Substance use and psychiatric symptoms in subjects referred to the Drug Addiction Services by the Prefecture

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Abnormalities of Thymic Stroma may Contribute to Immune Dysregulation in Murine Models of Leaky Severe Combined Immunodeficiency

Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky severe combined immune deficiency, carrying hypomorphic mutations in rag1 and lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs). While the ability of mTECs to express autoimmune regulator (Aire) is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens is severely reduced. Similarly, the ability of CD4+ T cells to differentiate into Foxp3+ natural regulatory T cells is preserved in rag1 and lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation

HCV cirrhotic patients treated with direct acting antivirals: detection of tubular dysfunction and resolution after viral clearance

Background/aims: Hepatitis C virus (HCV) has been identified in tubular epithelial cells of infected patients, however the presence of tubular dysfunction, which is a risk factor for chronic kidney disease, has never been examined in vivo. The present prospective longitudinal study aimed to estimate the prevalence of tubular dysfunction alone or with glomerular damage and its evolution after HCV clearance in cirrhotic patients. Methods: One-hundred-thirty-five consecutive Child-Pugh-A cirrhotic patients were evaluated before antiviral treatment and six months after the end of therapy. Tubular dysfunction was evaluated by urinary-alpha1-microglobulin-to-creatinine-ratio (α1-MCR), glomerular damage was assessed by urinary-albumin-to-creatinine-ratio (ACR). Results: Almost all the patients (93.3%) showed a normal or mildly decreased e-GFR (KDIGO-G1/G2-categories). Tubular dysfunction was found in 23.7% (32/135) of patients, co-occurring with glomerular damage in 37.5% (12/32) of cases, while glomerular damage was found in 16.3% (22/135) of patients. In multiple logistic regression, glomerular damage and the concomitant presence of diabetes and hypertension were the only predictors significantly associated with tubular dysfunction. After HCV-clearance, patients experienced a significant reduction of α1-MCR levels (21.0 vs 10.5 μg/mg, p=0.009) and tubular dysfunction resolved in 57.1% of subjects. Conclusions: Tubular dysfunction is an unrecognized feature of HCV-related kidney disease in cirrhotic patients and its presence should be primarily investigated in subjects with glomerular damage, diabetes and hypertension, despite normal e-GFR. Tubular dysfunction resolves in the majority of cases after HCV clearance, however, it may persist after antiviral treatment and further studies should evaluate its long term impact on kidney function

Body mass index rather than the phenotype impacts precocious ultrasound cardiovascular risk markers in polycystic ovary syndrome

Objective Research into cardiovascular disease (CV) prevention has demonstrated a variety of ultrasound (US) markers predicting risk in the general population but which have been scarcely used for polycystic ovary syndrome (PCOS). Obesity is a major factor contributing to CV disease in the general population, and it is highly prevalent in PCOS. However, it is still unclear how much risk is attributable to hyperandrogenism. This study evaluates the most promising US CV risk markers in PCOS and compares them between different PCOS phenotypes and BMI values. Design Women fulfilling the Rotterdam criteria for PCOS were recruited from our outpatient clinic for this cross-sectional study. Methods Participants (n\u2009=\u2009102) aged 38.9 \ub1 7.4 years were stratified into the four PCOS phenotypes and the three BMI classes (normal-weight, overweight, obese). They were assessed for clinical and biochemical parameters together with the following US markers: coronary intima-media thickness (cIMT), flow-mediated vascular dilation (FMD), nitroglycerine-induced dilation (NTG), and epicardial fat thickness (EFT). Results There was no statistical difference among the four phenotypes in terms of cIMT, FMD, NTG or EFT, however all the US parameters except NTG showed significant differences among the three BMI classes. Adjusting for confounding factors in multiple regression analyses, EFT retained the greatest direct correlation with BMI and cIMT remained directly correlated but to a lesser degree. Conclusions This study showed that obesity rather than the hyperandrogenic phenotype negatively impacts precocious US CV risk markers in PCOS. In addition, EFT showed the strongest association with BMI, highlighting its potential for estimating CV risk in PCOS

Mexico City land subsidence in 2014-2015 with Sentinel-1 IW TOPS: results using the Intermittent SBAS (ISBAS) technique

Differential Interferometric Synthetic Aperture Radar (DInSAR) can be considered as an efficient and cost effective technique for monitoring land subsidence due to its large spatial coverage and high accuracy provided. The recent commissioning of the first Sentinel-1 satellite offers improved support to operational surveys using DInSAR due to regular observations from a wide-area product. In this paper we show the results of an intermittent small-baseline subset (ISBAS) time-series analysis of 18 Interferometric Wide swath (IW) products of a 39,000 km2 area of Mexico acquired between 3 October 2014 and 7 May 2015 using the Terrain Observation with Progressive Scans in azimuth (TOPS) imaging mode. The ISBAS processing was based upon the analysis of 143 small-baseline differential interferograms. After the debursting, merging and deramping steps necessary to process Sentinel-1 IW roducts, the method followed a standard approach to the DInSAR analysis. The Sentinel-1 ISBAS results confirm the magnitude and extent of the deformation that was observed in Mexico City, Chalco, Ciudad Nezahualcóyotl and Iztapalapa by other C-band and L-band DInSAR studies during the 1990s and 2000s. Subsidence velocities from the Sentinel-1 analysis are, in places, in excess of -24 cm/year along the satellite line-of-sight, equivalent to over ~-40 cm/year vertical rates. This paper demonstrates the potential of Sentinel-1 IW TOPS imagery to support wide-area DInSAR surveys over what is a very large and diverse area in terms of land cover and topography

Cardiac Magnetic Resonance to Predict Cardiac Mass Malignancy: The CMR Mass Score

Background: Multimodality imaging is currently suggested for the noninvasive diagnosis of cardiac masses. The identification of cardiac masses' malignant nature is essential to guide proper treatment. We aimed to develop a cardiac magnetic resonance (CMR)-derived model including mass localization, morphology, and tissue characterization to predict malignancy (with histology as gold standard), to compare its accuracy versus the diagnostic echocardiographic mass score, and to evaluate its prognostic ability. Methods: Observational cohort study of 167 consecutive patients undergoing comprehensive echocardiogram and CMR within 1-month time interval for suspected cardiac mass. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, by histology or radiological resolution after adequate anticoagulation treatment. Logistic regression was performed to assess CMR-derived independent predictors of malignancy, which were included in a predictive model to derive the CMR mass score. Kaplan-Meier curves and Cox regression were used to investigate the prognostic ability of predictors. Results: In CMR, mass morphological features (non-left localization, sessile, polylobate, inhomogeneity, infiltration, and pericardial effusion) and mass tissue characterization features (first-pass perfusion and heterogeneity enhancement) were independent predictors of malignancy. The CMR mass score (range, 0-8 and cutoff, ≥5), including sessile appearance, polylobate shape, infiltration, pericardial effusion, first-pass contrast perfusion, and heterogeneity enhancement, showed excellent accuracy in predicting malignancy (areas under the curve, 0.976 [95% CI, 0.96-0.99]), significantly higher than diagnostic echocardiographic mass score (areas under the curve, 0.932; P=0.040). The agreement between the diagnostic echocardiographic mass and CMR mass scores was good (κ=0.66). A CMR mass score of ≥5 predicted a higher risk of all-cause death (P<0.001; hazard ratio, 5.70) at follow-up. Conclusions: A CMR-derived model, including mass morphology and tissue characterization, showed excellent accuracy, superior to echocardiography, in predicting cardiac masses malignancy, with prognostic implications

Managing a Mass CO Poisoning: Critical Issues and Solutions From the Field to the Hyperbaric Chamber

Carbon monoxide acute intoxication is a common cause of accidental poisoning in industrialized countries and sometimes it produces a real mass casualty incident. The incident described here occurred in a church in the province of Verona, when a group of people was exposed to carbon monoxide due to a heating system malfunction. Fifty-seven people went to the Emergency Department. The mean carboxyhemoglobin (COHb) level was 10.1\ub15.7% (range: 3-25%). The clinicians, after medical examination, decided to move 37 patients to hyperbaric chambers for hyperbaric oxygen (HBO) therapy. This is the first case report that highlights and analyses the logistic difficulties of managing a mass carbon monoxide poisoning in different health care settings, with a high influx of patients in an Emergency Department and a complex liaison between emergency services. This article shows how it is possible to manage a complex situation with good outcome. (Disaster Med Public Health Preparedness. 2016;page 1 of 5)

The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis

The PRELP heparin sulfate–binding protein translocates to the nucleus, where it impairs NF-κB transcriptional activity, which in turn regulates bone homeostasis

Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency

The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro–B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP–keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell–activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia