Musical activity tape for wheelchair-bound children

This graduate project is concerned with physically disabled children and their need to experience childhood games. It is the proposal of this Master’s candidate to develop an adapted musical game tape and manual which could be used by special education teachers, public school teachers, and therapeutic recreators in a mainstreaming situation. The manual is a compilation of childrens musical activities specifically designed for the physically disabled. The activities have been divided into three domains of development: affective, cognitive and psycho-motor. There are ten activities on the thirty minute casette tape and in the manual which includes traditional childhood games, dancing, drama, verbal and arithmetic games and creative games. The activities are directed to and designed for wheelchair-bound children at the primary level, kindergarten through third grade. The casette tape and manual were field tested at Rancho Los Amigos Hospital and Lowman Elementary School with children that met the above requirements. The field testing showed that the activities were appropriate, useful and enjoyable for teachers and students.Includes recorded audio files in WAV and MP3 formats, 27:22 in length.Includes bibliographical references (page 55)California State University, Northridge. Department of Recreation and Leisure Studies

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity

Depression and stages of change for smoking in psychiatric outpatients

Abstract This article reports on the relations between depression and stages of change for smoking cessation. A convenience sample of 205 psychiatric outpatients (68% female, mean age 41) completed measures of depression Primary Care Evaluation of Mental Disorders [PRIME-MD] and Beck Depression Inventory-II [BDI-II]), all transtheoretical model constructs related to smoking (stages and processes of change, pros and cons of smoking, and situational temptations), and thoughts about abstinence. As hypothesized, patients who had never smoked showed substantially lower rates of currently diagnosed major depressive disorder (MDD) than those who had ever smoked. Patients in early stages of change did not show more MDD or depressive symptoms but, as hypothesized, showed more negative thoughts about abstinence. Findings are consistent with the documented association between smoking and depression and suggest the appropriateness of building smoking cessation interventions based on the transtheoretical model of change for use with psychiatric populations.

¡Míranos! a comprehensive preschool obesity prevention programme in low-income Latino children: 1-year results of a clustered randomised controlled trial

OBJECTIVE: Test a culturally tailored obesity prevention intervention in low-income, minority preschool-age children. DESIGN: A three-group clustered randomized controlled trial. SETTING: Twelve Head Start Centers were randomly assigned to a center-based intervention, a combined center- and home-based intervention, or control using a 1:1:1 ratio. The center-based intervention modified center physical activity and nutrition policies, staff practices, and child behaviors, while the home-based intervention supported parents for obesity prevention at home. STUDY OUTCOMES: The primary endpoint was change in children's body mass index (BMI; kg/m2) at posttest immediately following completion of the 8-month intervention. Secondary endpoints included standardized scores for BMI (BMIz) and body weight (WAZ), and BMI percentiles (BMI pctl). PARTICIPANTS: Three-year-old children enrolled in Head Start in San Antonio, Texas, with written parent consent (N=325), 87% Latino; 57% female with mean age (SD) of 3.58 years (0.29). RESULTS: Change in BMI at posttest was 1.28 (0.97), 1.28 (0.87), and 1.41 (0.71) in the center+home-based intervention, center-based intervention, and control, respectively. There was no significant difference in BMI change between center+home-based intervention and control or center-based intervention and control at posttest. BMIz (adjusted difference -0.12 [95% CI, -0.24 to 0.01], p = .06) and WAZ (adjusted difference, -0.09 [-0.17 to -0.002], p = .04) were reduced for children in center+home-based intervention compared to control group. CONCLUSIONS: There was no reduction in BMI at posttest in children who received the intervention. Findings shed light on methodological challenges in childhood obesity research and offer future directions to explore health equity-oriented obesity prevention

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Multiple interactions between the alpha2C- and beta1-adrenergic receptors influence heart failure survival

<p>Abstract</p> <p>Background</p> <p>Persistent stimulation of cardiac β₁-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the α_2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (<it>ADRB1 </it>and <it>ADRA2C</it>, respectively) on the risk of death/transplant in heart failure patients.</p> <p>Methods</p> <p>Sixteen sequence variations in <it>ADRA2C </it>and 17 sequence variations in <it>ADRB1 </it>were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation.</p> <p>Results</p> <p>Three polymorphisms in <it>ADRA2C </it>and five polymorphisms in <it>ADRB1 </it>were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18) relative to all other genotype classes.</p> <p>Conclusion</p> <p>Multiple polymorphisms act synergistically between the <it>ADRA2C </it>and <it>ADRB1 </it>genes to increase risk of death or cardiac transplant in heart failure patients.</p

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

Abstract DC Bead Ò is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40-45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC 50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 &amp; 30 mg ml -1 , like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 &amp; 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3-6.6 mg were shown to be welltolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83-1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2-0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity