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1.
BMC Public Health ; 24(1): 934, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561742

ABSTRACT

BACKGROUND: Despite the uncontested benefits of physical activity, its promotion lags behind in the public health agenda of low- and middle-income countries (LMICs). School-based interventions are promising strategies to foster health during childhood, but evidence of their effectiveness is limited and inconclusive for LMICs. Thus, further investigation is needed on contextual factors associated with intervention implementation in low-resource settings. We studied the acceptability and feasibility of the KaziKidz health promotion intervention and its implementation and make recommendations to improve future adoption and sustainability. METHODS: KaziKidz was implemented in four primary schools from low-income communities in South Africa in 2019. Semi-structured interviews with four school principals, three focus group interviews with 16 educators, and another three with 16 caregivers were conducted between October and November 2021. Participants were purposively recruited. Interview transcripts were analyzed via thematic analysis using a deductive and reflexive approach. RESULTS: Three main themes influencing intervention implementation and adoption were identified: (1) prioritizing teachers' needs (2), integrating the program into the school structure, and (3) creating opportunities in the community. Supporting recommendations included: (theme 1) adopting intervention approaches that are inclusive of educators' health and providing them with capacity development and external support; (theme 2) fostering a feeling of ownership and belonging among school stakeholders to adapt interventions to specific resources and needs; and (theme 3) raising community awareness to encourage individuals to claim power over and actively engage with the program. CONCLUSIONS: Comprehensive interventions comprising health support, adequate training, and ongoing assistance for educators combined with school-wide and community outreach actions seeking to strengthen program ownership, accountability, and engagement can enhance uptake of school-based interventions and long-term maintenance. TRIAL REGISTRATION: ISRCTN15648510, registered on 17/04/2020.


Subject(s)
Caregivers , Health Promotion , Humans , South Africa , Feasibility Studies , Schools
2.
BMC Med ; 20(1): 27, 2022 01 27.
Article in English | MEDLINE | ID: mdl-35081959

ABSTRACT

BACKGROUND: The prevalence of overweight and obesity is increasing among African children potentially predisposing them to greater obesity and non-communicable diseases (NCDs) in adulthood. This risk may be higher among growth-impaired children who may have greater fat mass. Therefore, we examined the effects of school-based physical activity (PA) promotion and multi-micronutrient supplementation (MMNS) on body composition among South African children enrolled in a longitudinal school-based randomized controlled trial. METHODS: Children were cluster-randomized by class to one of four groups: (a) a physical activity group (PA), (b) a multi-micronutrient supplementation group (MMNS), (c) a physical activity + multi-micronutrient supplementation group (PA + MMNS), and (d) control group, and were being followed for 3 years. Linear random effects regression models with random intercepts for school classes tested the associations of each intervention arm with overall fat mass (FM), fat-free mass (FFM), truncal fat mass (TrFM), and truncal fat-free mass (TrFFM) at 9 months (T2) for boys and girls. These differences were then explored among children who differed in height velocity (HV). RESULTS: A total of 1304 children (614 girls, 667 boys) in twelve clusters were assessed at baseline and after 9 months follow-up (T2). At baseline, approximately 15% of children were classified as overweight or obese while approximately 38% of children were classified as mildly stunted or moderately/severely stunted. Among girls, promotion of PA was associated with reduced FM and TrFM at T2 while MMNS was associated with increased FFM. Children with reduced HV in the PA arm had reduced FM while children in the MMNS arm with lower HV had increased FM compared to children in the control arm. Similarly, children with lower HV in the MM and PA groups had reduced TrFM compared to children in the control arm. CONCLUSIONS: Our study suggests that the promotion of school-based physical activity programs and micronutrient supplementation can reduce childhood adiposity and so reduce the risk of obesity and chronic diseases later in adulthood. TRIAL REGISTRATION: ISRCTN, ISRCTN29534081 . Registered on August 9, 2018. The trial was designed, analyzed, and interpreted based on the CONSORT protocol (Additional file 1: CONSORT checklist for randomized trial).


