Risk behavioral survey in the sample of Slovak adolescents.

OBJECTIVE: The study was aimed to assess risky behavioral factors in the sample of Slovak adolescents. BACKGROUND: Health-risk behavior contributes to the leading causes of morbidity and mortality among youth and adults. MATERIALS AND METHODS: The Youth and Parents Risk Factor Behavior Survey (YABS), based on bilateral US-Slovak project, is an ongoing cross-sectional school-based survey initiated in Bratislava as a model region. There were 798 questionnaires for students distributed; the response rate was 64 %. The sample involved 525 adolescents aged 15‒19 years from eight selected secondary schools in Bratislava, 38 % boys and 62 % girls. More than 90 % of fathers and mothers were employed, but some families nevertheless experienced a lack of finances (48.1 %), almost 70 % of students were from complete families. RESULTS: The study revealed a very high prevalence of risky behavioral characteristics in this pilot sample of adolescents significantly related to age, gender, type of school, completeness of the family and lower parental education.  CONCLUSION: The most important health risk behaviors were identified (tobacco, alcohol, drug consumption, violence, risky sexual behavior, inadequate sleep, physical inactivity, and excessive IT devices use). Targeted intervention proposals will be suggested in future (Tab. 5, Ref. 42).

Midwakh/dokha tobacco use in the Middle East: much to learn.

Many alternative tobacco products (ATPs), such as hookahs, have grown in popularity and use beyond their locale of origin and are therefore becoming a significant global public health concern. This article provides an overview of an under-reported and understudied ATP, dokha, which is smoked in a midwakh pipe. It describes the state of tobacco control in the Arabian Gulf region where midwakh smoking appears to be most common, the history of midwakh and dokha use, and what is known about midwakh smoking from the published literature. On the basis of the stark lack of data on midwakh use, we suggest priority areas to focus future research. Preliminary data and observations from health providers and the public health sector suggest that midwakh smoking may pose challenges to the tobacco control efforts in the Arabian Gulf region. If it is emerging as a new ATP outside this region, there could be a significant impact on tobacco control strategies globally.

Household exposure to secondhand smoke is associated with decreased physical and mental health of mothers in the USA.

Secondhand smoke is one of the most common toxic environmental exposures to children, and maternal health problems also have substantial negative effects on children. We are unaware of any studies examining the association of living with smokers and maternal health. To investigate whether non-smoking mothers who live with smokers have worse physical and mental health than non-smoking mothers who live in homes without smokers. Nationally representative data from the 2000-2004 Medical Expenditure Panel Survey were used. The health of non-smoking mothers with children <18 years (n = 18,810) was assessed, comparing those living with one or more smokers (n = 3,344) to those living in households with no adult smokers (n = 14,836). Associations between maternal health, household smoking, and maternal age, race/ethnicity, and marital, educational, poverty and employment status were examined in bivariable and multivariable analyses using SUDAAN software to adjust for the complex sampling design. Scores on the Medical Outcomes Short Form-12 (SF-12) Physical Component Scale (PCS) and Mental Component Scale (MCS) were used to assess maternal health. About 79.2% of mothers in the USA are non-smokers and 17.4% of them live with ≥1 adult smokers: 14.2% with 1 and 3.2% with ≥2 smokers. Among non-smoking mothers, the mean MCS score is 50.5 and mean PCS is 52.9. The presence of an adult smoker and increasing number of smokers in the home are both negatively associated with MCS and PCS scores in bivariable analyses (P < 0.001 for each). Non-smoking mothers with at least one smoker in the household had an 11% (95% CI = 0.80-0.99) lower odds of scoring at or above the mean MCS score and a 19% (95% CI = 0.73-0.90) lower odds of scoring at or above the mean PCS score compared to non-smoking mothers with no smokers in the household. There is an evidence of a dose response relationship with increasing number of smokers in the household for PCS (P < 0.001). These findings demonstrate a previously unrecognized child health risk: living with smokers is independently associated with worse physical and mental health among non-smoking mothers.

Caries status and overweight in 2- to 18-year-old US children: findings from national surveys.

BACKGROUND: The prevalence of overweight children in the United States continues to increase. OBJECTIVES: To examine the relationship between being overweight and caries in primary and permanent dentition in a nationally representative sample of children. METHODS: Data from the NHANES III (1988-1994) were analyzed using logistic regression and controlling for potential confounders for 10 180 children 2-18 years of age and from the NHANES 1999-2002 for 7568 children 2-18 years of age. RESULTS: For children 2-5 years of age, there was no difference in caries experience among normal weight, at risk for overweight or overweight children for NHANES III and for NHANES 1999-2002. For children 6-11 years of age (NHANES III), at risk for overweight and overweight children were less likely to have caries experience in the primary dentition than normal weight children; overweight children were less likely to have caries experience in the permanent dentition than normal weight children. For children 12-18 years of age (NHANES III), overweight children were less likely to have caries experience in the permanent dentition than normal weight children. For children 6-11 years of age and 12-18 years of age (NHANES 1999-2002), there was no difference in having caries experience among normal, at risk for overweight and overweight children. CONCLUSIONS: The data from NHANES III and NHANES 1999-2002 provide no evidence to suggest that overweight children are at an increased risk for dental caries. Although no differences in caries rates by weight were found in younger children, interestingly results from NHANES III suggest that being overweight may be associated with decreased rates of caries in older children.

Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding protein 2 into aggresomes.

Sequence-specific single-stranded DNA-binding protein 2 (SSBP2) is a candidate tumor suppressor for human acute myelogenous leukemia (AML). Inducible expression of SSBP2 causes growth arrest and partial differentiation in AML cells. Here, we report that the adenoviral oncoprotein E1B55K directly binds to endogenous SSBP2 protein and sequesters it into juxtanuclear bodies in adenovirally transformed human embryonic kidney (HEK) 293 cells. Similarly, transient expression of E1B55K in IMR90 fibroblasts and HeLa cells result in the formation of juxtanuclear bodies containing SSBP2. When nuclear export of E1B55K is prevented, SSBP2 remains associated with E1B55K in nuclear foci. A requirement for intact microtubules to retain the integrity of the juxtanuclear bodies suggests them to be E1B55K containing aggresomes. The adenoviral E1B55K protein has been shown to localize to the Mre11 complex and p53 to aggresome structures; together with the viral E4orf6 protein, E1B55K recruits a cellular E3 ubiquitin ligase that induces degradation of Mre11 and p53. However, our present studies reveal that E1B55K does not degrade SSBP2. These data demonstrate that E1B55K targets the candidate leukemia suppressor SSBP2 and suggest that subverting its function may contribute to cell transformation by viral oncoproteins.

Progressive severe visual loss after long-term withdrawal from thioridazine treatment.

PURPOSE: To report advanced thioridazine-induced retinopathy in a 50-year-old woman with evidence of progressive severe loss of vision over 30 years after withdrawal from thioridazine treatment. METHODS: The ocular fundus examination revealed areas of retinal pigment epithelium (RPE) clumping as well as generalized atrophy of the RPE and choroid. The patient experienced visual loss to the level of no light perception in both eyes despite the fact that the funduscopic appearances of her optic nerves and retinal vasculature remained relatively normal. CONCLUSIONS: This case demonstrates that severe progressive visual loss can occur several years after the cessation of chronic thioridazine treatment.

Effectiveness of influenza vaccine for the prevention of asthma exacerbations.

BACKGROUND: There is a lack of clinical evidence that annual vaccination against influenza prevents asthma exacerbations in children. METHODS: Retrospective cohort study of 800 children with asthma, where one half did, and the other half did not receive the influenza vaccine. The two groups were compared with respect to clinic visits, emergency department (ED) visits, and hospitalisations for asthma. In multivariable analyses, adjustment was made for baseline asthma severity, prior utilisation of health services, receipt of vaccine in the previous year, and demographic variables. RESULTS: After adjusting for other variables, the vaccine group had a significantly increased risk of asthma related clinic visits and ED visits (odds ratios 3.4 and 1.9, respectively). CONCLUSION: This study failed to provide evidence that the influenza vaccine prevents paediatric asthma exacerbations.

A genetic screen identifies a cellular regulator of adeno-associated virus.

Adeno-associated virus type 2 (AAV2) is a human parvovirus that has attracted attention as a vector for gene transfer. Replication and site-specific integration of the wild-type virus requires binding of the AAV2 Rep proteins to a cis-regulatory element named the Rep recognition sequence (RRS). RRS motifs are found within the cellular AAVS1 integration locus, the viral p5 promoter, and the inverted terminal repeats (ITRs). Here we report the design of a genetic screen based on the yeast one-hybrid assay to identify cellular RRS-binding proteins. We show that the human zinc finger 5 protein (ZF5) binds specifically to RRS motifs in vitro and in vivo. ZF5 is a highly conserved and ubiquitously expressed transcription factor that contains five C-terminal zinc fingers and an N-terminal POZ domain. Ectopic expression of ZF5 leads to an ITR-dependent repression of the autologous p5 promoter and reduces both AAV2 replication and the production of recombinant AAV2. By using deletion and substitution mutants we show that two different domains of ZF5 contribute to AAV2 repression. Negative regulation of the p5 promoter requires the POZ domain, whereas viral replication is inhibited by the zinc finger domain, likely by competing with Rep for binding to the ITR. Identification and characterization of proteins that bind the ITR, the only viral genetic element retained in AAV2 vectors, will lead to new insights into the unique life cycle of AAV2 and will suggest improvements important for its application as a gene therapy vector.

