Identification and characterization of repeat expansions in neurological disorders: Methodologies, tools, and strategies.

Tandem repeats are a common, highly polymorphic class of variation in human genomes. Their expansion beyond a pathogenic threshold is a process that contributes to a wide range of neurological and neuromuscular genetic disorders, of which over 60 have been identified to date. The last few years have seen a resurgence in repeat expansion discovery propelled by technological advancements, enabling the identification of over 20 novel repeat expansion disorders. These expansions can occur in coding or non-coding regions of genes, resulting in a range of pathogenic mechanisms. In this article, we review strategies, tools and methods that can be used for efficient detection and characterization of known repeat expansions and identification of new expansion disorders. Features that can be used to prioritize repeat expansions include anticipation, which is characterized by increased severity or earlier onset of symptoms across generations, and founder effects, which contribute to higher prevalence rates in certain populations. Classical technologies such as Southern blotting, repeat-primed polymerase chain reaction (PCR) and long-range PCR can still be used to detect known repeat expansions, although they usually have significant limitations linked to the absence of sequence context. Targeted sequencing of known expansions using either long-range PCR or CRISPR-Cas9 enrichment combined with long-read sequencing or adaptive nanopore sampling are usually better but more expensive alternatives. The development of new bioinformatics tools applied to short-read genome data can now be used to detect repeat expansions either in a targeted manner or at the genome-wide level. In addition, technological advances, particularly long-read technologies such as optical genome mapping (Bionano Genomics), Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio) HiFi sequencing, offer promising avenues for the detection of repeat expansions. Despite challenges in specific DNA extraction requirements, computation resources needed and data interpretation, these technologies have an immense potential to advance our understanding of repeat expansion disorders and improve diagnostic accuracy.

Do nascimento à morte: principais transições / From birth to the death: principals transitions

Centrado na análise da população brasileira como um todo desagregada apenas por sexo está dividido em cinco seções: introdução; uma breve descrição das principais fases do ciclo da vida que o indivíduo experimenta entre o nascimento e a morte; análise da participação dos homens brasileiros em eventos ligados ao mercado de trabalho e à constituição de família/domicílio; descrição da participação das mulheres brasileiras nestes eventos; sumariza os resultados destas participações. Fundamentado nas informações provenientes dos Censos Demográficos de 1980 e 2000, das Pesquisas Nacionais por Amostras de Domicílios (Pnads) de 1981 e 2001 e dos Sistemas de Informações sobre Mortalidade (SIM) do Ministério da Saúde.

Semelhanças e diferenças nas transições ao longo do ciclo da vida por regiões e cor/etnia / Similarities and differences between transitions during the life cycle by regions and colour/ethnic group

Objetiva analisar as diferenças e semelhanças no timing e no quantum das trajetórias para os principais eventos que marcam o ciclo da vida por regiões, aqui consideradas as regiões Nordeste e Sudeste, e por cor/etnia. Os grupos étnicos estudados foram os de brancos, pretos e pardos de todo o país. As principais trajetórias consideradas forma entrada na escola, mercado de trabalho, início de uma união conjugal, saída da casa dos pais ou de origem, nascimento do primeiro filho, entrada na aposentadoria, assunção da condição de viuvez e morte.

[Human Immunodeficiency Virus type 1 seroincidence estimate among a group of drug users: a new approach]. / Estimativa da seroincidência do vírus da imunodeficiência humana do tipo 1 num grupo de toxicodependentes: uma nova abordagem.

INTRODUCTION: Estimating Human Immunodeficiency Virus type 1 (HIV-1) infection remains one of the great challenges of the epidemiologic surveillance of HIV-1 epidemics. WHO has recently approved a laboratory based strategy that enables the identification of recent infections. OBJECTIVES: To identify the number of recent (incident) infections and estimate the seroincidence of HIV-1, using for the first time in Portugal, a new methodology based on the Avidity Index of HIV-1 antibodies. METHODS: Cross-sectional study of a HIV-1 positive group selected within drug users admitted in a Low Threshold Methadone Program in Lisbon during a one-year period. Avidity Index is calculated by testing a sample from each participant on the automated AxSYM HIV 1/2gO assay (Abbott) following a specific protocol. HIV-1 infections are classified as recent or established according to the Avidity Index value. RESULTS: The Low Threshold Methadone Program admitted 714 drug users and 175 were HIV-1 infected at admission (proportion of 24.5%; 95% confidence interval (CI): 21.3-27.7). Twenty recent infections were identified and the seroincidence of HIV-1 estimated as 3.58% (IC 95%, 2.0-5.1) (six-month value), which corresponds to an annual projection of 7.16% (IC 95%, 5.0-9.3). Comparative analysis between groups identified independent associations between incident HIV-1 infections and race/ethnicity (p=0.047), educational level (p=0.006) and presence of HBsAg (p=0.028). In the present study no association was found between incident HIV-1 infections and ever injected or syringe sharing. Independent determinants were found in logistic regression associated to HIV-1 incident infection: presence of HBsAg (odds-ratio (OR)=5.0; 95% CI 1.3-19.1) and race/ethnicity other than Caucasian (OR=4.0; 95% CI 1.1-14.7). CONCLUSION: The avidity index methodology is simple and rapid, allowing the identification of recent infections. So far, there are no published national or international studies, allowing us to assess our annual projection of HIV-1 seroincidence, due to the recent introduction of this methodology.

