Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA ...methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.
We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists ...of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism.
AbstractDengue, a mosquito-borne viral disease, is increasingly being identified as a cause of outbreaks in the United States. During July-December 2013, a total of three south Texas counties ...reported 53 laboratory-confirmed dengue cases; 26 were locally acquired, constituting the largest outbreak in Texas since 2005. Because dengue outbreaks are expected to continue in south Texas and early case identification and timely treatment can reduce mortality, we sought to determine clinicians' knowledge of dengue and its clinical management. A survey was sent to 2,375 south Texas clinicians; 217 (9%) completed the survey. Approximately half of participants demonstrated knowledge needed to identify dengue cases, including symptoms (56%), early indicators of shock (54%), or timing of thrombocytopenia (48%). Fewer than 20% correctly identified all prevention messages, severe dengue warning signs, or circumstances in which a dengue patient should return for care. Knowledge of clinical management was limited; few participants correctly identified scenarios when plasma leakage occurred (10%) or a crystalloid solution was indicated (7%); however, 45% correctly identified when a blood transfusion was indicated. Because of the ongoing threat of dengue, we recommend clinicians in south Texas receive dengue clinical management training.
The Care Of Childhood Obesity (COCO) clinic at the Bristol Royal Hospital for Children (BRHC) uses a multidisciplinary approach comprising a consultant, dietitian, and exercise specialist. The clinic ...has demonstrated efficacy in managing children's weight but similar clinics are scarce in the UK.
This pilot randomised controlled trial (RCT) aimed to examine the feasibility of undertaking a fully powered RCT and to gauge whether the COCO model could be effective as a nurse-led clinic in primary care settings.
Patients were randomised to a hospital-based childhood obesity clinic or a nurse-led clinic in a primary care setting in south-west England.
Children aged 5-16 years with a body mass index (BMI) ≥98th centile were referred by GPs to the consultant in charge of the COCO clinic at BRHC. Referred children were clinically screened for suitability and invited into the study. Consenting families were randomised to BRHC or a primary care clinic (PCC) and offered five appointments over 12 months. Clinical effectiveness was measured by change in body mass index standard deviation score (BMI SDS) at 12 months. Other measures included: treatment adherence, quality of life (QOL), and satisfaction. Feasibility was examined by assessing referral, screening, and recruitment data.
A total 152 patients were referred by GPs: 31 (20%) were screened out; 45 (30%) declined to participate. Seventy-six (50%) patients were randomised and 68 provided baseline data (PCC = 42; BRHC = 26); 52 provided outcome data (PCC = 29; BRHC = 23). Mean change in BMI SDS was PCC -0.17 (95% confidence interval CI = -0.27 to -0.07); BRHC -0.15 (95% CI = -0.26 to -0.05). QOL, adherence, and satisfaction data indicated similar positive patterns in both trial arms.
Screening and recruitment data indicate that primary care is a clinically appropriate setting and acceptable to families. The primary clinical outcome measure (reduction in BMI SDS), along with secondary outcome measures, indicate that primary care has the potential to be effective in providing weight management for children, using the COCO model.
Using seven waves of data, collected twice a year from the 8th through the 11th grades in a low-resource community in Cape Town, South Africa, we aimed to describe the developmental trends in three ...specific leisure experiences (leisure boredom, new leisure interests, and healthy leisure) and substance use (cigarettes, alcohol, and marijuana) behaviors and to investigate the ways in which changes in leisure experiences predict changes in substance use behaviors over time. Results indicated that adolescents’ substance use increased significantly across adolescence, but that leisure experiences remained fairly stable over time. We also found that adolescent leisure experiences predicted baseline substance use and that changes in leisure experiences predicted changes in substance use behaviors over time, with leisure boredom emerging as the most consistent and strongest predictor of alcohol, cigarette, and marijuana use. Implications for interventions that target time use and leisure experiences are discussed.
Sulfate-reducing bacteria are important players in the global sulfur cycle and of considerable commercial interest. The draft genome sequence of a sulfate-reducing bacterium of the family ...Desulfobacteraceae, assembled from a sulfate-reducing bioreactor metagenome, indicates that heavy-metal- and acid-resistance traits of this organism may be of importance for its application in acid mine drainage mitigation.
•We evaluated using real patient data, across multiple sample sizes, the degree that data-driven methods result in selection of inaccurate optimal cutoffs and bias in accuracy estimates.•We found ...that the optimal EPDS cutoffs identified in samples of different sizes varied widely, ranging from ≥ 5 to ≥ 17 for studies with n = 100 and ≥ 8 to ≥ 13 for n = 1,000.•We also found that the accuracy estimates were often overstated with mean overestimation of sensitivity and underestimation of specificity, respectively, of 6.5 percentage point (pp) and −1.3pp for n = 100 and 1.4pp and −1.0pp for n = 1000.•Researchers should avoid making recommendations about cutoffs to use in practice and accuracy when reporting results from small studies.•Clinicians should only select cutoffs generated from well-conducted meta-analyses or those that are identified consistently across multiple studies.
