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Most health care providers in Lagos State, Nigeria are private and are not required to offer breastfeeding counseling to women. From May 2019-April 2020, Alive & Thrive implemented a multicomponent breastfeeding promotion intervention in private health facilities in Lagos that included training and support to implement the Baby-Friendly Hospital Initiative and provide breastfeeding counseling and support to pregnant women and lactating mothers in person and on WhatsApp. We conducted a mixed methods process evaluation in 10 intervention and 10 comparison private health facilities to examine the feasibility and acceptability of integrating the intervention into routine health services. We conducted in-depth interviews with 20 health facility owners/managers and providers, 179 structured observations of health providers during service provision to pregnant and lactating women and 179 exit interviews with pregnant and lactating women. The in-depth interviews were transcribed and analyzed thematically. The structured observations and exit interviews were summarized using descriptive and inferential statistics. The in-depth interviews indicated that almost all health facility owners/managers and providers at the intervention health facilities had generally positive experiences with the intervention. However, the health providers reported implementation barriers including increased workload, use of personal time for counseling on WhatsApp, and some mothers' lack of access to WhatsApp support groups. Observations suggested that more breastfeeding counseling occurred at intervention compared with comparison health facilities. Third trimester exit interviews showed that 86% of women in the intervention health facilities were very confident they could carry out the breastfeeding advice they received, compared to 47% in the comparison health facilities. Our research suggests that provision of breastfeeding counseling and support through private health facilities is feasible and acceptable, but service delivery challenges must be considered for successful scale-up.

BackgroundThe Planetary Health Diet Index (PHDI) measures adherence to the sustainable dietary guidance proposed by the EAT-Lancet Commission on Food, Planet, Health. To justify incorporating sustainable dietary guidance such as the PHDI in the US, the index needs to be compared to health-focused dietary recommendations already in use. The objectives of this study were to compare the how the Planetary Health Diet Index (PHDI), the Healthy Eating Index-2015 (HEI-2015) and Dietary Approaches to Stop Hypertension (DASH) relate to cardiometabolic risk factors.Methods and findingsParticipants from the National Health and Nutrition Examination Survey (2015-2018) were assigned a score for each dietary index. We examined disparities in dietary quality for each index. We used linear and logistic regression to assess the association of standardized dietary index values with waist circumference, blood pressure, HDL-C, fasting plasma glucose (FPG) and triglycerides (TG). We also dichotomized the cardiometabolic indicators using the cutoffs for the Metabolic Syndrome and used logistic regression to assess the relationship of the standardized dietary index values with binary cardiometabolic risk factors. We observed diet quality disparities for populations that were Black, Hispanic, low-income, and low-education. Higher diet quality was associated with improved continuous and binary cardiometabolic risk factors, although higher PHDI was not associated with high FPG and was the only index associated with lower TG. These patterns remained consistent in sensitivity analyses.ConclusionsSustainability-focused dietary recommendations such as the PHDI have similar cross-sectional associations with cardiometabolic risk as HEI-2015 or DASH. Health-focused dietary guidelines such as the forthcoming 2025-2030 Dietary Guidelines for Americans can consider the environmental impact of diet and still promote cardiometabolic health.

Little is known about the mental health consequences of the COVID-19 pandemic in healthcare workers (HCWs). Past literature has shown that chronic strain caused by pandemics can adversely impact a variety of mental health outcomes in HCWs. There is growing recognition of the risk of stress and loss of resilience to HCWs during the COVID-19 pandemic, although the risk of post-traumatic stress disorder (PTSD) symptoms in HCWs during the COVID-19 pandemic remains poorly understood. We wanted to understand the relationship between the COVID-19 pandemic and the risk of PTDS symptoms in HCWs during the COVID-19 pandemic. We surveyed 2038 health care workers enrolled in the Healthcare Worker Exposure Response & Outcomes (HERO) study, which is a large standardized national registry of health care workers. Participants answered questions about demographics, COVID-19 exposure, job burnout, and PTSD symptoms. We characterize the burden of PTSD symptoms among HCWs, and determined the association between high PTSD symptoms and race, gender, professional role, work setting, and geographic region using multivariable regression. In a fully adjusted model, we found that older HCWs were less likely to report high PTSD symptoms compared with younger HCWs. Additionally, we found that physicians were less likely to report high PTSD symptoms compared with nurses. These data add to the growing literature on increased risks of mental health challenges to healthcare workers during the COVID-19 pandemic.

