An Examination of Gender Differences in the National Diabetes Prevention Program's Lifestyle Change Program.

PURPOSE: The purpose of the study was to examine how gender was related to enrollment and number of sessions attended in the National Diabetes Prevention Program's Lifestyle Change Program (DPP LCP). METHODS: To better understand program uptake, a population of those who would be eligible for the LCP was compared to those who enrolled. Estimates of those eligible were computed using data from the National Health and Nutrition Examination Survey, whereas enrollment and sessions attended were computed using data from the Centers for Disease Control and Prevention's Diabetes Prevention Recognition Program. RESULTS: Results revealed that although similar numbers of males and females were eligible for the program, only 39 321 males versus 121 007 females had enrolled in the National DPP LCP by the end of 2017 (odds ratio = 3.20; 95% CI, 3.17-3.24). The gender differences persisted even when stratifying by age or race/ethnicity. In contrast, no significant gender differences were found between the average number of sessions attended for males (14.0) and females (13.8). DISCUSSION: Results of the study can help inform efforts to market and tailor programs to appeal more directly to men and other groups that are underrepresented in the National DPP LCP.

DeepRiPP integrates multiomics data to automate discovery of novel ribosomally synthesized natural products.

Microbial natural products represent a rich resource of evolved chemistry that forms the basis for the majority of pharmacotherapeutics. Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a particularly interesting class of natural products noted for their unique mode of biosynthesis and biological activities. Analyses of sequenced microbial genomes have revealed an enormous number of biosynthetic loci encoding RiPPs but whose products remain cryptic. In parallel, analyses of bacterial metabolomes typically assign chemical structures to only a minority of detected metabolites. Aligning these 2 disparate sources of data could provide a comprehensive strategy for natural product discovery. Here we present DeepRiPP, an integrated genomic and metabolomic platform that employs machine learning to automate the selective discovery and isolation of novel RiPPs. DeepRiPP includes 3 modules. The first, NLPPrecursor, identifies RiPPs independent of genomic context and neighboring biosynthetic genes. The second module, BARLEY, prioritizes loci that encode novel compounds, while the third, CLAMS, automates the isolation of their corresponding products from complex bacterial extracts. DeepRiPP pinpoints target metabolites using large-scale comparative metabolomics analysis across a database of 10,498 extracts generated from 463 strains. We apply the DeepRiPP platform to expand the landscape of novel RiPPs encoded within sequenced genomes and to discover 3 novel RiPPs, whose structures are exactly as predicted by our platform. By building on advances in machine learning technologies, DeepRiPP integrates genomic and metabolomic data to guide the isolation of novel RiPPs in an automated manner.

Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation.

BACKGROUND: For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. OBJECTIVE: The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. METHODS: We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. RESULTS: Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). CONCLUSIONS: The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.

Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review.

BACKGROUND: Folate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data. METHODS AND FINDINGS: We conducted a systematic review and searched multiple databases for NTD prevalence estimates and abstracted data from peer-reviewed literature, birth defects surveillance registries, and reports published between January 1990 and July 2014 that had greater than 5,000 births and were not solely based on mortality data. We classified countries according to World Health Organization (WHO) regions and World Bank income classifications. The initial search yielded 11,614 results; after systematic review we identified 160 full text manuscripts and reports that met the inclusion criteria. Data came from 75 countries. Coverage by WHO region varied in completeness (i.e., % of countries reporting) as follows: African (17%), Eastern Mediterranean (57%), European (49%), Americas (43%), South-East Asian (36%), and Western Pacific (33%). The reported NTD prevalence ranges and medians for each region were: African (5.2-75.4; 11.7 per 10,000 births), Eastern Mediterranean (2.1-124.1; 21.9 per 10,000 births), European (1.3-35.9; 9.0 per 10,000 births), Americas (3.3-27.9; 11.5 per 10,000 births), South-East Asian (1.9-66.2; 15.8 per 10,000 births), and Western Pacific (0.3-199.4; 6.9 per 10,000 births). The presence of a registry or surveillance system for NTDs increased with country income level: low income (0%), lower-middle income (25%), upper-middle income (70%), and high income (91%). CONCLUSIONS: Many WHO member states (120/194) did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.