To evaluate, across multiple sample sizes, the degree that data-driven methods result in (1) optimal cutoffs different from population optimal cutoff and (2) bias in accuracy estimates.
A total of 1,000 samples of sample size 100, 200, 500 and 1,000 each were randomly drawn to simulate studies of different sample sizes from a database (n = 13,255) synthesized to assess Edinburgh Postnatal Depression Scale (EPDS) screening accuracy. Optimal cutoffs were selected by maximizing Youden's J (sensitivity+specificity–1). Optimal cutoffs and accuracy estimates in simulated samples were compared to population values.
Optimal cutoffs in simulated samples ranged from ≥ 5 to ≥ 17 for n = 100, ≥ 6 to ≥ 16 for n = 200, ≥ 6 to ≥ 14 for n = 500, and ≥ 8 to ≥ 13 for n = 1,000. Percentage of simulated samples identifying the population optimal cutoff (≥ 11) was 30% for n = 100, 35% for n = 200, 53% for n = 500, and 71% for n = 1,000. Mean overestimation of sensitivity and underestimation of specificity were 6.5 percentage point (pp) and -1.3 pp for n = 100, 4.2 pp and -1.1 pp for n = 200, 1.8 pp and -1.0 pp for n = 500, and 1.4 pp and -1.0 pp for n = 1,000.
Small accuracy studies may identify inaccurate optimal cutoff and overstate accuracy estimates with data-driven methods.
Breast cancer survival rates are lower for African American women than for white women. Obesity, high-fat diets, and lack of regular physical activity increase risk for breast cancer recurrence, ...comorbid conditions, and premature death. Eighty-two percent of African American women are overweight or obese, partly because of unhealthy eating and exercise patterns. Although successful weight loss and lifestyle interventions for breast cancer survivors are documented, none has considered the needs of African American breast cancer survivors. This study assessed the feasibility and impact of Moving Forward, a culturally tailored weight loss program for African American breast cancer survivors.
The study used a pre-post design with a convenience sample of 23 African American breast cancer survivors. The 6-month intervention was theory-based and incorporated qualitative data from focus groups with the targeted community, urban African American breast cancer survivors. Data on weight, body mass index (BMI), diet, physical activity, social support, and quality of life were collected at baseline and at 6 months.
After the intervention, we noted significant differences in weight, BMI, dietary fat intake, vegetable consumption, vigorous physical activity, and social support.
This is the first published report of Moving Forward, a weight loss intervention designed for African American breast cancer survivors. Although a randomized trial is needed to establish efficacy, the positive results of this intervention suggest that this weight loss intervention may be feasible for African American breast cancer survivors. Lifestyle interventions may reduce the disparities in breast cancer mortality rates.
Although pertussis is increasingly recognized as a cause of prolonged cough illness in adolescents and adults, its prevalence is not well established. We evaluated pertussis infection in 442 ...adolescents and adults ⩾12 years old (mean age, 41.3 years) who had a cough-related illness of 7–56 days' duration. For 4 patients (0.9%), results of nasopharyngeal culture or PCR were positive for Bordetella pertussis; for 10 patients (2.3%), either results of culture or PCR were positive or pertussis antibody titers increased 4-fold. Eighty-eight patients (19.9%) had either laboratory-confirmed pertussis or laboratory evidence of pertussis. These patients had significantly longer duration of cough than did patients without laboratory evidence of pertussis (56 days vs. 46 days), and more of them had vomiting with cough (45.5% vs. 28.5%, respectively). Pertussis is a common cause of prolonged cough illness in adolescents and adults and is frequently associated with other symptoms of whooping cough.
Print pharmaceutical advertisements in the United States require inclusion of a brief summary of side effects, warnings, precautions, and contraindications from the labeling. The full package insert, ...which sponsors have traditionally used to fulfill the brief summary requirement, does not adhere to health literacy best practices, limiting its value to consumers. This study compared the understandability and usability of brief summaries in 3 formats designed to be more consumer friendly.
Three brief summary formats were tested: (1) 2-column "Question and Answer"; (2) "Prescription Drug Facts Box," similar to current US over-the-counter drug facts labeling; and (3) "Health Literacy," based on clear communication principles. Researchers evaluated the formats using the Suitability Assessment of Materials (SAM) tool and conducted structured, scripted, one-on-one interviews (usability tests) with participants with estimated low to average education levels. This research was replicated across 2 therapeutic areas (type 2 diabetes and plaque psoriasis).
SAM scores showed that the Health Literacy format outperformed the Question and Answer format and the Prescription Drug Facts Box format in both therapeutic areas, with both Health Literacy brief summaries rated on the SAM as "superior." Qualitative usability tests supported the SAM findings, with the Health Literacy format preferred consistently over the Question and Answer format, and more often than not over the Prescription Drug Facts Box format.
Sponsors can employ a user-tested Health Literacy format to improve the understandability and usability of brief summaries with patients.
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