Accumulation of major depressive episodes over time in a prospective study indicates that retrospectively assessed lifetime prevalence estimates are too low

<p>Abstract</p> <p>Background</p> <p>Most epidemiologic studies concerned with Major Depressive Disorder have employed cross-sectional study designs. Assessment of lifetime prevalence in such studies depends on recall of past depressive episodes. Such studies may underestimate lifetime prevalence because of incomplete recall of past episodes (recall bias). An opportunity to evaluate this issue arises with a prospective Canadian study called the National Population Health Survey (NPHS).</p> <p>Methods</p> <p>The NPHS is a longitudinal study that has followed a community sample representative of household residents since 1994. Follow-up interviews have been completed every two years and have incorporated the Composite International Diagnostic Interview short form for major depression. Data are currently available for seven such interview cycles spanning the time frame 1994 to 2006. In this study, cumulative prevalence was calculated by determining the proportion of respondents who had one or more major depressive episodes during this follow-up interval.</p> <p>Results</p> <p>The annual prevalence of MDD ranged between 4% and 5% of the population during each assessment, consistent with existing literature. However, 19.7% of the population had at least one major depressive episode during follow-up. This included 24.2% of women and 14.2% of men. These estimates are nearly twice as high as the lifetime prevalence of major depressive episodes reported by cross-sectional studies during same time interval.</p> <p>Conclusion</p> <p>In this study, prospectively observed cumulative prevalence over a relatively brief interval of time exceeded lifetime prevalence estimates by a considerable extent. This supports the idea that lifetime prevalence estimates are vulnerable to recall bias and that existing estimates are too low for this reason.</p

Tiling Histone H3 Lysine 4 and 27 Methylation in Zebrafish Using High-Density Microarrays

BACKGROUND: Uncovering epigenetic states by chromatin immunoprecipitation and microarray hybridization (ChIP-chip) has significantly contributed to the understanding of gene regulation at the genome-scale level. Many studies have been carried out in mice and humans; however limited high-resolution information exists to date for non-mammalian vertebrate species. PRINCIPAL FINDINGS: We report a 2.1-million feature high-resolution Nimblegen tiling microarray for ChIP-chip interrogations of epigenetic states in zebrafish (Danio rerio). The array covers 251 megabases of the genome at 92 base-pair resolution. It includes ∼15 kb of upstream regulatory sequences encompassing all RefSeq promoters, and over 5 kb in the 5' end of coding regions. We identify with high reproducibility, in a fibroblast cell line, promoters enriched in H3K4me3, H3K27me3 or co-enriched in both modifications. ChIP-qPCR and sequential ChIP experiments validate the ChIP-chip data and support the co-enrichment of trimethylated H3K4 and H3K27 on a subset of genes. H3K4me3- and/or H3K27me3-enriched genes are associated with distinct transcriptional status and are linked to distinct functional categories. CONCLUSIONS: We have designed and validated for the scientific community a comprehensive high-resolution tiling microarray for investigations of epigenetic states in zebrafish, a widely used developmental and disease model organism

LEARN 2 MOVE 0-2 years:effects of a new intervention program in infants at very high risk for cerebral palsy; a randomized controlled trial

Background: It is widely accepted that infants at risk for cerebral palsy need paediatric physiotherapy. However, there is little evidence for the efficacy of physiotherapeutic intervention. Recently, a new intervention program, COPCA (Coping with and Caring for infants with special needs - a family centered program), was developed. COPCA has educational and motor goals. A previous study indicated that the COPCA-approach is associated with better developmental outcomes for infants at high risk for developmental disorders. LEARN 2 MOVE 0-2 years evaluates the efficacy and the working mechanisms of the COPCA program in infants at very high risk for cerebral palsy in comparison to the efficacy of traditional infant physiotherapy in a randomized controlled trial. The objective is to evaluate the effects of both intervention programs on motor, cognitive and daily functioning of the child and the family and to get insight in the working elements of early intervention methods.Methods/design: Infants are included at the corrected age of 1 to 9 months and randomized into a group receiving COPCA and a group receiving traditional infant physiotherapy. Both interventions are given once a week during one year. Measurements are performed at baseline, during and after the intervention period and at the corrected age of 21 months. Primary outcome of the study is the Infant Motor Profile, a qualitative evaluation instrument of motor behaviour in infancy. Secondary measurements focus on activities and participation, body functions and structures, family functioning, quality of life and working mechanisms. To cope with the heterogeneity in physiotherapy, physiotherapeutic sessions are video-recorded three times (baseline, after 6 months and at the end of the intervention period). Physiotherapeutic actions will be quantified and related to outcome.Discussion: LEARN 2 MOVE 0-2 years evaluates and explores the effects of COPCA and TIP. Whatever the outcome of the project, it will improve our understanding of early intervention in children with cerebral palsy. Such knowledge is a prerequisite for tailor-made guidance of children with CP and their families.Trial registration: The trial is registered under NTR1428.</p

