Opinions about Smoking, Secondhand Smoke Exposure, and Smoking Behaviors of Freshmen College Students

The purpose of this project was to assess first semester freshman college students’ opinions about smoking, secondhand smoke exposure, and smoking behaviors on a smoke-free campus. This research used an online cross-sectional survey. For two years, surveys were emailed via Zoomerang to all first semester freshmen students at Valparaiso University. Survey questions contained 60 forced-choice or open-ended options. Data were analyzed using descriptive statistics. A total of 630 students responded. Subjects were primarily female (58.4%) and Caucasian (84.9%). Twenty-five percent of the respondents reported being exposed to secondhand smoke in their environments. Twenty-nine percent were unaware that the campus is a smoke-free environment, 79% have seen smoking on campus, and 25% believed the smoke-free policy is not enforced. Seventy-seven percent of the respondents agreed or strongly agreed that the campus should be a smoke-free environment. Thirty-four percent of respondents admitted to smoking at some point in their lifetime. Fourteen percent (n=91) indicated that they had smoked during the previous 30 days, with only 28% of these identifying themselves as “current” smokers. The majority of the respondents supported a smoke-free environment and believed the current campus policy is enforced. Data from this study will add to the growing body of evidence about college students’ smoking behaviors

Global exponential convergence of delayed inertial Cohen–Grossberg neural networks

In this paper, the exponential convergence of delayed inertial Cohen–Grossberg neural networks (CGNNs) is studied. Two methods are adopted to discuss the inertial CGNNs, one is expressed as two first-order differential equations by selecting a variable substitution, and the other does not change the order of the system based on the nonreduced-order method. By establishing appropriate Lyapunov function and using inequality techniques, sufficient conditions are obtained to ensure that the discussed model converges exponentially to a ball with the prespecified convergence rate. Finally, two simulation examples are proposed to illustrate the validity of the theorem results

Supporting Underserved Pregnant Women through Smoking Cessation

This project assessed smoking behaviors and supported smoking cessation in underserved pregnant women. Using a longitudinal design, women were recruited from a community prenatal center. Using the Transtheoretical model, interventions were designed to support the subjects’ movement along the stages of change. Subjects willing to quit were given a smoking cessation “quit kit.” For subjects not contemplating smoking cessation, information about the harmful effects of smoking was distributed to encourage movement towards quitting. Women who were smoking were followed throughout their pregnancy and up to one year after delivery. Subjects (N = 134) ranged in age from 18 to 41; 71% were single; and 63% had household incomes less than $20,000 per year. Subjects were primarily African American (40%). 57% had previously smoked. 35% were current smokers. Of the smokers (n = 27), 26% were not considering quitting (pre-contemplation), 56% had planned to quit (contemplation), and 18% had an action plan (preparation). Six weeks post-delivery (n = 12), one woman quit smoking and the others were planning to quit. Six months post-delivery (n = 7), two women quit smoking and the remaining smokers were planning to quit. One year post-delivery (n = 9), one woman quit smoking and of the remaining smokers only six planned to quit. Results will add to the growing body of evidence about smoking patterns of underserved pregnant women

The role of PKCzeta in cord blood T-cell maturation towards Th1 cytokine profile and its epigenetic regulation by fish oil

While immunodeficiency of immaturity of the neonate has been considered important as the basis for unusual susceptibility to infection, it has also been recognized that the ability to progress from an immature Th2 cytokine predominance to a Th1 profile has relevance in determining whether children will develop allergy, providing an opportunity for epigenetic regulation through environmental pressures. However, this notion remains relatively unexplored. Here, we present evidence that there are two major control points to explain the immunodeficiency in cord blood (CB) T-cells, a deficiency in interleukin (IL)-12 (IL-12) producing and IL-10 overproducing accessory cells, leading to a decreased interferon γ (IFNγ) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) ζ (PKCζ) expression. An important finding was that human CB T-cells rendered deficient in PKCζ, by shRNA knockdown, develop into low tumour necrosis factor α (TNFα) and IFNγ but increased IL-13 producing cells. Interestingly, we found that the increase in PKCζ levels in CB T-cells caused by prenatal supplementation with fish oil correlated with modifications of histone acetylation at the PKCζ gene (PRKCZ) promoter. The data demonstrate that PKCζ expression regulates the maturation of neonatal T-cells into specific functional phenotypes and that environmental influences may work via PKCζ to regulate these phenotypes and disease susceptibility.Hani Harb, James Irvine, Manori Amarasekera, Charles S. Hii, Dörthe A. Kesper, YueFang Ma, Nina D′Vaz, Harald Renz, Daniel P. Potaczek, Susan L. Prescott and Antonio Ferrant

Essential Role of the Small GTPase Ran in Postnatal Pancreatic Islet Development

The small GTPase Ran orchestrates pleiotropic cellular responses of nucleo-cytoplasmic shuttling, mitosis and subcellular trafficking, but whether deregulation of these pathways contributes to disease pathogenesis has remained elusive. Here, we generated transgenic mice expressing wild type (WT) Ran, loss-of-function Ran T24N mutant or constitutively active Ran G19V mutant in pancreatic islet β cells under the control of the rat insulin promoter. Embryonic pancreas and islet development, including emergence of insulin+ β cells, was indistinguishable in control or transgenic mice. However, by one month after birth, transgenic mice expressing any of the three Ran variants exhibited overt diabetes, with hyperglycemia, reduced insulin production, and nearly complete loss of islet number and islet mass, in vivo. Deregulated Ran signaling in transgenic mice, adenoviral over-expression of WT or mutant Ran in isolated islets, or short hairpin RNA (shRNA) silencing of endogenous Ran in model insulinoma INS-1 cells, all resulted in decreased expression of the pancreatic and duodenal homeobox transcription factor, PDX-1, and reduced β cell proliferation, in vivo. These data demonstrate that a finely-tuned balance of Ran GTPase signaling is essential for postnatal pancreatic islet development and glucose homeostasis, in vivo

