BackgroundCCR5 and CCR2 gene polymorphisms (SNPs) have been associated with protection against HIV transmission in adults and with delayed progression to AIDS. The CCR5 Δ32 deletion and SNP -2459G are associated with reduced expression of the CCR5 protein.Methodology/Principal FindingsWe investigated the association between infant CCR2/CCR5 diplotype and HIV mother to child transmission (MTCT) in Malawi. Blood samples from infants (n = 552) of HIV positive women who received nevirapine were genotyped using a post-PCR multiplex ligase detection reaction and haplotypes were identified based on 8 CCR2/CCR5 SNPs and the open reading frame 32 base pair deletion. Following verification of Hardy-Weinberg equilibrium, log linear regression was performed to examine the association between mutations and MTCT. Overall, protection against MTCT was weakly associated with two CCR5 SNPs, -2459G (Risk ratio [RR], 0.78; confidence interval [CI], 0.54–1.12), and the linked CCR5 -2135T (RR, 0.78; CI, 0.54–1.13). No child carried the CCR5 Δ32 SNP. Maternal Viral Load (MVL) was found to be an effect measure modifier. Among mothers with low MVL, statistically significant protection against MTCT was observed for -2459G (RR, 0.50; CI, 0.27–0.91), and -2135T (RR, 0.51; CI, 0.28–0.92). Statistically significant protection was not found at high MVL.Conclusions/SignificanceResults from this study suggest that CCR5 SNPs -2459G and -2135T associated with reduced receptor expression protect against MTCT of HIV at low MVLs, whereas high MVLs may over-ride differences in coreceptor availability.
Major risk factors for hepatocellular carcinoma (HCC) are hepatitis viruses and exposure to aflatoxins, including aflatoxin B1 (AFB1). The mutagenic effect of AFB1 results from hepatic bioactivation to AFB1-exo-8,9-epoxide. This is in part catalysed by CYP3A5, an enzyme expressed polymorphically. We investigated the role of CYP3A5 polymorphisms in the formation of AFB1-exo-8,9-epoxide in The Gambia, a population exposed to high aflatoxin levels.Common CYP3A5 polymorphisms were identified in an African-American population. Subsequently, 288 Gambian subjects were genotyped and CYP3A5 activity predicted using haplotypes of the three variant loci (CYP3A5*3, *6 and *7) associated with decreases in protein expression. CYP3A5 expression was then compared to aflatoxin-albumin (AF-alb) adduct, a biomarker of AFB1 bioactivation; data were also analysed in relation to expression of other aflatoxin-metabolizing enzymes.CYP3A5 haplotypes reflecting high CYP3A5 protein expression were associated with increased AF-alb. Compared to individuals with predicted low expression those predicted to express CYP3A5 from one allele displayed 16.1% higher AF-alb (95% CI: -2.5, 38.2, P = 0.093) and homozygous expressers displayed 23.2% higher AF-alb levels (95% CI: -0.01, 52.0, P = 0.051). The effect of the CYP3A5 polymorphism was strongest in individuals with low CYP3A4 activity with a 70.1% increase in AF-alb (95% CI: 11.8, 158.7, P < 0.05) in high compared to low expressers. A similar effect was observed for individuals with null alleles of GSTM1, which conjugates the AFB1-exo-8,9-epoxide to reduced glutathione.The CYP3A5 polymorphism is associated with increased levels of the mutagenic AFB1-exo-8,9-epoxide, particularly in individuals with low CYP3A4, and this may modulate individual risk of HCC.
The mechanism of mother-to-child transmission (MTCT) of HIV-1 is not well described.Of 328 HIV-infected mother-infant pairs, we identified 91 that had discordant angiotensin I-converting enzyme and glutathione S-transferase M1 alleles. Maternal alleles in cord blood were quantified with real-time polymerase chain reaction, as indicators of microtransfusions.HIV-1 infected infants had more maternal DNA in cord blood than their uninfected counterparts. Increased maternal DNA in cord blood was associated with preterm delivery, low birth weight, and maternal immunosuppression.Intrapartum MTCT was associated with placental microtransfusions. The associations among placental microtransfusion, in-utero MTCT, maternal immunosuppression, and poor birth outcome should be further investigated.
We conducted a meta-analysis of 25 randomized controlled trials published in English-language journals before February 2004, to assess the effect of dietary fiber intake on blood pressure (BP).Using a standardized protocol, information on study design, sample size, participant characteristics, duration of follow-up and change in mean BP, was abstracted. The data from each study were pooled using a random effects model to provide an overall estimate of dietary fiber intake on BP.Dietary fiber intake was the only significant intervention difference between the active and control groups.Overall, dietary fiber intake was associated with a significant -1.65 mmHg [95% confidence interval (CI), -2.70 to -0.61] reduction in diastolic BP (DBP) and a non-significant -1.15 mmHg (95% CI, -2.68 to 0.39) reduction in systolic BP (SBP). A significant reduction in both SBP and DBP was observed in trials conducted among patients with hypertension (SBP -5.95 mmHg, 95% CI, -9.50 to -2.40; DBP -4.20 mmHg, 95% CI, -6.55 to -1.85) and in trials with a duration of intervention > or = 8 weeks (SBP -3.12 mmHg, 95% CI, -5.68 to -0.56; DBP -2.57 mmHg, 95% CI, -4.01 to -1.14).Our results indicate that increased intake of dietary fiber may reduce BP in patients with hypertension and suggests a smaller, non-conclusive, reduction in normotensives. An intervention period of at least 8 weeks may be necessary to achieve the maximum reduction in BP. Our findings warrant conduct of additional clinical trials with a larger sample size and longer period of intervention to examine the effect of dietary fiber intake on BP.
ABSTRACT We characterized the fish assemblages in second to fifth order streams of the upper Little Sioux River basin in northwest Iowa, USA and compared our results with historical surveys. The fish assemblage consisted of over twenty species, was dominated numerically by creek chub, sand shiner, central stoneroller and other cyprinids, and was dominated in biomass by common carp. Most of the species and the great majority of all individuals present were at least moderately tolerant to environmental degradation, and biotic integrity at most sites was characterized as fair. Biotic integrity declined with increasing stream size, and degraded habitat in larger streams is a possible cause. No significant changes in species richness or the relative distribution of species' tolerance appear to have occurred since the 1930s.
'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(10)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(20)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(40)'/%3e%3c/g%3e%3cuse xlink:href='%23e' transform='rotate(-80)'/%3e%3c/g%3e%3cpath d='M-225-21.5h450v7.5h-450z'/%3e%3cpath fill='%23339E35' d='M-225 86h450v100h-450z'/%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)