Movement and habitat use of the snapping turtle in an urban landscape

In order to effectively manage urban habitats, it is important to incorporate the spatial ecology and habitat use of the species utilizing them. Our previous studies have shown that the distribution of upland habitats surrounding a highly urbanized wetland habitat, the Central Canal (Indianapolis, IN, USA) influences the distribution of map turtles (Graptemys geographica) and red-eared sliders (Trachemys scripta) during both the active season and hibernation. In this study we detail the movements and habitat use of another prominent member of the Central Canal turtle assemblage, the common snapping turtle, Chelydra serpentina. We find the same major upland habitat associations for C. serpentina as for G. geographica and T. scripta, despite major differences in their activity (e.g., C. serpentina do not regularly engage in aerial basking). These results reinforce the importance of recognizing the connection between aquatic and surrounding terrestrial habitats, especially in urban ecosystems

KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS-mutation and bone metastasis

Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17.4%), brain (16.8%), pleura (15.6%) and liver (11%). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p=0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17% (p<0.001) and 16% (p=0.02) vs 33%, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRAS-wild-type vs KRAS-mutant; median OS 9.7v 3.7 months; HR, 0.49; 95% CI, 0.31 to 0.79; p =0.003). Our study suggests that KRAS mutation frequency in LADC patients shows a metastatic site dependent variation and, moreover, that the presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases.(VLID)469049

The effect of major depression on participation in preventive health care activities

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to determine whether major depressive episodes (MDE) contribute to a lower rate of participation in three prevention activities: blood pressure checks, mammograms and Pap tests.</p> <p>Methods</p> <p>The data source for this study was the Canadian National Population Health Survey (NPHS), a longitudinal study that started in 1994 and has subsequently re-interviewed its participants every two years. The NPHS included a short form version of the Composite International Diagnostic Interview (CIDI-SF) to assess past year MDE and also collected data on participation in preventive activities. Initially, we examined whether respondents with MDE in a particular year were less likely to participate in screening during that same year. In order to assess whether MDE negatively altered the pattern of participation, those successfully screened at the baseline interview in 1994 were identified and divided into cohorts depending on their MDE status. Proportional hazard models were used to quantify the effect of MDE on subsequent participation in screening.</p> <p>Results</p> <p>No effect of MDE on participation in the three preventive activities was identified either in the cross-sectional or longitudinal analysis. Adjustment for a set of relevant covariates did not alter this result.</p> <p>Conclusion</p> <p>Whereas MDE might be expected to reduce the frequency of participation in screening activities, no evidence for this was found in the current analysis. Since people with MDE may contact the health system more frequently, this may offset any tendency of the illness itself to reduce participation in screening.</p

Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways

INTRODUCTION: Molecular characterization of the normal epithelial cell types that reside in the mammary gland is an important step toward understanding pathways that regulate self-renewal, lineage commitment, and differentiation along the hierarchy. Here we determined the gene expression signatures of four distinct subpopulations isolated from the mouse mammary gland. The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks. METHODS: RNA was prepared from freshly sorted mouse mammary cell subpopulations (mammary stem cell (MaSC)-enriched, committed luminal progenitor, mature luminal and stromal cell) and used for gene expression profiling analysis on the Illumina platform. Gene signatures were derived and compared with those previously reported for the analogous normal human mammary cell subpopulations. The mouse and human epithelial subset signatures were then subjected to Ingenuity Pathway Analysis (IPA) to identify conserved pathways. RESULTS: The four mouse mammary cell subpopulations exhibited distinct gene signatures. Comparison of these signatures with the molecular profiles of different mouse models of mammary tumorigenesis revealed that tumors arising in MMTV-Wnt-1 and p53-/- mice were enriched for MaSC-subset genes, whereas the gene profiles of MMTV-Neu and MMTV-PyMT tumors were most concordant with the luminal progenitor cell signature. Comparison of the mouse mammary epithelial cell signatures with their human counterparts revealed substantial conservation of genes, whereas IPA highlighted a number of conserved pathways in the three epithelial subsets. CONCLUSIONS: The conservation of genes and pathways across species further validates the use of the mouse as a model to study mammary gland development and highlights pathways that are likely to govern cell-fate decisions and differentiation. It is noteworthy that many of the conserved genes in the MaSC population have been considered as epithelial-mesenchymal transition (EMT) signature genes. Therefore, the expression of these genes in tumor cells may reflect basal epithelial cell characteristics and not necessarily cells that have undergone an EMT. Comparative analyses of normal mouse epithelial subsets with murine tumor models have implicated distinct cell types in contributing to tumorigenesis in the different models

