272 research outputs found

    Determination of cyclosporine concentration in bile

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    Mindfulness-Based Programs: Why, When, and How to Adapt?

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    This paper provides a framework for understanding why, when and how to adapt mindfulness-based programs (MBPs) to specific populations and contexts, based on research that developed and adapted multiple MBPs. In doing so, we hope to support teachers, researchers and innovators who are considering adapting an MBP to ensure that changes made are necessary, acceptable, effective, cost-effective, and implementable. Specific questions for reflection are provided such as (1) Why is an adaptation needed? (2) Does the theoretical premise underpinning mainstream MBPs extend to the population you are considering? (3) Do the benefits of the proposed adaptation outweigh the time and costs involved to all in research and implementation? (4) Is there already an evidenced-based approach to address this issue in the population or context? Fundamental knowledge that is important for the adaptation team to have includes the following: (1) essential ingredients of MBPs, (2) etiology of the target health outcome, (3) existing interventions that work for the health outcome, population, and context, (4) delivery systems and settings, and (5) culture, values, and communication patterns of the target population. A series of steps to follow for adaptations is provided, as are case examples. Adapting MBPs happens not only by researchers, but also by MBP teachers and developers, who endeavor to best serve the populations and contexts they work within. We hope that these recommendations for best practice provide a practical framework for skilfully understanding why, when, and how to adapt MBPs; and that this careful approach to adaptation maximizes MBP safety and efficacy

    Helping rural women in Pakistan to prevent postpartum hemorrhage: A quasi experimental study

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    BACKGROUND: According to the Pakistan Demographic and Health Survey from 2006–2007, the maternal mortality ratio in rural areas is 319 per 100,000 live births. Postpartum hemorrhage is the leading cause of maternal deaths in Pakistan. The objectives of the study were to document the feasibility of distribution of misoprostol tablets by community-based providers mainly traditional birth attendants and acceptability and use of misoprostol by women who gave birth at home. METHODS: A quasi-experimental design, comprising intervention and comparison areas, was used to document the acceptability of providing misoprostol tablets to pregnant women to prevent postpartum hemorrhage in the rural community setting in Pakistan. Data were collected using structured questionnaires administered to women before and after delivery at home and their birth attendants. RESULTS: Out of 770 women who delivered at home, 678 (88%) ingested misoprostol tablets and 647 (84%) ingested the tablets after the birth of the neonate but prior to the delivery of the placenta. The remaining women took misoprostol tablets after delivery of the placenta. Side effects were experienced by 40% of women and were transitory in nature. Among women who delivered at home, 80% said that they would use misoprostol tablets in the future and 74% were willing to purchase them in the future. CONCLUSIONS: Self-administration of misoprostol in the home setting is feasible. Community-based providers, such as traditional birth attendants and community midwives with proper training and counseling, play an important role in reducing postpartum hemorrhage. Proper counseling and information exchange are helpful for introducing new practices in resource-constrained rural communities. Until such a time that skilled birth attendance is made more universally available in the rural setting, alternative strategies, such as training and using the services of traditional birth attendants to provide safe pregnancy care, must be considered

    Folate deficiency increases the incidence of dolutegravir-associated foetal defects in a mouse pregnancy model

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    Background: Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model. / Methods: C57BL/6 mice fed a folate-deficient diet for 2 weeks, were mated and then randomly allocated to control (water), or 1xDTG (2.5 mg/kg), or 5xDTG (12.5 mg/kg) both administered orally with 50 mg/kg tenofovir disoproxil fumarate 33.3 mg/kg emtricitabine. Treatment was administered once daily from gestational day (GD) 0.5 to sacrifice (GD15.5). Foetuses were assessed for gross anomalies. Maternal and foetal folate levels were quantified. / Findings: 313 litters (103 control, 106 1xDTG, 104 5xDTG) were assessed. Viability, placental weight, and foetal weight did not differ between groups. NTDs were only observed in the DTG groups (litter rate: 0% control; 1.0% 1xDTG; 1.3% 5xDTG). Tail, abdominal wall, limb, craniofacial, and bleeding defects all occurred at higher rates in the DTG groups versus control. Compared with our previous findings on DTG usage in folate-replete mouse pregnancies, folate deficiency was associated with higher rates of several defects, including NTDs, but in the DTG groups only. We observed a severe left-right asymmetry phenotype that was more frequent in DTG groups than controls. / Interpretation: Maternal folate deficiency may increase the risk for DTG-associated foetal defects. Periconceptional folic acid supplementation could be considered for women with HIV taking DTG during pregnancy, particularly in countries lacking folate fortification programs. / Funding: This project has been funded by Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I and award #R01HD104553. LS is supported by a Tier 1 Canada Research Chair in Maternal-Child Health and HIV. HM is supported by a Junior Investigator award from the Ontario HIV Treatment Network

    Increased Birth Weight Associated with Regular Pre-Pregnancy Deworming and Weekly Iron-Folic Acid Supplementation for Vietnamese Women

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    Low birth weight is an important risk factor for neonatal and infant morbidity and mortality and may impact on growth and development. Maternal iron deficiency anaemia contributes to intrauterine growth restriction and low birth weight. Hookworm infections and an iron-depleted diet may lead to iron deficiency anaemia, and both are common in many developing countries. A pilot program of deworming and weekly iron-folic acid supplementation for non-pregnant women aiming to prevent iron deficiency was implemented in northern Vietnam. We compared the birth weight of babies born to women who had had access to the intervention to babies born in districts where the intervention had not been implemented. The mean birth weight of the intervention districts' babies was 124 g more than the control districts' babies; the prevalence of low birth weight was also reduced. These results suggest that providing women with deworming and weekly iron-folic acid supplements before pregnancy is associated with increased birth weight in rural Vietnam. This intervention was provided as a health system integrated program which could be replicated in other at-risk rural areas. If so it could increase the impact of prenatal and antenatal programs, improving the health of both women and newborns

    Global burden of disease due to smokeless tobacco consumption in adults : analysis of data from 113 countries

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    BACKGROUND: Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults. METHODS: The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population's exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease-specific risk estimates (relative risks/odds ratios) associated with it. Country-specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies. RESULTS: We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia. CONCLUSIONS: Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control

    A Forward-Genetic Screen and Dynamic Analysis of Lambda Phage Host-Dependencies Reveals an Extensive Interaction Network and a New Anti-Viral Strategy

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    Latently infecting viruses are an important class of virus that plays a key role in viral evolution and human health. Here we report a genome-scale forward-genetics screen for host-dependencies of the latently-infecting bacteriophage lambda. This screen identified 57 Escherichia coli (E. coli) genesβ€”over half of which have not been previously associated with infectionβ€”that when knocked out inhibited lambda phage's ability to replicate. Our results demonstrate a highly integrated network between lambda and its host, in striking contrast to the results from a similar screen using the lytic-only infecting T7 virus. We then measured the growth of E. coli under normal and infected conditions, using wild-type and knockout strains deficient in one of the identified host genes, and found that genes from the same pathway often exhibited similar growth dynamics. This observation, combined with further computational and experimental analysis, led us to identify a previously unannotated gene, yneJ, as a novel regulator of lamB gene expression. A surprising result of this work was the identification of two highly conserved pathways involved in tRNA thiolationβ€”one pathway is required for efficient lambda replication, while the other has anti-viral properties inhibiting lambda replication. Based on our data, it appears that 2-thiouridine modification of tRNAGlu, tRNAGln, and tRNALys is particularly important for the efficient production of infectious lambda phage particles

    A Re-Examination of Global Suppression of RNA Interference by HIV-1

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    The nature of the interaction between replicating HIV-1 and the cellular RNAi pathway has been controversial, but it is clear that it can be complex and multifaceted. It has been proposed that the interaction is bi-directional, whereby cellular silencing pathways can restrict HIV-1 replication, and in turn, HIV-1 can suppress silencing pathways. Overall suppression of RNAi has been suggested to occur via direct binding and inhibition of Dicer by the HIV-1 Tat protein or through sequestration of TRBP, a Dicer co-factor, by the structured TAR element of HIV-1 transcripts. The role of Tat as an inhibitor of Dicer has been questioned and our results support and extend the conclusion that Tat does not inhibit RNAi that is mediated by either exogenous or endogenous miRNAs. Similarly, we find no suppression of silencing pathways in cells with replicating virus, suggesting that viral products such as the TAR RNA elements also do not reduce the efficacy of cellular RNA silencing. However, knockdown of Dicer does allow increased viral replication and this occurs at a post-transcriptional level. These results support the idea that although individual miRNAs can act to restrict HIV-1 replication, the virus does not counter these effects through a global suppression of RNAi synthesis or processing
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