Undernutrition is a health condition caused by a lack of enough food intake, not having enough of the right combination of food nutrients, or the body's failure to utilize the food eaten resulting in ...either, stunting, being underweight, or wasting. Globally, undernutrition affects more than 149 million under-five children, while in Uganda about 3 in every 10 children suffer from undernutrition. Undernutrition and its risk factors among under-five children in Uganda were unevenly distributed across the country and a study that focused on spatial distribution was prudent to examine the nature of the problem and salient factors associated with it. The current study addressed the issues of spatial heterogeneity of undernutrition and its determinants with the goal to identify hot spots and advise policymakers on the best actions to be taken to address the problem.
Data were obtained from the 2016 Uganda Demographic and Health Survey. Prevalence rates and percentages of risk factors were combined with the Uganda district shape file to allow spatial analysis. Moran's I, Getis-Ord (GI*), and Geographically Weighted Regressions were respectively used to establish the local, global, and geographically weighted regressions across the country. Stata 15 and ArcGIS 10. 7 soft wares were used.
The results indicate that undernutrition in Uganda shows varies spatially across regions. Evidence of hot spots exists in the Karamoja and Arua regions, cold spot areas exist around the central part of the country while the greatest part of Western Uganda, Northern, and Eastern were not significant.
The study reveals that a variation in the distribution of undernutrition throughout the country. Significant spatial patterns associated with undernutrition as identified through the hotspot and cold spot analysis do exist in Uganda. Programs targeting to reduce the undernutrition of under-five children in Uganda should consider the spatial distribution of undernutrition and its determinants whereby priority should be given to hotspot areas. The spatial intensity of undernutrition and its determinants indicate that focus should be tailored to meet the local needs as opposed to a holistic national approach.
Death registration in Uganda remains extremely low, yet mortality statistics are vital in health policy, planning, resource allocation and decision-making. According to NIRA, only 1% of deaths are ...registered annually, while Uganda Bureau of Statistics estimates death registration at 24% for the period 2011-2016. The wide variation between the administrative and survey statistics can be attributed to the restriction to only certified death registration by NIRA while survey statistics relate to all forms of death notification and registration at the different sub-national levels. Registration of deaths is of critical importance to individuals and a country's government. Legally, it grants administrative rights in management of a deceased's estate, and access to social (insurance and pension) benefits of a deceased person. It is also essential for official statistics and planning purposes. There is an urgent need for continuous and real-time collection of mortality data or statistics in Uganda. These statistics are of significance in public health for identifying the magnitude and distribution of major disease problems, and are essential for the design, implementation, monitoring, and assessment of health programmes and policies. Lack of such continuous and timely data has negative consequences for the achievement of both national and Sustainable Development Goals 3, 11, 16, and 17. This study assessed the determinants of death registration and certification, using a survey of 2018-2019 deaths in 2,100 households across four administrative regions of Uganda and Kampala district. Multivariate-binary logistic regression was used to model factors associated with the likelihood of a death being registered or certified. We find that around one-third of deaths were registered while death certificates were obtained for less than 5% of the total deaths. Death registration and certification varied notably within Uganda. Uptake of death registration and certification was associated with knowledge on death registration, region, access to mass media, age of the deceased, place of death, occupation of the deceased, relationship to household head and request for death certificate. There is need for decentralization of death registration services; massive sensitization of communities and creating demand for death registration.