LEARN 2 MOVE 2-3: a randomized controlled trial on the efficacy of child-focused intervention and context-focused intervention in preschool children with cerebral palsy

<p>Abstract</p> <p>Background</p> <p>Little is known about the efficacy and the working mechanisms of physical and occupational therapy interventions for children with cerebral palsy (CP). In recent years a shift from a child-focused intervention approach to a more context-focused intervention approach can be recognized. Until now the evidence on the efficacy and the working mechanisms of these interventions for children with CP is inconclusive. This study aims to evaluate the efficacy and working mechanisms of two intervention approaches compared to regular care intervention in improving mobility and self-care skills of children (2-3 years) with CP and their families: a child-focused intervention approach and a context-focused intervention approach.</p> <p>Methods/Design</p> <p>A multi-centre, randomized controlled trial research design will be used. Ninety-four children with CP (Gross Motor Function Classification System (GMFCS) level I-IV; age 2 to 3 years), their parents, and service providers (physical and occupational therapists) will be included. During a period of six months children will receive child-focused, context-focused or regular care intervention. Therapists will be randomly assigned to deliver either a child-focused intervention approach, a context-focused intervention approach or regular care intervention. Children follow their therapist into the allocated intervention arm. After the six months study-intervention period, all participants return to regular care intervention. Outcomes will be evaluated at baseline, after six months and at a three months follow-up period. Primary outcome is the capability of functional skills in self-care and mobility, using the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory (PEDI). Other outcomes will be quality of life and the domains of the International Classification of Functioning, Disability and Health - for Children and Youth (ICF-CY), including body function and structure, activities (gross motor capacity and performance of daily activities), social participation, environmental variables (family functioning, parental empowerment).</p> <p>Discussion</p> <p>This paper presents the background information, design, description of interventions and protocol for this study on the efficacy and working mechanisms of child-focused intervention approach and context-focused intervention approach compared to regular care intervention in mobility and self-care skills of children (2-3 years) with CP.</p> <p>Trial registration</p> <p>This study is registered in the Dutch Trial Register as NTR1900</p

Pregnancy in the mature adult mouse does not alter the proportion of mammary epithelial stem/progenitor cells

Introduction In humans, an early full-term pregnancy reduces lifetime breast cancer risk by up to 50% whereas a later pregnancy (>35 years old) can increase lifetime risk. Several mechanisms have been suggested, including changes in levels of circulating hormones, changes in the way the breast responds to these hormones, changes in gene expression programmes which may alter susceptibility to transformation and changes to mammary stem cell numbers or behaviour. Previous studies have shown that the mammary tissue isolated from both virgin and parous mice has the ability to repopulate a cleared mammary fat pad in transplant experiments. Limited dilution transplant assays have demonstrated that early pregnancy (at 5 weeks of age) reduces stem/progenitor cell numbers in the mouse mammary epithelium by twofold. However, the effects on stem/progenitor cell numbers in the mammary epithelium of a pregnancy in older animals have not yet been tested. Methods Mice were put through a full-term pregnancy at 9 weeks of age, when the mammary epithelium is mature. The total mammary epithelium was purified from parous 7-week post-lactation and age-matched virgin mice and analysed by flow cytometry and limiting dilution cleared fat pad transplants. Results There were no significant differences in the proportions of different mammary epithelial cell populations or numbers of CD24+/Low Sca-1- CD49fHigh cells (stem cell enriched basal mammary epithelial compartment). There was no significant difference in stem/progenitor cell frequency based on limiting dilution transplants between the parous and age-matched virgin epithelium. Conclusions Although differences between parous and virgin mammary epithelium at later time points post lactation or following multiple pregnancies cannot be ruled out, there are no differences in stem/progenitor cell numbers between mammary epithelium isolated from parous animals which were mated at 9 weeks old and virgin animals. However, a recent report has suggested that animals that were mated at 5 weeks old have a twofold reduction in stem/progenitor cell numbers. This is of interest given the association between early, but not late, pregnancy and breast cancer risk reduction in humans. However, a mechanistic connection between stem cell numbers and breast cancer risk remains to be established