Subject(s)
Body Composition , Pediatric Obesity , Adult , Body Height , Body Mass Index , Child , Exercise , Female , Health Promotion/methods , Humans , Male , Pediatric Obesity/epidemiology , Pediatric Obesity/prevention & control , South Africa/epidemiology
3.
Clin Exp Allergy ; 52(5): 670-683, 2022 05.
Article in English | MEDLINE | ID: mdl-35073608

ABSTRACT

BACKGROUND: Inconsistent data exist regarding the influence of parasitic infection on the prevalence of allergic sensitization and disorders. OBJECTIVE: To investigate the impact of geohelminth and protozoan infections on sensitization patterns and allergic symptoms of children living in low-income communities in Gqeberha, South Africa. METHODS: In a cross-sectional study, 587 schoolchildren aged 8-12 years were recruited in June 2016 and screened for reactivity to common allergens by skin prick tests (SPTs) and for parasitic infections by stool examination. Additionally, questionnaires were completed to record allergic symptoms the children may have experienced. RESULTS: Positive SPTs were found in 237/587 children (40.4%), and about one-third of whom were polysensitized. Sensitizations were most frequently detected against the house dust mites (HDM) Dermatophagoides spp. (31.9%) and Blomia tropicalis (21.0%). Infections with geohelminths (Ascaris lumbricoides, Trichuris trichiura) were found in 26.8% and protozoan infections (Giardia intestinalis, Cryptosporidia spp.) in 13.9% of study participants. Mixed logistic regression analyses revealed negative associations between parasite infection and sensitization to Blomia tropicalis (OR: 0.54, 95% CI 0.33-0.89) and to Dermatophagoides spp. (OR 0.65, 95% CI 0.43-0.96), and between protozoan infection and allergic sensitization to any aeroallergen, although these associations were not significant when adjusted for false discovery. Geohelminth infection and intensity of geohelminth infection were both associated with reduced risk of polysensitization (OR 0.41, 95% CI 0.21-0.86), and this association remained significant with adjustment for false discovery. Reported respiratory symptoms were associated with HDM sensitization (ORs from 1.54 to 2.48), but not with parasite infection. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that geohelminth infection and high geohelminth infection intensity are associated with a reduced risk of polysensitization.


Subject(s)
Allergens , Hypersensitivity , Animals , Child , Cross-Sectional Studies , Humans , Pyroglyphidae , Skin Tests , South Africa/epidemiology
4.
BMC Public Health ; 21(1): 852, 2021 05 03.
Article in English | MEDLINE | ID: mdl-33941121

ABSTRACT

BACKGROUND: Cardiovascular fitness has been associated with both executive function and academic achievement in multiple cohort studies including children and adolescents. However, research is scarce among children from low- and middle-income countries. Hence, this paper focuses on South African primary schoolchildren living in marginalized areas and examines if academic achievement and inhibitory control can be explained by children's age, socioeconomic status, soil-transmitted helminth infections, food insecurity, stunting, grip strength, and cardiorespiratory fitness. METHODS: The sample of this cross-sectional study consisted of 1277 children (48% girls, mean age: 8.3 years). Data were assessed via questionnaires, stool samples, anthropometric measurements, 20 m shuttle run test, grip strength test, Flanker task, and school grades. Data were analysed with mixed linear regression models with random intercepts for school classes, separately for boys and girls. RESULTS: Higher socioeconomic status was most closely associated with academic achievement among boys (p < 0.05), whereas higher levels of cardiorespiratory fitness and not being stunted explained most variance in academic achievement in girls (p < 0.05). Higher age turned out to be associated with better performance in the Flanker task (p < 0.01). Additionally, in boys, higher grip strength was associated with better information processing and inhibitory control of attention (p < 0.01), whereas in girls, higher cardiorespiratory fitness levels were positively associated with these cognitive abilities (p < 0.05). CONCLUSIONS: Academic performance has been shown to be compromised in schoolchildren living in marginalised areas, compared to schoolchildren in less disadvantaged parts of South Africa. The present study suggests that cardiorespiratory fitness and grip strength are two potentially modifiable factors that are associated with children's academic achievement and cognitive performance, and that should be targeted in future school-based interventions.


Subject(s)
Academic Success , Helminths , Adolescent , Animals , Child , Cross-Sectional Studies , Female , Food Insecurity , Growth Disorders/epidemiology , Humans , Male , Physical Fitness , Soil , South Africa/epidemiology
5.
J Sports Sci ; 39(21): 2454-2467, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34334121

ABSTRACT

Childhood hypertension drives hypertension in later life; hence, assessing blood pressure in children is an important measure to determine current and future cardiovascular health. There is, however, a paucity of childhood blood pressure data, particularly for sub-Saharan Africa. This study explores blood pressure and associations with age, sex, socioeconomic status, physical activity, fitness, and cardiovascular risk markers. In the 'Disease, Activity and Schoolchildren's Health' (DASH) study, a cross-sectional analysis was conducted in disadvantaged neighbourhoods in the Eastern Cape province of South Africa. Assessments included blood pressure, accelerometer-measured physical activity, physical fitness, and cardiovascular risk markers. The study consisted of 785 children (383 boys, 402 girls, M = 12.4±0.9 years). Overall, 18% of the children were classified as hypertensive, while 20% were either overweight/obese, and almost four out of ten children did not meet global daily physical activity recommendations. Hypertensive children were more likely to be overweight/obese, χ2 (2,785) = 14.42, p < 0.01, but only if they did not meet physical activity recommendations, χ2 (2,295) = 11.93, p < 0.01. Considering the moderating effect which sufficient activity has on the relationship between hypertension and body weight, more emphasis should be placed on early primary health intervention and education strategies.


Subject(s)
Exercise/physiology , Heart Disease Risk Factors , Hypertension/epidemiology , Physical Fitness/physiology , Poverty , Age Factors , Body Composition , Cardiorespiratory Fitness/physiology , Child , Comorbidity , Cross-Sectional Studies , Female , Hand Strength/physiology , Humans , Male , Overweight/epidemiology , Pediatric Obesity/epidemiology , Prehypertension/epidemiology , Prevalence , Sex Factors , Social Class , South Africa/epidemiology
6.
Prev Med ; 112: 104-110, 2018 07.
Article in English | MEDLINE | ID: mdl-29626554

ABSTRACT

People from low- and middle-income countries still face challenges stemming from parasitic infections. Additionally, non-communicable diseases (NCDs) and their risk factors are rapidly increasing, which puts South African children at an elevated risk of a dual disease burden, with negative consequences for child development and wellbeing. Contrastingly, regular physical activity (PA) is associated with decreased cardiovascular disease (CVD) risk. Therefore, the objective of this study was to examine whether PA is associated with the double infection-CVD phenotype burden in South African schoolchildren. 801 children (402 boys, 399 girls; mean age 9.5 years) from eight schools from disadvantaged neighbourhoods were included. Data assessment took place between February and March 2015 in Port Elizabeth, South Africa. Children who achieved PA recommendations (physically active on 6-7 days/week for at least 60 min), who were active, but below recommended standards (2-5 physically active days/week), or who were insufficiently active on almost all days (0-1 physically active days/week) were compared with regard to systolic and diastolic blood pressure, body mass index (BMI), percent body fat, and infection with soil-transmitted helminths. Moderate and high self-reported PA levels were associated with lower BMI, lower body fat, and lower risk of being hypertensive. Conversely, children with high self-reported PA were more likely to be infected with soil-transmitted helminths than peers with low PA levels. Promoting PA in disadvantaged areas is worthwhile to prevent NCD later in life, but should be combined with regular anthelminthic treatment to comprehensively improve children's health and wellbeing.


Subject(s)
Cardiovascular Diseases/prevention & control , Exercise/physiology , Helminthiasis/diagnosis , Intestinal Diseases, Parasitic/diagnosis , Self Report , Vulnerable Populations , Animals , Blood Pressure/physiology , Child , Cross-Sectional Studies , Developing Countries , Female , Helminthiasis/epidemiology , Helminths/classification , Humans , Male , Obesity/prevention & control , Risk Factors , Schools , South Africa/epidemiology
7.
Qual Life Res ; 27(1): 205-216, 2018 01.
Article in English | MEDLINE | ID: mdl-28965191

ABSTRACT

PURPOSE: The relationship between health-related quality of life (HRQoL), physical activity (PA), and cardiorespiratory fitness (CRF) among disadvantaged communities in low- and middle-income countries is poorly understood. In South Africa, children from socioeconomically deprived households are at an elevated risk of sedentary lifestyles and poor HRQoL. We examined whether higher self-reported PA and higher CRF levels are associated with better HRQoL in South African schoolchildren from disadvantaged neighbourhoods. METHODS: Overall, 832 children aged 8-12 years participated in this cross-sectional study. HRQoL was assessed through five dimensions of the KIDSCREEN-27 tool. Self-reported PA was measured using a single item of the Health-Behaviour of School-Aged Children test, and CRF with the 20-m shuttle run test. RESULTS: Higher self-reported PA was significantly and positively related to HRQoL. Significant, but small group differences existed across all dimensions of HRQoL between low and high self-reported PA. No significant associations were observed between CRF levels and HRQoL. CONCLUSIONS: Schoolchildren reporting PA of at least 60 min on at least 6 days a week (the recommended minimum) report higher HRQoL than their peers with lower PA levels.


Subject(s)
Exercise/psychology , Quality of Life/psychology , Schools/standards , Vulnerable Populations/psychology , Child , Cross-Sectional Studies , Female , Humans , Male , South Africa
8.
J Virol ; 90(16): 7159-70, 2016 08 15.
Article in English | MEDLINE | ID: mdl-27226379

ABSTRACT

UNLABELLED: The release of infectious hepatitis C virus (HCV) particles from infected cells remains poorly characterized. We previously demonstrated that virus release is dependent on the endosomal sorting complex required for transport (ESCRT). Here, we show a critical role of trans-Golgi network (TGN)-endosome trafficking during the assembly, but principally the secretion, of infectious virus. This was demonstrated by both small interfering RNA (siRNA)-mediated silencing of TGN-associated adaptor proteins and a panel of dominant negative (DN) Rab GTPases involved in TGN-endosome trafficking steps. Importantly, interfering with factors critical for HCV release did not have a concomitant effect on secretion of triglycerides, ApoB, or ApoE, indicating that particles are likely released from Huh7 cells via pathways distinct from that of very-low-density lipoprotein (VLDL). Finally, we show that HCV NS2 perturbs TGN architecture, redistributing TGN membranes to closely associate with HCV core protein residing on lipid droplets. These findings support the notion that HCV hijacks TGN-endosome trafficking to facilitate particle assembly and release. Moreover, although essential for assembly and infectivity, the trafficking of mature virions is seemingly independent of host lipoproteins. IMPORTANCE: The mechanisms by which infectious hepatitis C virus particles are assembled and released from the cell are poorly understood. We show that the virus subverts host cell trafficking pathways to effect the release of virus particles and disrupts the structure of the Golgi apparatus, a key cellular organelle involved in secretion. In addition, we demonstrate that the mechanisms used by the virus to exit the cell are distinct from those used by the cell to release lipoproteins, suggesting that the virus effects a unique modification to cellular trafficking pathways.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Endosomes/metabolism , Hepatitis C/metabolism , Lipoproteins, VLDL/metabolism , Liver Neoplasms/metabolism , Virus Release/physiology , trans-Golgi Network/metabolism , Biological Transport , Blotting, Western , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Endosomes/genetics , Endosomes/virology , Golgi Apparatus/genetics , Golgi Apparatus/metabolism , Golgi Apparatus/virology , Hepacivirus/physiology , Hepatitis C/genetics , Hepatitis C/virology , Humans , Liver Neoplasms/genetics , Liver Neoplasms/virology , Microscopy, Fluorescence , Secretory Vesicles/metabolism , Virion/metabolism , Virus Replication , trans-Golgi Network/genetics , trans-Golgi Network/virology
9.
Nucleic Acids Res ; 41(11): 5912-26, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23595147