The Cell Cycle Regulated Transcriptome of Trypanosoma brucei

Progression of the eukaryotic cell cycle requires the regulation of hundreds of genes to ensure that they are expressed at the required times. Integral to cell cycle progression in yeast and animal cells are temporally controlled, progressive waves of transcription mediated by cell cycle-regulated transcription factors. However, in the kinetoplastids, a group of early-branching eukaryotes including many important pathogens, transcriptional regulation is almost completely absent, raising questions about the extent of cell-cycle regulation in these organisms and the mechanisms whereby regulation is achieved. Here, we analyse gene expression over the Trypanosoma brucei cell cycle, measuring changes in mRNA abundance on a transcriptome-wide scale. We developed a “double-cut” elutriation procedure to select unperturbed, highly synchronous cell populations from log-phase cultures, and compared this to synchronization by starvation. Transcriptome profiling over the cell cycle revealed the regulation of at least 430 genes. While only a minority were homologous to known cell cycle regulated transcripts in yeast or human, their functions correlated with the cellular processes occurring at the time of peak expression. We searched for potential target sites of RNA-binding proteins in these transcripts, which might earmark them for selective degradation or stabilization. Over-represented sequence motifs were found in several co-regulated transcript groups and were conserved in other kinetoplastids. Furthermore, we found evidence for cell-cycle regulation of a flagellar protein regulon with a highly conserved sequence motif, bearing similarity to consensus PUF-protein binding motifs. RNA sequence motifs that are functional in cell-cycle regulation were more widespread than previously expected and conserved within kinetoplastids. These findings highlight the central importance of post-transcriptional regulation in the proliferation of parasitic kinetoplastids

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

ADAPTAÇÃO CULTURAL E VALIDAÇÃO PSICOMÉTRICA DO QUESTIONÁRIO SELF EFFICIENCY AND PERFORMANCE IN SELF-MANAGEMENT SUPPORT (SEPSS) EM ESTUDANTES DE GRADUAÇÃO EM ENFERMAGEM E MEDICINA DE BANGLADESH

In an aging society, healthcare professionals and students face increasing demands to actively involve patients in the decision-making process regarding their health conditions and lifestyles. Self-management support is considered a best practice that aligns with the patient-centered care paradigm in Bangladesh. However, there is currently no instrument available to assess healthcare professionals’ competencies in this field, particularly during their early education and training period. The aim of this study was to translate the Self Efficiency and Performance in Self-management Support (SEPSS) instrument into Bangla and validate its psychometric properties in a sample of undergraduate healthcare students in Bangladeshi higher education institutions. A cross-sectional study was conducted to assess the reliability, validity, and cultural appropriateness of the Bangla version of SEPSS-36 among 486 nursing and medical students. Confirmatory factor analysis was carried out using the chi-square model fit index (CMIN), comparative fit index (CFI), and Root Mean Square Error of Approximation (RMSEA) as fit indices. The internal consistency was estimated by the Cronbach alpha coefficient. The results indicate that the CMIN (2.658) and RMSEA (.058) values suggest that the sample data and hypothetical model are an acceptable fit in the analysis, with satisfactory CFI values (.895). The reliability for all SEPSS dimensions was acceptable. The Bangla version of the SEPSS questionnaire is a valid and reliable instrument that can assist healthcare educators and researchers in determining students’ competencies within this domain.Numa sociedade envelhecida, os profissionais de saúde e os estudantes enfrentam exigências cada vez maiores para envolver ativamente os pacientes no processo de tomada de decisão em relação às suas condições de saúde e estilos de vida. O apoio à autogestão é considerado uma prática recomendada que está alinhada com o paradigma de cuidados centrados no paciente em Bangladesh. No entanto, atualmente não existe um instrumento disponível para avaliar as competências dos profissionais de saúde nesse campo, especialmente durante o período inicial de educação e formação. O objetivo deste estudo foi traduzir o instrumento Self Efficiency and Performance in Self-management Support (SEPSS) para o bengali e validar as suas propriedades psicométricas numa amostra de estudantes de saúde de graduação em instituições de ensino superior de Bangladesh. Foi realizado um estudo transversal para avaliar a confiabilidade, validade e adequação cultural da versão em bengali do SEPSS-36 entre 486 estudantes de enfermagem e medicina. A análise fatorial confirmatória foi conduzida utilizando o índice de ajustamento do modelo qui-quadrado (CMIN), o índice de ajustamento comparativo (CFI) e o erro quadrado médio de aproximação (RMSEA) como índices de ajustamento. A consistência interna foi estimada pelo coeficiente alfa de Cronbach. Os resultados indicam que os valores de CMIN (2,658) e RMSEA (0,058) sugerem que os dados da amostra e o modelo hipotético têm um ajustamento aceitável na análise, com valores de CFI satisfatórios (0,895). A confiabilidade de todas as dimensões do SEPSS foi aceitável. A versão em bengali do questionário SEPSS é um instrumento válido e fiável que pode ajudar os educadores e investigadores em saúde a determinar as competências dos estudantes nesta área