Improving the simulation of the West African Monsoon (WAM) system is paramount to increasing confidence in the projections of the region’s monsoon rainfall change. This work aims to thoroughly ...analyze the representation of the WAM system in two state-of-the-art, high-resolution (~ 25 km) regional climate models (RCMs) in order to highlight the causes of models’ biases through a process-oriented evaluation approach. Model results generally feature a north (Sahel) - south (Guinea Coast) dipole-like rainfall bias, although, sometimes, positive or negative rainfall biases are evident almost over the whole of West Africa. Our analysis shows that biases in the sea- and land-surface temperature on the one hand, and biases in the sea-level and land-surface pressure, on the other hand, lead to biases in the simulated temperature and pressure contrasts between the west African landmass and the eastern Atlantic ocean. As a consequence, biases appear in the modeled monsoon flow strength, which, in turn, lead to errors in the amount of advected moisture in the interior of the continent via southwesterlies and the West African westerly jet (WAWJ) on the one hand, and the extent of deepening of the monsoon flux inland on the other hand. In addition, the African easterly jet (AEJ) is underestimated, inducing an underestimation of the African easterly waves (AEWs) activity and a weakening of the cyclonic convective circulation resulting from the AEWs’ troughs, leading to a decrease in the southwesterly flow feeding mesoscale convective systems (MCSs) embedded within the AEJ. The modeled equatorward or northward shifting of the AEJ is likewise found to contribute to the models' wet or dry biases over the Sahel. Finally, there is no consistency between models and reanalyses on the one hand, and between RCM experiments on the other hand, in the way, the simulated atmospheric instability/stability modulates the convection, especially over the Sahel.
Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection ...LTBI). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain.
A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach.
Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional.
These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.
Abstract
Intracranial electrical recordings and stimulation of neurosurgical patients have been central to the advancement of human neuroscience. The use of these methods has rapidly expanded over ...the last decade due to theoretical and technical advances, as well as the growing number of neurosurgical patients undergoing functional procedures for indications such as epilepsy, tumor resection, and movement disorders. These methods pose the potential for ethical conflict, as they involve basic neuroscientific research utilizing invasive procedures in human patients undergoing treatment for neurological illnesses. This review addresses technical aspects, clinical contexts, and issues of ethical concern, utilizing a framework that is informed by, but also departs from, existing bioethical literature on matters in clinical research. We conclude with proposals for improving informed consent processes to address potential problems specific to intracranial electrophysiology research, a general schema for scrutinizing research-related risk associated with different methods, and a call for the development of consensus to ensure continuing scientific progress alongside crucial patient protections in this promising area of human neuroscience.
More than a pore: ion channel signaling complexes Lee, Amy; Fakler, Bernd; Kaczmarek, Leonard K ...
The Journal of neuroscience,
2014-Nov-12, 2014-11-12, 20141112, Letnik:
34, Številka:
46
Journal Article
Recenzirano
Odprti dostop
Voltage- and ligand-gated ion channels form the molecular basis of cellular excitability. With >400 members and accounting for ∼1.5% of the human genome, ion channels are some of the most well ...studied of all proteins in heterologous expression systems. Yet, ion channels often exhibit unexpected properties in vivo because of their interaction with a variety of signaling/scaffolding proteins. Such interactions can influence the function and localization of ion channels, as well as their coupling to intracellular second messengers and pathways, thus increasing the signaling potential of these ion channels in neurons. Moreover, functions have been ascribed to ion channels that are largely independent of their ion-conducting roles. Molecular and functional dissection of the ion channel proteome/interactome has yielded new insights into the composition of ion channel complexes and how their dysregulation leads to human disease.
Determining true genetic dissimilarity between individuals is an important and decisive point for clustering and analysing diversity within and among populations, because different dissimilarity ...indices may yield conflicting outcomes. We show that there are no acceptable universal approaches to assessing the dissimilarity between individuals with molecular markers. Different measures are relevant to dominant and codominant DNA markers depending on the ploidy of organisms. The Dice coefficient is the suitable measure for haploids with codominant markers and it can be applied directly to (0,1)‐vectors representing banding profiles of individuals. None of the common measures, Dice, Jaccard, simple mismatch coefficient (or the squared Euclidean distance), is appropriate for diploids with codominant markers. By transforming multiallelic banding patterns at each locus into the corresponding homozygous or heterozygous states, a new measure of dissimilarity within locus was developed and expanded to assess dissimilarity between multilocus states of two individuals by averaging across all codominant loci tested. There is no rigorous well‐founded solution in the case of dominant markers. The simple mismatch coefficient is the most suitable measure of dissimilarity between banding patterns of closely related haploid forms. For distantly related haploid individuals, the Jaccard dissimilarity is recommended. In general, no suitable method for measuring genetic dissimilarity between diploids with dominant markers can be proposed. Banding patterns of diploids with dominant markers and polyploids with codominant markers represent individuals’ phenotypes rather than genotypes. All dissimilarity measures proposed and developed herein are metrics.
