Seeking Optimal Means to Address Micronutrient Deficiencies in Food Supplements: A Case Study from the Bangladesh Integrated Nutrition Project

In seeking to improve the micronutrient contents of a food supplement used in a major community-based nutrition project in Bangladesh, operations research was conducted to compare the provision of needed micronutrients through additional food sources (fresh or dried fruits or vegetables), a micronutrient multi-mix, and a combination of the two. Micronutrient gaps (the difference between micronutrient requirements and actual micronutrient intake) were estimated for four groups of project beneficiaries, with target intakes defined as requirements for iron, calcium, zinc, vitamin A, vitamin C, riboflavin, niacin, and vitamin B12 recommended by the Food and Agriculture Organization/World Health Organization. Primary focus was placed on iron and vitamin A. Cost and bulk constraint analyses, based on cost of supplement, feasibility of delivery, and serving volume needed to achieve micronutrient targets, were used for comparing the supplement options. In terms of these analyses, the micronutrient multi-mix proved, by far, to be the most advantageous. Food options, however, are arguably desirable in that they provide dietary benefits additional to that of known micronutrients and may increase demand to boost production of domestic fruits and vegetables for the population as a whole. The study concludes that it is cost-effective to use powdered micronutrient mixes for such specific purposes as enrichment of supplementary food and food fortification, but encourages production and consumption of micronutrient-rich foods through programme messages and activities

A developing country response to Lavery et al. "In global health research, is it legitimate to stop clinical trials early on account of their opportunity costs?"

<p>Abstract</p> <p>Background</p> <p>A recent paper presents an argument and mechanism for the possible stopping of clinical trials early based on opportunity costs.</p> <p>Discussion</p> <p>Although we agree that the costs and opportunity costs of clinical trials need to be reduced wherever possible, we raise concerns about the motivation and mechanism for stopping clinical trials early raised by Lavery <it>et al</it>.</p> <p>Summary</p> <p>We argue that there are already enough acceptable criteria and actors in the clinical trials arena to justify early stoppage of clinical trials, and argue that factors other than efficacy need to be carefully considered, especially in developing country contexts.</p

Indoor Social Networks in a South African Township: Potential Contribution of Location to Tuberculosis Transmission

CITATION: Wood, R. et al. 2012. Indoor social networks in a South African township : potential contribution of location to tuberculosis transmission. PLoS ONE, 7(6): e39246, doi:10.1371/journal.pone.0039246.The original publication is available at http://journals.plos.org/plosoneBackground We hypothesized that in South Africa, with a generalized tuberculosis (TB) epidemic, TB infection is predominantly acquired indoors and transmission potential is determined by the number and duration of social contacts made in locations that are conducive to TB transmission. We therefore quantified time spent and contacts met in indoor locations and public transport by residents of a South African township with a very high TB burden. Methods A diary-based community social mixing survey was performed in 2010. Randomly selected participants (n = 571) prospectively recorded numbers of contacts and time spent in specified locations over 24-hour periods. To better characterize age-related social networks, participants were stratified into ten 5-year age strata and locations were classified into 11 types. Results Five location types (own-household, other-households, transport, crèche/school, and work) contributed 97.2% of total indoor time and 80.4% of total indoor contacts. Median time spent indoors was 19.1 hours/day (IQR:14.3–22.7), which was consistent across age strata. Median daily contacts increased from 16 (IQR:9–40) in 0–4 year-olds to 40 (IQR:18–60) in 15–19 year-olds and declined to 18 (IQR:10–41) in ≥45 year-olds. Mean daily own-household contacts was 8.8 (95%CI:8.2–9.4), which decreased with increasing age. Mean crèche/school contacts increased from 6.2/day (95%CI:2.7–9.7) in 0–4 year-olds to 28.1/day (95%CI:8.1–48.1) in 15–19 year-olds. Mean transport contacts increased from 4.9/day (95%CI:1.6–8.2) in 0–4 year-olds to 25.5/day (95%CI:12.1–38.9) in 25–29 year-olds. Conclusions A limited number of location types contributed the majority of indoor social contacts in this community. Increasing numbers of social contacts occurred throughout childhood, adolescence, and young adulthood, predominantly in school and public transport. This rapid increase in non-home socialization parallels the increasing TB infection rates during childhood and young adulthood reported in this community. Further studies of the environmental conditions in schools and public transport, as potentially important locations for ongoing TB infection, are indicated.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039246Publisher's versio