ABSTRACT

All orthobunyaviruses possess three genome segments of single-stranded negative sense RNA that are encapsidated with the virus-encoded nucleocapsid (N) protein to form a ribonucleoprotein (RNP) complex, which is uncharacterized at high resolution. We report the crystal structure of both the Bunyamwera virus (BUNV) N-RNA complex and the unbound Schmallenberg virus (SBV) N protein, at resolutions of 3.20 and 2.75 Å, respectively. Both N proteins crystallized as ring-like tetramers and exhibit a high degree of structural similarity despite classification into different orthobunyavirus serogroups. The structures represent a new RNA-binding protein fold. BUNV N possesses a positively charged groove into which RNA is deeply sequestered, with the bases facing away from the solvent. This location is highly inaccessible, implying that RNA polymerization and other critical base pairing events in the virus life cycle require RNP disassembly. Mutational analysis of N protein supports a correlation between structure and function. Comparison between these crystal structures and electron microscopy images of both soluble tetramers and authentic RNPs suggests the N protein does not bind RNA as a repeating monomer; thus, it represents a newly described architecture for bunyavirus RNP assembly, with implications for many other segmented negative-strand RNA viruses.


Subject(s)
Nucleocapsid Proteins/chemistry , Orthobunyavirus , RNA/chemistry , Ribonucleoproteins/chemistry , Amino Acid Sequence , Models, Molecular , Molecular Sequence Data , Nucleocapsid Proteins/metabolism , Orthobunyavirus/physiology , Protein Binding , Protein Multimerization , RNA/metabolism , Ribonucleoproteins/metabolism , Ribonucleoproteins/ultrastructure , Transcription, Genetic , Virus Replication
10.
BMC Public Health ; 15: 1285, 2015 Dec 23.
Article in English | MEDLINE | ID: mdl-26700478

ABSTRACT

BACKGROUND: An in-depth epidemiological investigation on intestinal parasite infections in an impoverished area of Port Elizabeth, South Africa provides a unique opportunity for research on its impact on children's physical fitness, cognitive performance and psychosocial health. Additionally, we will screen risk factors for the development of diabetes and hypertension in adulthood. METHODS/DESIGN: A 2-year longitudinal cohort study will be conducted, consisting of three cross-sectional surveys (baseline and two follow-ups), in eight historically black and coloured (mixed race) primary schools located in different townships in Port Elizabeth, South Africa. Approximately 1000 Grade 4 primary schoolchildren, aged 8 to 12 years, will be enrolled and followed. At each survey, disease status, anthropometry and levels of physical fitness, cognitive performance and psychosocial health will be assessed. After each survey, individuals diagnosed with parasitic worm infections will be treated with anthelminthic drugs, while children with other infections will be referred to local clinics. Based on baseline results, interventions will be tailored to the local settings, embedded within the study and implemented in half of the schools, while the remaining schools will serve as controls. Implementation of the interventions will take place over two 8-week periods. The effect of interventions will be determined with predefined health parameters. DISCUSSION: This study will shed new light on the health burden incurred by children in deprived urban settings of South Africa and provide guidance for specific health interventions. Challenges foreseen in the conduct of this study include: (i) difficulty in obtaining written informed consent from parents/guardians; (ii) administration of questionnaires in schools where three languages are spoken (Afrikaans, Xhosa and English); (iii) challenges in grasping concepts of psychosocial health among schoolchildren using a questionnaire; and (iv) loss to follow-up due to the study setting where illiteracy, mobility and violence are common. Finally, designing the health interventions together with local principals and teachers will allow all concerned with the research to bolster a sense of community ownership and sustained use of the interventions after the study has ceased. TRIAL REGISTRATION: Controlled-trials.com; identifier: ISRCTN68411960 (date assigned: 14 February 2014).


Subject(s)
Child Welfare/statistics & numerical data , Health Promotion/methods , Intestinal Diseases, Parasitic/epidemiology , Intestinal Diseases, Parasitic/prevention & control , Anthelmintics/therapeutic use , Child , Child Development/drug effects , Cohort Studies , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Risk Factors , Schools , South Africa , Surveys and Questionnaires
11.
Am J Prev Med ; 66(6): 1078-1088, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38309672

ABSTRACT

INTRODUCTION: Physical activity (PA) promotion combined with multimicronutrient supplementation (MMNS) among school-age children may reduce fat mass accrual and increase muscle mass through different mechanisms and so benefit child health. This study determined the efficacy of combined interventions on body composition among South African schoolchildren and determined if micronutrients mediate these effects. STUDY DESIGN: Longitudinal cluster randomized controlled trial of children followed from 2019 to 2021. Statistical analyses carried from 2022 to 2023. SETTING/PARTICIPANTS: A total of 1,304 children 6-12 years of age recruited from public schools in Gqeberha, South Africa. INTERVENTION: Children were randomized by classes to either: (a) a physical activity group (PA); (b) a MMNS group; (c) a physical activity + multimicronutrient supplementation group (PA + MMNS); and (d) a placebo control group. MAIN OUTCOME MEASURES: Trajectories of overall and truncal fat free mass (FFM) and fat mass (FM) estimates in modeled at 9 and 21 months using latent growth curve models (LGCM). Changes in micronutrient concentrations at 9 months from baseline. RESULTS: An increased FFM trajectory was found among children in the MMNS arm at 9 months (Beta 0.16, 95% CI = 0.12, 0.31). The PA and MMNS arms both had positive indirect effects on this trajectory at 9 months (Beta 0.66, 95% CI = 0.44, 0.88 and Beta 0.32 95% CI = 0.1 0.5, respectively) and similarly at 21 months when mediated by zinc concentration changes. A reduced FM trajectory was found among children in the PA promotion arm at 9 months when using this collection point as the referent intercept. This arm was inversely associated with the FM trajectory at 9 months when mediated by zinc changes. CONCLUSIONS: PA and MMNS promotion in school-based interventions directly contributed to reductions in FM and increased FFM among South African children and indirectly through changes in micronutrient status. TRIAL REGISTRATION: ISRCTN, ISRCTN29534081. Registered on August 9, 2018 Institutional review board: Ethikkommission Nordwest- und Zentralschweiz" (EKNZ, project number: Req-2018-00608). Date of approval: 2018.


Subject(s)
Body Composition , Dietary Supplements , Exercise , Micronutrients , Humans , South Africa , Micronutrients/administration & dosage , Child , Male , Female , Exercise/physiology , Longitudinal Studies
12.
J Gen Virol ; 94(Pt 12): 2657-2663, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24026670

ABSTRACT

The 5' untranslated region (5'UTR) of the recently described non-primate hepacivirus (NPHV) contains a region with sequence homology to the internal ribosomal entry site (IRES) of hepatitis C virus (HCV) and GB virus B (GBV-B). Here, we demonstrated internal translation initiation by the NPHV 5'UTR in a bicistronic vector. An RNA stem-loop upstream of the NPHV IRES was structurally distinct from corresponding regions in HCV and GBV-B, and was not required for IRES function. Insertion of the NPHV stem-loop into the corresponding region of the HCV 5'UTR within the HCV subgenomic replicon significantly impaired RNA replication, indicating that long-range interactions between the 5'UTR and cis-acting downstream elements within the NPHV genome are not interchangeable with those of HCV. Despite similarities in IRES structure and function between hepaciviruses, replication elements in the NPHV 5'UTR appear functionally distinct from those of HCV.


Subject(s)
5' Untranslated Regions/genetics , Hepacivirus/genetics , Peptide Chain Initiation, Translational , Ribosomes/metabolism , 5' Untranslated Regions/physiology , Animals , Cell Line , HEK293 Cells , Hepacivirus/metabolism , Hepacivirus/physiology , Humans , Nucleic Acid Conformation , Primates/genetics , Primates/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , Replicon/genetics , Replicon/physiology , Virus Replication/genetics
13.
J Gen Virol ; 94(Pt 5): 1073-1078, 2013 May.
Article in English | MEDLINE | ID: mdl-23343628