Self-Reported Prevalence of Alcohol Screening Among U.S. Adults.

INTRODUCTION: The U.S. Preventive Services Task Force recommends for adults alcohol screening and brief behavioral counseling interventions in primary care settings. However, there is a paucity of population-based data on the prevalence of alcohol screening. This study examines adherence to this U.S. Preventive Services Task Force recommendation by estimating the prevalence of alcohol screening by demographic characteristics and binge drinking. METHODS: A cross-sectional analysis was conducted in 2013 and 2014 on data from the 2013 fall wave of the ConsumerStyles survey. ConsumerStyles is drawn from an Internet panel randomly recruited by probability-based sampling to be representative of the U.S. POPULATION: Data from 2,592 adult respondents who visited primary care physicians in the last year were analyzed to determine the prevalence of alcohol screening. RESULTS: Only 24.7% of respondents reported receiving alcohol screening. The prevalence of screening was similar among women (24.9%) and men (24.5%). Black non-Hispanics reported a significantly lower prevalence of screening than white non-Hispanics (16.2% vs 26.9%, prevalence ratio=0.60, 95% CI=0.40, 0.90). College graduates reported a significantly higher prevalence of screening than respondents with a high school degree or less (28.1% vs 20.8%, prevalence ratio=1.35, 95% CI=1.08, 1.69). CONCLUSIONS: Only about one in four respondents who visited a primary care physician in the last year reported being screened for alcohol misuse. Therefore, many men and women who misuse alcohol are unlikely to be identified. Increased screening may help reduce alcohol misuse and related negative health outcomes.

Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines.

Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 µg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention.

Characteristics and behaviors of mothers who have a child with fetal alcohol syndrome.

Fetal alcohol syndrome (FAS) is a leading cause of birth defects and developmental disabilities. The objective of this study was to identify the characteristics and behaviors of mothers of children with FAS in the United States using population-based data from the FAS Surveillance Network (FASSNet). FASSNet used a multiple source methodology that identified FAS cases through passive reporting and active review of records from hospitals, specialty clinics, private physicians, early intervention programs, Medicaid, birth certificates and other vital records, birth defects surveillance programs, and hospital discharge data. The surveillance included children born during January 1, 1995-December 31, 1997. In the four states included in our analysis - Arizona, New York, Alaska, and Colorado - there were 257 confirmed cases and 96 probable cases for a total of 353 FAS cases. Compared to all mothers in the states where surveillance occurred, mothers of children with FAS were significantly more likely to be older, American Indians/Alaska Natives, Black, not Hispanic, unmarried, unemployed, and without prenatal care, to smoke during pregnancy, to have a lower educational level, and to have more live born children. A significant proportion of mothers (9-29%) had another child with suspected alcohol effects. Compared to all US mothers, they were also significantly more likely to be on public assistance, to be on Medicaid at their child's birth, to have received treatment for alcohol abuse, to have confirmed alcoholism, to have used marijuana or cocaine during pregnancy, to have their baby screen positive for alcohol or drugs at birth, to have had an induced abortion, to have had a history of mental illness, to have been involved in binge drinking during pregnancy, and to have drunk heavily (7 days/week) during pregnancy. These findings suggest that it is possible to identify women who are at high risk of having a child with FAS and target these women for interventions.

Lack of evidence for human herpesvirus-8 transmission via blood transfusion in a historical US cohort.

BACKGROUND: Recent studies have found evidence of occasional human herpesvirus (HHV)-8 transmission via blood transfusion. However, because these studies were conducted outside the United States or did not have linked donor-recipient pairs, they have a limited ability to inform US blood-banking policy. METHODS: We investigated HHV-8 transmission via blood transfusion in the United States by conducting HHV-8 serologic testing among participants of the Transfusion-Transmitted Viruses Study (TTVS), who enrolled during the 1970s. RESULTS: HHV-8 seroprevalence was 2.8% (29/1023) among blood donors, 7.1% (96/1350) among transfusion recipients, 7.7% (46/599) among surgical control patients who did not receive transfusions, and 96.3% (77/80) among control patients with Kaposi sarcoma. One transfusion recipient seroconverted (0.08% [1/1259]), but this patient did not receive any HHV-8-seropositive blood units, suggesting that the infection was not related to blood transfusion. One of the surgical control patients who did not receive transfusions also seroconverted (0.18% [1/556]). Rates of seroconversion were 1.6 per 1000 person-years (95% confidence interval [CI], 0.04-8.9 per 1000 person-years) for the transfusion recipients and 3.6 per 1000 person-years (95% CI, 0.09-20.1 per 1000 person-years) for the surgical control patients who did not receive transfusions (P = .61). CONCLUSIONS: Rates of HHV-8 seroconversion in the transfusion and nontransfusion groups were not statistically different, and the historical nature of the cohort (e.g., before leukoreduction) suggests that any current transmission via blood transfusion is rare.

