A developmental in vivo 1H NMR study in mice with genetic redox dysregulation: an animal model with relevance to schizophrenia

Glutathione (GSH), a major redox regulator and anti-oxidant, is decreased in cerebrospinal fluid and prefrontal cortex of schizophrenia patients. The gene of the key GSH-synthesizing enzyme, glutamate-cysteine ligase, modifier (GCLM) subunit, is associated with schizophrenia, suggesting that the deficit in the GSH system is of genetic origin. Using the GCLM knock-out (KO) mouse model with 60% decreased brain GSH levels, we have shown that redox dysregulation results in abnormal brain morphology and function. Current theory holds that schizophrenia is a developmental disease involving progressive anatomical and functional brain pathology. Here, we used GCLM KO mice to investigate the impact of a genetically dysregulated redox system on the neurochemical profile of the developing brain. The anterior and posterior cortical neurochemical profile of male and female GCLM KO, heterozygous and wildtype mice was determined by localised in vivo 1H NMR spectroscopy at 14.1 T (Varian/Magnex spectrometer) on post-natal days 10, 20, 30, 60 and 90. We show, for the first time, (1) that high quality 1H NMR spectra can be acquired from early developing mouse brains and (2) that recurrent anaesthesia by itself when administered at the same developmental days has no adverse effects on brain metabolites nor on adult behaviour. (3) Most importantly, our results reveal genotype and age specific changes for a number of metabolites revealing insight into normal brain development and about the impact of genetic GSH dysregulation.

Measuring Instruments In Cardiology Adapted Into Portuguese Language Of Brazil: A Systematic Review

This was a systematic review aimed at identifying and characterizing measuring instruments, developed in the context of cardiology, which were adapted into Portuguese language of Brazil. Systematic searches were performed in six databases. Information extracted included cultural adaptation process and measurement properties. To assess the methodological quality of studies, criteria based on international guidelines for cultural adaptation of instruments were used. Among the 114 articles found, 14 were eligible for review. Of these, most evaluated quality of life (35.7%) and health knowledge/learning (28.6%). Most studies followed all stages of the adaptation process recommended in the literature. With respect to measurement properties, internal consistency, verified by Cronbach’s alpha, was the property reported in the majority of the studies, as well as construct and criterion validity. This study is expected to provide to the scientific community a critical evaluation of adapted questionnaires available in the context of cardiology.


Association study of 182 candidate genes in anorexia nervosa.

We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case-control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathway-based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN.

The role of LEKTI in fate determination of keratinocyte stem cells

SPINK5 (serine protease inhibitor Kazal-type 5) encodes the putative proteinase inhibitor LEKTI (lympho-epithelial Kazal-type related inhibitor). In skin, LEKTI expression is restricted to the stratum granulosum of the epidermis and the inner root sheath of hair follicles. Mutations that create premature termination codons in SPINK5 have been reported as the cause of Netherton syndrome (NS), a human autosomal recessive disorder characterized by congenital ichthyosis with defective cornification, a specific hair shaft defect known as trichorrexis invaginata or 'bamboo hair', and severe atopic manifestations, including atopic dermatitis and hayfever. Althought recombinant human LEKTI inhibits a battery of serine proteases including plasmin, trypsin, subtilisin A, cathepsin G, and elastase, the precise role of LEKTI in the physiopathology of NS remains unclear. Spink5−/− mice display a NS-like phenotype. Surprisingly, a psoriasis-like hyperplasia, basement membrane breakdown followed by evagination of spindle-shaped epidermal cells into the dermal compartment, and the presence of numerous sweat gland-like structures were also observed when the skin of Spink5−/− newborn mice, which die at birth, was transplanted onto the back of nude mice. Collectively, these observations suggest that LEKTI may play a role on cell proliferation and stem cell fate. Our current work aims at elucidating the mechanisms by which LEKTI impact these biological processes. Using keratinocyte stem cells obtained from NS patients, we have identified LEKTI as a regulator node in several signaling pathways involved in stem cell behavior.

Efficacy of brief motivational intervention at army conscription to address alcohol use and related problems: a randomized controlled trial

Objectives: The aim of this study was to evaluate the efficacy of brief motivational intervention (BMI) in reducing alcohol use and related problems among binge drinkers randomly selected from a census of 20 year-old French speaking Swiss men and to test the hypothesis that BMI contributes to maintain low-risk drinking among non-bingers. Methods: Randomized controlled trial comparing the impact of BMI on weekly alcohol use, frequency of binge drinking and occurrence of alcohol-related problems. Setting: Army recruitment center. Participants: A random sample of 622 men were asked to participate, 178 either refused, or missed appointment, or had to follow military assessment procedures instead, resulting in 418 men randomized into BMI or control conditions, 88.7% completing the 6-month follow-up assessment. Intervention: A single face-to-face BMI session exploring alcohol use and related problems in order to stimulate behaviour change perspective in a non-judgmental, empathic manner based on the principles of motivational interviewing (MI). Main outcome measures: Weekly alcohol use, binge drinking frequency and the occurrence of 12 alcohol-related consequences. Results: Among binge drinkers, we observed a 20% change in drinking induced by BMI, with a reduction in weekly drinking of 1.5 drink in the BMI group, compared to an increase of 0.8 drink per week in the control group (incidence rate ratio 0.8, 95% confidence interval 0,66 to 0,98, p = 0.03). BMI did not influence the frequency of binge drinking and the occurrence of 12 possible alcohol-related consequences. However, BMI induced a reduction in the alcohol use of participants who, after drinking over the past 12 months, experienced alcohol-related consequences, i.e., hangover (-20%), missed a class (-53%), got behind at school (-54%), argued with friends (-38%), engaged in unplanned sex (-45%) or did not use protection when having sex (-64%). BMI did not reduce weekly drinking in those who experienced the six other problems screened. Among non-bingers, BMI did not contribute to maintain low-risk drinking. Conclusions: At army conscription, BMI reduced alcohol use in binge drinkers, particularly in those who recently experienced alcohol-related adverse consequences. No preventive effect of BMI was observed among non-bingers. BMI is an interesting preventive option in young binge drinkers, particularly in countries with mandatory army recruitment.

Revitalização dos Patrimónios Arquitectónicos da Cidade Da Ponta Do Sol – Uma Proposta

O objectivo deste trabalho foi de propor propostas de revitalização dos patrimónios arquitectónicos, históricos e culturais da cidade de Ponta do Sol, no intuito de que essa acção pudesse contribuir, de forma significativa, para a preservação dos patrimónios e um possível crescimento económico de Santo Antão, sobretudo do ponto de vista turístico. A cidade de Ponta do Sol, no passado, teve grande importância no que tange à produção e escoamento de vários produtos a exemplo do café, aguardente e quina, tanto para as outras ilhas como para países europeus. Mantém em seu espaço várias e belas construções dos tempos coloniais, entretanto esquecidas, e muitas delas já destruídas e outras encontrando-se em elevado estado de degradação. Além disso, possui uma grande presença judaica e também uma diversidade de herança histórica e cultural, que precisa continuar existindo para que não se perca a identidade cultural da comunidade, uma vez que há presença de tentativas de homogeneização da cultura, imposta principalmente pelos países desenvolvidos e pela globalização. Sendo assim, a preservação e revitalização dos edifícios, tanto público como privado, como do centro histórico em geral, poderá servir de base promotora para o fortalecimento da actividade turística da cidade. Para isso utilizaram-se como fontes bibliográficas, vários documentos, livros diversos, entrevistas, fotografias e trabalho de campo. Depois, com a recolha de dados foi possível constatar que a cidade de Ponta do Sol está atravessando um processo de degradação e modernização. Apesar de ainda activo e vivo, o centro está-se deteriorando, e se não houver intervenções que revertam esse processo, este perderá muito da sua identidade, da sua história-cultural e principalmente os seus patrimónios. Mas, propostas, projectos intervencionistas e acções executoras podem ainda reverter parte dessa situação e dando soluções ao centro da Cidade. Algumas propostas serão implementadas e até mesmo aglutinadas a novas propostas, podendo ser benéficas tanto para a cidade como também para a população. The aim of this work is to make proposals for the revitalization of the historic, cultural and architectural heritage of the city of Ponta do Sol, hoping that this action could contribute in a meaningful way to preserve the patrimony and the possible economic growth of Santo Antão, an island which is particularly considered for the production and trade of different products, especially coffee, liquor and quinine for other islands as well as for European countries. It displays several beautiful colonial constructions. However, they have been forgotten and some of degradation. Besides, this city hosts a great Judaic presence and also some diversity of the cultural identity, since there is the presence of attempts for the homogenization of the culture, imposed mainly by developed countries and the globalization. Thus, the preservation and revitalization of both public and private buildings as well as of the historic centre in general, can serve of a promotion basis for the strength of the historic activity in this town. That´s why a lot of documents, several books, interviews, photos, and field work as local evidence were used as bibliography. Afterwards, with the collected data it was possible to notice that the city of Ponta do Sol is facing a process of degradation and modernization. In spite of still being active and alive, the center is up deteriorating and if on interventions are made to revert this process, it will lose a lot of its identity, cultural history and mainly its patrimony. But proposals, interventionist projects and executive actions can still revert part of this situation and get solutions for the City centre. Some proposal which will be implemented and even be agglutinated to new proposal can be helpful for the city as well as for the population.

Meningococcal disease in a kidney transplant recipient with mannose-binding lectin (MBL) deficiency

Background: There is an increasing amount of data associating MBL deficiency with a higher susceptibility to meningococca[ disease. In addition, meningococca[ disease has been reported in patients with various immunosuppressive conditions. However, to our knowledge, only three cases of meningococca[ disease have been reported in solid organ recipients (SOT). Methods & Results: A 32 year-old male patient underwent cadaveric kidney transplantation for endstage renal disease of unknown origin. On day 71 post-transplantation he developed fever (39.6°C), shaking chilis, and tachycardia without hypotension. At this time, immunosuppression consisted of tacro[imus, prednisone 10mg daily and mycopheno[ ate mofeti[ 2 g daily. Physical examination on admission was normal, except for two small petechia[ lesions on the forearm. No meningeal signs were present. Three sets of blood cultures grew Neisseria meningitidis group C susceptible to ceftriaxone (MIC=0.003mg/[). Antibiotic therapy consisted in intravenous ceftriaxone 2 g per day for a total duration of 7 days. Serum immunog[obu[in levels, C3, C4 and CHS0 were normal However, using a method to screen for the functional activity of a[[ three pathways of complement (Wies[ab, Lund, Sweden), no activation via the MBL pathway could be detected (0%). A subsequent quantification of MBL pathway components revealed normal levels of MASP 2 but undetectab[e amounts of MBL (below 10 ng/m[, normal range: >500 ng/m[). Conclusion: Since the exact incidence and the possible relationship between meningococca[ disease and organ transplantation is not we[[ understood, we strongly encourage transplantation centers to report additional cases. The potential clinical usefu[ ness of screening SOT candidates for MBL deficiency in relation to infectious complications after transplantation remains to be determined.