Rep-dependent initiation of adeno-associated virus type 2 DNA replication by a herpes simplex virus type 1 replication complex in a reconstituted system.

Productive infection by adeno-associated virus type 2 (AAV) requires coinfection with a helper virus, e.g., adenovirus or herpesviruses. In the case of adenovirus coinfection, the replication machinery of the host cell performs AAV DNA replication. In contrast, it has been proposed that the herpesvirus replication machinery might replicate AAV DNA. To investigate this question, we have attempted to reconstitute AAV DNA replication in vitro using purified herpes simplex virus type 1 (HSV-1) replication proteins. We show that the HSV-1 UL5, UL8, UL29, UL30, UL42, and UL52 gene products along with the AAV Rep68 protein are sufficient to initiate replication on duplex DNA containing the AAV origins of replication, resulting in products several hundred nucleotides in length. Initiation can occur also on templates containing only a Rep binding site and a terminal resolution site. We further demonstrate that initiation of DNA synthesis can take place with a subset of these factors: Rep68 and the UL29, UL30, and UL42 gene products. Since the HSV polymerase and its accessory factor (the products of the UL30 and UL42 genes) are unable to efficiently perform synthesis by strand displacement, it is likely that in addition to creating a hairpin primer, the AAV Rep protein also acts as a helicase for DNA synthesis. The single-strand DNA binding protein (the UL29 gene product) presumably prevents reannealing of complementary strands. These results suggest that AAV can use the HSV replication apparatus to replicate its DNA. In addition, they may provide a first step for the development of a fully reconstituted AAV replication assay.

Where do adolescents get their condoms?

PURPOSE: To determine where adolescents obtain their condoms; the availability and accessibility of condoms; condom availability in relationship to different sexually transmitted disease (STD) rates; and the availability of safer sex information in places where condoms are sold. METHODS: We conducted a random digit-dialed telephone survey of 259 14-19-year-old adolescents in Monroe County, New York. Self-reported health services use, knowledge and use of confidential services, and where adolescents obtained or intended to obtain condoms were assessed. Research assistants visited all retail establishments in five areas of similar population size with gonorrhea rates from 887 to 12,427 per 100,000 adolescents to assess how available and accessible condoms were in each store. Perceived access and actual condom availability and accessibility were compared using Chi-square and Student's t-tests. RESULTS: Trained interviewers dialed 11,800 numbers in 1993, identifying 4449 (40%) households among 11,065 numbers reached successfully. Of these, 393 (8.8%) had eligible adolescents and 259 (66%) completed interviews. Most adolescents reported obtaining, or planning to obtain, condoms in stores rather than from free health care settings. Adolescents who have used condoms more often reported having obtained them without cost than having purchased them. Condoms were available at 101 (83%) of 122 stores identified. All drug stores and 75% of supermarkets sold condoms and displayed them openly. Most small grocery stores also sold condoms (92%), but were less likely to openly display them. No stores displayed or provided safer sex information. Areas with higher STD rates had more stores (p <.01), and more stores that sold condoms (p <.01). There was no difference in condom cost by area. CONCLUSIONS: Many adolescents obtain their condoms in retail stores. Condom accessibility varied by store type and area STD rate. Increasing condom visibility in private grocery stores may increase the accessibility of condoms to adolescents in areas with highest STD rates.

Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids.

The human parvovirus adeno-associated virus type 2 (AAV-2) possesses many features that make it an attractive vector for gene delivery in vivo. However, its broad host range may limit its usefulness and effectivity in several gene therapy applications in which transgene expression needs to be limited to a specific organ or cell type. In this study, we explored the possibility of directing recombinant AAV-2 transduction by incorporating targeting peptides previously isolated by in vivo phage display. Two putative loops within the AAV-2 capsid were examined as sites for incorporation of peptides. We tested the effects of deleting these loops and different strategies for the incorporation of several targeting peptides. The tumor-targeting sequence NGRAHA and a Myc epitope control were incorporated either as insertions or as replacements of the original capsid sequence. Viruses were assessed for packaging, accessibility of incorporated peptides, heparin binding, and transduction in a range of cell lines. Whereas recombinant viruses containing mutant capsid proteins were produced efficiently, transduction of several cell lines was significantly impaired for most modifications. However, certain mutants containing the peptide motif NGR, which binds CD13 (a receptor expressed in angiogenic vasculature and in many tumor cell lines), displayed an altered tropism toward cells expressing this receptor. Based on this work and previous studies, possible strategies for achieving in vivo targeting of recombinant AAV-2 are discussed.

Promoting education, mentorship, and support for pediatric research.

