3p21, 5q21, 9p21 and 17p13.1 allelic deletions are potential markers of individuals with a high risk of developing adenocarcinoma in Barrett's epithelium without dysplasia

BACKGROUND/AIMS: A common genetic abnormality detected in Barrett's adenocarcinoma is LOH (loss of heterozygosity) at the sites of known or putative tumor suppressor genes. Thus, some deletions have also been determined in peritumoral Barrett's epithelium. These findings suggest that a tissue field of somatic genetic alterations precede the histopathological phenotypic changes of carcinoma. We investigated 32 cases of Barrett's esophagus with no evidence of dysplasia for LOH at 5q21 (APC), 3p21, 9p21 (p16) and 17p13.1 (p53) chromosomal regions. METHODOLOGY: Two groups were randomly selected and compared: 16 cases of Barrett's epithelium adjacent to adenocarcinoma and 16 cases of Barrett's epithelium with no evidence of malignant transformation in a 5-10 years follow-up period. In three adenocarcinomas cases several previous endoscopic biopsies of Barrett's esophagus were available. RESULTS: We determined frequent allelic losses in adenocarcinomas at p53 (54%), p16 (50%), 3p21 (40%) and 5q21 (33%). Identical LOH was present in most cases in the Barrett's epithelium adjacent to adenocarcinoma. LOH at these loci was unusual in Barrett's epithelium with no evidence of malignant transformation. However, in cases where sequential endoscopic biopsies were performed in advance to the adenocarcinoma diagnosis LOH was already present in the Barrett's epithelium. CONCLUSIONS: We suggest that LOH at these loci may be present before the onset of the malignant growth and LOH studies may supplement the histopathological evaluation of Barrett's epithelium. LOH at 3p21, 5q21, 9p21 and 17p13 chromosomal regions in cells of Barrett's epithelium without dysplasia may have a role as a potential marker for individuals with a high risk of developing adenocarcinoma.     

Protective effects of N-(2-mercaptopropionyl)-glycine against ischemia–reperfusion injury in hypertrophied hearts

The beneficial effects of N-(2-mercaptopropionyl)-glycine (MPG) against ischemia–reperfusion injury in normotensive animals have been previously studied. Our objective was to test the action of MPG during ischemia and reperfusion in hearts from spontaneously hypertensive rats (SHR). Isolated hearts from SHR and age-matched normotensive rats Wistar Kyoto (WKY) were subjected to 50-min global ischemia (GI) and 2-hour reperfusion (R). In other hearts MPG 2 mM was administered during 10 min before GI and the first 10 min of R. Infarct size (IS) was assessed by TTC staining technique and expressed as percentage of risk area. Postischemic recovery of myocardial function was assessed. Reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and SOD cytosolic activity — as estimators of oxidative stress and MnSOD cytosolic activity — as an index of (mPTP) opening were determined. In isolated mitochondria H₂O₂-induced mPTP opening was also measured. The treatment with MPG decreased infarct size, preserved GSH levels and decreased SOD and MnSOD cytosolic activities, TBARS concentration, and H₂O₂ induced-mPTP opening in both rat strains. Our results show that in both hypertrophied and normal hearts an attenuation of mPTP opening via reduction of oxidative stress appears to be the predominant mechanism involved in the cardioprotection against reperfusion injury MPG-mediated.     

Psychiatric Clinical Profiles and Pharmacological Interactions in COVID-19 Inpatients Referred to a Consultation Liaison Psychiatry Unit: a Cross-Sectional Study

Psychiatric Quarterly - The Coronavirus Disease 2019 (COVID-19) can affect mental health in different ways. There is little research about psychiatric complications in hospitalized patients with...     

Anti-Soluble Liver Antigen (SLA) Antibodies in Chronic HCV Infection

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP^(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.     

