264 research outputs found

    Adolescent depressive disorders and family based interventions in the family options multicenter evaluation: study protocol for a randomized controlled trial

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    BackgroundThere is increasing community and government recognition of the magnitude and impact of adolescent depression. Family based interventions have significant potential to address known risk factors for adolescent depression and could be an effective way of engaging adolescents in treatment. The evidence for family based treatments of adolescent depression is not well developed. The objective of this clinical trial is to determine whether a family based intervention can reduce rates of unipolar depressive disorders in adolescents, improve family functioning and engage adolescents who are reluctant to access mental health services.Methods/DesignThe Family Options study will determine whether a manualized family based intervention designed to target both individual and family based factors in adolescent depression (BEST MOOD) will be more effective in reducing unipolar depressive disorders than an active (standard practice) control condition consisting of a parenting group using supportive techniques (PAST). The study is a multicenter effectiveness randomized controlled trial. Both interventions are delivered in group format over eight weekly sessions, of two hours per session. We will recruit 160 adolescents (12 to 18 years old) and their families, randomized equally to each treatment condition. Participants will be assessed at baseline, eight weeks and 20 weeks. Assessment of eligibility and primary outcome will be conducted using the KID-SCID structured clinical interview via adolescent and parent self-report. Assessments of family mental health, functioning and therapeutic processes will also be conducted. Data will be analyzed using Multilevel Mixed Modeling accounting for time x treatment effects and random effects for group and family characteristics. This trial is currently recruiting. Challenges in design and implementation to-date are discussed. These include diagnosis and differential diagnosis of mental disorders in the context of adolescent development, non-compliance of adolescents with requirements of assessment, questionnaire completion and treatment attendance, breaking randomization, and measuring the complexity of change in the context of a family-based intervention

    Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD

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    This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the licenseRATIONALE: Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised. Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression. The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown. METHODS: 31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy. The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR. RESULTS: A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B mRNA: fourfold, p=0.011). miR-1 expression was associated with smoking history, lung function, fat-free mass index, 6 min walk distance and percentage of type 1 fibres. miR-133 and miR-206 were negatively correlated with daily physical activity. Insulin-like growth factor 1 mRNA was increased in the patients and miR-1 was negatively correlated with phosphorylation of the kinase Akt. Furthermore, the protein levels of histone deacetylase 4, another miR-1 target, were increased in the patients. CONCLUSIONS: Downregulation of the activity of the MRTF-SRF axis and the expression of muscle-specific microRNAs, particularly miR-1, may contribute to COPD-associated skeletal muscle dysfunction.BBSRC, Wellcome Trust and the National Institute for Health Research (NIHR) Respiratory Biomedical Unit at the Royal Brompton Hospital and Imperial College. AL is a BBSRC PhD student, SAN received a Wellcome Trust Fellowship, AD received a NIHR Respiratory Biomedical Unit fellowship and WM is a NIHR Clinician Scientist. NSH is a HEFCE Clinical Senior Lecturer. MIP's salary is part funded by the NIHR Respiratory Biomedical Unit at the Royal Brompton Hospital and National Heart & Lung Institute

    MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

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    MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

    Development and testing of the Measure of Innovation-Specific Implementation Intentions (MISII) using Rasch measurement theory

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    © 2018 The Author(s). Background: Implementation is proposed to be a multiphase, multilevel process. After a period of exploration, an adoption decision is made, typically at the upper management or policy level. Nevertheless, movement through each of the subsequent phases of the implementation process involves clinicians or providers at the individual level to adopt the innovation and then change their behavior to use/deliver the innovation. Multiple behavioral change theories propose that intentions are a critical determinant of implementation behavior. However, there is a need for the development and testing of pragmatic measures of providers' intentions to use a specific innovation or evidence-based practice (EBP). Methods: Nine items were developed to assess providers' intentions to use a specific innovation or EBP. Motivational interviewing was the EBP in the study. Items were administered, as part of larger survey, to 179 providers across 38 substance use disorder treatment (SUDT) programs within five agencies in California, USA. Rasch analysis was conducted using RUMM2030 software to assess the items, their overall fit to the Rasch model, the response scale used, individual item fit, differential item functioning (DIF), and person separation. Results: Following a stepwise process, the scale was reduced from nine items to three items to increase the feasibility and acceptability of the scale while maintaining suitable psychometric properties. The three-item unidimensional scale showed good person separation (PSI =.872), no disordering of thresholds, and no evidence of uniform or non-uniform DIF. Rasch analysis supported the viability of the scale as a measure of implementation intentions. Conclusions: The Measure of Innovation-Specific Implementation Intentions (MISII) is a sound measure of providers' intentions to use a specific innovation or EBP. Future evaluation of convergent, divergent, and predictive validity are needed. The study also demonstrates the value of Rasch analysis for testing the psychometric properties of pragmatic implementation measures

    The rise in narghile (shisha, hookah) waterpipe tobacco smoking: A qualitative study of perceptions of smokers and non smokers

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    <p>Abstract</p> <p>Background</p> <p>The prevalence of waterpipe tobacco smoking (WTS) in the Middle East region and worldwide is increasing. There is evidence to indicate both short term and long term health effects of WTS, resulting in the issuance of an advisory note by the World Health Organization.</p> <p>Methods</p> <p>This research aimed at gaining an in-depth understanding of the factors contributing to the rise in WTS in Lebanon. Qualitative focus groups (25) and in-depth interviews (9) were conducted with adults in Lebanon in 2007. Participants were recruited to represent diversity in smoking status, gender, age groups and urban/rural residence. The interviews and focus groups were thematically analyzed, and recurrent themes noted and summarized.</p> <p>Results</p> <p>The main themes identified were availability, affordability, innovation, influence of media, lack of a policy framework, and the sensory characteristics evoked from WTS. Men and women, smokers and non-smokers, and younger and older participants differed in their emphases on the above themes. These themes, though specific to waterpipe, are similar to themes manipulated by the cigarette industry, and eventually controlled through tobacco control policies.</p> <p>Conclusions</p> <p>Understanding reasons behind the rise in waterpipe tobacco use is important if appropriate prevention, cessation, and policy interventions are to be formulated. Strict adherence to the FCTC is warranted, with careful and vigilant attention that all tobacco products are covered by laws in both high as well as middle to lower income countries.</p

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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    Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment
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