The prevention of lower urinary tract symptoms (PLUS) research consortium: A transdisciplinary approach toward promoting bladder health and preventing lower urinary tract symptoms in women across the life course

Lower urinary tract symptoms (LUTS) are highly prevalent in women, and are expected to impose a growing burden to individuals and society as the population ages. The predominance of research related to LUTS has focused on underlying pathology, disease mechanisms, or the efficacy of treatments for women with LUTS. Although this research has been vital for helping to reduce or ameliorate LUTS conditions, it has done little to prevent the onset of LUTS. Health promotion and prevention require an expansion of scientific inquiry beyond the traditional paradigm of studying disease mechanisms and treatment to the creation of an evidence base to support recommendations for bladder health promotion and, in turn, prevention of LUTS. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) introduced the concept of prevention as an important priority for women's urologic research as a prelude to supporting the formation of the Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium. In this article, we introduce the PLUS research consortium to the scientific community; share the innovative paradigms by which the consortium operates; and describe its unique research mission: to identify factors that promote bladder health across the life course and prevent the onset of LUTS in girls and women

Higher self-reported physical activity Is associated with lower systolic blood pressure: The Dietary Intervention Study in Childhood (DISC)

Objective: Children participating in a dietary clinical trial were studied to assess physical activity patterns in boys and girls longitudinally from late childhood through puberty; and to determine the association of level of physical activity on systolic blood pressure (SBP), low density lipoprotein (LDL) cholesterol, and body mass index (BMI). Patients and Methods: In the Dietary Intervention Study in Childhood (DISC), a randomized clinical trial of a reduced saturated fat and cholesterol diet in 8-10 year olds with elevated LDL, a questionnaire that determined time spent in five intensity levels of physical activity was completed at baseline and at 1 and 3 years. A MET score was calculated for weekly activity; hours per week were calculated for intense activities. We hypothesized that weekly self-reported physical activity would be associated with lower SBP, LDL, and BMI over three years. Longitudinal data analyses were performed for each outcome (SBP, LDL, and BMI) using generalized estimating equations with MET score per week as the independent variable adjusted for visit, gender, and Tanner stage (BMI was included in models for SBP and LDL). Results: The initial study cohort comprised 663 youths (362 male; age 9.7 years, 301 female; age 9.0 years) of whom 623 (94%) completed the 3-year visit. For every 100 MET-hours of physical activity, there was a decrease of 1.15 mmHg of SBP (p=0.0038). There was a 1.28 mg/dl decline in LDL (p=0.10) for a similar energy expenditure. For BMI, an analysis of intense physical activity showed that for every 10 hours of intense activity, there was a trend toward significance with a 0.2 kg/m2 decrease (p=0.06). Conclusion: Children with elevated cholesterol who lead a more physically active lifestyle have lower SBP and a trend toward lower LDL over a 3-year interval. Long-term participation in intense physical activity may reduce BMI as well

Design of the Trial of Activity in Adolescent Girls (TAAG)

The primary aim of the Trial of Activity in Adolescent Girls (TAAG) is to test an intervention to reduce by half the age-related decline in moderate to vigorous physical activity (MVPA) in middle school girls. The intervention will be evaluated using a group-randomized trial involving 36 middle schools. The primary endpoint is the mean difference in intensity-weighted minutes (i.e., MET-minutes) of MVPA between intervention and comparison schools assessed using accelerometry

Longitudinal impact of a youth tobacco education program

BACKGROUND: Information on the effectiveness of elementary school level, tobacco-use prevention programs is generally limited. This study assessed the impact of a structured, one-time intervention that was designed to modify attitudes and knowledge about tobacco. Participants were fifth-grade students from schools in western New York State. METHODS: Twenty-eight schools, which were in relatively close geographic proximity, were randomized into three groups; Group 1 was used to assess whether attitudes/knowledge were changed in the hypothesized direction by the intervention, and if those changes were retained four months later. Groups 2 and 3, were used as comparison groups to assess possible test-retest bias and historical effects. Groups 1 and 3 were pooled to assess whether attitudes/knowledge were changed by the intervention as measured by an immediate post-test. The non-parametric analytical techniques of Wilcoxon-Matched Pairs/Sign Ranks and the Mann-Whitney-Wilcoxon Rank Sums Tests were used to compare proportions of correct responses at each of the schools. RESULTS: Pooled analyses showed that short-term retention on most items was achieved. It was also found that retention on two knowledge items 'recognition that smokers have yellow teeth and fingers' and 'smoking one pack of cigarettes a day costs several hundred dollars per year' was maintained for four months. CONCLUSIONS: The findings suggest that inexpensive, one-time interventions for tobacco-use prevention can be of value. Changes in attitudes and knowledge conducive to the goal of tobacco-use prevention can be achieved for short-term retention and some relevant knowledge items can be retained for several months

A Clinical Trial of the Effects of Dietary Patterns on Blood Pressure

BACKGROUND: It is known that obesity, sodium intake, and alcohol consumption factors influence blood pressure. In this clinical trial, Dietary Approaches to Stop Hypertension, we assessed the effects of dietary patterns on blood pressure. METHODS: We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg. For three weeks, the subjects were fed a control diet that was low in fruits, vegetables, and dairy products, with a fat content typical of the average diet in the United States. They were then randomly assigned to receive for eight weeks the control diet, a diet rich in fruits and vegetables, or a "combination" diet rich in fruits, vegetables, and low-fat dairy products and with reduced saturated and total fat. Sodium intake and body weight were maintained at constant levels. RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg, respectively. The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more, respectively, than the control diet (P or =140 mm Hg; diastolic pressure, > or =90 mm Hg; or both), the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more, respectively, than the control diet (P<0.001 for each); among the 326 subjects without hypertension, the corresponding reductions were 3.5 mm Hg (P<0.001) and 2.1 mm Hg (P=0.003). CONCLUSIONS: A diet rich in fruits, vegetables, and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure. This diet offers an additional nutritional approach to preventing and treating hypertension

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

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

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

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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

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

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