White matter integrity as a predictor of response to treatment in first episode psychosis

The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P < 0.05; family-wise error-corrected), mainly in the uncinate, cingulum and corpus callosum, whereas responders were indistinguishable from healthy control subjects. After 12 weeks, there was an increase in fractional anisotropy in both responders and non-responders, positively correlated with antipsychotic exposure. This represents one of the largest, controlled investigations of white matter integrity and response to antipsychotic treatment early in psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response

Collagenofibrotic Glomerulopathy: Three Case Reports in Brazil

<p>Abstract</p> <p>Background</p> <p>We are reporting the first Collagenofibrotic Glomerulopathy (CG) in South America. So, this collagen type III glomerulopathy is not limited to Japan but may be found throughout the world.</p> <p>Case Reports</p> <p>We describe three patients that presented some factors in common, such as sex, age and the presence of non-nephrotic proteinuria associated with microscopic hematuria. The findings with the immunofluorescence microscopy, of immunoglobulins, and components of the complement were usually negative. The picrosyrius staining showed the presence of reddish material in the mesangium, when it was seen under standard microscopy; however, when it was seen with birefringence, it became greenish under polarized light, showed the collagen found in this area of the glomerulus. The identification of CG was made through electronic microscopic scanning, and curved and disorganized fibers were found.</p> <p>Conclusion</p> <p>These cases are the first from South America to be reported, and they are about an idiopathic renal disease that is not related to any specific races or locations. The reports contribute to a better understanding of this disease, which although not so prevalent, should be considered as an importantly differential diagnostic of cases of proteinuria.</p

Delivering amoxicillin at the infection site-a rational design through lipid nanoparticles

Purpose: Amoxicillin is a commonly used antibiotic, although degraded by the acidic pH of the stomach. This is an important limitation for the treatment of Helicobacter pylori infections. The purpose of this work was to encapsulate amoxicillin in lipid nanoparticles, increasing the retention time at the site of infection (gastric mucosa), while protecting the drug from the harsh conditions of the stomach lumen. Materials and methods: The nanoparticles were produced by the double emulsion technique and optimized by a three-level Box-Behnken design. Tween 80 and linolenic acid were used as potential therapeutic adjuvants and dioleoylphosphatidylethanolamine as a targeting agent to Helicobacter pylori. Nanoparticles were characterized regarding their physico-chemical features, their storage stability, and their usability for oral administration (assessment of in vitro release, in vitro cell viability, permeability, and interaction with mucins). Results: The nanoparticles were stable for at least 6 months at 4°C. In vitro release studies revealed a high resistance to harsh conditions, including acidic pH and physiologic temperature. The nanoparticles have a low cytotoxicity effect in both fibroblasts and gastric cell lines, and they have the potential to be retained at the gastric mucosa. Conclusion: Overall, the designed formulations present suitable physico-chemical features for being henceforward used by oral administration to treat Helicobacter pylori infections.DLC, RMP, TS, and CN are thankful to Fundação para a Ciência e Tecnologia (FCT) for the PhD Grant (PD/ BD/105957/2014), Research Grant (PD/BI/128326/2017), post-doctorate grant (SFRH/BPD/103113/2014), and Investigator Grant (IF/00293/2015), respectively. This work was supported by FCT through the FCT PhD Programmes and by Programa Operacional Capital Humano (POCH), specifically by the BiotechHealth Programe (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences). The authors are also grateful to Dr Rui Fernandes (Histology and Electron Microscopy Service – Instituto de Investigação e Inovação em Saúde, Universidade do Porto) for the expertise and technical assistance with transmission electron microscopy and to Manuela Barros for administrative and technical support. The authors thank the financial support under Program PT2020 (UID/QUI/50006/2019). SACL and BS thanks Operação NORTE-01-0145-FEDER-000011 and NORTE-01-0145-FEDER-000012, respectively, for their Investigator contract

Predicting suicides after outpatient mental health visits in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).

