Vitamin supplementation for prevention of mother-to-child transmission of HIV and pre-term delivery: a systematic review of randomized trial including more than 2800 women

BACKGROUND: Observational studies have suggested that low serum vitamin levels are associated with increased mother-to-child transmission (MTCT) of HIV and increased preterm delivery. We aimed to determine the efficacy of vitamins on the prevention of MTCT and preterm delivery by systematically reviewing the available randomized controlled trials [RCTs]. We conducted systematic searches of 7 electronic databases. We extracted data from the RCTs independently, in duplicate. RESULTS: We included 4 trials in our review. Of the three trials on Vitamin A, two suggested no difference in MTCT, while the third and largest trial (n = 1078) suggested an increased risk of MTCT (Relative Risk 1.35, 95% Confidence Interval [CI], 1.11–1.66, P = 0.009). Two of the vitamin A trials addressed the impact of supplementation on pre-term delivery; one suggested a benefit (RR 0.65, 95% CI, 0.44–0.94) and the other no difference. All three vitamin A trials found no significant effect on infant mortality at 1 year. Of the two trials that looked at multivitamin use, only one addressed the prevention of MTCT, and found a non-significant RR of 1.04 (95% CI, 0.82–1.32). Two of the multivitamin trials found no significant effects on pre-term delivery. The single multivitamin trial examining children's mortality at 1 year yielded a non-significant RR of 0.91 (95% CI, 0.17–1.17). CONCLUSION: Randomized trials of vitamins to prevent MTCT have yielded conflicting results without strong evidence of benefit and have failed to exclude the possibility of harm

Does ratification of human-rights treaties have effects on population health?

Human-rights treaties indicate a country's commitment to human rights. Here, we assess whether ratification of human-rights treaties is associated with improved health and social indicators. Data for health (including HIV prevalence, and maternal, infant, and child [<5 years] mortalities) and social indicators (child labour, human development index, sex gap, and corruption index), gathered from 170 countries, showed no consistent associations between ratification of human-rights treaties and health or social outcomes. Established market economy states had consistently improved health compared with less wealthy settings, but this was not associated with treaty ratification. The status of treaty ratification alone is not a good indicator of the realisation of the right to health. We suggest the need for stringent requirements for ratification of treaties, improved accountability mechanisms to monitor compliance of states with treaty obligations, and financial assistance to support the realisation of the right to health

Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer

<p>Abstract</p> <p>Background</p> <p>SULF1 (sulfatase 1) selectively removes the 6-O-sulphate group from heparan sulfate, changing the binding sites for extracellular growth factors. <it>SULF1 </it>expression has been reported to be decreased in various cancers, including ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) of <it>SULF1 </it>would impact clinicopathologic characteristics.</p> <p>Methods</p> <p>We genotyped five common (minor allele frequency>0.05) regulatory SNPs with predicted functionalities (rs2623047 G>A, rs13264163 A>G, rs6990375 G>A, rs3802278 G>A, and rs3087714 C>T) in 168 patients with primary epithelial ovarian cancer, using the polymerase chain reaction-restriction fragment length polymorphism method.</p> <p>Results</p> <p>We found that rs2623047 G>A was significantly associated with an early age of onset of ovarian cancer in the G allele dose-response manner (<it>P </it>= 0.027; <it>P_trend</it>= 0.007) and that rs2623047 GG/GA genotypes were associated with longer progression-free survival; rs6990375 G>A was also associated with the early age of onset in the A allele dose-response manner (<it>P </it>= 0.013; <it>P_trend</it>= 0.009). The significant differences in age of disease onset persisted among carriers of haplotypes of rs2623047 and rs6990375 (<it>P </it>= 0.014; <it>P_trend</it>= 0.004). In luciferase reporter gene assays, rs2623047 G allele showed a slightly higher promoter activity than the A allele in the SKOV3 tumorigenic cell line.</p> <p>Conclusions</p> <p>These findings suggest that genetic variations in <it>SULF1 </it>may play a role in ovarian cancer onset and prognosis. Further studies with large sample sizes and of the mechanistic relevance of <it>SULF1 </it>SNPs are warranted.</p

Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion.

Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple-negative" breast cancer (TNBC). Because phosphatases regulate the function of kinase signaling pathways, in this study, we investigated whether phosphatases are also differentially expressed in ER-negative compared to those in ER-positive breast cancers. We compared RNA expression in 98 human breast cancers (56 ER-positive and 42 ER-negative) to identify phosphatases differentially expressed in ER-negative compared to those in ER-positive breast cancers. We then examined the effects of one selected phosphatase, dual specificity phosphatase 4 (DUSP4), on proliferation, cell growth, migration and invasion, and on signaling pathways using protein microarray analyses of 172 proteins, including phosphoproteins. We identified 48 phosphatase genes are significantly differentially expressed in ER-negative compared to those in ER-positive breast tumors. We discovered that 31 phosphatases were more highly expressed, while 11 were underexpressed specifically in ER-negative breast cancers. The DUSP4 gene is underexpressed in ER-negative breast cancer and is deleted in approximately 50&nbsp;% of breast cancers. Induced DUSP4 expression suppresses both in vitro and in vivo growths of breast cancer cells. Our studies show that induced DUSP4 expression blocks the cell cycle at the G1/S checkpoint; inhibits ERK1/2, p38, JNK1, RB, and NFkB p65 phosphorylation; and inhibits invasiveness of TNBC cells. These results suggest that that DUSP4 is a critical regulator of the growth and invasion of triple-negative breast cancer cells

In the Era of Systematic Reviews, Does the Size of an Individual Trial Still Matter?

Background to the debate: Systematic reviews that combine high-quality evidence from several trials are now widely considered to be at the top of the hierarchy of clinical evidence. Given the primacy of systematic reviews—and the fact that individual clinical trials rarely provide definitive answers to a clinical research question—some commentators question whether the sample size calculation for an individual trial still matters. Others point out that small trials can still be potentially misleading

Factors affecting cellular uptake of anthocyanins: the role of pH, glucose and anthocyanin structure

Anthocyanins have poor bioavailability but factors affecting this remain unclear. Uptake into cells could impact the bioavailability and therefore, understanding factors affecting antho-cyanin uptake is pivotal to improve their bioavailability as well as reveal the mechanism for their uptake. This study aimed to investigate the effect of anthocyanin structure, pH and glucose on the uptake of anthocyanins by Caco-2 cells. Anthocyanin extract from strawberry and red grape at 10 or 20 µM was added to Caco-2 cells. Anthocyanin toxicity to the cells was firstly examined to ensure the same cell viability. The uptake was carried out at pH 7 and 6.5 to evaluate the effect of pH. Glucose of 1mM was used to investigate the effect of glucose. The result shows that anthocyanins toxicity was dependent on the concentration and length of exposure. Anthocyanin uptake was concentration-dependent and affected by their structures in which cyanidin-3-glucoside uptake was higher than pelargonidin-3-glucoside. No metabolites from Caco-2 cell activity were detected. An increased uptake with the decrease in pH was observed which may be linked to the increase in anthocyanins stability and may indicate the role of proton co-transporter. This also suggests that the jejunum would be the favorable section of small intestine for anthocyanin uptake. Reduced anthocyanin uptake in the presence of glucose suggested that facilitative glucose transporter could be involved in the uptake of anthocyanins by Caco-2 cells

Functional consequence of the MET-T1010I polymorphism in breast cancer.

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials

Users' Guides to the Medical Literature: How to Use an Article About Mortality in a Humanitarian Emergency

The accurate interpretation of mortality surveys in humanitarian crises is useful for both public health responses and security responses. Recent examples suggest that few medical personnel and researchers can accurately interpret the validity of a mortality survey in these settings. Using an example of a mortality survey from the Democratic Republic of Congo (DRC), we demonstrate important methodological considerations that readers should keep in mind when reading a mortality survey to determine the validity of the study and the applicability of the findings to their settings

Oxygen adsorption on Au clusters and a rough Au(111) surface: The role of surface flatness, electron confinement, excess electrons, and band gap

It has been shown recently that while bulk gold is chemically inert, small Au clusters are catalytically active. The reasons for this activity and its dramatic dependence on cluster size are not understood. We use density functional theory to study O2 binding to Au clusters and to a Au(111) surface modified by adsorption of Au clusters on it. We find that O2 does not bind to a flat face of a planar Au cluster, even though it binds well to its edge. Moreover, O2 binds to Au clusters deposited on a Au(111) surface, even though it does not bind to Au(111). This indicates that a band gap is not an essential factor in binding O2, but surface roughness is. Adding electrons to the surface of a Au(111) slab, on which one has deposited a Au cluster, increases the binding energy of O2. However, adding electrons to a flat Ausurface has no effect on O2binding energy. These observations have a simple explanation: in clusters and in the rough surface, the highest occupied molecular orbital (HOMO) is localized and its charge density sticks out in the vacuum. This facilitates charge transfer into the π* orbital of O2, which induces the molecule to bind to gold. A flat face of a cluster or a flat bulk surface tends to delocalize the HOMO, diminishing the ability of the surface to bind O2. The same statements are true for the LUMO orbital, which is occupied by the additional electron given to the system to charge the system negatively