE can occur in other esophageal diseases, notably GERD. As such, the finding of intraepithelial eosinophilia in any number is not specific for IEE. When a patient with GERD has an esophageal biopsy with an eosinophil count >20/hpf, it does not mean that the patient has IEE.     

The CarboMedics supraannular top hat valve improves prosthesis size in the aortic root

BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement can result in patient-valve mismatch and attenuated left ventricular remodeling. Using CarboMedics mechanical valves, we examined if the supraannular Top Hat prosthesis provided a size advantage over the intraannular valve. METHODS: Seventeen patients with aortic stenosis and aortic root < or = 23 mm were randomized to receive a CarboMedics supraannular Top Hat valve (n = 7) or an intraannular valve (n = 10). Doppler echocardiography was performed preoperatively, and after three months. RESULTS: There was no difference in aortic annulus size, but mean prosthesis size was significantly larger in the Top Hat group than in the intraannular group (25.00 mm versus 21.60 mm); the mean size improvement for Top Hat patients was 3.14 mm. After three months, all patients had excellent functional improvement and low transvalvular pressure gradients, with slightly higher effective valve opening area in the Top Hat group. CONCLUSION: The supraannular Top Hat valve provides an advantage of one to two sizes over the intraannular valve, and improves the effective valve opening area. Both valves offer favorable hemodynamic performance and functional improvement.     

A network-based meta-analysis for characterizing the genetic landscape of human aging

Great amounts of omics data are generated in aging research, but their diverse and partly complementary nature requires integrative analysis approaches for investigating aging processes and connections to age-related diseases. To establish a broader picture of the genetic and epigenetic landscape of human aging we performed a large-scale meta-analysis of 6600 human genes by combining 35 datasets that cover aging hallmarks, longevity, changes in DNA methylation and gene expression, and different age-related diseases. To identify biological relationships between aging-associated genes we incorporated them into a protein interaction network and characterized their network neighborhoods. In particular, we computed a comprehensive landscape of more than 1000 human aging clusters, network regions where genes are highly connected and where gene products commonly participate in similar processes. In addition to clusters that capture known aging processes such as nutrient-sensing and mTOR signaling, we present a number of clusters with a putative functional role in linking different aging processes as promising candidates for follow-up studies. To enable their detailed exploration, all datasets and aging clusters are made freely available via an interactive website (https://gemex.eurac.edu/bioinf/age/).