Molecular regulation of GABAergic neuron differentiation and diversity in the developing midbrain.

The midbrain GABAergic neurones control several aspects of behaviour, play important roles in psychiatric disease and are targets of medical treatments as well as drugs of abuse. However, their molecular diversity and regulation of development are only beginning to be understood. In this review, we briefly introduce distinct subpopulations of the midbrain GABAergic neurones and discuss knowledge on their development, including the developmental origins of midbrain GABAergic neurones as well as transcriptional regulatory mechanisms guiding their differentiation and identity. Important GABAergic neuron subpopulations are found within the dopaminergic (DA) nuclei in the ventral midbrain. GABAergic substantia nigra pars reticulata is the main output pathway of the basal ganglia system regulating voluntary movements. Recent studies have also highlighted importance of the GABAergic neurones associated with the ventral tegmental area for the control of DA neuron activity and motivated behaviours. Interestingly, the development of the GABAergic neurones associated with the DA nuclei is very different from the rest of the midbrain. Knowledge on developmental regulation can lead to insights into the molecular, structural and functional diversity of the midbrain GABAergic neurones and their subpopulations, cell groups of great physiological and medical interest.

The adult intestinal core microbiota is determined by analysis depth and health status.

High-throughput molecular methods are currently exploited to characterize the complex and highly individual intestinal microbiota in health and disease. Definition of the human intestinal core microbiota, i.e. the number and the identity of bacteria that are shared among different individuals, is currently one of the main research questions. Here we apply a high-throughput phylogenetic microarray, for a comprehensive and high-resolution microbiota analysis, and a novel computational approach in a quantitative study of the core microbiota in over 100 individuals. In the approach presented we study how the criteria for the phylotype abundance or prevalence influence the resulting core in parallel with biological variables, such as the number and health status of the study subjects. We observed that the core size is highly conditional, mostly depending on the depth of the analysis and the required prevalence of the core taxa. Moreover, the core size is also affected by biological variables, of which the health status had a larger impact than the number of studied subjects. We also introduce a computational method that estimates the expected size of the core, given the varying prevalence and abundance criteria. The approach is directly applicable to sequencing data derived from intestinal and other host-associated microbial communities, and can be modified to include more informative definitions of core microbiota. Hence, we anticipate its utilization will facilitate the conceptual definition of the core microbiota and its consequent characterization so that future studies yield conclusive views on the intestinal core microbiota, eliminating the current controversy.

Population-based enrolment of adolescents in a long-term follow-up trial of human papillomavirus vaccine efficacy.

We evaluated a study setting for assessment of the long-term vaccine efficacy (VE) of human papillomavirus (HPV) virus-like-particle (VLP) vaccine against cervical carcinoma. A total of 22,412 16- to 17-year old adolescent women from seven cities in Finland were invited by letter to participate in a phase III study of a quadrivalent HPV (types 6, 11, 16, 18) VLP vaccine, between September 2002 and March 2003. A total of 30,947 18-year old women were invited to participate as unvaccinated controls. These women were asked about their willingness to participate in an HPV vaccination trial and to fill a health questionnaire. These three population-based cohorts of adolescent women, including women vaccinated with HPV vaccine or placebo vaccine and unvaccinated control women, are systematically followed over time. The study cohort database will be linked with the Finnish Cancer Registry using cervical carcinoma in situ (CIS) and invasive cervical carcinoma (ICC) as endpoints. Assuming that the cumulative incidence of CIS and ICC over 15 years is 0.45%, and that there is no loss to follow-up, and power of 80%, the determination of 70% total VE will require 3357 HPV vaccine recipients, 3357 placebo vaccine recipients, and 6714 unvaccinated controls. At the baseline, 2632 (12%) of the invited adolescents volunteered to the phase III vaccination trial, and 6790 (22%) responded to the questionnaire study. During a recruitment period of 10 months, 874 HPV vaccine recipients, 875 placebo recipients and 1919 unvaccinated controls were enrolled. Population-based enrollment of large cohorts of vaccinated and unvaccinated adolescents for passive registry-based follow-up with cervical carcinoma as the end-point is feasible and currently going on in Finland.

Record linkage in a regional mental health planning study: accuracy of unique identifiers, reliability of sociodemographics, and estimating identification error.

Assembling information about individuals over time allows health managers and researchers to describe the progression of diseases, the care history of individuals and the sequences of care episodes that potentially result in improving individuals' health status. However, current mental health statistics generally focus on sets of events rather than groups of individuals making it impossible to distinguish between two different persons being admitted and the same person being admitted twice. Accurate figures on treatment prevalence cannot be generated and multiservice users across time or across agencies will inflate the statistics used to plan needed services. The capacity to link consistently defined bits of information together is critical to developing a reliable information system. This article examines the adequacy of using unique identifier codes to accomplish linkage by focusing on one example of record linkage that incorporates mental health information from both community and institutional sectors in one region of Ontario, Canada. Findings indicate that unique "cradle to grave" identifiers do not guarantee accuracy if manual transcription is involved.

Microbial adherence to vulvar epithelial cells.

Under uniform experimental conditions, different degrees of selective attachment of Staphylococcus aureus and Candida albicans to epithelial cells of the labium majus, the labium minus, and the vagina were compared and contrasted with those found in studies with cells of the buccal and nasal mucosa and forearm skin by a novel analysis of adherence density. For both micro-organisms, the larger, rougher cells of the labium majus gave the highest adherence scores matched only by the interaction of S. aureus with fully keratinised nasal epithelial cells. Increasing acidity to pH 3.5 enhanced microbial adherence to vaginal cells. Menstruation also influenced attachment; highest densities were reached between the third and fourth weeks of the cycle. Autogenous ribitol teichoic acid was found to block the attachment of S. aureus to labium majus and labium minus cells by 76% and 81% respectively, and to vaginal cells by 66%. Adherence is considered to be an important attribute of vulvar ecology and may be a determinant of infectious disease.