Corticotherapy for traumatic brain-injured Patients - The Corti-TC trial: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury (TBI) is a main cause of severe prolonged disability of young patients. Hospital acquired pneumonia (HAP) add to the morbidity and mortality of traumatic brain-injured patients. In one study, hydrocortisone for treatment of traumatic-induced corticosteroid insufficiency (CI) in multiple injured patients has prevented HAP, particularly in the sub-group of patients with severe TBI. Fludrocortisone is recommended in severe brain-injured patients suffering from acute subarachnoid hemorrhage. Whether an association of hydrocortisone with fludrocortisone protects from HAP and improves neurological recovery is uncertain. The aim of the current study is to compare corticotherapy to placebo for TBI patients with CI.</p> <p>Methods</p> <p>The CORTI-TC (Corticotherapy in traumatic brain-injured patients) trial is a multicenter, randomized, placebo controlled, double-blind, two-arms study. Three hundred and seventy six patients hospitalized in Intensive Care Unit with a severe traumatic brain injury (Glasgow Coma Scale ≤ 8) are randomized in the first 24 hours following trauma to hydrocortisone (200 mg.day^-1for 7 days, 100 mg on days 8-9 and 50 mg on day-10) with fludrocortisone (50 μg for 10 days) or double placebo. The treatment is stopped if patients have an appropriate adrenal response. The primary endpoint is HAP on day-28. The endpoint of the ancillary study is the neurological status on 6 and 12 months.</p> <p>Discussion</p> <p>The CORTI-TC trial is the first randomized controlled trial powered to investigate whether hydrocortisone with fludrocortisone in TBI patients with CI prevent HAP and improve long term recovery.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01093261">NCT01093261</a></p

Modification of Salmonella Typhimurium Motility by the Probiotic Yeast Strain Saccharomyces boulardii

BACKGROUND: Motility is an important component of Salmonella enterica serovar Typhimurium (ST) pathogenesis allowing the bacteria to move into appropriate niches, across the mucus layer and invade the intestinal epithelium. In vitro, flagellum-associated motility is closely related to the invasive properties of ST. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is widely prescribed for the prophylaxis and treatment of diarrheal diseases caused by bacteria or antibiotics. In case of Salmonella infection, S.b-B has been shown to decrease ST invasion of T84 colon cell line. The present study was designed to investigate the impact of S.b-B on ST motility. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed on human colonic T84 cells infected by the Salmonella strain 1344 alone or in the presence of S.b-B. The motility of Salmonella was recorded by time-lapse video microscopy. Next, a manual tracking was performed to analyze bacteria dynamics (MTrackJ plugin, NIH image J software). This revealed that the speed of bacterial movement was modified in the presence of S.b-B. The median curvilinear velocity (CLV) of Salmonella incubated alone with T84 decreased from 43.3 µm/sec to 31.2 µm/sec in the presence of S.b-B. Measurement of track linearity (TL) showed similar trends: S.b-B decreased by 15% the number of bacteria with linear tract (LT) and increased by 22% the number of bacteria with rotator tract (RT). Correlation between ST motility and invasion was further established by studying a non-motile flagella-deficient ST strain. Indeed this strain that moved with a CLV of 0.5 µm/sec, presented a majority of RT and a significant decrease in invasion properties. Importantly, we show that S.b-B modified the motility of the pathogenic strain SL1344 and significantly decreased invasion of T84 cells by this strain. CONCLUSIONS: This study reveals that S.b-B modifies Salmonella's motility and trajectory which may account for the modification of Salmonella's invasion

