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Background: The GATA transcription factors play multifaceted roles in modulating vital physiological processes in plants. However, the GATA transcription factor family in onion (Allium cepa L.) has been explored to a limited extent. In the present study, a genome-wide survey of the GATA family and the subsequent characterization has been carried out in the onion genome., Results: In total, 24 A. cepa GATAs (AcGATA1-AcGATA24) have been identified in the onion genome. Chromosomal mapping revealed that all identified genes could be mapped onto different onion chromosomes or scaffolds. The gene duplication, synteny, and collinearity analysis of the AcGATAs suggested their divergence, expansion, and selection in onions. Phylogenetic analysis of the AcGATAs divided them into five groups along with other plant GATAs. Gene ontology and cis-regulatory element analysis results suggested that the AcGATAs could regulate crucial processes, such as growth and development, phytohormone signalling, and stress response. The tissue-specific expression study indicated that the AcGATAs expressed in multiple onion tissues. The expression analysis under subjected chromium and salt stress revealed that multiple AcGATAs get induced in response to the applied stresses. Lastly, the protein interaction network study predicted some key interacting partners of the AcGATAs that can regulate vital physiological processes in onions., Conclusions: The present study identified and characterized the GATA gene family in onions. Functional predictions and interaction network analysis suggested the roles of AcGATAs in modulating multiple onion physiological processes. The induced expression of AcGATAs under chromium and salt stress indicated their involvement in abiotic stress response in onions. Overall, the study provides newer insights into the GATA gene family and their possible roles in onions., Competing Interests: Declarations. Ethics approval and consent to participate: No experiments were performed on animals or humans. The experiments conducted on plants, including plant stress subjection and sample collection were done in compliance with the institutional, national, and international guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Non-invasive clinic-based tools for assessing PAD are not without limitations. Therefore, costly tests like Doppler study, CT angiography and MR angiography are often required to make a diagnosis. Ankle brachial index (ABI), commonly used for assessment of PAD, has high false positivity rates in sclerosed, calcified arteries which render them non-compressible. Toe brachial index (TBI) can be an alternative, as digital arteries are relatively unaffected by these changes., Aim: To compare the reliability of ABI and TBI in diagnosing PAD in type 2 diabetes using CT angiography (CTA) as the reference., Methods: 175 adults with T2D were selected. ABI &TBI were measured with an automated vascular Doppler XT 6 ports bilaterally for all subjects. For any subject, the limb with lower ABI and TBI was included for analysis. ABI < 0.9 & TBI < 0.6 were taken as evidence of PAD. CTA showing > 50% narrowing was taken as evidence of PAD., Results: 24% of our study subjects had CTA confirmed PAD. ABI has low sensitivity of 35.29% (95% CI 0.21-0.52) compared to TBI being 82.35% (95% CI 0.66-0.92). The specificity however was similar. ABI < 0.9 was able to detect CTA confirmed PAD, but ABI > 0.9, including the so-called normal ABI (0.9-1.3) was unable to detect PAD. ROC showed ABI at 1.005 has sensitivity 64.71% (95% CI 0.48- 0.79) and specificity 61.7% (95% CI 0.53-0.69) and TBI at 0.6 has sensitivity 82.35% (95% CI 0.66-0.92) & specificity 92% (95% CI 0.87-0.96). Utilizing Cohen's Kappa, the reliability of ABI with respect to CTA showed fair agreement (K = 0.225, p = 0.001), whereas the reliability of TBI with respect to CTA showed substantial agreement (K = 0.759, p < 0.0001)., Conclusion: ABI < 0.9 detects PAD reliably, but presence of PAD in patients with ABI > 9.0 including the normal of ABI (0.9-1.3) can be confirmed with TBI, which correlated strongly with CTA. TBI is also non-inferior for PAD detection, when ABI < 0.9. TBI and not ABI can be utilized for initial assessment of PAD in subjects with T2D., (© 2024. The Author(s).)