Pediatricians have an important role to play in the advancement of child health research and should be encouraged and supported to pursue research activities. Education and training in child health research should be part of every level of pediatric training. Continuing education and access to research advisors should be available to practitioners and academic faculty. Recommendations to promote additional research education and support at all levels of pediatric training, from premedical to continuing medical education, as well as suggestions for means to increase support and mentorship for research activities, are outlined in this statement.

Impact of low birth weight on early childhood asthma in the United States.

OBJECTIVE: To estimate the independent contribution of birth weight to asthma prevalence among children younger than 4 years in the United States and to compare the magnitude of its effect on asthma between African American and white children. DESIGN: Cross-sectional analysis using the 1988 National Maternal-Infant Health Survey and 1991 Longitudinal Follow-up Survey. SETTING: United States. PATIENTS: Eight thousand seventy-one subjects, selected from a randomized, systematic population-based sample and weighted to be nationally representative, who completed both initial and longitudinal follow-up surveys and reported information on asthma diagnosis. MAIN OUTCOME MEASURES: Birth weight and other sociodemographic factors linked to birth outcome were analyzed for independent association with physician-diagnosed asthma by age 3 years. RESULTS: The prevalence of asthma varied by birth weight category: 6.7% in children 2500 g or more at birth, 10.9% in children 1500 to 2499 g at birth, and 21.9% in children less than 1500 g at birth (very low birth weight [VLBW]) (P<.001). Some of the characteristics shown to be independently associated with asthma included: VLBW (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.3-3.6), moderately low birth weight (OR, 1.4; 95% CI, 1.1-1.8), and African American race (OR, 1.9; 95% CI, 1.6-2.4). In stratified analyses, the independent association between VLBW and asthma in white and African American populations was: OR(white), 3.1 (95% CI, 2.2-4.3) and OR(African American), 2.5 (95% CI, 2.0-3.3). The prevalence of VLBW, however, was tripled in African American compared with white children (1.8% vs 0.6%). CONCLUSIONS: These data confirm findings of other studies that identify a strong independent association between low birth weight and asthma. For this 1988 national birth cohort, an estimated 4000 excess asthma cases were attributable to birth weight less than 2500 g. Although the strength of the independent association between VLBW and asthma was smaller in the African American population, the substantially increased prevalence of VLBW in this community may contribute to the disproportionately increased prevalence of asthma among African American children.

Residential exposures associated with asthma in US children.

OBJECTIVE: Residential exposures are recognized risk factors for childhood asthma, but the relative contribution of specific risk factors and the overall contribution of housing to asthma in US children is unknown. The objective of this study was to identify risk factors and estimate the population attributable risk of residential exposures for doctor-diagnosed asthma for US children. METHODS: A cross-sectional survey was conducted from 1988 to 1994. Survey participants were 8257 children who were <6 years old and who participated in the Third National Health and Nutrition Examination Survey, a survey of the health and nutritional status of children and adults in the United States. The main outcome measure was doctor-diagnosed asthma, as reported by the parent. RESULTS: Six percent of children had doctor-diagnosed asthma. The prevalence of asthma was higher among boys (6.7%) than girls (5.1%) and was higher among black children (8.9%) than white children (5.2%). Risk factors for doctor-diagnosed asthma included a family history of atopy (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.5, 3.1), child's history of allergy to a pet (OR: 24.2; 95% CI: 8.4, 69.5), exposure to environmental tobacco smoke (OR: 1.8; 95% CI: 1.2-2.6), use of a gas stove or oven for heat (OR: 1.8; 95% CI: 1.02-3.2), and presence of a dog in the household (OR: 1.6; 95% CI: 1.1, 2.3). The population attributable risk of >/=1 residential exposure for doctor-diagnosed asthma in US children <6 years old was 39.2%, or an estimated 533 000 excess cases, whereas having a family history of atopy accounted for 300 000. The attributable cost of asthma as a result of residential exposures for children <6 years old was $402 million (95% CI: $296-$507 million) annually. CONCLUSIONS: The elimination of identified residential risk factors, if causally associated with asthma, would result in a 39% decline in doctor-diagnosed asthma among US children <6 years old.

Quantitative CMV antigenemia correlated with ophthalmoscopic screening for CMV retinitis in AIDS patients.

To assess the efficacy of the cytomegalovirus (CMV) antigen test in detecting the clinical presence of CMV retinitis. A retrospective chart review was conducted on 86 HIV positive patients who underwent dilated fundus exams for CMV retinitis. All patients had a CMV antigen assay performed within three months of their retinal exam. At a level of 45, the antigen test has a sensitivity of 96% in correctly detecting CMV retinitis and a specificity of 90.2%. The negative and positive predictive values of the antigen test were 98.2% and 80%, respectively. CMV antigen blood test provides a useful screening tool in detecting the presence or absence of CMV retinitis. An antigen level less than 45 strongly suggests the absence of retinitis.