Tuberculose endometrial simulando um carcinoma do ovário

Female genital tuberculosis remains a major health problem in developing countries and is an important cause of infertility. As symptoms, laboratory data and physical fndings are non-specifc, its diagnosis can be diffcult. We describe a case of a 39-year-old woman suffering from peri-umbilical pain and increased abdominal size for one year, anorexia, asthenia, weight loss, occasionally dysuria and dyspareunia, and four months amenorrhea. Laboratory data revealed cancer antigen 125 (CA-125) level of 132.3 U/mL, erythrocyte sedimentation rate of 42 mm/h, and gamma-globulins of 2.66 g/dL. Computer Tomography scan showed loculated ascites. It was initially suspected a carcinomatous origin, but ascites evaluation was negative for malignant cells. Magnetic Resonance Imaging from another hospital showed endometrial heterogeneity. Therefore, an endometrial biopsy was performed demonstrating an infammatory infltrate with giant cells of type Langhans and bacteriological culture identifed Mycobacterium tuberculosisA tuberculose genital feminina continua a representar uma patologia importante nos países em desenvolvimento e constitui uma causa importante de infertilidade. Os seus sintomas, achados laboratoriais e exame físico não são específcos, tornando difícil o seu diagnóstico. Descrevemos o caso de uma doente do sexo feminino, de 39 anos, com dor peri-umbilical e aumento do volume abdominal desde há um ano, anorexia, astenia, perda ponderal, ocasionalmente disúria e dispareunia, assim como amenorreia desde há quatro meses. Os dados laboratoriais mostraram valores de 132,3 U/mL do marcador tumoral CA-125, 42 mm/h de velocidade de sedimentação e 2,66 g/dL de gama-globulinas. A tomografa computadorizada mostrou ascite loculada. Inicialmente suspeitou-se de etiologia maligna, mas o exame citológico do líquido ascítico foi negativo para células malignas. Foi efectuada ressonância magnética pélvica, noutra instituição, que revelou heterogeneidade do endométrio. Foi então realizada biópsia endometrial que revelou um infltrado infamatório com células gigantes de Langhans e o exame bacteriológico isolou Mycobacterium tuberculosi

YAP enhances the pro-proliferative transcriptional activity of mutant p53 proteins

Mutant p53 proteins are present in more than half of human cancers. Yes-associated protein (YAP) is a key transcriptional regulator controlling organ growth, tissue homeostasis, and cancer. Here, we report that these two determinants of human malignancy share common transcriptional signatures. YAP physically interacts with mutant p53 proteins in breast cancer cells and potentiates their pro-proliferative transcriptional activity. We found YAP as well as mutant p53 and the transcription factor NF-Y onto the regulatory regions of cyclin A, cyclin B, and CDK1 genes. Either mutant p53 or YAP depletion down-regulates cyclin A, cyclin B, and CDK1 gene expression and markedly slows the growth of diverse breast cancer cell lines. Pharmacologically induced cytoplasmic re-localization of YAP reduces the expression levels of cyclin A, cyclin B, and CDK1 genes both in vitro and in vivo. Interestingly, primary breast cancers carrying p53 mutations and displaying high YAP activity exhibit higher expression levels of cyclin A, cyclin B, and CDK1 genes when compared to wt-p53 tumors

Recent results and perspectives on cosmology and fundamental physics from microwave surveys

Recent cosmic microwave background data in temperature and polarization have reached high precision in estimating all the parameters that describe the current so-called standard cosmological model. Recent results about the integrated Sachs-Wolfe effect from cosmic microwave background anisotropies, galaxy surveys, and their cross-correlations are presented. Looking at fine signatures in the cosmic microwave background, such as the lack of power at low multipoles, the primordial power spectrum and the bounds on non-Gaussianities, complemented by galaxy surveys, we discuss inflationary physics and the generation of primordial perturbations in the early Universe. Three important topics in particle physics, the bounds on neutrinos masses and parameters, on thermal axion mass and on the neutron lifetime derived from cosmological data are reviewed, with attention to the comparison with laboratory experiment results. Recent results from cosmic polarization rotation analyses aimed at testing the Einstein equivalence principle are presented. Finally, we discuss the perspectives of next radio facilities for the improvement of the analysis of future cosmic microwave background spectral distortion experiments.Comment: 27 pages, 9 figures. Review Article. International Journal of Modern Physics D, in press. [Will appear also on the proceedings of the Fourteenth Marcel Grossmann Meeting University of Rome "La Sapienza" - Rome, July 12-18, 2015 (http://www.icra.it/mg/mg14/), eds. Robert T. Jantzen, Kjell Rosquist, Remo Ruffini. World Scientific, Singapore

Prevalence of Rheumatic Heart Disease in North Madagascar: An echocardiographic screening in young and adult populations

BackgroundRheumatic Heart Disease (RHD) prevalence in Madagascar is poorly known. Echocardiographic screening detects a higher prevalence of RHD than clinical examination.AimsWe aimed to describe RHD prevalence in children and adults in North Madagascar using the most updated World Heart Federation (WHF) criteria for RHD echocardiographic diagnosis.Methods Children aged 5–19 years (Group One) and adults aged more than 20 years (Group Two) underwent a four-steps visit: clinical questionnaire, physical examination, laboratory test - oropharyngeal swab for Group One and Anti-streptolysin O (ASO) titre for Group Two - and echocardiogram using a portable machine..Results Among 859 people (522 in Group One, 337 in Group Two) RHD prevalence was 2.1 per cent. Group Two had a higher risk of having RHD than Group One (OR 4.39, CI 1.39–13.9, p=0.004), while clinical findings were more frequent in Group One (children had a higher risk of heart murmur (O.R. 3.85 C.I. 1.08–13.72; p=0.029)). RHD prevalence was 1.34 per cent in children. Those positive to oropharyngeal swab had a higher risk of RHD (OR 14.5, CI 3.04–69.44, p=0.0024); children with history of fever and sore-throat had a higher risk of positive oropharyngeal swab (OR 15.97, CI 3.14–81.19, p=0.002). RHD prevalence was 3.3 per cent in adults. None of those had history of fever and throat-pain, positive ASO titre and cardiac murmur simultaneously. ConclusionThis is the first study describing prevalence of RHD in Madagascar. Our results, although preliminary, are important to enhance prevention programs in this country

Reciprocal Regulation Between Smad7 and Sirt1 in the Gut

In inflammatory bowel disease (IBD) mucosa, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine transforming growth factor-β1, due to post-transcriptional mechanisms that enhance Smad7 acetylation status thus preventing ubiquitination-mediated proteosomal degradation of the protein. IBD-related inflammation is also marked by defective expression of Sirt1, a class III NAD+-dependent deacetylase, which promotes ubiquitination-mediated proteosomal degradation of various intracellular proteins and triggers anti-inflammatory signals. The aim of our study was to determine whether, in IBD, there is a reciprocal regulation between Smad7 and Sirt1. Smad7 and Sirt1 were examined in mucosal samples of IBD patients and normal controls by Western blotting and immunohistochemistry, and Sirt1 activity was assessed by a fluorimetric assay. To determine whether Smad7 is regulated by Sirt1, normal or IBD lamina propria mononuclear cells (LPMC) were cultured with either Sirt1 inhibitor (Ex527) or activator (Cay10591), respectively. To determine whether Smad7 controls Sirt1 expression, ex vivo organ cultures of IBD mucosal explants were treated with Smad7 sense or antisense oligonucleotide. Moreover, Sirt1 expression was evaluated in LPMC isolated from Smad7-transgenic mice given dextran sulfate sodium (DSS). Upregulation of Smad7 was seen in both the epithelial and lamina propria compartments of IBD patients and this associated with reduced expression and activity of Sirt1. Activation of Sirt1 in IBD LPMC with Cay10591 reduced acetylation and enhanced ubiquitination-driven proteasomal-mediated degradation of Smad7, while inhibition of Sirt1 activation in normal LPMC with Ex527 increased Smad7 expression. Knockdown of Smad7 in IBD mucosal explants enhanced Sirt1 expression, thus suggesting a negative effect of Smad7 on Sirt1 induction. Consistently, mucosal T cells of Smad7-transgenic mice contained reduced levels of Sirt1, a defect that was amplified by induction of DSS colitis. The data suggest the existence of a reciprocal regulatory mechanism between Smad7 and Sirt1, which could contribute to amplify inflammatory signals in the gut

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative

Roadmap on thermoelectricity

The increasing energy demand and the ever more pressing need for clean technologies of energy conversion pose one of the most urgent and complicated issues of our age. Thermoelectricity, namely the direct conversion of waste heat into electricity, is a promising technique based on a long-standing physical phenomenon, which still has not fully developed its potential, mainly due to the low efficiency of the process. In order to improve the thermoelectric performance, a huge effort is being made by physicists, materials scientists and engineers, with the primary aims of better understanding the fundamental issues ruling the improvement of the thermoelectric figure of merit, and finally building the most efficient thermoelectric devices. In this Roadmap an overview is given about the most recent experimental and computational results obtained within the Italian research community on the optimization of composition and morphology of some thermoelectric materials, as well as on the design of thermoelectric and hybrid thermoelectric/photovoltaic devices

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982