Background: To assess the association of lipid and lipid-derived toxic molecules in pathogenesis and severity of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM)., Methods: The present cross-sectional study included 14 healthy individuals (HC) without T2DM, 22 T2DM subjects without DR (DNR), 24 T2DM subjects with mild non-proliferative DR (MNPDR), and 24 T2DM subjects with high-risk proliferative DR (HRPDR). All subjects underwent plasma and vitreous analysis for estimation of total lipid (TL), free fatty acid (FFA), lipid peroxides (LPOs) like malondialdehyde (MDA), 4-Hydroxy-noneal (HNE), the advanced lipoxidation end product (ALE) like Hexanoyl-lysine (HLY) and vascular endothelial growth factor (VEGF) following standard spectrophotometric and enzyme-linked immunosorbent assay (ELISA) methods respectively., Results: The concentration of TL, FFA, markers of lipid peroxidation and lipoxidation as well as VEGF in plasma and vitreous were found to be significantly elevated stepwise inT2DM subjects (HRPDR > MNPDR > DNR) compared to healthy controls (HC).Further, plasma conventional lipid components like total cholesterol (TCH), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG), FFA and TL showed their significant positive correlations with vitreous level of different LPOs, ALE and VEGF in the DR group., Conclusion: Total lipid and lipid-derived detrimental biomolecules ultimately result in increased secretion of VEGF and thus not only add as associated mediators in the pathogenesis of DR, these also accelerate the severity of microangiopathy in T2DM., (© 2022. The Author(s).)

Background: Maternal mortality is a public health problem that disproportionately affects low and lower-middle income countries (LMICs). Appropriate data sources are lacking to effectively track maternal mortality and monitor changes in this health indicator over time., Methods: We analyzed data from women enrolled in the NICHD Global Network for Women's and Children's Health Research Maternal Newborn Health Registry (MNHR) from 2010 through 2018. Women delivering within research sites in the Democratic Republic of Congo, Guatemala, India (Nagpur and Belagavi), Kenya, Pakistan, and Zambia are included. We evaluated maternal and delivery characteristics using log-binomial models and multivariable models to obtain relative risk estimates for mortality. We used running averages to track maternal mortality ratio (MMR, maternal deaths per 100,000 live births) over time., Results: We evaluated 571,321 pregnancies and 842 maternal deaths. We observed an MMR of 157 / 100,000 live births (95% CI 147, 167) across all sites, with a range of MMRs from 97 (76, 118) in the Guatemala site to 327 (293, 361) in the Pakistan site. When adjusted for maternal risk factors, risks of maternal mortality were higher with maternal age > 35 (RR 1.43 (1.06, 1.92)), no maternal education (RR 3.40 (2.08, 5.55)), lower education (RR 2.46 (1.54, 3.94)), nulliparity (RR 1.24 (1.01, 1.52)) and parity > 2 (RR 1.48 (1.15, 1.89)). Increased risk of maternal mortality was also associated with occurrence of obstructed labor (RR 1.58 (1.14, 2.19)), severe antepartum hemorrhage (RR 2.59 (1.83, 3.66)) and hypertensive disorders (RR 6.87 (5.05, 9.34)). Before and after adjusting for other characteristics, physician attendance at delivery, delivery in hospital and Caesarean delivery were associated with increased risk. We observed variable changes over time in the MMR within sites., Conclusions: The MNHR is a useful tool for tracking MMRs in these LMICs. We identified maternal and delivery characteristics associated with increased risk of death, some might be confounded by indication. Despite declines in MMR in some sites, all sites had an MMR higher than the Sustainable Development Goals target of below 70 per 100,000 live births by 2030., Trial Registration: The MNHR is registered at NCT01073475 .

Background: Due to high fertility rates in some low and lower-middle income countries, the interval between pregnancies can be short, which may lead to adverse maternal and neonatal outcomes., Methods: We analyzed data from women enrolled in the NICHD Global Network Maternal Newborn Health Registry (MNHR) from 2013 through 2018. We report maternal characteristics and outcomes in relationship to the inter-delivery interval (IDI, time from previous delivery [live or stillborn] to the delivery of the index birth), by category of 6-17 months (short), 18-36 months (reference), 37-60 months, and 61-180 months (long). We used non-parametric tests for maternal characteristics, and multivariable logistic regression models for outcomes, controlling for differences in baseline characteristics., Results: We evaluated 181,782 women from sites in the Democratic Republic of Congo, Zambia, Kenya, Guatemala, India, and Pakistan. Women with short IDI varied by site, from 3% in the Zambia site to 20% in the Pakistan site. Relative to a 18-36 month IDI, women with short IDI had increased risk of neonatal death (RR = 1.89 [1.74, 2.05]), stillbirth (RR = 1.70 [1.56, 1.86]), low birth weight (RR = 1.38 [1.32, 1.44]), and very low birth weight (RR = 2.35 [2.10, 2.62]). Relative to a 18-36 month IDI, women with IDI of 37-60 months had an increased risk of maternal death (RR 1.40 [1.05, 1.88]), stillbirth (RR 1.14 [1.08, 1.22]), and very low birth weight (RR 1.10 [1.01, 1.21]). Relative to a 18-36 month IDI, women with long IDI had increased risk of maternal death (RR 1.54 [1.10, 2.16]), neonatal death (RR = 1.25 [1.14, 1.38]), stillbirth (RR = 1.50 [1.38, 1.62]), low birth weight (RR = 1.22 [1.17, 1.27]), and very low birth weight (RR = 1.47 [1.32,1.64]). Short and long IDIs were also associated with increased risk of obstructed labor, hemorrhage, hypertensive disorders, fetal malposition, infection, hospitalization, preterm delivery, and neonatal hospitalization., Conclusions: IDI varies by site. When compared to 18-36 month IDI, women with both short IDI and long IDI had increased risk of adverse maternal and neonatal outcomes., Trial Registration: The MNHR is registered at NCT01073475 .

Background: Neuroinflammation, typified by elevated levels of interleukin-1 (IL-1) α and β, and deficits in proteostasis, characterized by accumulation of polyubiquitinated proteins and other aggregates, are associated with neurodegenerative disease independently and through interactions of the two phenomena. We investigated the influence of IL-1β on ubiquitination via its impact on activation of the E3 ligase parkin by either phosphorylated ubiquitin (P-Ub) or NEDD8., Methods: Immunohistochemistry and Proximity Ligation Assay were used to assess colocalization of parkin with P-tau or NEDD8 in hippocampus from Alzheimer patients (AD) and controls. IL-1β effects on PINK1, P-Ub, parkin, P-parkin, and GSK3β-as well as phosphorylation of parkin by GSK3β-were assessed in cell cultures by western immunoblot, using two inhibitors and siRNA knockdown to suppress GSK3β. Computer modeling characterized the binding and the effects of P-Ub and NEDD8 on parkin. IL-1α, IL-1β, and parkin gene expression was assessed by RT-PCR in brains of 2- and 17-month-old PD-APP mice and wild-type littermates., Results: IL-1α, IL-1β, and parkin mRNA levels were higher in PD-APP mice compared with wild-type littermates, and IL-1α-laden glia surrounded parkin- and P-tau-laden neurons in human AD. Such neurons showed a nuclear-to-cytoplasmic translocation of NEDD8 that was mimicked in IL-1β-treated primary neuronal cultures. These cultures also showed higher parkin levels and GSK3β-induced parkin phosphorylation; PINK1 levels were suppressed. In silico simulation predicted that binding of either P-Ub or NEDD8 at a singular position on parkin opens the UBL domain, exposing Ser 65 for parkin activation., Conclusions: The promotion of parkin- and NEDD8-mediated ubiquitination by IL-1β is consistent with an acute neuroprotective role. However, accumulations of P-tau and P-Ub and other elements of proteostasis, such as translocated NEDD8, in AD and in response to IL-1β suggest either over-stimulation or a proteostatic failure that may result from chronic IL-1β elevation, easily envisioned considering its early induction in Down's syndrome and mild cognitive impairment. The findings further link autophagy and neuroinflammation, two important aspects of AD pathogenesis, which have previously been only loosely related.

