Fluctuating position-related cognitive disturbances and recurrent cerebral ischemic attacks as presenting symptoms in a patient with platypnea-orthodeoxya syndrome

Platypnea-orthodeoxia syndrome is a condition of dyspnea and hypoxia whilst in the upright position, which improves in the recumbent position. We present a case of platypnea-orthodeoxia due to a fenestrated atrial septal aneurysm that induced recurrent strokes and a recent condition of fluctuating confusion and cognitive impairment, modified by position, associated with rapid variations of O2 saturation position related. The suspect of platypnea-orthodeoxia syndrome may be hypothesized in case of patients with recurrent cerebral ischemia and fluctuating cognitive disturbances induced by change of position. In those cases a careful echocardiographic evaluation and O2 saturation determination in up and downright position are required

Otimização Operacional de um Sistema de Trigeração para Atender Demandas Variáveis

Este trabalho visa apresentar e discutir os procedimentos e resultados da otimização das estratégias operacionais de um sistema de trigeração de um centro de pesquisa para atender a demanda horosazonal de eletricidade, vapor e água gelada de modo que, minimize o custo de operação da planta. Nos dias atuais cada vez mais os sistemas térmicos estão mais complexos. Com isso, busca-se o melhor aproveitamento, com o objetivo de ter uma melhor produção e minimização dos custos produtivos. O centro de pesquisa em questão é composto de um sistema de cogeração que produz eletricidade e também calor (na forma de vapor e água quente) para acionar dois chillers por absorção (um a vapor e outro a água quente). Este centro ainda conta com outros grupos geradores e chillers complementares. Além destes equipamentos também tem a opção de usar uma demanda elétrica adicional contratada com a concessionária. O principal objetivo da otimização é determinar como operar o sistema de trigeração do centro e quando ou como usar a demanda contratada. Para se chegar a este resultado, todos os dados dos equipamentos e custos da central, e também os dados da demanda do centro, foram levantados e o modelo matemático foi desenvolvido. Nessa visão de otimização existe muitos métodos que podem ser empregados. Neste trabalho é usada a otimização matemática através do método do gradiente reduzido generalizado (GRG), com o auxílio do Solver no Microssoft Excel. Os resultados mostram que o método de otimização é muito eficaz dando resultados favoráveis a sua utilização

Use of insulin degludec in pregnancy: two case reports and a literature review

Abstract As of now, insulin Degludec has no indication for use in pregnancy, because of the lack of studies that prove its safety for foetus. However it isn't infrequent that some women conceive while treating with insulin Degludec. So, before deciding to change the type of insulin therapy during pregnancy, an evaluation of the risk associated to a possible temporary worsening of glycaemic control, due to that insulin replacement, is needed. Referring to case series reported in the scientific literature could provide a support when a clinical decision need to be taken. We report two cases of women affected by type 1 diabetes who had unplanned pregnancies during treatment with insulin Degludec. In order to avoid the risk of a possible worsening of glycaemic control due to insulin switch, we decided to continue the treatment with Degludec during their pregnancies, after obtaining the patients' written informed consent. Daily insulin requirement gradually increased for both women pregnancy progressed, and glycated haemoglobin (HbA1c) values improved from the first observation to delivery: 55 mmol/mol (7.2%) at 9 weeks to 47 mmol/mol (6.5%) at 36 weeks, in Patient 1 (P1); 44 mmol/mol (6.2%) at 8 weeks to 33 mmol/mol (5.2%) at 36 weeks, in Patient 2 (P2). P1 delivered at week 37 with a caesarean section due to failed induction. The newborn, a girl of 3398 g at birth, developed neonatal hypoglycaemia and respiratory distress (Apgar 6-6). Six days after birth she underwent colectomy because of necrotizing enterocolitis and was finally diagnosed with atypical cystic fibrosis. P2 gave birth to a healthy girl (weight 2745g at birth, Apgar 7-9) at 37 weeks, undergoing a caesarean section for maternal cervical dystocia, without neonatal complications. Our experience provides additional evidence on the safety of insulin Degludec in pregnancy without any maternal or neonatal outcome suggesting its toxicity

Analysis of BRCA1 and RAD51C promoter methylation in italian families at high-risk of breast and ovarian cancer

Previous studies on breast and ovarian carcinoma (BC and OC) revealed constitutional BRCA1 and RAD51C promoter hypermethylation as epigenetic alterations leading to tumor predisposition. Nevertheless, the impact of epimutations at these genes is still debated. One hundred and eight women affected by BC, OC, or both and considered at very high risk of carrying BRCA1 germline mutations were studied. All samples were negative for pathogenic variants or variants of uncertain significance at BRCA testing. Quantitative BRCA1 and RAD51C promoter methylation analyses were performed by Epityper mass spectrometry on peripheral blood samples and results were compared with those in controls. All the 108 analyzed cases showed methylation levels at the BRCA1/RAD51C promoter comparable with controls. Mean methylation levels (\ub1 stdev) at the BRCA1 promoter were 4.3% (\ub1 1.4%) and 4.4% (\ub1 1.4%) in controls and patients, respectively (p > 0.05; t-test); mean methylation levels (\ub1 stdev) at the RAD51C promoter were 4.3% (\ub1 0.9%) and 3.7% (\ub1 0.9%) in controls and patients, respectively (p > 0.05; t-test). Based on these observations; the analysis of constitutional methylation at promoters of these genes does not seem to substantially improve the definition of cancer risks in patients. These data support the idea that epimutations represent a very rare event in high-risk BC/OC populations