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Motivations and barriers to uptake and use of female-initiated, biomedical HIV prevention products in sub-Saharan Africa: an adapted meta-ethnography

Abstract: Background: Women bear a disproportionate burden of HIV throughout the world prompting extensive research into HIV prevention products for women which has met with varied success. With an aim of informing future policy and programming, this review examines the barriers and motivations to the uptake and use of female initiated products in sub-Saharan countries. Methods: We conducted a systematic review as an adapted meta-ethnography of qualitative data focused on actual use of products. After deduplication, 10,581 and 3861 papers in the first and second round respectively were screened. Following the PRISMA guidance, 22 papers were selected and synthesized using Malpass’s definitions of first, second, and third order constructs. First order constructs, consisting of participant data published in the selected papers, were extracted and categorised by second and third order constructs for analysis. A weight of evidence review was conducted to compare and assess quality across the papers. Results: The 22 papers selected span 11 studies in 13 countries. We derived 23 s order constructs that were translated into seven overarching third order constructs: Sexual Satisfaction, Trust, Empowerment and Control, Personal Well-being, Product use in the social-cultural environment, Practical Considerations, Risk Reduction, and Perceptions of Efficacy. Relationships and trust were seen to be as or more important for product use as efficacy. These constructs reveal an inherent inter-relationality where decision making around HIV prevention uptake and use cannot be binary or mono-faceted, but rather conducted on multiple levels. We developed a framework illustrating the central and proximal natures of constructs as they relate to the decision-making process surrounding the use of prevention products. Conclusions: Health systems, structural, and individual level HIV prevention interventions for women should adopt a holistic approach. Interventions should attend to the ways in which HIV prevention products can serve to reduce the likelihood of HIV transmission, as well as help to protect partnerships, enhance sexual pleasure, and take into account woman’s roles in the social environment. Stigma, as well as sexuality, is likely to continue to influence product uptake and use and should be prominently taken into account in large-scale interventions. Trial registration: Not applicable

Validated stability-indicating spectrofluorimetric methods for the determination of ebastine in pharmaceutical preparations

Two sensitive, selective, economic, and validated spectrofluorimetric methods were developed for the determination of ebastine (EBS) in pharmaceutical preparations depending on reaction with its tertiary amino group. Method I involves condensation of the drug with mixed anhydrides (citric and acetic anhydrides) producing a product with intense fluorescence, which was measured at 496 nm after excitation at 388 nm

14-3-3 Mediates Histone Cross-Talk during Transcription Elongation in Drosophila

Post-translational modifications of histone proteins modulate the binding of transcription regulators to chromatin. Studies in Drosophila have shown that the phosphorylation of histone H3 at Ser10 (H3S10ph) by JIL-1 is required specifically during early transcription elongation. 14-3-3 proteins bind H3 only when phosphorylated, providing mechanistic insights into the role of H3S10ph in transcription. Findings presented here show that 14-3-3 functions downstream of H3S10ph during transcription elongation. 14-3-3 proteins localize to active genes in a JIL-1–dependent manner. In the absence of 14-3-3, levels of actively elongating RNA polymerase II are severely diminished. 14-3-3 proteins interact with Elongator protein 3 (Elp3), an acetyltransferase that functions during transcription elongation. JIL-1 and 14-3-3 are required for Elp3 binding to chromatin, and in the absence of either protein, levels of H3K9 acetylation are significantly reduced. These results suggest that 14-3-3 proteins mediate cross-talk between histone phosphorylation and acetylation at a critical step in transcription elongation

CpG-ODN and MPLA Prevent Mortality in a Murine Model of Post-Hemorrhage-Staphyloccocus aureus Pneumonia

Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferon-beta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8+ cDCs- and CD8- cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia