A randomised controlled trial to compare the efficacy, safety, and tolerability of low dose, short course primaquine in adults with uncomplicated P. vivax malaria in two hospitals in India

Background: Plasmodium vivax remains a major challenge for malaria control and elimination due to its ability to cause relapsing illness. To prevent relapses the Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends treatment with primaquine at a dose of 0.25 mg/kg/day provided over 14 days. Shorter treatment courses may improve adherence and treatment effectiveness. Methods: This is a hospital-based, randomised, controlled, open-label trial in two centres in India. Patients above the age of 16 years, with uncomplicated vivax malaria, G6PD activity of ≥ 30% of the adjusted male median (AMM) and haemoglobin levels ≥ 8 g/dL will be recruited into the study and randomised in a 1:1 ratio to receive standard schizonticidal treatment plus 7-day primaquine at 0.50 mg/kg/day or standard care with schizonticidal treatment plus 14-day primaquine at 0.25 mg/kg/day. Patients will be followed up for 6 months. The primary endpoint is the incidence risk of any P. vivax parasitaemia at 6 months. Safety outcomes include the incidence risk of severe anaemia (haemoglobin 25% fall in haemoglobin and an acute drop in haemoglobin of > 5 g/dL during primaquine treatment. Discussion: This study will evaluate the efficacy and safety of a 7-day primaquine regimen compared to the standard 14-day regimen in India. Results from this trial are likely to directly inform national treatment guidelines. Trial registration: Trial is registered on CTRI portal, Registration No: CTRI/2022/12/048283

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

Sepsis Enhances Epithelial Permeability with Stretch in an Actin Dependent Manner

Ventilation of septic patients often leads to the development of edema and impaired gas exchange. We hypothesized that septic alveolar epithelial monolayers would experience stretch-induced barrier dysfunction at a lower magnitude of stretch than healthy alveolar epithelial monolayers. Alveolar epithelial cells were isolated from rats 24 hours after cecal ligation and double puncture (2CLP) or sham surgery. Following a 5-day culture period, monolayers were cyclically stretched for 0, 10, or 60 minutes to a magnitude of 12% or 25% change in surface area (ΔSA). Barrier function, MAPk and myosin light chain (MLC) phosphorylation, tight junction (TJ) protein expression and actin cytoskeletal organization were examined after stretch. Significant increases in epithelial permeability were observed only in 2CLP monolayers at the 12% ΔSA stretch level, and in both 2CLP and sham monolayers at the 25% ΔSA stretch level. Increased permeability in 2CLP monolayers was not associated with MAPk signaling or alterations in expression of TJ proteins. 2CLP monolayers had fewer actin stress fibers before stretch, a more robust stretch-induced actin redistribution, and reduced phosphorylated MLCK than sham monolayers. Jasplakinolide stabilization of the actin cytoskeleton in 2CLP monolayers prevented significant increases in permeability following 60 minutes of stretch to 12% ΔSA. We concluded that septic alveolar epithelial monolayers are more susceptible to stretch-induced barrier dysfunction than healthy monolayers due to actin reorganization

Role of anatomical sites and correlated risk factors on the survival of orthodontic miniscrew implants:a systematic review and meta-analysis

