A reappraisal of the quantitative relationship between sugar intake and dental caries: the need for new criteria for developing goals for sugar intake

There is a clear relation between sugars and caries. However, no analysis has yet been made of the lifetime burden of caries induced by sugar to see whether the WHO goal of 10% level is optimum and compatible with low levels of caries. The objective of this study was to re-examine the dose-response and quantitative relationship between sugar intake and the incidence of dental caries and to see whether the WHO goal for sugar intake of 10% of energy intake (E) is optimum for low levels of caries in children and adults

Vitamin D Status and its Association with Morbidity including Wasting and Opportunistic Illnesses in HIV-Infected Women in Tanzania.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings

Effect of household-based drinking water chlorination on diarrhoea among children under five in Orissa, India: a double-blind randomised placebo-controlled trial.

BACKGROUND: Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five. METHODS AND FINDINGS: We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC) tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence) among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC), an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating equations to account for clustering at the household level. The impact of the intervention on weight-for-age z scores (WAZ) was analysed using random effect linear regression. Over the follow-up period, 84,391 child-days of observations were recorded, representing 88% of total possible child-days of observation. The longitudinal prevalence of diarrhoea among intervention children was 1.69% compared to 1.74% among controls. After adjusting for clustering within household, the prevalence ratio of the intervention to control was 0.95 (95% CI 0.79-1.13). The mean WAZ was similar among children of the intervention and control groups (-1.586 versus -1.589, respectively). Among intervention households, 51% reported their child's drinking water to be treated with the tablets at the time of visit, though only 32% of water samples tested positive for residual chlorine. Faecal contamination of drinking water was lower among intervention households than controls (geometric mean TTC count of 50 [95% CI 44-57] per 100 ml compared to 122 [95% CI 107-139] per 100 ml among controls [p<0.001] [n = 4,546]). CONCLUSIONS: Our study was designed to overcome the shortcomings of previous double-blinded trials of household water treatment in low-income settings. The sample size was larger, the follow-up period longer, both urban and rural populations were included, and adherence and water quality were monitored extensively over time. These results provide no evidence that the intervention was protective against diarrhoea. Low compliance and modest reduction in water contamination may have contributed to the lack of effect. However, our findings are consistent with other blinded studies of similar interventions and raise additional questions about the actual health impact of household water treatment under these conditions. TRIAL REGISTRATION: ClinicalTrials.govNCT01202383 Please see later in the article for the Editors' Summary

The endocanabinnoid system and diabetes - critical analyses of studies conducted with rimonabant

Rimonabant is the first CB1 receptor inhibitor available in the Brazilian market. This new drug has been approved for the treatment of obese or overweight patients associated with cardiovascular risk factors. In this article it is compared the effects of rimonabant treatment in obese patients with cardiovascular risk factors to usual obesity pharmacological treatment

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Changes in energy expenditure associated with ingestion of high protein, high fat versus high protein, low fat meals among underweight, normal weight, and overweight females

Background: Metabolic rate is known to rise above basal levels after eating, especially following protein consumption. Yet, this postprandial rise in metabolism appears to vary among individuals. This study examined changes in energy expenditure in response to ingestion of a high protein, high fat (HPHF) meal versus an isocaloric high protein, low fat (HPLF) meal in underweight, normal weight, or overweight females (n = 21) aged 19–28 years. Methods: Energy expenditure, measured using indirect calorimetry, was assessed before and every 30 minutes for 3.5 hours following consumption of the meals on two separate occasions. Height and weight were measured using standard techniques. Body composition was measured using bioelectrical impedance analysis. Results: Significant positive correlations were found between body mass index (BMI) and baseline metabolic rate (MR) (r = 0.539; p = 0.017), between body weight and baseline MR (r = 0.567; p = 0.011), between BMI and average total change in MR (r = 0.591; p = 0.008), and between body weight and average total change in MR (r = 0.464; p = 0.045). Metabolic rate (kcal/min) was significantly higher in the overweight group than the normal weight group, which was significantly higher than the underweight group across all times and treatments. However, when metabolic rate was expressed per kg fat free mass (ffm), no significant difference was found in postprandial energy expenditure between the overweight and normal groups. Changes in MR (kcal/min and kcal/min/kg ffm) from the baseline rate did not significantly differ in the underweight (n = 3) or in the overweight subjects (n = 5) following consumption of either meal at any time. Changes in MR (kcal/min and kcal/min/kg ffm) from baseline were significantly higher in normal weight subjects (n = 11) across all times following consumption of the HPHF meal versus the HPLF meal. Conclusion: There is no diet-induced thermogenic advantage between the HPHF and HPLF meals in overweight and underweight subjects. In contrast, in normal weight subjects, ingestion of a HPHF meal significantly increases MR (69.3 kcal/3.5 hr) versus consumption of a HPLF meal and provides a short-term metabolic advantage

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record