The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded

Immunoglobulin genes implicated in glioma risk

Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped the IGHG locus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus

O Valor Prognóstico do Ponto Ótimo Cardiorrespiratório após Prova de Esforço Cardiorrespiratória Submáxima na Insuficiência Cardíaca

Introduction: Peak oxygen consumption (pVO2) is a key parameter for assessing the prognosis of heart failure with reduced ejection fraction (HFrEF). However, it is less reliable when the cardiopulmonary exercise test (CPET) is not maximal. Objective: To compare the prognostic power of various exercise parameters in submaximal CPET. Methods: Adult patients with HFrEF undergoing CPET in a tertiary center were prospectively assessed. Submaximal CPET was defined as a respiratory exchange ratio ≤1.10. Patients were followed for one year for the primary endpoint of cardiac death and urgent heart transplantation (HT). Various CPET parameters were analyzed as potential predictors of the combined endpoint and their prognostic power (area under the curve [AUC]) was compared using the Hanley-McNeil test. Results: CPET was performed in 442 HFrEF patients (mean age 56±12 years, 80% male), of whom 290 (66%) had a submaximal CPET. Seventeen patients (6%) reached the primary endpoint. The cardiorespiratory optimal point (COP) had the highest AUC value (0.989, p<0.001), and significantly higher prognostic power than other tested parameters, with pVO2 presenting an AUC of 0.753 (p=0.001). COP ≥36 had significantly lower survival free of HT during follow-up (p<0.001) and presented a sensitivity of 100% and a specificity of 89% for the primary endpoint. Conclusion: COP had the highest prognostic power of all parameters analyzed in a submaximal CPET. This parameter can help stratify HFrEF patients who are physiologically unable to reach a maximal level of exercise.info:eu-repo/semantics/publishedVersio

Caracterização dos Hábitos de Sono na Primeira Infância numa População Clínica

Introdução: Os problemas de sono fazem parte das queixas mais referidas, nomeadamente as dificuldades para as crianças se tranquilizarem e adormecerem na hora de dormir e os despertares noturnos frequentes. O objectivo deste estudo foi caracterizar os hábitos de sono na primeira infância. Materiais e Métodos: Construção de questionário sobre os hábitos de sono na primeira infância, aplicando-o a uma população de crianças atendidas em primeira consulta de pedopsiquiatria no Centro de Estudos do Bebé e da Criança / Unidade da Primeira Infância (n=93), dos 0 aos 3 anos de idade, durante o ano de 2014. Resultados: A média de idades é de 27 meses, variando entre 1 e 36 meses. Não existem diferenças estatisticamente significativas entre sexos e idades relativamente ao ambiente em que dormem. 77% das crianças têm rotinas antes de adormecer. As crianças que têm rotinas, têm menor dificuldade em adormecer (p=0,028). 38,04% dos pais considera que existem problemas de sono. A média do número total de horas de sono entre os 3 e os 11 meses foi de 12h e entre os 12 e os 35 meses de 11h. Discussão: Concordante com a literatura, a maioria das crianças acorda durante a noite (61,3%), o número e a duração de sestas diminui ao longo da vida e os problemas de sono são frequentes (38,04%), apesar de neste estudo terem uma prevalência ligeiramente superior. A duração de sono das crianças é inferior ao recomendado. Conclusão: Verifica-se uma associação significativa entre a inexistência de rotinas e a dificuldade em adormecer e uma associação significativa entre crianças que dormem sozinhas e ausência de problemas de sono.info:eu-repo/semantics/publishedVersio

Evolução na utilização e nos gastos de uma operadora de saúde

Brazil’s aging population and the rising number of people reliant upon the country’s supplementary healthcare system have elicited the concern of public and private managers regarding the increase in healthcare costs. In this paper, the costs per gender, per type of medical expenses and per age group of a major Brazilian self-managed healthcare provider between 2007 and 2013 were analyzed. This healthcare provider is of interest because, besides portraying a single condition of revenue growth restricted to the existing contributors, it also replicates the demographic profile expected for Brazil in 2050, when approximately one-third of its population will be over 60 years of age. The analyses confirm the current literature as they show an increase in healthcare plan usage by the elderly and the difference between admission rates by gender. They also reveal an increase in average length of stay in hospital and the increase in medical costs far above inflation, especially for materials and medicines. It is hoped that this study will help scholars and others interested in comparisons of medical expense trends, especially by age and sex, and that it encourages further collaboration on the sustainability of health insurance providers in Brazil