Strong-motion parameters of the Mw=6.3 Abruzzo (Central Italy) earthquake

INGVPublished1.1. TTC - Monitoraggio sismico del territorio nazionaleope

A comparative study of diagnostic and imaging techniques for osteoarthritis of the trapezium

Objectives. The aims of this study were to determine whether micro-CT is a reliable investigation method to evaluate the severity of OA in the trapezium and to develop a novel micro-CT scoring system based on a quantitative assessment of the subchondral bone thickness in order to better assess OA through an objective parameter.Methods. We compared different diagnostic and imaging techniques performed consecutively on each sample: X-ray, visual analysis, micro-CT and histology. OA and healthy trapezia were subjected to semi-quantitative and quantitative analyses to be classified in four degrees of severity in OA (control, OA-2, OA-3 and OA-4). Specifically, samples were analysed using Dell's score for X-ray, Brown's score for visual analysis and Mankin's score for histology. Micro-CT was scored using a novel quantitative scoring system based on subchondral bone thickness measurements. Results obtained with each technique were then compared and correlated.Results. X-ray analysis showed a higher frequency of OA-2 (27%) and OA-3 (32%) compared with OA-4 (5%), whereas visual analysis, micro-CT and histology showed a lower percentage for OA-2 (18%, 18% and 14%) and OA-3 (23%) and increased frequency for OA-4 (45%, 32% and 40%). Only the micro-CT score of subchondral bone thickness correlated significantly with all the other techniques (P < 0.05).Conclusion. This is the first comparison of techniques proposing a novel scoring system based on objective and quantitative micro-CT data that can be applied as a useful diagnostic tool for OA, providing a deeper comprehension of the pathophysiology of OA in trapezium

WDR5 inhibition halts metastasis dissemination by repressing the mesenchymal phenotype of breast cancer cells

Background: Development of metastases and drug resistance are still a challenge for a successful systemic treatment in breast cancer (BC) patients. One of the mechanisms that confer metastatic properties to the cell relies in the epithelial-to-mesenchymal transition (EMT). Moreover, both EMT and metastasis are partly modulated through epigenetic mechanisms, by repression or induction of specific related genes. Methods: We applied shRNAs and drug targeting approaches in BC cell lines and metastatic patient-derived xenograft (PDX) models to inhibit WDR5, the core subunit of histone H3 K4 methyltransferase complexes, and evaluate its role in metastasis regulation. Result: We report that WDR5 is crucial in regulating tumorigenesis and metastasis spreading during BC progression. In particular, WDR5 loss reduces the metastatic properties of the cells by reverting the mesenchymal phenotype of triple negative- and luminal B-derived cells, thus inducing an epithelial trait. We also suggest that this regulation is mediated by TGF\u3b21, implying a prominent role of WDR5 in driving EMT through TGF\u3b21 activation. Moreover, such EMT reversion can be induced by drug targeting of WDR5 as well, leading to BC cell sensitization to chemotherapy and enhancement of paclitaxel-dependent effects. Conclusions: We suggest that WDR5 inhibition could be a promising pharmacologic approach to reduce cell migration, revert EMT, and block metastasis formation in BC, thus overcoming resistance to standard treatments

Does PGE1 vasodilator prevent orthopaedic implant-related infection in diabetes? Preliminary results in a mouse model

Background: Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE1 vasodilator on the incidence of surgical infections in diabetic mice was investigated. Methodology: A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE1 vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses. Results: The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE1 and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment. Conclusions: The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model

Diabetic Mouse Model of Orthopaedic Implant-Related Staphylococcus Aureus Infection

BACKGROUND: Periprosthetic bacterial infections represent one of the most challenging orthopaedic complications that often require implant removal and surgical debridement and carry high social and economical costs. Diabetes is one of the most relevant risk factors of implant-related infection and its clinical occurrence is growing worldwide. The aim of the present study was to test a model of implant-related infection in the diabetic mouse, with a view to allow further investigation on the relative efficacy of prevention and treatment options in diabetic and non-diabetic individuals. METHODOLOGY: A cohort of diabetic NOD/ShiLtJ mice was compared with non-diabetic CD1 mice as an in vivo model of S. aureus orthopaedic infection of bone and soft tissues after femur intramedullary pin implantation. We tested control and infected groups with 1 7103 colony-forming units of S. aureus ATCC 25923 strain injected in the implant site. At 4 weeks post-inoculation, host response to infection, microbial biofilm formation, and bone damage were assessed by traditional diagnostic parameters (bacterial culture, C-reactive protein and white blood cell count), histological analysis and imaging techniques (micro computed tomography and scanning electron microscopy). RESULTS: Unlike the controls and the CD1 mice, all the diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitic changes around the implant. CONCLUSIONS: Our findings demonstrate for the first time that the diabetic mouse can be successfully used in a model of orthopaedic implant-related infection. Furthermore, the same bacteria inoculum induced periprosthetic infection in all the diabetic mice but not in the controls. This animal model of implant-related infection in diabetes may be a useful tool to test in vivo treatments in diabetic and non-diabetic individuals