Background: In many low and low-middle income countries, the incidence of polyhydramnios is unknown, in part because ultrasound technology is not routinely used. Our objective was to report the incidence of polyhydramnios in five low and low-middle income countries, to determine maternal characteristics associated with polyhydramnios, and report pregnancy and neonatal outcomes., Methods: We performed a secondary analysis of the First Look Study, a multi-national, cluster-randomized trial of ultrasound during prenatal care. We evaluated all women enrolled from Guatemala, Pakistan, Zambia, Kenya and the Democratic Republic of Congo (DRC) who received an examination by prenatal ultrasound. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models with general estimating equations to control for cluster-level effects. The diagnosis of polyhydramnios was confrimed by an U.S. based radiologist in a majority of cases (62%)., Results: We identified 305/18,640 (1.6%) cases of polyhydramnios. 229 (75%) cases were from the DRC, with an incidence of 10%. A higher percentage of women with polyhydramnios experienced obstructed labor (7% vs 4%) and fetal malposition (4% vs 2%). Neonatal death was more common when polyhydramnios was present (OR 2.43; CI 1.15, 5.13)., Conclusions: Polyhydramnios occured in these low and low-middle income countries at a rate similar to high-income contries except in the DRC where the incidence was 10%. Polyhydramnios was associated with obstructed labor, fetal malposition, and neonatal death., Trial Registration: NCT01990625 , November 21, 2013.

Background: Neonatal mortality comprises an increasing proportion of childhood deaths in the developing world. Essential newborn care practices as recommended by the WHO may improve neonatal outcomes in resource limited settings. Our objective was to pilot a Helping Babies Breathe and Essential Care for Every Baby (HBB and ECEB) implementation package using HBB-ECEB training combined with supportive supervision in rural Nicaragua., Methods: We employed an HBB-ECEB implementation package in El Ayote and Santo Domingo, two rural municipalities in Nicaragua and used a pre- and post- data collection design for comparison. Following a period of pre-intervention data collection (June-August 2015), care providers were trained in HBB and ECEB using a train-the- trainer model. An external supportive supervisor monitored processes of care and collected data. Data on newborn care processes and short-term outcomes such as hypothermia were collected from facility medical records and analyzed using standard run charts. Home visits were used to determine breastfeeding rates at 7, 30 and 60 days., Results: There were 480 institutional births during the study period (June 2015-June 2016). Following the HBB-ECEB implementation package, cord care improved (pre-intervention median 66%; post-intervention shift to ≥85%) and early skin-to-skin care improved (pre-intervention median 0%; post-intervention shift to ≥56%, with a high of 92% in June 2016). Rates of administration of ophthalmic ointment and vitamin K were high pre-intervention (median 97%) and remained high. Early initiation of breastfeeding increased with a pre-intervention median of 25% and post-intervention shift to ≥28%, with a peak of 81% in June 2016. Exclusive breastfeeding rates increased short-term but were not significantly different by 60-days of life (9% pre-intervention versus 21% post-intervention)., Conclusions: The implementation of the HBB-ECEB programs combined with supportive supervision improved the quality of care for newborns in terms of cord care, early skin-to-skin care and early initiation of breastfeeding. The rates of administration of ophthalmic ointment and vitamin K were high pre- intervention and remained high afterwards. These findings show that HBB-ECEB programs implemented with supportive supervision can improve quality of care for newborns.

Background: One-quarter of neonatal and infant deaths are due to infection, and the majority of these deaths occur in developing countries. Standard treatment for infection, which includes parenteral treatment only, is often not available in low-resource settings. Infant mortality will not be reduced in developing countries without a reduction in deaths due to infection. We participated in a multi-site trial that demonstrated the effectiveness of three simplified antibiotic regimens compared to standard treatment (The AFRINEST Trial: parent study). For this report, we examined the site-specific data for the Democratic Republic Congo (DRC), the most impoverished of the countries that participated in the study, to determine if outcomes in the DRC were similar to outcomes across all sites., Methods: The parent study was an individually randomized, open-label, equivalence trial. Infants with clinical signs of severe infection were randomized to receive one of four regimens: 1) injectable penicillin-gentamicin for 7 days (standard therapy; regimen A), 2) injectable gentamicin and oral amoxicillin for 7 days (regimen B), 3) injectable penicillin-gentamicin for 2 days then oral amoxicillin for 5 days (regimen C), or 4) injectable gentamicin for 2 days and oral amoxicillin for 5 days (regimen D). In the DRC, we enrolled 574 infants, of whom 560 met the per-protocol criteria for analysis of treatment effect. The main outcome was treatment failure within the first week of enrollment., Results: Treatment failure occurred in 52 (9.3%) infants: 17 (11.6%) with the referent treatment regimen, 13 (9.6%) with regimen B (risk difference [RD] -2.0%; CI -9.2% to 5.2%), 13 (9.0%) with regimen C (RD -2.6%; CI -9.6% to 4.4%), and 9 (6.7%) with regimen D (RD -5.0%; CI -11.7% to 1.7%)., Conclusion: As in the parent study, the risk difference between each of the experimental treatments and the reference treatment suggests equivalence. These findings suggest that the conclusion from the parent study, that a simplified antibiotic regimen can be used for the community-based management of possible severe infection in young infants where referral to a hospital for standard care is often not possible, is true in the DRC. We speculate that the widespread use of a simplified, community-based treatment could result in increased coverage with treatment and improved survival in poor areas., Trial Registration: ACTRN12610000286044 on April 9, 2010., Competing Interests: This study was approved by the ethics committees at the World Health Organization and the Kinshasa School of Public Health. This study is registered with the Australian New Zealand Clinical Trials Registry on April 9,2010, number ACTRN12610000286044.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Essential Care for Every Baby (ECEB) is an evidence-based educational program designed to increase cognitive knowledge and develop skills of health care professionals in essential newborn care in low-resource areas. The course focuses on the immediate care of the newborn after birth and during the first day or until discharge from the health facility. This study assessed the overall design of the course; the ability of facilitators to teach the course; and the knowledge and skills acquired by the learners., Methods: Testing occurred at 2 global sites. Data from a facilitator evaluation survey, a learner satisfaction survey, a multiple choice question (MCQ) examination, performance on two objective structured clinical evaluations (OSCE), and pre- and post-course confidence assessments were analyzed using descriptive statistics. Pre-post course differences were examined. Comments on the evaluation form and post-course group discussions were analyzed to identify potential program improvements., Results: Using ECEB course material, master trainers taught 12 facilitators in India and 11 in Kenya who subsequently taught 62 providers of newborn care in India and 64 in Kenya. Facilitators and learners were satisfied with their ability to teach and learn from the program. Confidence (3.5 to 5) and MCQ scores (India: pre 19.4, post 24.8; Kenya: pre 20.8, post 25.0) improved (p < 0.001). Most participants demonstrated satisfactory skills on the OSCEs. Qualitative data suggested the course was effective, but also identified areas for course improvement. These included additional time for hands-on practice, including practice in a clinical setting, the addition of video learning aids and the adaptation of content to conform to locally recommended practices., Conclusion: ECEB program was highly acceptable, demonstrated improved confidence, improved knowledge and developed skills. ECEB may improve newborn care in low resource settings if it is part of an overall implementation plan that addresses local needs and serves to further strengthen health systems.