ObjectiveThere is scant research on the effectiveness of permanent supportive housing for homeless women with mental illness. This study examines the effectiveness of Housing First with an unprecedentedly large sample of homeless women from five Canadian cities, and explore baseline risk factors that predict social, health and well-being outcomes over a 24 month-period.MethodsThe At Home/Chez Soi multi-site randomized controlled Housing First trial recruited over 600 women between October 2009 and July 2011. This is a post-hoc subgroup exploratory analysis of self-identified women with at least one follow-up interview who were randomized to Housing First (HF) (n = 374) or treatment-as-usual (TAU) (n = 279) and had at least one follow-up interview. Linear mixed models and generalized estimating equations were used after multiple imputation was applied to address missing data.ResultsAt the end of follow-up, the mean percentage of days spent stably housed was higher for women in the intervention 74.8% (95%CI = 71.7%-77.8%) compared with women in the treatment-as-usual group, 37.9% (95%CI = 34.4%-41.3%), pConclusionsHousing First interventions ensured that women experiencing homelessness are quickly and consistently stably housed. However, they did not differentially impact health and social measures compared to treatment as usual. Ensuring positive health and social outcomes may require greater supports at enrolment for subgroups such as those with low educational attainment, and additional attention to severity of baseline mental health challenges, such as suicidality.Trial registrationInternational Standard Randomized Control Trial Number Register Identifier: ISRCTN42520374.

While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid-based nutrient supplements (LNS) or a control group, to investigate each vitamers contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography-fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra-performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin-pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9-4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151 μg/L (TMP), 13.3 versus 10.5 μg/L (free thiamin, p

The infant gut microbiome progresses in composition and function during the introduction of solid foods throughout the first year of life. The purpose of this study was to characterize changes in healthy infant gut microbiome composition, metagenomic functional capacity, and associated metabolites over the course of the complementary feeding period. Fecal samples were obtained at three 'snapshot' timepoints from infants participating in the 'Nourish to Flourish' pilot study: before the introduction of solid foods at approximately 4 months of age, after introducing solid foods at 9 months of age, and after continued diet diversification at 12 months of age. KEGG and taxonomy assignments were correlated with LC-MS metabolomic profiles to identify patterns of co-abundance. The composition of the microbiome diversified during the first year of life, while the functional capacity present in the gut microbiome remained stable. The introduction of solid foods between 4 and 9 months of age corresponded to a larger magnitude of change in relative abundance of sequences assigned to KEGG pathways and taxonomic assignments, as well as to stronger correlations with metabolites, compared to the magnitude of changes and number of correlations seen during continued diet diversification between 9 and 12 months of age. Changes in aqueous fecal metabolites were more strongly correlated with KEGG pathway assignments, while changes in lipid metabolites associated with taxonomic assignments, particularly between 9 and 12 months of age. This study establishes trends in microbiome composition and functional capacity occurring during the complementary feeding period and identifies potential metabolite targets for future investigations.

Mycobacteriophages--viruses of mycobacterial hosts--are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages--Corndog, Catdawg, Dylan, Firecracker, and YungJamal--designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange.

Cooking with polluting and inefficient fuels and technologies is responsible for a large set of global harms, ranging from health and time losses among the billions of people who are energy poor, to environmental degradation at a regional and global scale. This paper presents a new decision-support model-the BAR-HAP Tool-that is aimed at guiding planning of policy interventions to accelerate transitions towards cleaner cooking fuels and technologies. The conceptual model behind BAR-HAP lies in a framework of costs and benefits that is holistic and comprehensive, allows consideration of multiple policy interventions (subsidies, financing, bans, and behavior change communication), and realistically accounts for partial adoption and use of improved cooking technology. It incorporates evidence from recent efforts to characterize the relevant set of parameters that determine those costs and benefits, including those related to intervention effectiveness. Practical aspects of the tool were modified based on feedback from a pilot testing workshop with multisectoral users in Nepal. To demonstrate the functionality of the BAR-HAP tool, we present illustrative calculations related to several cooking transitions in the context of Nepal. In accounting for the multifaceted nature of the issue of household air pollution, the BAR-HAP model is expected to facilitate cross-sector dialogue and problem-solving to address this major health, environment and development challenge.

Background Correct certification of cause of death by physicians (i.e. completing the medical certificate of cause of death or MCCOD) and correct coding according to International Classification of Diseases (ICD) rules are essential to produce quality mortality statistics to inform health policy. Despite clear guidelines, errors in medical certification are common. This study objectively measures the impact of different medical certification errors upon the selection of the underlying cause of death. Methods A sample of 1592 error-free MCCODs were selected from the 2017 United States multiple cause of death data. The ten most common types of errors in completing the MCCOD (according to published studies) were individually simulated on the error-free MCCODs. After each simulation, the MCCODs were coded using Iris automated mortality coding software. Chance-corrected concordance (CCC) was used to measure the impact of certification errors on the underlying cause of death. Weights for each error type and Socio-demographic Index (SDI) group (representing different mortality conditions) were calculated from the CCC and categorised (very high, high, medium and low) to describe their effect on cause of death accuracy. Findings The only very high impact error type was reporting an ill-defined condition as the underlying cause of death. High impact errors were found to be reporting competing causes in Part 1 [of the death certificate] and illegibility, with medium impact errors being reporting underlying cause in Part 2 [of the death certificate], incorrect or absent time intervals and reporting contributory causes in Part 1, and low impact errors comprising multiple causes per line and incorrect sequence. There was only small difference in error importance between SDI groups. Conclusions Reporting an ill-defined condition as the underlying cause of death can seriously affect the coding outcome, while other certification errors were mitigated through the correct application of mortality coding rules. Training of physicians in not reporting ill-defined conditions on the MCCOD and mortality coders in correct coding practices and using Iris should be important components of national strategies to improve cause of death data quality.

BackgroundThe widely-used estimates of completeness of birth registration collected by Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) and published by UNICEF primarily rely on registration status of children as reported by respondents. However, these self-reported estimates may be inaccurate when compared with completeness as assessed from nationally-reported official birth registration statistics, for several reasons, including over-reporting of registration due to concern about penalties for non-registration. This study assesses the concordance of self-reported birth registration and certification completeness with completeness calculated from civil registration and vital statistics (CRVS) systems data for 57 countries.MethodsSelf-reported estimates of birth registration and certification completeness, at ages less than five years and 12-23 months, were compiled and calculated from the UNICEF birth registration database, DHS and MICS. CRVS birth registration completeness was calculated as birth registrations reported by a national authority divided by estimates of live births published in the United Nations (UN) World Population Prospects or the Global Burden of Disease (GBD) Study. Summary measures of concordance were used to compare completeness estimates.FindingsBirth registration completeness (based on ages less than five years) calculated from self-reported data is higher than that estimated from CRVS data in most of the 57 countries (31 countries according to UN estimated births, average six percentage points (p.p.) higher; 43 countries according to GBD, average eight p.p. higher). For countries with CRVS completeness less than 95%, self-reported completeness was higher in 26 of 28 countries, an average 13 p.p. and median 9-10 p.p. higher. Self-reported completeness is at least 30 p.p. higher than CRVS completeness in three countries. Self-reported birth certification completeness exhibits closer concordance with CRVS completeness. Similar results are found for self-reported completeness at 12-23 months.ConclusionsThese findings suggest that self-reported completeness figures over-estimate completeness when compared with CRVS data, especially at lower levels of completeness, partly due to over-reporting of registration by respondents. Estimates published by UNICEF should be viewed cautiously, especially given their wide usage.

Background and objectiveMany countries have used the new ANACONDA (Analysis of Causes of National Death for Action) tool to assess the quality of their cause of death data (COD), but no cross-country analysis has been done to verify how different or similar patterns of diagnostic errors and data quality are in countries or how they are related to the local cultural or epidemiological environment or to levels of development. Our objective is to measure whether the usability of COD data and the patterns of unusable codes are related to a country's level of socio-economic development.MethodsWe have assessed the quality of 20 national COD datasets from the WHO Mortality Database by assessing their completeness of COD reporting and the extent, pattern and severity of garbage codes, i.e. codes that provide little or no information about the true underlying COD. Garbage codes were classified into four groups based on the severity of the error in the code. The Vital Statistics Performance Index for Quality (VSPI(Q)) was used to measure the overall quality of each country's mortality surveillance system.FindingsThe proportion of 'garbage codes' varied from 7 to 66% across the 20 countries. Countries with a high SDI generally had a lower proportion of high impact (i.e. more severe) garbage codes than countries with low SDI. While the magnitude and pattern of garbage codes differed among countries, the specific codes commonly used did not.ConclusionsThere is an inverse relationship between a country's socio-demographic development and the overall quality of its cause of death data, but with important exceptions. In particular, some low SDI countries have vital statistics systems that are as reliable as more developed countries. However, in low-income countries, where most people die at home, the proportion of unusable codes often exceeds 50%, implying that half of all cause-specific mortality data collected is of little or no use in guiding public policy. Moreover, the cause of death pattern identified from the data is likely to seriously under-represent the true extent of the leading causes of death in the population, with very significant consequences for health priority setting. Garbage codes are prevalent at all ages, contrary to expectations. Further research into effective strategies deployed in these countries to improve data quality can inform efforts elsewhere to improve COD reporting systems.

INTRODUCTION:Adult male and female mortality declines in Japan have been slower than in most high-income countries since the early 1990s. This study compares Japan's recent life expectancy trends with the more favourable trends in Australia, measures the contribution of age groups and causes of death to differences in these trends, and places the findings in the context of the countries' risk factor transitions. METHODS:The study utilises data on deaths by age, sex and cause in Australia and Japan from 1950-2016 from the Global Burden of Disease Study. A decomposition method measures the contributions of various ages and causes to the male and female life expectancy gap and changes over four distinct phases during this period. Mortality differences by cohort are also assessed. FINDINGS:Japan's two-year male life expectancy advantage over Australia in the 1980s closed in the following 20 years. The trend was driven by ages 45-64 and then 65-79 years, and the cohort born in the late 1940s. Over half of Australia's gains were from declines in ischaemic heart disease (IHD) mortality, with lung cancer, chronic respiratory disease and self-harm also contributing substantially. Since 2011 the trend has reversed again, and in 2016 Japan had a slightly higher male life expectancy. The advantage in Japanese female life expectancy widened over the period to 2.3 years in 2016. The 2016 gap was mostly from differential mortality at ages 65 years and over from IHD, chronic respiratory disease and cancers. CONCLUSIONS:The considerable gains in Australian male life expectancy from declining non-communicable disease mortality are attributable to a range of risk factors, including declining smoking prevalence due to strong public health interventions. A recent reversal in life expectancy trends could continue because Japan has greater scope for further falls in smoking and far lower levels of obesity. Japan's substantial female life expectancy advantage however could diminish in future because it is primarily due to lower mortality at old ages.

