Effectiveness of a sports-based HIV prevention intervention in the Dominican Republic: a quasi-experimental study.

Previous observational and quasi-experimental studies in sub-Saharan Africa have suggested the effectiveness of youth-targeted HIV prevention interventions using sport as an educational tool. No studies have yet assessed the effect of similar programs in the Caribbean. A quasi-experimental trial was conducted to assess the effectiveness of a sports-based intervention in six migrant settlements in the Puerto Plata Province of the Dominican Republic. A total of 397 structured interviews were conducted with 140 adolescents prior to, immediately following, and four months following 10-hour interventions using the Grassroot Soccer curriculum. Interview responses were coded, aggregated into composite scores, and analyzed using logistic regression, adjusting for baseline differences as well as age, sex, community, and descent. At post-intervention, significant differences were observed between groups in HIV-related knowledge (adjOR = 13.02, 95% CI = 8.26, 20.52), reported attitudes (adjOR = 12.01, 95% CI = 7.61, 18.94), and reported communication (adjOR = 3.13, 95% CI = 1.91, 5.12). These differences remained significant at four-month follow-up, though declines in post-intervention knowledge were observed in the Intervention group while gains in knowledge and reported attitudes were observed in the Control group. Results suggest that this sports-based intervention could play a valuable role in HIV prevention efforts in the Caribbean, particularly those targeting early adolescents. Further evaluation of sports-based interventions should include indicators assessing behavioral and biological outcomes, longer-term follow-up, a larger sample, randomization of study participants, and strenuous efforts to minimize loss-to-follow-up.

Localization of the Na(+)-coupled neutral amino acid transporter 2 in the cerebral cortex.

We studied the distribution and cellular localization of Na(+)-coupled neutral amino acid transporter 2, a member of the system A family of amino acid transporters, in the rat and human cerebral cortex using immunocytochemical methods. Na(+)-coupled neutral amino acid transporter 2-positive neurons were pyramidal and non-pyramidal, and Na(+)-coupled neutral amino acid transporter 2/GABA double-labeling studies revealed that Na(+)-coupled neutral amino acid transporter 2 was highly expressed by GABAergic neurons. Double-labeling studies with the synaptophysin indicated that rare axon terminals express Na(+)-coupled neutral amino acid transporter 2. Na(+)-coupled neutral amino acid transporter 2-immunoreactivity was also found in astrocytes, leptomeninges, ependymal cells and choroid plexus. Electron microscopy showed robust Na(+)-coupled neutral amino acid transporter 2-immunoreactivity in the somato-dendritic compartment of neurons and in glial processes, but, as in the case of double-labeling studies, failed to reveal Na(+)-coupled neutral amino acid transporter 2-immunoreactivity in terminals. To rule out the possibility that the absence of Na(+)-coupled neutral amino acid transporter 1- and Na(+)-coupled neutral amino acid transporter 2-positive terminals was due to insufficient antigen detection, we evaluated Na(+)-coupled neutral amino acid transporter 1/synaptophysin and Na(+)-coupled neutral amino acid transporter 2/synaptophysin coexpression using non-standard immunocytochemical procedures and found that Na(+)-coupled neutral amino acid transporter 1 and Na(+)-coupled neutral amino acid transporter 2+ terminals were rare in all conditions. These findings indicate that Na(+)-coupled neutral amino acid transporter 1 and Na(+)-coupled neutral amino acid transporter 2 are virtually absent in cortical terminals, and suggest that they do not contribute significantly to replenishing the Glu and GABA transmitter pools through the glutamate-glutamine cycle. The strong expression of Na(+)-coupled neutral amino acid transporter 2 in the somato-dendritic compartment and in non-neuronal elements that are integral parts of the blood-brain and brain-cerebrospinal fluid barrier suggests that Na(+)-coupled neutral amino acid transporter 2 plays a role in regulating the levels of Gln and other amino acids in the metabolic compartment of cortical neurons.

Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS.

