Association of sickle cell disease with anthropometric indices among under-five children: evidence from 2018 Nigeria Demographic and Health Survey

BACKGROUND: Malnutrition continues to affect under-five children in Africa to an overwhelming proportion. The situation is further compounded by the burden of sickle cell disease (SCD). However, association of SCD with stunting, wasting, and underweight in a nationally representative sample of under-five children remains unexplored. We aimed to describe prevalence of undernutrition by sickle cell status, to evaluate its association with growth faltering ascertained by anthropometric indices, and to explore mediating role of hemoglobin. METHODS: We availed data from the 2018 Nigeria Demographic and Health Survey (DHS) and the sample comprised 11,233 children aged 6-59 months who were successfully genotyped for SCD. The DHS employed a two-stage, stratified sampling strategy. SickleSCAN rapid diagnostic test was used for SCD genotyping. Z-scores of length/height-for-age (HAZ), weight-for-height (WHZ), and weight-for-age (WAZ) were computed against the 2006 World Health Organization Child Growth Standards. We fitted logistic regression models to evaluate association of SCD with stunting, wasting, and underweight. Mediation analysis was performed to capture the indirect effect of and proportion of total effect mediated through hemoglobin level in SCD-anthropometric indices association. RESULTS: Prevalences of stunting, wasting, and underweight among children with SCD were 55.4% (54.5-56.4), 9.1% (8.6-9.7), and 38.9% (38.0-39.8), respectively. The odds of stunting were 2.39 times higher (adjusted odds ratio (aOR) 2.39, 95% CI: 1.26-4.54) among sickle children than those with normal hemoglobin. SCD was also significantly associated with underweight (aOR 2.64, 95% CI: 1.25-5.98), but not with wasting (aOR: 1.60, 95% CI 0.85-3.02). Association of SCD with all three anthropometric indices was significantly mediated through hemoglobin level: for SCD-HAZ, the adjusted indirect effect (aIE) was - 0.328 (95% CI: - 0.387, - 0.270); for SCD-WHZ, the aIE was - 0.080 (95% CI: - 0.114, - 0.050); and for SCD-WAZ, the aIE was - 0.245 (95% CI: - 0.291, - 0.200). CONCLUSION: We presented compelling evidence of the negative impact of SCD on anthropometric indices of nutritional status of under-five children. Integration of a nutrition-oriented approach into a definitive SCD care package and its nationwide implementation could bring promising results by mitigating the nutritional vulnerability of children with SCD

Scaling Up Safer Birth Bundle Through Quality Improvement in Nepal (SUSTAIN)a stepped wedge cluster randomized controlled trial in public hospitals

BackgroundEach year, 2.2 million intrapartum-related deaths (intrapartum stillbirths and first day neonatal deaths) occur worldwide with 99% of them taking place in low- and middle-income countries. Despite the accelerated increase in the proportion of deliveries taking place in health facilities in these settings, the stillborn and neonatal mortality rates have not reduced proportionately. Poor quality of care in health facilities is attributed to two-thirds of these deaths. Improving quality of care during the intrapartum period needs investments in evidence-based interventions. We aim to evaluate the quality improvement packageScaling Up Safer Bundle Through Quality Improvement in Nepal (SUSTAIN)on intrapartum care and intrapartum-related mortality in public hospitals of Nepal.MethodsWe will conduct a stepped wedge cluster randomized controlled trial in eight public hospitals with each having least 3000 deliveries a year. Each hospital will represent a cluster with an intervention transition period of 2months in each. With a level of significance of 95%, the statistical power of 90% and an intra-cluster correlation of 0.00015, a study period of 19months should detect at least a 15% change in intrapartum-related mortality. Quality improvement training, mentoring, systematic feedback, and a continuous improvement cycle will be instituted based on bottleneck analyses in each hospital. All concerned health workers will be trained on standard basic neonatal resuscitation and essential newborn care. Portable fetal heart monitors (Moyo (R)) and neonatal heart rate monitors (Neobeat (R)) will be introduced in the hospitals to identify fetal distress during labor and to improve neonatal resuscitation. Independent research teams will collect data in each hospital on intervention inputs, processes, and outcomes by reviewing records and carrying out observations and interviews. The dose-response effect will be evaluated through process evaluations.DiscussionWith the global momentum to improve quality of intrapartum care, better understanding of QI package within a health facility context is important. The proposed package is based on experiences from a similar previous scale-up trial carried out in Nepal. The proposed evaluation will provide evidence on QI package and technology for implementation and scale up in similar settings.Trial registration numberISRCTN16741720. Registered on 2 March 2019.</p

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Systems responses to progressive water stress in durum wheat

Durum wheat is susceptible to terminal drought which can greatly decrease grain yield. Breeding to improve crop yield is hampered by inadequate knowledge of how the physiological and metabolic changes caused by drought are related to gene expression. To gain better insight into mechanisms defining resistance to water stress we studied the physiological and transcriptome responses of three durum breeding lines varying for yield stability under drought. Parents of a mapping population (Lahn x Cham1) and a recombinant inbred line (RIL2219) showed lowered flag leaf relative water content, water potential and photosynthesis when subjected to controlled water stress time transient experiments over a six-day period. RIL2219 lost less water and showed constitutively higher stomatal conductance, photosynthesis, transpiration, abscisic acid content and enhanced osmotic adjustment at equivalent leaf water compared to parents, thus defining a physiological strategy for high yield stability under water stress. Parallel analysis of the flag leaf transcriptome under stress uncovered global trends of early changes in regulatory pathways, reconfiguration of primary and secondary metabolism and lowered expression of transcripts in photosynthesis in all three lines. Differences in the number of genes, magnitude and profile of their expression response were also established amongst the lines with a high number belonging to regulatory pathways. In addition, we documented a large number of genes showing constitutive differences in leaf transcript expression between the genotypes at control non-stress conditions. Principal Coordinates Analysis uncovered a high level of structure in the transcriptome response to water stress in each wheat line suggesting genome-wide co-ordination of transcription. Utilising a systems-based approach of analysing the integrated wheat's response to water stress, in terms of biological robustness theory, the findings suggest that each durum line transcriptome responded to water stress in a genome-specific manner which contributes to an overall different strategy of resistance to water stress