Background: Nearly half the world's babies are born at home. We sought to evaluate the training, knowledge, skills, and access to medical equipment and testing for home birth attendants across 7 international sites., Methods: Face-to-face interviews were done by trained interviewers to assess level of training, knowledge and practices regarding care during the antenatal, intrapartum and postpartum periods. The survey was administered to a sample of birth attendants conducting home or out-of-facility deliveries in 7 sites in 6 countries (India, Pakistan, Guatemala, Democratic Republic of the Congo, Kenya and Zambia)., Results: A total of 1226 home birth attendants were surveyed. Less than half the birth attendants were literate. Eighty percent had one month or less of formal training. Most home birth attendants did not have basic equipment (e.g., blood pressure apparatus, stethoscope, infant bag and mask manual resuscitator). Reporting of births and maternal and neonatal deaths to government agencies was low. Indian auxilliary nurse midwives, who perform some home but mainly clinic births, were far better trained and differed in many characteristics from the birth attendants who only performed deliveries at home., Conclusions: Home birth attendants in low-income countries were often illiterate, could not read numbers and had little formal training. Most had few of the skills or access to tests, medications and equipment that are necessary to reduce maternal, fetal or neonatal mortality.

Background: Because of a physician shortage in many low-income countries, the use of nonphysicians to classify perinatal mortality (stillbirth and early neonatal death) using verbal autopsy could be useful., Objective: To determine the extent to which underlying perinatal causes of deaths assigned by nonphysicians in Guatemala, Pakistan, Zambia, and the Democratic Republic of the Congo using a verbal autopsy method are concordant with underlying perinatal cause of death assigned by physician panels., Methods: Using a train-the-trainer model, 13 physicians and 40 nonphysicians were trained to determine cause of death using a standardized verbal autopsy training program. Subsequently, panels of two physicians and individual nonphysicians from this trained cohort independently reviewed verbal autopsy data from a sample of 118 early neonatal deaths and 134 stillbirths. With the cause of death assigned by the physician panel as the reference standard, sensitivity, specificity, positive and negative predictive values, and cause-specific mortality fractions were calculated to assess nonphysicians' coding responses. Robustness criteria to assess how well nonphysicians performed were used., Results: Causes of early neonatal death and stillbirth assigned by nonphysicians were concordant with physician-assigned causes 47% and 57% of the time, respectively. Tetanus filled robustness criteria for early neonatal death, and cord prolapse filled robustness criteria for stillbirth., Conclusions: There are significant differences in underlying cause of death as determined by physicians and nonphysicians even when they receive similar training in cause of death determination. Currently, it does not appear that nonphysicians can be used reliably to assign underlying cause of perinatal death using verbal autopsy.

Background: In many developing countries, the majority of births are attended by traditional birth attendants, who lack formal training in neonatal resuscitation and other essential care required by the newly born infant. In these countries, the major causes of neonatal mortality are birth asphyxia, infection, and low-birth-weight/prematurity. Death from these causes is potentially modifiable using low-cost interventions, including neonatal resuscitation training. The purpose of this study was to evaluate the effect on perinatal mortality of training birth attendants in a rural area of the Democratic Republic of Congo (DRC) using two established programs., Methods: This study, a secondary analysis of DRC-specific data collected during a multi-country study, was conducted in two phases. The effect of training using the WHO Essential Newborn Care (ENC) program was evaluated using an active baseline design, followed by a cluster randomized trial of training using an adaptation of a neonatal resuscitation program (NRP). The perinatal mortality rates before ENC, after ENC training, and after randomization to additional NRP training or continued care were compared. In addition, the influence of time following resuscitation training was investigated by examining change in perinatal mortality during sequential three-month increments following ENC training., Results: More than two-thirds of deliveries were attended by traditional birth attendants and occurred in homes; these proportions decreased after ENC training. There was no apparent decline in perinatal mortality when the outcome of all deliveries prior to ENC training was compared to those after ENC but before NRP training. However, there was a gradual but significant decline in perinatal mortality during the year following ENC training (RR 0.73; 95% CI: 0.56-0.96), which was independently associated with time following training. The decline was attributable to a decline in early neonatal mortality. NRP training had no demonstrable effect on early neonatal mortality., Conclusion: Training DRC birth attendants using the ENC program reduces perinatal mortality. However, a period of utilization and re-enforcement of training may be necessary before a decline in mortality occurs. ENC training has the potential to be a low cost, high impact intervention in developing countries., Trial Registration: This trial has been registered at http://www.clinicaltrials.gov (identifier NCT00136708).