Uptake hydrogenase in cyanobacteria: novel input from non-heterocystous strains.

Most of the research to date on cyanobacterial uptake hydrogenases has been performed on filamentous heterocystous strains. However, recent results on the hup gene cluster organization and its transcriptional regulation in non-heterocystous strains has contributed to the widening of knowledge in this field. In the present study, we outline the recent findings on uptake hydrogenases from non-heterocystous cyanobacteria, comparing it with the presently available data from heterocystous strains, and draw attention to potential areas for future research.

Correlates of fitness for duty in hazardous materials firefighters.

BACKGROUND AND METHODS: From a statewide medical examination program, we identified firefighters who were deemed unfit for duty by attending physicians (ATTENDING FAIL, n=9) and those who would have been disqualified by the application of selected numerical criteria from the 1997 National Fire Protection Association (NFPA) guidelines (NFPA FAIL, n=27) and criteria from a Medical Workshop (WORK FAIL, n=16). The subjects who were unfit for duty or failed numerical criteria were compared with those who were fit for duty and passed all objective criteria (FIT group, n=302). All subjects were given an overall morbidity rating by a board certified internist. Comparisons on two surrogate measures of fitness, VO(2) max predicted and predicted coronary heart disease (CHD) risk, were also performed. RESULTS: We found a significant tendency towards worse results (e.g. higher blood pressure or lower spirometric function) among the three FAIL groups compared with the FIT group. The FAIL groups shared only a small overlap, however, with the firefighters with the highest morbidity ratings, lowest predicted VO(2) max, and highest CHD risks. Increasing morbidity was associated with higher age, lower spirometric function, lower predicted VO(2) max, increasing cholesterol, greater BMI, and higher predicted 10 year CHD risk. CONCLUSIONS: Although the presence of a single serious or poorly controlled condition may render an individual unfit for safe performance as a firefighter, examination of our cohort suggests that multiple risk factor models or overall clinical assessments are superior means of identifying firefighters with poor health status and increased CHD risk.

Correlates of body mass index in hazardous materials firefighters.

We analyzed results from the medical examinations of 340 hazardous materials (HAZMAT) firefighters and observed the relationships between selected parameters and body mass index (BMI). Heights and weights were available for 98% of the subjects (333 of 340). The mean BMI was 28.9 +/- 4.1 kg/m2. Eighty-seven percent (290 of 333) of subjects were overweight (BMI > or = 25) and 34% (113 of 333) were obese (BMI > or = 30). Two percent (7 of 333) were morbidly obese (BMI > or = 39). For comparison purposes, we divided subjects into low (BMI < 27), medium (BMI 27 to < 30), and high (BMI > or = 30) BMI groups. The results demonstrated adverse associations between increasing BMI and resting blood pressures, forced vital capacity, alanine aminotransferase, aspartate aminotransferase, serum cholesterol, and overall morbidity scores. The high prevalence of overweight and obesity and the associated adverse health effects support the development and implementation of fitness-promotion programs for firefighters.

Analysis of peptidogalactomannans from the mycelial surface of Aspergillus fumigatus.

Peptidogalactomannans (pGMs) from mycelium of two strains of Aspergillus fumigatus were fractionated by Cetavlon precipitation and size exclusion chromatography and their carbohydrate structures analysed using methylation-fragmentation analysis, partial acetolysis and 13C-nuclear magnetic resonance spectroscopy. The most significant difference between the pGMs of the two strains was the degree of branching and the proportion of non-reducing ends of alpha-D-Manp and beta-D-Galf units. Methylation data showed that the pGM from AF 2109 contained alpha-D-Manp and beta-D-Galf non-reducing end units in a proportion of 3:1 while, in contrast, the proportion of these structures in pGM from AF 2140 was 7:1, resulting in a highly branched structure. The immunoreactivity of the pGM fractions was tested by indirect immunofluorescence. The fractions were also tested in an ELISA system with rabbit antiserum raised to whole cells of A. fumigatus NCPF 2140 and with serum from patients with either proven aspergilloma or ABPA. The carbohydrate moiety of the pGM appears to be responsible for the antigenicity. Periodate treatment, partial acid hydrolysis and beta-elimination removed most of the antibody binding capacity.