ADRB2, brain white matter integrity and cognitive ageing in the Lothian Birth Cohort 1936

The non-synonymous mutations arg16gly (rs1042713) and gln27glu (rs1042714) in the adrenergic β-2 receptor gene (ADRB2) have been associated with cognitive function and brain white matter integrity. The current study aimed to replicate these findings and expand them to a broader range of cognitive and brain phenotypes. The sample used is a community-dwelling group of older people, the Lothian Birth Cohort 1936. They had been assessed cognitively at age 11 years, and undertook further cognitive assessments and brain diffusion MRI tractography in older age. The sample size range for cognitive function variables was N = 686–765, and for neuroimaging variables was N = 488–587. Previously-reported findings with these genetic variants did not replicate in this cohort. Novel, nominally significant associations were observed; notably, the integrity of the left arcuate fasciculus mediated the association between rs1042714 and the Digit Symbol Coding test of information processing speed. No significant associations of cognitive and brain phenotypes with ADRB2 variants survived correction for false discovery rate. Previous findings may therefore have been subject to type 1 error. Further study into links between ADRB2, cognitive function and brain white matter integrity is required.     

Influenza vaccination status in multiple sclerosis patients from Latin America

Journal of NeuroVirology - The objective of the present study was to identify the frequency of MS patients in Latin America (LATAM) that received the influenza vaccine during the most recent season...     

Weaning from neonatal and pediatric ECMO with stand-by cannula

Journal of Artificial Organs - The precise moment for weaning a patient off extracorporeal membrane oxygenation (ECMO) is not always easy to establish. Also, mechanical causes may obligate to...     

Titanium dioxide nanotubes with triazine-methacrylate monomer to improve physicochemical and biological properties of adhesives

ObjectiveFormulate experimental adhesives containing titanium dioxide nanotubes (nt-TiO₂) or titanium dioxide nanotubes with a triazine-methacrylate monomer (nt-TiO₂:TAT) and evaluate the effect of these fillers on the physical, chemical, and biological properties of the adhesives.MethodsFirst, nt-TiO₂ were synthesized via a hydrothermal method. The nt-TiO₂ were mixed with a triazine-methacrylate monomer (TAT) to formulate nt-TiO₂:TAT, which were characterized by transmission electron microscopy (TEM). The nt-TiO₂, TAT, and nt-TiO₂:TAT were evaluated via Fourier Transform Infrared, Ultraviolet–visible, and micro-Raman spectroscopies. An experimental adhesive resin was formulated with bisphenol A glycerolate dimethacrylates, 2-hydroxyethyl methacrylate, and photoinitiator/co-initiator system. nt-TiO₂ or nt-TiO₂:TAT were incorporated at 2.5 wt.% and 5 wt.% in the adhesive. The base resin without nt-TiO₂ or nt-TiO₂:TAT was used as a control group. The adhesives were evaluated for antibacterial activity, cytotoxicity, polymerization kinetics, degree of conversion (DC), Knoop hardness, softening in solvent (ΔKHN%), ultimate tensile strength (UTS), 24 h- and 1 year- microtensile bond strength (μ-TBS).ResultsTEM confirmed the nanotubular morphology of TiO₂. FTIR, UV–vis, and micro-Raman analyses showed the characteristic peaks of each material, indicating the impregnation of TAT in the nt-TiO₂. Adhesives with nt-TiO₂:TAT showed antimicrobial activity against biofilm formation compared to control (p < 0.05), without differences in the viability of planktonic bacteria (p > 0.05). All groups showed high percentages of pulp cell viability. The polymerization kinetics varied among groups, but all presented DC above 50%. The addition of 5 wt.% of nt-TiO₂ and both groups containing nt-TiO₂:TAT showed higher values ??of Knoop hardness compared to the control (p < 0.05). The groups with nt-TiO₂:TAT presented lower ΔKHN% (p < 0.05) and higher UTS (p < 0.05) than the control group. After one year, the group with 5 wt.% of nt-TiO₂, as well as both groups containing nt-TiO₂:TAT, showed higher μ-TBS than the control (p < 0.05).SignificanceThe mixing of a triazine-methacrylate monomer with the nt-TiO₂ generated a filler that improved the physicochemical properties of the adhesive resins and provided antibacterial activity, which could assist in preventing carious lesions around tooth-resin interfaces. The set of physical, chemical, and biological properties of the formulated polymer, together with the greater stability of the bond strength over time, make nt-TiO₂:TAT a promising filler for dental adhesive resins.