Presynaptic P2X(7) receptors are thought to play a role in the modulation of transmitter release and have been localised to terminals with the location and morphology typical of excitatory boutons. To test the hypothesis that this receptor is preferentially associated with excitatory terminals we combined immunohistochemistry for the P2X(7) receptor subunit (P2X(7)R) with that for two vesicular glutamate transporters (VGLUT1 and VGLUT2) in the rat CNS. This confirmed that P2X(7)R immunoreactivity (IR) is present in glutamatergic terminals; however, whether it was co-localised with VGLUT1-IR or VGLUT2-IR depended on the CNS region examined. In the spinal cord, P2X(7)R-IR co-localised with VGLUT2-IR. In the brainstem, co-localisation of P2X(7)R-IR with VGLUT2-IR was widespread, but co-localisation with VGLUT1-IR was seen only in the external cuneate nucleus and spinocerebellar tract region of the ventral medulla. In the cerebellum, P2X(7)R-IR co-localised with both VGLUT1 and VGLUT2-IR in the granular layer. In the hippocampus it was co-localised only with VGLUT1-IR, including in the polymorphic layer of the dentate gyrus and the substantia radiatum of the CA3 region. In other forebrain areas, P2X(7)R-IR co-localised with VGLUT1-IR throughout the amygdala, caudate putamen, striatum, reticular thalamic nucleus and cortex and with VGLUT2-IR in the dorsal lateral geniculate nucleus, amygdala and hypothalamus. Dual labelling studies performed using markers for cholinergic, monoaminergic, GABAergic and glycinergic terminals indicated that in certain brainstem and spinal cord nuclei the P2X(7)R is also expressed by subpopulations of cholinergic and GABAergic/glycinergic terminals. These data support our previous hypothesis that the P2X(7)R may play a role in modulating glutamate release in functionally different systems throughout the CNS but further suggest a role in modulating release of inhibitory transmitters in some regions.

Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours.

Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.

Folic acid supplements during pregnancy and risk of miscarriage.

BACKGROUND: Although taking supplements that contain 400 microg of folic acid before and during early pregnancy reduces a woman's risk for having a baby with a neural-tube defect (NTD), the effects of such supplements on other pregnancy outcomes remain unclear. We examined whether the use of such supplements affects the occurrence of miscarriage. METHODS: Participants were women in China who had taken part in a recent folic acid campaign to prevent NTDs and who had registered in this campaign before they became pregnant for the first time. We examined the risk for miscarriage among women who had confirmed pregnancies and who had or had not taken pills containing only 400 microg of folic acid before and during early pregnancy. RESULTS: The overall rate of miscarriage was 9.1% (2155/23806). The rates of miscarriage among women who had and had not taken folic acid pills before and during the first trimester were 9.0% and 9.3%, respectively (risk ratio 0.97 [95% CI 0.84-1.12]). The distributions of gestational age at pregnancy diagnosis and at miscarriage were similar for both groups of women. INTERPRETATION: In this population-based study of a cohort of women whose use of folic acid supplements while pregnant had been previously documented and who had been pregnant for the first time, we found no evidence that daily consumption of 400 microg of folic acid before and during early pregnancy influenced their risk for miscarriage.

A case-control study of maternal alcohol consumption and intrauterine growth retardation.

PURPOSE: Heavy maternal drinking during pregnancy causes fetal alcohol syndrome, but whether more moderate alcohol consumption is associated with such adverse pregnancy outcomes as intrauterine growth retardation (IUGR) remains controversial. METHODS: Using data from a case-control study, we examined the association between maternal alcohol consumption and risk for IUGR among 701 case and 336 control infants born during 1993-1995 in Monroe County, New York. RESULTS: Our results provide no evidence of an independent association between moderate maternal alcohol consumption (<14 drinks per week) and risk for IUGR. The risk for IUGR among heavy drinkers (> or =14 drinks per week) around the time of conception was OR = 1.4 (95% CI 0.7-2.6) for IUGR < or = 5th percentile and OR = 1.4 (95% CI 0.7-2.8) for IUGR 5th-10th percentile. For heavy drinkers during the first trimester, the OR was 1.3 (95% CI 0.4-4.5) for IUGR < or = 5th percentile and OR = 1.3 (95% CI 0.4-4.8) for IUGR 5th-10th percentile. CONCLUSIONS: Since IUGR is a heterogeneous outcome with a possible multifactorial origin, further studies are needed to examine the combined effects of alcohol and other environmental and genetic factors on IUGR risk for subgroups of IUGR.