Abstract Objectives The aim of this review was to systematically evaluate the failure rates of miniscrews related to their specific insertion site and explore the insertion site dependent risk factors contributing to their failure. Search methods An electronic search was conducted in the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Knowledge, Scopus, MEDLINE and PubMed up to October 2017. A comprehensive manual search was also performed. Eligibility criteria Randomised clinical trials and prospective non-randomised studies, reporting a minimum of 20 inserted miniscrews in a specific insertion site and reporting the miniscrews’ failure rate in that insertion site, were included. Data collection and analysis Study selection, data extraction and quality assessment were performed independently by two reviewers. Studies were sub-grouped according to the insertion site, and the failure rates for every individual insertion site were analysed using a random-effects model with corresponding 95% confidence interval. Sensitivity analyses were performed in order to test the robustness of the reported results. Results Overall, 61 studies were included in the quantitative synthesis. Palatal sites had failure rates of 1.3% (95% CI 0.3–6), 4.8% (95% CI 1.6–13.4) and 5.5% (95% CI 2.8–10.7) for the midpalatal, paramedian and parapalatal insertion sites, respectively. The failure rates for the maxillary buccal sites were 9.2% (95% CI 7.4–11.4), 9.7% (95% CI 5.1–17.6) and 16.4% (95% CI 4.9–42.5) for the interradicular miniscrews inserted between maxillary first molars and second premolars and between maxillary canines and lateral incisors, and those inserted in the zygomatic buttress respectively. The failure rates for the mandibular buccal insertion sites were 13.5% (95% CI 7.3–23.6) and 9.9% (95% CI 4.9–19.1) for the interradicular miniscrews inserted between mandibular first molars and second premolars and between mandibular canines and first premolars, respectively. The risk of failure increased when the miniscrews contacted the roots, with a risk ratio of 8.7 (95% CI 5.1–14.7). Conclusions Orthodontic miniscrew implants provide acceptable success rates that vary among the explored insertion sites. Very low to low quality of evidence suggests that miniscrews inserted in midpalatal locations have a failure rate of 1.3% and those inserted in the zygomatic buttress have a failure rate of 16.4%. Moderate quality of evidence indicates that root contact significantly contributes to the failure of interradicular miniscrews placed between the first molars and second premolars. Results should be interpreted with caution due to methodological drawbacks in some of the included studies

Interaction between Dysfunctional Connectivity at Rest and Heroin Cues-Induced Brain Responses in Male Abstinent Heroin-Dependent Individuals

BACKGROUND: The majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU). METHODOLOGY/PRINCIPAL FINDINGS: We employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities. CONCLUSIONS: These results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence

FungalRV: adhesin prediction and immunoinformatics portal for human fungal pathogens

<p>Abstract</p> <p>Background</p> <p>The availability of sequence data of human pathogenic fungi generates opportunities to develop Bioinformatics tools and resources for vaccine development towards benefitting at-risk patients.</p> <p>Description</p> <p>We have developed a fungal adhesin predictor and an immunoinformatics database with predicted adhesins. Based on literature search and domain analysis, we prepared a positive dataset comprising adhesin protein sequences from human fungal pathogens <it>Candida albicans, Candida glabrata, Aspergillus fumigatus, Coccidioides immitis, Coccidioides posadasii, Histoplasma capsulatum, Blastomyces dermatitidis, Pneumocystis carinii, Pneumocystis jirovecii and Paracoccidioides brasiliensis</it>. The negative dataset consisted of proteins with high probability to function intracellularly. We have used 3945 compositional properties including frequencies of mono, doublet, triplet, and multiplets of amino acids and hydrophobic properties as input features of protein sequences to Support Vector Machine. Best classifiers were identified through an exhaustive search of 588 parameters and meeting the criteria of best Mathews Correlation Coefficient and lowest coefficient of variation among the 3 fold cross validation datasets. The "FungalRV adhesin predictor" was built on three models whose average Mathews Correlation Coefficient was in the range 0.89-0.90 and its coefficient of variation across three fold cross validation datasets in the range 1.2% - 2.74% at threshold score of 0. We obtained an overall MCC value of 0.8702 considering all 8 pathogens, namely, <it>C. albicans, C. glabrata, A. fumigatus, B. dermatitidis, C. immitis, C. posadasii, H. capsulatum </it>and <it>P. brasiliensis </it>thus showing high sensitivity and specificity at a threshold of 0.511. In case of <it>P. brasiliensis </it>the algorithm achieved a sensitivity of 66.67%. A total of 307 fungal adhesins and adhesin like proteins were predicted from the entire proteomes of eight human pathogenic fungal species. The immunoinformatics analysis data on these proteins were organized for easy user interface analysis. A Web interface was developed for analysis by users. The predicted adhesin sequences were processed through 18 immunoinformatics algorithms and these data have been organized into MySQL backend. A user friendly interface has been developed for experimental researchers for retrieving information from the database.</p> <p>Conclusion</p> <p>FungalRV webserver facilitating the discovery process for novel human pathogenic fungal adhesin vaccine has been developed.</p