Human herpesvirus 8 presence and viral load are associated with the progression of AIDS-associated Kaposi's sarcoma.

OBJECTIVE: We present the largest longitudinal study to date that examines the association between Kaposi's Sarcoma (KS) disease progression and the presence and viral load of human herpesvirus 8 (HHV-8). METHODS: Ninety-six men were enrolled at HIV clinics in Atlanta, Georgia, who had KS (n = 47) or were without KS but seropositive for HHV-8. Visits occurred at 6-month intervals for 2 years at which the patient's KS status was evaluated and oral fluid and blood were collected for quantification of HHV-8 DNA and antibodies. RESULTS: The presence of HHV-8 DNA in blood was more common (P < 0.001) and the viral load higher (P < 0.001) in men with KS in comparison with men without KS. Mean HHV-8 viral loads in blood and oral fluids were associated with disease status, being highest among patients with progressing KS, intermediate among patients with stable KS, and lowest among patients with regressing KS. Consistent with our previous report high antibody titers to HHV-8 orf 65 were inversely associated with HHV-8 shedding in oral fluid. CONCLUSIONS: We observed a significant association between changes in KS disease severity and the presence and viral load of HHV-8. HHV-8 viral load in blood may provide useful information to clinicians for assessment of the risk of further disease progression in patients with KS.

Possible transmission of human herpesvirus-8 by blood transfusion in a historical United States cohort.

BACKGROUND: Transmission of human herpesvirus-8 (HHV-8) by blood transfusion in the United States appears plausible but has not been demonstrated. The objective of this study was to evaluate evidence of HHV-8 transmission via blood transfusion. STUDY DESIGN AND METHODS: Serum specimens were collected before and 6 months after surgery from 406 patients who enrolled in the Frequency of Agents Communicable by Transfusion study (FACTS) in Baltimore, Maryland, from 1986 to 1990. The change in HHV-8 serostatus was measured by a lytic-antigen immunofluorescence assay. RESULTS: Of the 284 patients who were initially HHV-8-seronegative and who received transfusions, 2 seroconverted, 1 with a postsurgery antibody titer of 1:160 and the other with a titer of 1:1280. These patients received 12 and 13 units of blood, respectively. None of the HHV-8-seronegative patients who did not receive transfusions seroconverted. If seroconversion was caused by transfused blood, the transmission risk per transfused component was 0.082 percent. CONCLUSIONS: This is the first report suggesting transmission of HHV-8 via blood components in the United States. Because linked donor specimens were not available, other routes of transmission cannot be excluded; however, the evidence is consistent with infection being caused by transfusion. Future studies should include contemporary US populations with linked donor specimens and populations at higher risk for HHV-8 infection.

Evidence for both lytic replication and tightly regulated human herpesvirus 8 latency in circulating mononuclear cells, with virus loads frequently below common thresholds of detection.

To address whether human herpesvirus 8 (HHV-8) DNA in peripheral blood mononuclear cells (PBMCs) might be the product of latent or lytic infection and to shed light on sporadic detection of HHV-8 DNA in individuals seropositive for the virus, we studied the frequency of infected cells, total virus load, and virus load per infected cell in PBMCs from men coinfected with HHV-8 and human immunodeficiency virus (HIV), some of whom had Kaposi's sarcoma. The low frequencies of infected cells detected (fewer than one per million cells in some individuals) suggest that the prevalence of the virus in circulating leukocytes was underestimated in previous studies that employed more conventional sampling methods (single, small-volume specimens). Mean virus loads ranged from 3 to 330 copies per infected PBMC; these numbers can represent much higher loads in individual lytically infected cells (>10(3) genomes/cell) in mixtures that consist predominantly of latently (relatively few genomes) infected cells. The presence in some subjects of high HHV-8 mean genome copy numbers per infected cell, together with viral DNA being found in plasma only from subjects with positive PBMCs, supports earlier suggestions that the virus can actively replicate in PBMCs. In some individuals, mean virus loads were less than 10 genomes per infected cell, suggesting a tightly controlled purely latent state. HHV-8 genome copy numbers are substantially higher in latently infected cells derived from primary effusion lymphomas; thus, it appears that HHV-8 is able to adopt more than one latency program, perhaps analogous to the several types of Epstein-Barr virus latency.

Repeated measures study of human herpesvirus 8 (HHV-8) DNA and antibodies in men seropositive for both HHV-8 and HIV.

OBJECTIVE: To study the natural history and pathogenesis of human herpesvirus 8 (HHV-8) infection in HHV-8-seropositive, immunosuppressed men. DESIGN: Longitudinal study of 87 HHV-8- and HIV-seropositive men [42 with Kaposi's sarcoma (KS)] during four visits over a 2 month period. METHODS: : Patients provided oral fluid and blood. HHV-8 antibody titers were measured with peptide-based enzyme-linked immunosorbent assays (ELISA) for ORF65 and K8.1; HHV-8 DNA was detected with polymerase chain reaction ELISA. RESULTS: HHV-8 DNA was present in oral fluid or peripheral blood mononuclear cells (PBMC) at one or more of the four visits in 71% of men with KS and 56% of men without KS. The strongest correlate of HHV-8 DNA in PBMC was the presence of KS [odds ratio (OR), 8.7; 95% confidence interval (CI), 3.4-22]. Detection of HHV-8 DNA in oral fluid or PBMC was often intermittent, but individuals who shed virus at one time point were more likely to shed at other times. Some men had incomplete epitope recognition in their anti-HHV-8 antibody response. High antibody titers were associated with the absence of circulating HHV-8, particularly for the ORF65 seroassay (OR, 0.16; 95% CI, 0.05-0.51). CONCLUSIONS: Among HHV-8 seropositive men, circulating virus is common even in the absence of disease. The link between KS and HHV-8 DNA in PBMC suggests that anti-herpes drugs may impede KS development or progression. Seroassays should target multiple epitopes to achieve maximal sensitivity. HHV-8 replication may be limited by high antibody titers or other immune function for which antibodies are a marker.

Human herpesvirus 8: current issues.

Although human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi sarcoma (KS), there are no formal guidelines for the clinical management of HHV-8 infection. In patients infected with human immunodeficiency virus (HIV), highly active antiretroviral therapy (HAART) is the best tool for the prevention of KS. In patients who have undergone transplantation, KS is often managed by curtailing immunosuppressive therapies, despite the potential adverse consequences for graft survival. Interventions related to HHV-8 infection might improve the management of KS in immunocompromised patients. However, knowledge from HHV-8 research cannot yet be translated into clinically useful interventions. Achieving clinical utility will require the commercial development of diagnostic tools currently available only in research settings and the evaluation of potential interventions. Such interventions might include the use of HHV-8 diagnostics to identify patients at high risk and to aid in the early detection of KS, prophylaxis with antiherpes drugs to prevent KS, treatment of KS with antiherpes drugs, and donor/recipient screening for organ transplantation.

Prevalence of and risk factors for viral infections among human immunodeficiency virus (HIV)-infected and high-risk HIV-uninfected women.

Viruses that can persist in the host are of special concern in immunocompromised populations. Among 871 human immunodeficiency virus (HIV)-infected and 439 high-risk HIV-uninfected women, seroprevalences of cytomegalovirus, hepatitis B virus, hepatitis C virus, and herpes simplex virus types 1 and 2 and prevalence of human papillomavirus DNA in cervicovaginal lavage fluids were all >50% and were 2-30 times higher than prevalences in the general population. Prevalences were highest among HIV-infected women, of whom 44.2% had >or=5 other infections, and were relatively high even among the youngest women (age 16-25 years). In multivariate analyses, viral infections were independently associated not only with behaviors such as injection drug use and commercial sex but also with low income, low levels of education, and black race. Disadvantaged women and women who engage in high-risk behaviors are more likely to be coinfected with HIV and other viruses and, thus, may be at high risk of serious disease sequelae.