Human embryonic stem cells (hESCs) share an identical genome with lineage-committed cells, yet possess the remarkable properties of self-renewal and pluripotency. The diverse cellular properties in ...different cells have been attributed to their distinct epigenomes, but how much epigenomes differ remains unclear. Here, we report that epigenomic landscapes in hESCs and lineage-committed cells are drastically different. By comparing the chromatin-modification profiles and DNA methylomes in hESCs and primary fibroblasts, we find that nearly one-third of the genome differs in chromatin structure. Most changes arise from dramatic redistributions of repressive H3K9me3 and H3K27me3 marks, which form blocks that significantly expand in fibroblasts. A large number of potential regulatory sequences also exhibit a high degree of dynamics in chromatin modifications and DNA methylation. Additionally, we observe novel, context-dependent relationships between DNA methylation and chromatin modifications. Our results provide new insights into epigenetic mechanisms underlying properties of pluripotency and cell fate commitment.
► 11 histone modifications mapped in human embryonic stem cells and fibroblasts ► Dramatic redistributions of repressive H3K9me3 and H3K27me3 marks ► Context-dependent relationship between DNA methylation and chromatin modifications ► Multiple distinct modes of repression of genes important for pluripotency
A very high proportion of cases of intellectual disability are genetic in origin and are associated with the occurrence of epileptic seizures during childhood. These two disorders together effect ...more than 5% of the world’s population. One feature linking the two diseases is that learning and memory require the synthesis of new synaptic components and ion channels, while maintenance of overall excitability also requires synthesis of similar proteins in response to altered neuronal stimulation. Many of these disorders result from mutations in proteins that regulate mRNA processing, translation initiation, translation elongation, mRNA stability or upstream translation modulators. One theme that emerges on reviewing this field is that mutations in proteins that regulate changes in translation following neuronal stimulation are more likely to result in epilepsy with intellectual disability than general translation regulators with no known role in activity-dependent changes. This is consistent with the notion that activity-dependent translation in neurons differs from that in other cells types in that the changes in local cellular composition, morphology and connectivity that occur generally in response to stimuli are directly coupled to local synaptic activity and persist for months or years after the original stimulus.
•Intellectual disability (ID) is frequently associated with epilepsy in childhood.•Mutations in genes that regulate mRNA translation may cause either condition.•Disruption of activity-dependent translation preferentially produces epilepsy with ID.
The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation and characterization, including ...single-cell RNA-seq, of neocortical and spinal cord neuroepithelial stem (NES) cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. By analyzing human NES cells, organotypic fetal brain slices, and a ZIKV-infected micrencephalic brain, we show that ZIKV infects both neocortical and spinal NES cells as well as their fetal homolog, radial glial cells (RGCs), causing disrupted mitoses, supernumerary centrosomes, structural disorganization, and cell death. ZIKV infection of NES cells and RGCs causes centrosomal depletion and mitochondrial sequestration of phospho-TBK1 during mitosis. We also found that nucleoside analogs inhibit ZIKV replication in NES cells, protecting them from ZIKV-induced pTBK1 relocalization and cell death. We established a model system of human neural stem cells to reveal cellular and molecular mechanisms underlying neurodevelopmental defects associated with ZIKV infection and its potential treatment.
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•Derivation of human neocortical and spinal cord neuroepithelial stem (NES) cells•Zika virus (ZIKV) infects NES cells and radial glia, impairing mitosis and survival•ZIKV induces mitochondrial sequestration of centrosomal phospho-TBK1•Nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death
Onorati et al. establish neuroepithelial stem (NES) cells as a model for studying human neurodevelopment and ZIKV-induced microcephaly. Together with analyses in human brain slices and microcephalic human fetal tissue, they find that ZIKV predominantly infects NES and radial glial cells, reveal a pivotal role for pTBK1, and find that nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death.
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