The purpose of this study was to quantitatively assess gait characteristics and weight-bearing forces during ambulation in goats free of lameness using a pressure-sensing walkway as a biometric tool for stride, gait, and force analysis. Forty-six non-lame adult goats ranging in age from 5 to 6 years, mixed-breeds, and with a mean body weight of 52 ± 7.1 kgs were used. Goats were trained to walk over a pressure-sensing walkway. Data for analysis was collected on 2 different days, 3 days apart. On each day, 2 to 5 walking passes, in the same direction, were captured for each goat. Data from 2 valid passes meeting the criteria for consistent walking gait on each day were averaged then used for analysis. Analysis was performed, including the day-effect, for stride, gait, and force characteristics. Of the 46 goats enrolled in the study, complete data sets were achieved in 33 (72%) goats. Gait biometrics were similar among the assessment days; therefore, all data was pooled for the purpose of characterizing data for individual limb and biometric parameter comparisons at the individual goat level. Statistical analysis revealed that no difference within the paired limbs, and that there were significant differences between the front limbs and hind limbs. Maximum force and maximum peak pressure were significantly greater for the front limbs as compared with the hind limbs (p < 0.001). Based on the results, gait and force characteristics can be consistently measured in goats using a pressure-sensing walkway during a consistent walking gait. Goats apply greater force to the forelimbs during the weight-bearing phase of stride as compared with the hind limbs. The use of objective assessment tools is expected to improve the ability of researchers and clinicians to monitor changes in weight bearing and gait and will contribute to improved animal welfare.

Advancements in wearable technology have facilitated performance monitoring in a number of sports. Figure skating may also benefit from this technology, but the inherent movements present some unique challenges. The purpose of this study was to evaluate the feasibility of using an inertial measurement unit (IMU) to monitor three aspects of figure skating jumping performance: jump count, jump height, and rotation speed. Seven competitive figure skaters, outfitted with a waist-mounted IMU, performed a total of 59 isolated multi-revolution jumps and their competition routines, which consisted of 41 multi-revolution jumps along with spins, footwork, and other skills. The isolated jumps were used to develop a jump identification algorithm, which was tested on the competition routines. Four algorithms to estimate jump height from flight time were then evaluated using calibrated video as a gold standard. The identification algorithm counted 39 of the 41 program jumps correctly, with one false positive. Flight time and jump height errors under 7% and 15% respectively were found using a peak-to-peak scaling algorithm. Rotation speeds up to 1,500°/s were noted, with peak speeds occurring just over halfway between takeoff and landing. Overall, jump monitoring via IMUs may be an efficient aid for figure skaters training multi-revolution jumps.

Many national and subnational governments need to routinely measure the completeness of death registration for monitoring and statistical purposes. Existing methods, such as death distribution and capture-recapture methods, have a number of limitations such as inaccuracy and complexity that prevent widespread application. This paper presents a novel empirical method to estimate completeness of death registration at the national and subnational level.Random-effects models to predict the logit of death registration completeness were developed from 2,451 country-years in 110 countries from 1970-2015 using the Global Burden of Disease 2015 database. Predictors include the registered crude death rate, under-five mortality rate, population age structure and under-five death registration completeness. Models were developed separately for males, females and both sexes.All variables are highly significant and reliably predict completeness of registration across a wide range of registered crude death rates (R-squared 0.85). Mean error is highest at medium levels of observed completeness. The models show quite close agreement between predicted and observed completeness for populations outside the dataset. There is high concordance with the Hybrid death distribution method in Brazilian states. Uncertainty in the under-five mortality rate, assessed using the dataset and in Colombian departmentos, has minimal impact on national level predicted completeness, but a larger effect at the subnational level.The method demonstrates sufficient flexibility to predict a wide range of completeness levels at a given registered crude death rate. The method can be applied utilising data readily available at the subnational level, and can be used to assess completeness of deaths reported from health facilities, censuses and surveys. Its utility is diminished where the adult mortality rate is unusually high for a given under-five mortality rate. The method overcomes the considerable limitations of existing methods and has considerable potential for widespread application by national and subnational governments.

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.

Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35-46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) using nebulized lipopolysaccharide (LPS) in a non-invasive approach, focusing on its short and long-term effects.Mice received nebulized LPS or vehicle only (control group). Blood, BALF and lung tissue were collected 24 hours (LPS 24h) or 5 weeks (LPS 5w) after the nebulized LPS-induced lung injury. Inflammatory cytokines were assessed in the blood serum, BALF and lung tissue. Stereological analyses and remodeling changes were assessed by histology and immunohistochemistry at the specified time points.The LPS 24h group showed increased pro-inflammatory cytokine levels, intense cell influx, increased total septal volume, septal thickening and decreased surface density of the alveolar septa. The LPS 5w group showed persistent lung inflammation, septal thickening, increased total lung volume, accentuated collagen deposition, especially of collagen type I, and decreased MMP-2 protein expression.We present a feasible, reproducible and non-invasive nebulized-LPS animal model that allows the assessment of both the acute and late phases of acute lung injury. The presence of lung remodeling with collagen deposition after 5 weeks makes it useful to study the pathophysiology, complications, and possible therapeutic intervention studies that aim to understand and reduce pulmonary fibrosis in the late phases of ALI.

BACKGROUND:The effectiveness of prenatal care for improving birth and subsequent child outcomes in low-income countries remains controversial, with much of the evidence to date coming from high-income countries and focused on early-life outcomes. We examined associations between prenatal care visits and birth weight, height-for-age at 24 months and attained schooling in four low- and middle-income countries. METHODS:We pooled data from prospective birth-cohort studies from Brazil, Guatemala, Philippines and South Africa. We created a prenatal care utilization index based on the number and timing of prenatal visits. Associations were examined between this index and birth weight, height-for-age at 24 months, and highest attained schooling grade until adulthood. RESULTS:Among 7203 individuals in the analysis, 68.9% (Philippines) to 96.7% (South Africa) had at least one prenatal care visit, with most having at least four visits. Over 40% of Brazilians and Guatemalans had their first prenatal visit in the first trimester, but fewer Filipinos (13.9%) and South Africans (19.8%) did so. Prenatal care utilization was not significantly associated with birth weight (p>0.05 in pooled data). Each unit increase in the prenatal care utilization index was associated with 0.09 (95% CI 0.04 to 0.15) higher height-for-age z-score at 24 months and with 0.26 (95% CI 0.17 to 0.35) higher schooling grades attained. Although there was some heterogeneity and greater imprecision across sites, the results were qualitatively similar among the four different populations. CONCLUSIONS:While not related to birth weight, prenatal care utilization was associated with important outcomes later in life, specifically higher height-for-age at 24 months and higher attained school grades. These results suggest the relevance of prenatal care visits for human capital outcomes important over the lifecycle.

While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid-based nutrient supplements (LNS) or a control group, to investigate each vitamer's contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography-fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra-performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin-pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9-4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151 μg/L (TMP), 13.3 versus 10.5 μg/L (free thiamin, p

Hand-held dynamometry (HHD) has never previously been used to examine isometric muscle power. Rate of force development (RFD) is often used for muscle power assessment, however no consensus currently exists on the most appropriate method of calculation. The aim of this study was to examine the reliability of different algorithms for RFD calculation and to examine the intra-rater, inter-rater, and inter-device reliability of HHD as well as the concurrent validity of HHD for the assessment of isometric lower limb muscle strength and power.30 healthy young adults (age: 23±5 yrs, male: 15) were assessed on two sessions. Isometric muscle strength and power were measured using peak force and RFD respectively using two HHDs (Lafayette Model-01165 and Hoggan microFET2) and a criterion-reference KinCom dynamometer. Statistical analysis of reliability and validity comprised intraclass correlation coefficients (ICC), Pearson correlations, concordance correlations, standard error of measurement, and minimal detectable change.Comparison of RFD methods revealed that a peak 200 ms moving window algorithm provided optimal reliability results. Intra-rater, inter-rater, and inter-device reliability analysis of peak force and RFD revealed mostly good to excellent reliability (coefficients ≥ 0.70) for all muscle groups. Concurrent validity analysis showed moderate to excellent relationships between HHD and fixed dynamometry for the hip and knee (ICCs ≥ 0.70) for both peak force and RFD, with mostly poor to good results shown for the ankle muscles (ICCs = 0.31-0.79).Hand-held dynamometry has good to excellent reliability and validity for most measures of isometric lower limb strength and power in a healthy population, particularly for proximal muscle groups. To aid implementation we have created freely available software to extract these variables from data stored on the Lafayette device. Future research should examine the reliability and validity of these variables in clinical populations.

To assess if the maternal pre-pregnancy weight status (MPWS) alters the association of early infant feeding pattern (at one and third months) with infant body mass index (BMI) in the first two years of life.A cohort of 2,220 neonates were recruited in a community-based study conducted in China. Body weight and length were measured at birth, at age one and two, with BMI calculated accordingly. The BMI z-scores (BMI-Z) were computed according to the World Health Organization Growth Standard (2006). Feeding patterns were classified as exclusive breastfeeding (EBF), mixed feeding (MF), and formula feeding (FF). General linear models (GLM) were employed to estimate main and interaction effects of EBF and MPWS on children's BMI-Z.No main effect of MPWS was found on child BMI-Z at ages one and two, nor the feeding patterns. An interaction between MPWS and feeding patterns was detected (p