In vitro testing of surface-modified biomaterials.

The influence of surface modification treatments such as ion implantation and sputter coating on an in vitro rat bone-marrow cell culture was studied by scanning electron microscopy and X-ray microanalysis. 316 L stainless steel, Ti-6Al-4V and Ti-5Al-2.5Fe were nitrogen ion-implanted with three fluences: 10(15), 10(16) and 10(17) ion cm-2 with an energy beam of 40 keV. Both nitrogen and carbon sputter-coated 316 L stainless steel samples were also studied. Polished 316 L stainless steel, Ti-6Al-4V, Ti-5Al-2.5Fe and Thermanox were also studied, in order to give comparative information. The materials were inoculated with a droplet of cell suspension and were maintained for 3 wk. A mineralized extracellular matrix was formed on all materials except on nitrogen sputter-coated 316 L stainless steel. The morphology of the cell cultures obtained on nitrogen-ion implanted materials was similar to those obtained on the untreated materials and Thermanox. The observation of the interface between the cell layer and the substrata showed the presence of calcium- and phosphorus-rich globular deposits associated with collagen fibres. A higher density of these globular deposits was observed on the ion-implanted materials.

Influence of substrate material and surface finishing on the morphology of the calcium-phosphate coating.

The formation of an apatite-like layer was achieved by immersing Ti-6A1-4V, Ti-Al-2.5Fe, and 316 L stainless-steel substrata in Hank's balanced salt solution (HBSS). The layer was characterized by surface analysis techniques, namely X-ray microanalysis and X-ray diffraction, and the morphology was observed by scanning electron microscopy and atomic force microscopy. The concentrations of Ca and P were monitored as a function of time. The morphology of the precipitate layer seems to be dependent both on the type of metal substrate and its surface finish. Polished Ti-6A1-4V and Ti-Al-2.5Fe surfaces exhibit a plate precipitate morphology, whereas rougher surfaces show scattered crystal-like precipitation. The results suggest that the layer produced by immersion of polished titanium alloys in HBSS is constituted by an amorphous apatite.

XPS characterization of surface films formed on surface-modified implant materials after cell culture.

Nitrogen ion-implanted Ti-6Al-4V, Ti-5Al-2.5Fe and 316 L stainless steel and nitrogen or carbon sputter-coated samples were inoculated with rat bone marrow. The interface between the cell layer and the substrata was studied by X-ray photo-electron spectrometry and observed by scanning electron microscopy (SEM). Ca and P were detected on all materials after in vitro cell culture. Titanium appears to be present mainly in the form of TiO2.

Electrochemical and surface modifications on N+-ion-implanted 316 L stainless steel.

The effect of nitrogen-ion implantation on the electrochemical behaviour of 316 L stainless steel in a simulated physiological solution (HBSS-Hank's Balanced Salt Solution) was studied by open-circuit potential versus time and cyclic polarization techniques, with the aim of characterizing the surfaces and choosing the best nitrogen-ion fluence. Three fluences (10(15), 10(16) and 10(17) ions/cm2) were used. The 10(16) ions/cm2 N+ fluence improves the corrosion resistance of the 316 L stainless steel.

Perimenstrual nonvesicular dermatitis herpetiformis.

A case of nonvesicular dermatitis herpetiformis with clear-cut perimenstrual exacerbations is described and differentiated from autoimmune progesterone dermatitis.

Hipotalamotomia posterior estereotaxica em doentes mentais. Relato de cinco casos. / Stereotaxic posterior hypotalamotomy in mental patients.Report of 5 cases

Faz-se a analise de cinco casos de doentes mentais submetidos a hipotalamotomia posterior estereotaxica no Servico de Neurocirurgia do Prof. Gianni Temponi do INDC-UFRJ, desde 1981 ate meados de 1983. Uma pequena analise de fisiologia do hipotalamo e do sistema nervoso autonomo e feita, a titutlo de introducao

Cistos e pseudocistos intracranianos. / Intracranial cysts and pseudocysts

Os autores apresentam tres casos vistos no Servico de Neurocirurgia do INDC-UFRJ a partir de l982. O diagnostico diferencial entre cisto e pseudocisto, no que respeita a sua localizacao intracraniana, e de primordial importancia com vistas ao tratamento a ser efetuado. Dois destes casos foram considerados pseudocistos e um, cisto. Um dos pseudocistos e o cisto foram submetidos a tratamento cirurgico e sao tecidos comentarios a respeito. E relevada a importancia da cintilografia do espaco subaracnoideo para o diagnostico correto nesses casos