Background: The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, such as artesunate (AS), are poorly understood. In this analysis, the population pharmacokinetics of oral AS, and its active metabolite dihydroartemisinin (DHA), were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC., Methods: Data were obtained from 26 pregnant women in the second (22-26 weeks) or the third (32-36 weeks) trimester of pregnancy and from 25 non-pregnant female controls. All subjects received 200 mg AS. Plasma AS and DHA were measured using a validated LC-MS method. Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling., Results: A simultaneous parent-metabolite model was developed consisting of mixed zero-order, lagged first-order absorption of AS, a one-compartment model for AS, and a one-compartment model for DHA. Complete conversion of AS to DHA was assumed. The model displayed satisfactory goodness-of-fit, stability, and predictive ability. Apparent clearance (CL/F) and volume of distribution (V/F) estimates, with 95% bootstrap confidence intervals, were as follows: 195 L (139-285 L) for AS V/F, 895 L/h (788-1045 L/h) for AS CL/F, 91.4 L (78.5-109 L) for DHA V/F, and 64.0 L/h (55.1-75.2 L/h) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant, with a pregnancy-associated increase in DHA CL/F of 42.3% (19.7-72.3%)., Conclusions: In this analysis, pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS. These findings, in conjunction with a previous non-compartmental analysis of the modelled data, provide further evidence that higher AS doses would be required to maintain similar DHA levels in pregnant women as achieved in non-pregnant controls.

Background: In many malaria-endemic countries, increasing resistance may soon compromise the efficacy of sulphadoxine-pyrimethamine (SP) for intermittent preventative treatment (IPT) of malaria in pregnancy. Artemisinin-based IPT regimens represent a promising potential alternative to SP. Pharmacokinetic and safety data supporting the use of artemisinin derivatives in pregnancy are urgently needed., Methods: Subjects included pregnant women with asymptomatic falciparum parasitaemia between 22-26 weeks (n = 13) or 32-36 weeks gestation (n = 13), the same women at three months postpartum, and 25 non-pregnant parasitaemic controls. All subjects received 200 mg orally administered AS. Plasma total and free levels of AS and its active metabolite DHA were determined using a validated LC-MS method. Non-compartmental pharmacokinetic analysis was performed using standard methods., Results: All pregnant women delivered live babies. The median birth weight was 3025 grams [range 2130, 3620]; 2 of 26 babies had birth weights less than 2500 grams. Rates of parasite clearance by 12 hours post-dose were high and comparable among the groups. Rapid elimination of AS was observed in all three groups. The 90% CI for the pregnancy:postpartum ratio of geometric means for total and free AUC fell within the pre-specified 0.66 - 1.50 therapeutic equivalence interval. However, more pronounced pharmacokinetic differences were observed between the pregnancy and control subjects, with the 90% CI for the pregnancy:control ratio of geometric means for both total 0.68 (90% CI 0.57-0.81) and free AUC 0.78 (90% CI 0.63-0.95) not fully contained within the 0.66 - 1.50 interval. All subjects cleared parasites rapidly, and there was no difference in the percentage of women who were parasitaemic 12 hours after dosing., Conclusions: A single dose of orally administered AS was found to be both effective and without adverse effects in this study of second and third trimester pregnant women in the DRC. Although DHA AUC during pregnancy and postpartum were similar, the AUC for the pregnant group was less than the non-pregnant controls. The findings of this study suggest that additional studies on the pharmacokinetics of AS in pregnant women are needed., Trial Registration: ClinicalTrials.gov: NCT00538382.

Background: Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated., Methods/design: A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months); neurocognitive development (12 and 18 months); and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial., Discussion: Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale for global efforts to enhance local supplies of meat as a complementary food for young children., Trial Registration: NCT01084109.