Studies have reported that exposure to diesel exhaust particles (DEPs) induces lung inflammation and increases oxidative stress, and both effects are susceptible to changes via regular aerobic exercise in rehabilitation programs. However, the effects of exercise on lungs exposed to DEP after the cessation of exercise are not clear. Therefore, the aim of this study was to evaluate the effects of high-intensity swimming on lung inflammation and oxidative stress in mice exposed to DEP concomitantly and after exercise cessation. Male Swiss mice were divided into 4 groups: Control (n = 12), Swimming (30 min/day) (n = 8), DEP (3 mg/mL-10 μL/mouse) (n = 9) and DEP+Swimming (n = 8). The high-intensity swimming was characterized by an increase in blood lactate levels greater than 1 mmoL/L between 10th and 30th minutes of exercise. Twenty-four hours after the final exposure to DEP, the anesthetized mice were euthanized, and we counted the number of total and differential inflammatory cells in the bronchoalveolar fluid (BALF), measured the lung homogenate levels of IL-1β, TNF-α, IL-6, INF-ϫ, IL-10, and IL-1ra using ELISA, and measured the levels of glutathione, non-protein thiols (GSH-t and NPSH) and the antioxidant enzymes catalase and glutathione peroxidase (GPx) in the lung. Swimming sessions decreased the number of total cells (p

Mycobacteriophages--viruses of mycobacterial hosts--are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages--Corndog, Catdawg, Dylan, Firecracker, and YungJamal--designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange.

Objective: There is scant research on the effectiveness of permanent supportive housing for homeless women with mental illness. This study examines the effectiveness of Housing First with an unprecedentedly large sample of homeless women from five Canadian cities, and explore baseline risk factors that predict social, health and well-being outcomes over a 24 month-period. Methods: The At Home/Chez Soi multi-site randomized controlled Housing First trial recruited over 600 women between October 2009 and July 2011. This is a post-hoc subgroup exploratory analysis of self-identified women with at least one follow-up interview who were randomized to Housing First (HF) (n = 374) or treatment-as-usual (TAU) (n = 279) and had at least one follow-up interview. Linear mixed models and generalized estimating equations were used after multiple imputation was applied to address missing data. Results: At the end of follow-up, the mean percentage of days spent stably housed was higher for women in the intervention 74.8% (95%CI = 71.7%–77.8%) compared with women in the treatment-as-usual group, 37.9% (95%CI = 34.4%–41.3%), p<0.001. With few exceptions, social and mental health outcomes were similar for both groups at 6-, 12-, 18- and 24-months post-enrollment. Suicidality was a consistent predictor of increased mental health symptoms (beta = 2.85, 95% CI 1.59–4.11, p<0.001), decreased quality of life (beta = -3.99, 95% CI -6.49 to -1.49, p<0.001), decreased community functioning (beta = -1.16, 95% CI -2.10 to -0.22, p = 0.015) and more emergency department visits (rate ratio = 1.44, 95% CI 1.10–1.87, p<0.001) over the study period. Lower education was a predictor of lower community functioning (beta = -1.32, 95% CI -2.27 to -0.37, p = 0.006) and higher substance use problems (rate ratio = 1.27, 95% CI 1.06–1.52, p = 0.009) during the study. Conclusions: Housing First interventions ensured that women experiencing homelessness are quickly and consistently stably housed. However, they did not differentially impact health and social measures compared to treatment as usual. Ensuring positive health and social outcomes may require greater supports at enrolment for subgroups such as those with low educational attainment, and additional attention to severity of baseline mental health challenges, such as suicidality. Trial registration: International Standard Randomized Control Trial Number Register Identifier: ISRCTN42520374. [ABSTRACT FROM AUTHOR]

A rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen administered by oral route showed gastroprotective activity against acute lesions induced by ethanol. In this study, we investigated the gastric ulcer healing effect of RGal and its mechanisms of action. Intraperitoneal treatment of animals with RGal protected the gastric mucosa against acute lesions induced by ethanol, with participation of gastric mucus. Furthermore, in the chronic ulcer model, oral administration of RGal accelerates the gastric ulcer healing, accompanied by increasing of cellular proliferation and gastric mucus content, reducing inflammatory parameters and oxidative stress. In addition, the repeated 7 days-treatment of animals with RGal did not show alterations of clinical and behavioral symptoms, body and organs weights or plasmatic biochemical parameters. Collectively, these results showed that RGal has an interesting antiulcerogenic activity and could constitute an attractive molecule of interest for the development of new antiulcer agents.

Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)). The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively). In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress.

Currently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.Affymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic cancer. Patients with high-risk scores had significantly higher risk of death compared to patients with low-risk scores (HR 2.27, p = 0.002). When the 13-gene score was combined with lymph node status the risk-score further discriminated the length of patient survival time (p

S-(+)-dicentrine is an aporphinic alkaloid found in several plant species, mainly from Lauraceae family, which showed significant antinociceptive activity in an acute model of visceral pain in mice. In this work, we extended the knowledge on the antinociceptive properties of S-(+)-dicentrine and showed that this alkaloid also attenuates mechanical and cold hypersensitivity associated with cutaneous inflammation induced by Complete Freund's Adjuvant in mice. Given orally, S-(+)-dicentrine (100 mg/kg) reversed CFA-induced mechanical hypersensitivity, evaluated as the paw withdrawal threshold to von Frey hairs, and this effect lasted up to 2 hours. S-(+)-dicentrine also reversed CFA-induced cold hypersensitivity, assessed as the responses to a drop of acetone in the injured paw, but did not reverse the heat hypersensitivity, evaluated as the latency time to paw withdrawal in the hot plate (50°C). Moreover, S-(+)-dicentrine (100 mg/kg, p.o.) was effective in inhibit nociceptive responses to intraplantar injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by capsaicin, a TRPV1 activator. When administered either by oral or intraplantar routes, S-(+)-dicentrine reduced the licking time (spontaneous nociception) and increased the latency time to paw withdrawal in the cold plate (cold hypersensitivity), both induced by the intraplantar injection of cinnamaldehyde. Taken together, our data adds information about antinociceptive properties of S-(+)-dicentrine in inflammatory conditions, reducing spontaneous nociception and attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent mechanism. It also indicates that S-(+)-dicentrine might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain, especially under inflammatory conditions.