Analysis of point mutants in the Caenorhabditis elegans vesicular acetylcholine transporter reveals domains involved in substrate translocation.

Cholinergic neurotransmission depends upon the regulated release of acetylcholine. This requires the loading of acetylcholine into synaptic vesicles by the vesicular acetylcholine transporter (VAChT). Here, we identify point mutants in Caenorhabditis elegans that map to highly conserved regions of the VAChT gene of Caenorhabditis elegans (CeVAChT) (unc-17) and exhibit behavioral phenotypes consistent with a reduction in vesicular transport activity and neurosecretion. Several of these mutants express normal amounts of VAChT protein and exhibit appropriate targeting of VAChT to synaptic vesicles. By site-directed mutagenesis, we have replaced the conserved amino acid residues found in human VAChT with the mutated residue in CeVAChT and stably expressed these cDNAs in PC-12 cells. These mutants display selective defects in initial acetylcholine transport velocity (K(m)), with values ranging from 2- to 8-fold lower than that of the wild-type. One of these mutants has lost its specific interaction with vesamicol, a selective inhibitor of VAChT, and displays vesamicol-insensitive uptake of acetylcholine. The relative order of behavioral severity of the CeVAChT point mutants is identical to the order of reduced affinity of VAChT for acetylcholine in vitro. This indicates that specific structural changes in VAChT translate into specific alterations in the intrinsic parameters of transport and in the storage and synaptic release of acetylcholine in vivo.

Congenital heart defects, maternal febrile illness, and multivitamin use: a population-based study.

We assessed the relation between febrile illness during pregnancy and cardiac defects in the offspring in a population-based case-control study in metropolitan Atlanta. Case infants (905) with cardiac defects were actively ascertained from multiple sources. Control infants (3,029) were infants without birth defects who were selected from birth certificates by stratified random sampling. We compared those whose mothers reported febrile illness from 1 month before pregnancy through the third month of pregnancy with those whose mothers reported no illness during the same period. Febrile illness was positively associated with the occurrence of heart defects in the offspring (odds ratio [OR] = 1.8; 95% confidence interval = 1.4-2.4). When influenzalike illness was the reported febrile illness, the OR was 2.1 (95% confidence interval = 0.8-5.5). The association with febrile illness was strongest for tricuspid atresia (OR = 5.2), left obstructive defects (OR = 2.7), transposition of the great arteries (OR = 1.9), and ventricular septal defects (OR = 1.8). These ORs were generally lower among mothers who used multivitamins during the periconceptional period.

Continued occurrence of Accutane-exposed pregnancies.

BACKGROUND: Accutane a teratogenic prescription drug licensed to treat severe, recalcitrant nodular acne. First-trimester pregnancy exposure can cause major birth defects. The manufacturer began a Pregnancy Prevention Program (PPP) in 1988; however, exposed pregnancies continue to occur. In 1996, the manufacturer began a direct-to-consumer advertising campaign, raising concerns of more exposed pregnancies. METHODS: We examined trends in Accutane use by reproductive-aged women. We also interviewed a series of 14 women in California who had recent Accutane-exposed pregnancies to identify opportunities for prevention. RESULTS: The estimated number of Accutane prescriptions for reproductive-aged women has more than doubled in the past 10 years; it is the most widely used teratogenic drug in the United States, with approximately 2.5 per 1,000 reproductive-aged women exposed to Accutane in 1999. One-half of the women interviewed reported seeing an advertisement for prescription acne treatment before taking Accutane. Eight of the 14 women used no contraception at the time of the exposed pregnancy; 13 of the 14 women did not use two forms of contraception. Four of the 14 women did not have pregnancy tests before starting Accutane. None reported seeing all PPP components, and four saw only the information on the pill packet. These 14 pregnancies resulted in four live infants who had no apparent birth defects, one live-born infant with multiple defects, four spontaneous abortions, and five induced abortions. CONCLUSIONS: The increase in Accutane use observed among females may be exacerbated by advertising. Physicians and patients must use more caution with teratogenic prescription drugs. Published 2001 Wiley-Liss, Inc.

Interpretations of a teratogen warning symbol.