Risk factors for Kaposi's sarcoma in men seropositive for both human herpesvirus 8 and human immunodeficiency virus.

OBJECTIVE: To identify risk factors for Kaposi's sarcoma (KS) among men seropositive for both human herpesvirus 8 (HHV-8) and HIV. DESIGN: Cross-sectional study of 91 HHV-8 seropositive, HIV seropositive men who have sex with men (57 with KS), and 70 controls at lower risk for KS. METHODS: Patients received clinical evaluations. Blood, oral fluids, semen, rectal brush, rectal swab, and urine were collected, and tests for HHV-8 were performed. RESULTS: Men with KS were more likely to have HHV-8 DNA in peripheral blood mononuclear cells (PBMC) than men without KS [35.1 versus 5.9%, odds ratio (OR), 8.6, 95% confidence interval (CI), 1.9-39.9]. The prevalence of HHV-8 DNA in oral fluids was similar for the two groups (37.0 versus 32.4%; OR, 1.2; 95% CI, 0.5-3.0). HHV-8 DNA was rarely detected in specimens of other types from these men, or in any specimens from the 70 controls. Among men with KS, HHV-8 DNA in PBMC was associated with new KS lesions (OR, 4.5; 95% CI, 1.4-14.5), and HHV-8 DNA in oral fluids was associated with oropharyngeal KS lesions (OR, 3.1; 95% CI, 1.0-10.1). Men with high HHV-8 antibody titers were more likely to have KS (OR, 9.6; 95% CI, 1.2-78.2), but were less likely to have new KS lesions (OR, 0.2; 95% CI, 0.0-1.1) or HHV-8 DNA in PBMC (OR, 0.2; 95% CI, 0.0-1.6) or oral fluids (OR, undefined; = 0.001). CONCLUSIONS: In HHV-8- and HIV-seropositive men, HHV-8 DNA is associated with KS. Among men without KS, HHV-8 DNA is most commonly found in oral fluids. High HHV-8 antibody titers may protect against circulating HHV-8 and new KS lesions.

Nutritional gains of underprivileged children attending a day care center in Säo Paulo City, Brazil: a nine month follow-up study

Avaliou-se a eficácia da frequência da creche padräo em promover recuperaçäo nutricional de crianças pertencentes a famílias de baixa renda. Foram coletados dados, por um período de nove meses, de 180 crianças que frequentavam uma creche localizada em uma favela. Em todos os dias úteis cada criança recebia no mínimo 100 por cento das recomendaçöes dietéticas diárias, acrescidas de leite fortificado para parasitoses intestinais. As análises estatísticas se limitaram a 168 crianças (93 por cento) para as quais se dispunham de medidas de pelo menos cinco meses. Como variáveis resposta, os escores Z das relaçöes peso para estatura, estatura para idade e peso para idade foram dicotomizados de forma que escore Z < -1 indicava risco nutricional. Foram estudadas as proporçöes de crianças em risco nutricional a cada mês e utilizadas técnicas estatísticas multivariadas para controlar eventuais fatores de confundimento e correlaçäo entre as medidas subsequentes da mesma criança. O percentual de crianças em risco nutricional diminuiu no decorrer do acompanhamento, de 10,1 por cento para 3,4 por cento na relaçäo peso estatura, de 29,8 por cento para 15,2 por cento na peso idade e de 50,0 por cento para 44,8 por cento na estatura idade. A maior parte das reduçöes ocorreram entre os terceiros e quarto meses de freqüência. Os modelos de dados correlacionados para as três vezes nos riscos nutricionais descritos pelos indicadores de peso-estatura (wasting) e peso-idade (underweight). Concluimos que a creche padräo diminui riscos nutricionais, sendo necessários aproximadamente quatro meses para que os benefícios sejam identificados