Effects of ambient air pollution on symptom severity and medication use in children with asthma.

BACKGROUND: Exposure to air pollutants has been investigated as a possible cause of asthma attacks in children. OBJECTIVE: To investigate the short-term effects of air pollutants on a panel of 133 children with asthma who enrolled in the Childhood Asthma Management Program. METHODS: During screening, the children completed daily diary cards for an average of 58 days to indicate their medication use and asthma severity. We used ordinal logistic regression to compare the odds of a more serious relative to a less serious asthma attack, and we used a Poisson model to analyze medication use. In both analyses we accommodate dependence in the data and different periods of observation for study subjects. RESULTS: Our results indicate that a 10-microg/m3 increase in particulate matter less than or equal to 2.5 microm (PM2.5) lagged 1 day was associated with a 1.20 times increased odds of having a more serious asthma attack [95% confidence interval (CI), 1.05 to 1.37] and a 1.08-fold increase in medication use (95% CI, 1.01 to 1.15). A 10-microg/m3 increase in particulate matter less than or equal to 10 microm (PM10) increased the odds of a more serious asthma attack (odds ratio = 1.12; 95% CI, 1.04 to 1.22) and also increased medication use (relative risk = 1.05; 95% CI, 1.00 to 1.09). CONCLUSIONS: Increases in PM2.5 and PM10 are significantly associated with an increased risk of more severe asthma attacks and medication use in Seattle area children with asthma. We also found associations with carbon monoxide, but we believe that carbon monoxide is a marker for exposure to combustion byproducts.     

Dissecting karyotypic patterns in renal cell carcinoma: an analysis of the accumulated cytogenetic data

Molecular cytogenetic analysis frequently shows human papillomavirus (HPV) integration near translocation breakpoints in cervical cancer cells. We have recently described a cluster of HPV18 integrations in the distal end of the common fragile site FRA8C at 8q24 in primary cervical carcinoma samples. Chromosome band 8q24 contains the MYC gene (alias c-MYC), FRA8C, and FRA8D. The MYC gene is frequently deregulated--usually by translocation or amplification--in various tumor types. In the present study, we performed a molecular cytogenetic analysis of HPV18 integration patterns and the 8q24 translocation in a primary cervical carcinoma and in HeLa cells using combined binary ratio-fluorescence in situ hybridization. Our aim was to determine how the chromosomal breaks involved in these events relate physically to the MYC gene; whether they map to the FRA8C site, the FRA8D site, or both; and how they correlate with the occurrence of DNA flexibility domains. The 8q24 translocation breakpoints mapped between stretches of integrated HPV18 sequences in the distal end of FRA8C. This region contained DNA helix flexibility clusters, several of which mapped in the vicinity of HPV integration sites and translocation breakpoints in cervical carcinomas. DNA helix flexibility clusters were also found near known MYC translocation breakpoints in Burkitt lymphomas (BL), but most BL breakpoints mapped clearly outside FRA8C. Our data revealed that FRA8C is involved in HPV integration and chromosomal translocations in cervical carcinoma; however, this fragile site is not involved in classical MYC translocations in most BLs. In the context of the familial nature of cervical cancer, FRA8C may be considered a candidate susceptibility region for cervical carcinoma.     

Testicular testosterone biosynthesis in male Saanen goats with XX sex chromosomes

Testosterone biosynthesis was examined in three pairs of twin male Saanen goats. In each pair, one goat was a phenotypically normal male of XY chromosome constitution; the other showed testicular hypoplasia of the sort typically associated with homozygosity for the dominant gene for polledness in genetic females, and was of XX chromosome constitution.
The histological and hormonal situations in the hypoplastic male goats resembled those found in Kleinfelter and XX human males, both in their nature and in their variability. Histological examination of the testes of the hypoplastic XX males showed various degrees of degeneration. In one case a "sperm pocket" full of spermatozoa was observed, and in this case sperm cells with heads separated from tails were observed in the semen. In the other two cases semen was devoid of sperm cells. In two cases plasma testosterone levels of the hypoplastic goats were lower than those of their normal counterparts, in one of the cases much lower. When testicular microsomal fractions of these goats were tested for their in vitro ability to bring about the conversion of androstenedione to testosterone, it was observed that 17β-hydroxysteroid dehydrogenase activity was either absent or lower in the hypoplastic goats than in their normal twins. In the third pair of animals, plasma testosterone levels were similar in both normal and hypoplastic animals. In this case, however, the increase in testosterone levels following HCG administration was lower in the hypoplastic than in the normal goats. 3β-hydroxysteroid dehydrogenase was the same in normal and hypoplastic goats. The variable effects on testosterone biosynthesis support the notion that the sex chromosomes, while affecting steroid biosynthesis in the testis, do so indirectly.     

SOST expression is restricted to the great arteries during embryonic and neonatal cardiovascular development.

Spatial-temporal regulation of bone morphogenetic protein (BMP) and Wnt activity is essential for normal cardiovascular development, and altered activity of these growth factors causes maldevelopment of the cardiac outflow tract and great arteries. In the present study, we show that SOST, a Dan family member reported to antagonize BMP and Wnt activity, is expressed within the medial vessel wall of the great arteries containing smooth muscle cells. The ascending aorta, aortic arch, brachiocephalic artery, common carotids, and pulmonary trunk were all associated with SOST expressing smooth muscle cells, while the heart itself, including the valves, and more distal arteries, that is, pulmonary arteries, subclavian arteries, and descending aorta, were negative. SOST was expressed from embryonic day 15.5 up to the neonatal period. SOST expression, however, did not correspond with inhibition of Smad-dependent BMP activity or beta-catenin-dependent Wnt activity in the great arteries. Activity of both signaling pathways was already down-regulated before induction of SOST expression.     

ELAV inhibits 3'-end processing to promote neural splicing of ewg pre-mRNA

The embryonic lethal abnormal visual system (ELAV) is a gene-specific regulator of alternative pre-mRNA processing in neurons of Drosophila. Here we define a functional in vivo binding site for ELAV in neurons through the development of a reporter gene system in transgenic animals in combination with in vitro binding assays. ELAV binds to erect wing (ewg) RNA 3' of a polyadenylation site in the terminal intron 6. At this polyadenylation site, ELAV inhibits 3'-end processing in vitro in a dose-dependent and sequence-specific manner, and ELAV binding is necessary in vivo to promote splicing of ewg intron 6. Further, the AAUAAA poly(A) complex recognition sequence, together with ELAV, is required to regulate neural 3' splice site choice in vivo. In addition, the use of segmentally labeled RNA substrates in UV cross-linking assays suggest that ELAV does not inhibit or redirect binding of cleavage factor dCstF64 at the regulated polyadenylation site on ewg RNA. These data indicate that binding of 3'-end processing factors, together with ELAV, can regulate alternative splicing.     

Correction to: Middle School Effects of the Dating Matters® Comprehensive Teen Dating Violence Prevention Model on Physical Violence,Bullying, and Cyberbullying: A Cluster-Randomized Controlled Trial

Prevention Science - The article “Middle School Effects of the Dating Matters® Comprehensive Teen Dating Violence Prevention Model on Physical Violence, Bullying, and Cyberbullying: a...     

Donor genetic variants as risk factors for thrombosis after liver transplantation: A genome-wide association study

Thrombosis after liver transplantation substantially impairs graft- and patient survival. Inevitably, heritable disorders of coagulation originating in the donor liver are transmitted by transplantation. We hypothesized that genetic variants in donor thrombophilia genes are associated with increased risk of posttransplant thrombosis. We genotyped 775 donors for adult recipients and 310 donors for pediatric recipients transplanted between 1993 and 2018. We determined the association between known donor thrombophilia gene variants and recipient posttransplant thrombosis. In addition, we performed a genome-wide association study (GWAS) and meta-analyzed 1085 liver transplantations. In our donor cohort, known thrombosis risk loci were not associated with posttransplant thrombosis, suggesting that it is unnecessary to exclude liver donors based on thrombosis-susceptible polymorphisms. By performing a meta-GWAS from children and adults, we identified 280 variants in 55 loci at suggestive genetic significance threshold. Downstream prioritization strategies identified biologically plausible candidate genes, among which were AK4 (rs11208611-T, p = 4.22 × 10⁻⁰⁵) which encodes a protein that regulates cellular ATP levels and concurrent activation of AMPK and mTOR, and RGS5 (rs10917696-C, p = 2.62 × 10⁻⁰⁵) which is involved in vascular development. We provide evidence that common genetic variants in the donor, but not previously known thrombophilia-related variants, are associated with increased risk of thrombosis after liver transplantation.     

Mental health of adolescents associated with sexual and reproductive outcomes: a systematic review

ObjectiveTo systematically review the literature on the mental health of adolescents associated with sexual and reproductive outcomes, and compare the mental health outcomes with that of other age groups.MethodsWe searched seven databases for relevant peer-reviewed articles published between 1 January 2010 and 25 April 2019. Our inclusion criteria required that the study included age-disaggregated data on adolescents, and focused and assessed mental health outcomes associated with pregnancy or sexually transmitted infections. We extracted data on the specific health event, the mental health outcome and the method of measuring this, and comparisons with other age groups.FindingsAfter initially screening 10 818 articles by title and abstract, we included 96 articles in our review. We observed that a wide-ranging prevalence of mental ill-health has been reported for adolescents. However, most studies of mental health during pregnancy did not identify an increased risk of depression or other mental disorders among adolescents compared with other age groups. In contrast, the majority of studies conducted during the postpartum period identified an increased risk of depression in adolescents compared with other age groups. Three studies reported on mental health outcomes following abortion, with varying results. We found no studies of the effect of sexually transmitted infections on mental health among adolescents.ConclusionWe recommend that sexual and reproductive health services should be accessible to adolescents to address their needs and help to prevent any adverse mental health outcomes.