BACKGROUND:Relevant preclinical models that recapitulate the key features of human pancreatic ductal adenocarcinoma (PDAC) are needed in order to provide biologically tractable models to probe disease progression and therapeutic responses and ultimately improve patient outcomes for this disease. Here, we describe the establishment and clinical, pathological, molecular and genetic validation of a murine, orthotopic xenograft model of PDAC. METHODS:Human PDACs were resected and orthotopically implanted and propagated in immunocompromised mice. Patient survival was correlated with xenograft growth and metastatic rate in mice. Human and mouse tumor pathology were compared. Tumors were analyzed for genetic mutations, gene expression, receptor tyrosine kinase activation, and cytokine expression. RESULTS:Fifteen human PDACs were propagated orthotopically in mice. Xenograft-bearing mice developed peritoneal and liver metastases. Time to tumor growth and metastatic efficiency in mice each correlated with patient survival. Tumor architecture, nuclear grade and stromal content were similar in patient and xenografted tumors. Propagated tumors closely exhibited the genetic and molecular features known to characterize pancreatic cancer (e.g. high rate of KRAS, P53, SMAD4 mutation and EGFR activation). The correlation coefficient of gene expression between patient tumors and xenografts propagated through multiple generations was 93 to 99%. Analysis of gene expression demonstrated distinct differences between xenografts from fresh patient tumors versus commercially available PDAC cell lines. CONCLUSIONS:The orthotopic xenograft model derived from fresh human PDACs closely recapitulates the clinical, pathologic, genetic and molecular aspects of human disease. This model has resulted in the identification of rational therapeutic strategies to be tested in clinical trials and will permit additional therapeutic approaches and identification of biomarkers of response to therapy.

BACKGROUND: Hepatitis C virus (HCV) coinfection was reported to negatively affect HIV disease and HIV infection has a deleterious effect on HCV-related liver disease. However, despite common occurrence of HCV/HIV coinfection little is known about the mechanisms of interactions between the two viruses. METHODS: We studied CD4+ and CD8+ T cell and CD19+ B cell apoptosis in 104 HIV-positive patients (56 were also HCV-positive) and in 22 HCV/HIV-coinfected patients treated for chronic hepatitis C with pegylated interferon and ribavirin. We also analyzed HCV/HIV coinfection in a Daudi B-cell line expressing CD4 and susceptible to both HCV and HIV infection. Apoptosis was measured by AnnexinV staining. RESULTS: HCV/HIV coinfected patients had lower CD4+ and CD8+ T cell apoptosis and higher CD19+ B cell apoptosis than those with HIV monoinfection. Furthermore, anti-HCV treatment of HCV/HIV coinfected patients was followed by an increase of CD4+ and CD8+ T cell apoptosis and a decrease of CD19+ B cell apoptosis. In the Daudi CD4+ cell line, presence of HCV infection facilitated HIV replication, however, decreased the rate of HIV-related cell death. CONCLUSION: In HCV/HIV coinfected patients T-cells were found to be destroyed at a slower rate than in HIV monoinfected patients. These results suggest that HCV is a molecular-level determinant in HIV disease.

One-half of the integrin α-subunit Propeller domains contain and extra vWFA domain (αA domain), which mediates integrin binding to extracellular physiologic ligands via its metal-ion-dependent adhesion site (MIDAS). We used electron microscopy to determine the 3D structure of the αA-containing ectodomain of the leukocyte integrin CD11b/CD18 (αMβ2) in its inactive state. A well defined density for αA was observed within a bent ectodomain conformation, while the structure of the ectodomain in complex with the Fab fragment of mAb107, which binds at the MIDAS face of CD11b and stabilizes the inactive state, further revealed that αA is restricted to a relatively small range of orientations relative to the Propeller domain. Using Fab 107 as probe in fluorescent lifetime imaging microscopy (FLIM) revealed that αA is positioned relatively far from the membrane surface in the inactive state, and a systematic orientation search revealed that the MIDAS face would be accessible to extracellular ligand in the inactive state of the full-length cellular integrin. These studies are the first to define the 3D EM structure of an αA-containing integrin ectodomain and to position the ligand-binding face of αA domain in relation to the plasma membrane, providing new insights into current models of integrin activation.

Laminin-332 is a heterotrimeric basement membrane component comprised of the α3, ß3, and γ2 laminin chains. Laminin-332 modulates epithelial cell processes, such as adhesion, migration, and differentiation and is prominent in many embryonic and adult tissues. In skin, laminin-332 is secreted by keratinocytes and is a key component of hemidesmosomes connecting the keratinocytes to the underlying dermis. In mice, lack of expression of any of the three Laminin-332 chains result in impaired anchorage and detachment of the epidermis, similar to that seen in human junctional epidermolysis bullosa, and death occurs within a few days after birth. To bypass the early lethality of laminin-332 deficiency caused by the knockout of the mouse laminin γ2 chain, we expressed a dox-controllable human laminin γ2 transgene under a keratinocyte-specific promoter on the laminin γ2 (Lamc2) knockout background. These mice appear similar to their wild-type littermates, do not develop skin blisters, are fertile, and survive >1.5 years. Immunofluorescence analyses of the skin showed that human laminin γ2 colocalized with mouse laminin α3 and ß3 in the basement membrane zone underlying the epidermis. Furthermore, the presence of "humanized" laminin-332 in the epidermal basement membrane zone rescued the alterations in the deposition of hemidesmosomal components, such as plectin, collagen type XVII/BP180, and integrin α6 and ß4 chains, seen in conventional Lamc2 knockout mice, leading to restored formation of hemidesmosomes. These mice will be a valuable tool for studies of organs deficient in laminin-332 and the role of laminin-332 in skin, including wound healing.

Diarrhea is a leading cause of morbidity among children under 5 years of age in low- and middle-income countries yet the additional effects and sequelae, such as cognitive impairment associated with diarrhea, have not been quantified.We quantified the association between diarrhea prevalence and cognitive outcomes while controlling for linear growth in 4 study populations. Cognition was assessed using different methods across sites and was expressed in standardized units. We built linear regression models for each study with standardized cognitive score as the outcome and diarrhea prevalence as the main predictor variable. We then conducted meta-analyses of the regression coefficients to generate pooled estimates of the association between diarrhea prevalence and cognition whilst controlling for anthropometric status and other covariates.Diarrhea was not a significant predictor of cognitive score in any site in the regression models or in the meta-analyses (Coefficient = 0.07; 95% CI: -0.1, 0.2). The length for age Z- score was negatively related to cognition in all sites (0.18; 95% CI: 0.14, 0.21), with coefficients remarkably similar across sites (Coefficient Range: 0.168-0.186).We did not demonstrate an association between diarrhea and cognition with stunting included in the model. The links between diarrhea, stunting, and cognition provide additional rationale for accelerating interventions to reduce diarrhea.

The labyrinth is the highly vascularized part of the rodent placenta that allows efficient transfer of gases, nutrients, wastes, and other molecules between the maternal and embryonic circulations. These two blood compartments are separated by blastocyst-derived trophoblasts and endothelial cells with an intervening basement membrane that contains laminin and other typical basement membrane components. Previously we reported that the labyrinth of laminin α5 knockout (LMα5-/-) embryos exhibits reduced vascularization and detachment of endothelial cells from the basement membrane, which normally contains LMα5. As very little is known about the origin of this vascular basement membrane, we investigated the cellular requirements for LMα5 expression in the mouse placental labyrinth. By fluorescence-activated cell sorting and RT-PCR we confirmed that both endothelial cells and trophoblasts normally express LMα5. Using Cre-loxP technology and doxycycline-mediated gene expression, we generated genetically mosaic placentas in which either the trophoblasts or the endothelial cells, but not both, expressed LMα5. We found that the overall architecture of the labyrinth was normal as long as one of these two cell types expressed LMα5, even if it was transgene-derived human laminin α5. These results suggest that laminin trimers containing α5 that are synthesized and secreted by endothelium or by trophoblasts are capable of integrating into the basement membrane and promoting normal vascularization of the placenta. Additional studies showed that endothelium-expressed human LMα5 can support vascularization of the kidney glomerulus, consistent with previous studies using a tissue grafting approach.

Litter decomposition rate (k) is typically estimated from proportional litter mass loss data using models that assume constant, normally distributed errors. However, such data often show non-normal errors with reduced variance near bounds (0 or 1), potentially leading to biased k estimates. We compared the performance of nonlinear regression using the beta distribution, which is well-suited to bounded data and this type of heteroscedasticity, to standard nonlinear regression (normal errors) on simulated and real litter decomposition data. Although the beta model often provided better fits to the simulated data (based on the corrected Akaike Information Criterion, AIC(c)), standard nonlinear regression was robust to violation of homoscedasticity and gave equally or more accurate k estimates as nonlinear beta regression. Our simulation results also suggest that k estimates will be most accurate when study length captures mid to late stage decomposition (50-80% mass loss) and the number of measurements through time is ≥ 5. Regression method and data transformation choices had the smallest impact on k estimates during mid and late stage decomposition. Estimates of k were more variable among methods and generally less accurate during early and end stage decomposition. With real data, neither model was predominately best; in most cases the models were indistinguishable based on AIC(c), and gave similar k estimates. However, when decomposition rates were high, normal and beta model k estimates often diverged substantially. Therefore, we recommend a pragmatic approach where both models are compared and the best is selected for a given data set. Alternatively, both models may be used via model averaging to develop weighted parameter estimates. We provide code to perform nonlinear beta regression with freely available software.