BACKGROUND: Warning symbols are used on teratogenic medications to communicate the message that women should (1) not take that medication if they may already be pregnant, and (2) not get pregnant while taking that medication. Communications research indicates that people interpret symbols or pictures in different ways. Other studies have shown that patients do not always receive education materials that are part of prescription protocol. Researchers at the Centers for Disease Control and Prevention (CDC) tested the interpretation of the teratogen warning symbol and its ability to convey the correct information without accompanying education. METHODS: A teratogen warning symbol currently printed on some medication packaging uses graphics and text warning the user not to get pregnant. Researchers interviewed women of childbearing age about their interpretation of the warning symbol and its meaning. Ninety-seven women were interviewed in a variety of locations, including public health clinics, literacy and job training offices, health clubs, and malls. RESULTS: Only 21% of women interpreted correctly without prompting that they should either not take the medication if they are pregnant or not get pregnant while taking the medication. Twenty-seven percent of women first thought the symbol meant the package contained birth control medication, and 24% said it simply indicated the package contained drugs or medicine. An additional 7% said they did not know what the symbol was supposed to mean; 39% of respondents offered circumstances in which prescription medications might be shared. CONCLUSIONS: Misinterpretation of warning symbols can result in serious consequences. This research should serve as an urgent call for mandating education for all patients receiving drugs with teratogenic properties, and careful pretesting and modification of warning symbols before they are used on medications with teratogenic effects. Published 2001 Wiley-Liss, Inc.

Illness-related concerns of mothers of children with congenital heart disease.

OBJECTIVE: This study examined concerns expressed by mothers of children with congenital heart disease (CHD). The relationships among mothers' concerns, medical severity, and mother's emotional state were examined at two points in time. METHOD: Thirty-eight mothers of children with CHD aged 3 to 16 completed semistructured interviews and rating scales during hospitalization and 2 to 4 weeks after discharge. Mothers rated their distress about illness-related concerns, as well as their own depressed mood and anxiety. Mothers and two cardiologists rated the medical severity of each child's disease. RESULTS: Mothers' concerns were reliably grouped into five categories: medical prognosis, quality of life, psychosocial functioning, effects on family, and financial issues. During hospitalization, mothers were most concerned about medical prognosis. Distress about most concerns decreased postdischarge, as did mother's anxiety and depressed mood. Mothers' perceptions of medical severity were associated with distress about psychosocial issues postdischarge. Mother's anxiety was not associated with number of concerns reported, or with distress about those concerns. Maternal depressed mood was associated with fewer illness-related concerns, but greater distress about those concerns. CONCLUSIONS: Illness-related concerns can be meaningfully categorized and are not necessarily a function of disease severity or mother's emotional state. An awareness of common concerns will improve clinical care by enabling practitioners to anticipate and address concerns in a proactive way. The results may inform the development of supportive mental health interventions for families of children with CHD.

Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects.

CONTEXT: Daily consumption of 400 microg of folic acid before conception and during early pregnancy dramatically reduces the occurrence of neural tube defects (NTDs). Before food fortification, however, only an estimated 29% of US reproductive-aged women were taking a supplement containing 400 microg of folic acid daily. The US Food and Drug Administration authorized addition of folic acid to enriched grain products in March 1996, with compliance mandatory by January 1998. OBJECTIVE: To evaluate the impact of food fortification with folic acid on NTD birth prevalence. DESIGN, SETTING, AND POPULATION: National study of birth certificate data for live births to women in 45 US states and Washington, DC, between January 1990 and December 1999. MAIN OUTCOME MEASURE: Birth certificate reports of spina bifida and anencephaly before fortification (October 1995 through December 1996) compared with after mandatory fortification (October 1998 through December 1999). RESULTS: The birth prevalence of NTDs reported on birth certificates decreased from 37.8 per 100 000 live births before fortification to 30.5 per 100 000 live births conceived after mandatory folic acid fortification, representing a 19% decline (prevalence ratio [PR], 0.81; 95% confidence interval [CI], 0.75-0.87). During the same period, NTD birth prevalence declined from 53.4 per 100 000 to 46.5 per 100 000 (PR, 0.87; 95% CI, 0.64-1.18) for women who received only third-trimester or no prenatal care. CONCLUSIONS: A 19% reduction in NTD birth prevalence occurred following folic acid fortification of the US food supply. However, factors other than fortification may have contributed to this decline.

Mortality associated with congenital heart defects in the United States: trends and racial disparities, 1979-1997.

BACKGROUND: Surgical series and some population-based studies have documented a decrease in mortality from heart defects. Recent population-based data for the United States are lacking, however. We examined population-based data for patterns, time trends, and racial differences of mortality from heart defects for the United States from 1979 through 1997. METHODS AND RESULTS: We examined the multiple-cause mortality files compiled by the National Center for Health Statistics of the CDC from all death certificates filed in the United STATES: From these data, we derived death rates (deaths per 100 000 population) by the decedent's age, race, year of death, and heart defect type. We also analyzed age at death as an indirect indicator of survival. From 1979 through 1997, mortality from heart defects (all ages) declined 39%, from 2.5 to 1.5 per 100 000 population; among infants, the decline was 39%, or 2.7% per year. In 1995 to 1997, heart defects contributed to 5822 deaths per year. Of these deaths, 51% were among infants and 7% among children 1 to 4 years old. Mortality was on average 19% higher among blacks than among whites; this gap does not appear to be closing. Age at death increased for most heart defects, although less among blacks than among whites. CONCLUSIONS: Mortality from heart defects is declining in the United States, although it remains a major cause of death in infancy and childhood. Age at death is increasing, suggesting that more affected persons are living to adolescence and adulthood. The racial discrepancies should be investigated to identify opportunities for prevention.

Racial and temporal variations in the prevalence of heart defects.

BACKGROUND: Documenting the prevalence and trends of congenital heart defects provides useful data for pediatric practice, health-care planning, and causal research. Yet, most population-based studies use data from the 1970s and 1980s. We sought to extend into more recent years the study of temporal and racial variations of heart defects occurrence in a well-defined population. METHODS: We used data from the Metropolitan Atlanta Congenital Defects Program, a population-based registry with active case ascertainment from multiple sources. Heart defects were identified among liveborn infants up to 1 year old, among stillborn infants, and among pregnancy terminations to mothers residing in metropolitan Atlanta. RESULTS: From 1968 through 1997, the registry ascertained 5813 major congenital heart defects among 937 195 infants, for a prevalence of 6.2 per 1000. The prevalence increased to 9.0 per 1000 births in 1995 through 1997. The prevalence of ventricular septal defects, tetralogy of Fallot, atrioventricular septal defects, and pulmonary stenosis increased, whereas that of transposition of the great arteries decreased. For some defects, prevalence and trends varied by race. CONCLUSIONS: The prevalence of congenital heart defects is increasing. Whereas most findings likely result from improved case ascertainment and reporting, others might be because of changes in the distribution of risk factors in the population. The basis of the racial variations is incompletely understood.

Fourier analysis of acetabular shape in native American Arikara populations before and after acquisition of horses.

The goal of this study was to identify changes in acetabular morphology associated with the use of horses by Native Americans. Previous studies reported "elongate" acetabula in horseback-riding members of the Omaha and Ponca populations. Such a difference in acetabular shape is a potentially useful osteological marker of habitual horseback riding. This report compares acetabula of adult males from two Native American Arikara populations known to have differed substantially in their use of horses. Population samples were from separate sites in South Dakota: Larson (nonriding) and Leavenworth (riding). Outlines of acetabular rims were digitized and analyzed, using a simplified 12-point Fourier analysis. A Fourier series with six terms accurately described acetabular shape. Significant differences (P<0.10) between riding and nonriding populations were observed in two Fourier coefficients. Acetabula of riding Arikara were found to have smaller B(4) coefficients (P = 0. 061) and more positive B(2) coefficients (P = 0.080), indicating expanded anterior-superior borders relative to acetabula of non-riding Arikara.

Molecular analysis of vesicular amine transporter function and targeting to secretory organelles.

Vesicular transporters are responsible for the loading of neurotransmitters into specialized secretory organelles in neurons and neuroendocrine cells to make them available for regulated neurosecretion. The exocytotic release of neurotransmitter therefore depends on the functional activity of the vesicular transporters and their efficient sorting to these secretory organelles. Molecular analysis of vesicular transport proteins has revealed important information regarding structural domains responsible for their functional properties, including substrate specificity and trafficking to various classes of secretory vesicles. These studies have established the existence of an important functional relationship between transporter activity and presynaptic quantal neurosecretion.