ABSTRACT

Providence virus (PrV) is the sole member of the family Carmotetraviridae (formerly Tetraviridae) sharing the characteristic T=4 capsid architecture with other tetravirus families. Despite significant structural similarities, PrV differs from other tetraviruses in terms of genome organization, non-structural protein sequence and regulation of gene expression. In addition, it is the only tetravirus that infects tissue culture cells. Previous studies showed that in persistently infected Helicoverpa zea MG8 cells, the PrV replicase associates with detergent-resistant membranes in punctate cytosolic structures, which is similar to the distribution of an alpha-like tetravirus replicase (Helicoverpa armigera stunt virus). Here, we demonstrate that the site of PrV vRNA replication coincides with the presence of PrV p40/p104 proteins in infected cells and that these replication proteins associate with the Golgi apparatus and secretory vesicles in transfected cells.


Subject(s)
Genome, Viral/genetics , Golgi Apparatus/virology , Moths/virology , RNA Viruses/physiology , Secretory Vesicles/virology , Virus Replication , Animals , Cells, Cultured , RNA Viruses/genetics , RNA Viruses/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , Recombinant Fusion Proteins , Viral Proteins/genetics , Viral Proteins/metabolism
14.
J Virol ; 86(20): 10914-23, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22875964

ABSTRACT

Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging tick-borne virus of the Bunyaviridae family that is responsible for a fatal human disease for which preventative or therapeutic measures do not exist. We solved the crystal structure of the CCHFV strain Baghdad-12 nucleocapsid protein (N), a potential therapeutic target, at a resolution of 2.1 Å. N comprises a large globular domain composed of both N- and C-terminal sequences, likely involved in RNA binding, and a protruding arm domain with a conserved DEVD caspase-3 cleavage site at its apex. Alignment of our structure with that of the recently reported N protein from strain YL04057 shows a close correspondence of all folds but significant transposition of the arm through a rotation of 180 degrees and a translation of 40 Å. These observations suggest a structural flexibility that may provide the basis for switching between alternative N protein conformations during important functions such as RNA binding and oligomerization. Our structure reveals surfaces likely involved in RNA binding and oligomerization, and functionally critical residues within these domains were identified using a minigenome system able to recapitulate CCHFV-specific RNA synthesis in cells. Caspase-3 cleaves the polypeptide chain at the exposed DEVD motif; however, the cleaved N protein remains an intact unit, likely due to the intimate association of N- and C-terminal fragments in the globular domain. Structural alignment with existing N proteins reveals that the closest CCHFV relative is not another bunyavirus but the arenavirus Lassa virus instead, suggesting that current segmented negative-strand RNA virus taxonomy may need revision.


Subject(s)
Hemorrhagic Fever Virus, Crimean-Congo/chemistry , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/metabolism , Amino Acid Sequence , Caspase 3/metabolism , Crystallography, X-Ray , Evolution, Molecular , Hemorrhagic Fever Virus, Crimean-Congo/classification , Hemorrhagic Fever Virus, Crimean-Congo/genetics , Hemorrhagic Fever Virus, Crimean-Congo/metabolism , Hemorrhagic Fever, Crimean/virology , Nucleocapsid , Phylogeny , Protein Conformation , Protein Structure, Tertiary , RNA, Viral/chemistry , RNA, Viral/genetics , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/metabolism , Sequence Alignment
15.
Front Public Health ; 11: 1199381, 2023.
Article in English | MEDLINE | ID: mdl-37304085

ABSTRACT

Introduction: Risk factors for noncommunicable diseases such as insufficient physical activity (PA), overweight or hypertension are becoming increasingly predominant among children globally. While school-based interventions are promising preventive strategies, evidence of their long-term effectiveness, especially among vulnerable populations, is scarce. We aim to assess the short-term effects of the physical and health KaziKidz intervention on cardiometabolic risk factors and the long-term, pre-and post-COVID-19 pandemic changes thereof in high-risk children from marginalized communities. Methods: The intervention was tested in a cluster-randomized controlled trial between January and October 2019 in eight primary schools near Gqeberha, South Africa. Children with overweight, elevated blood pressure, pre-diabetes, and/or borderline dyslipidemia were identified and re-assessed 2 years post-intervention. Study outcomes included accelerometry-measured PA (MVPA), body mass index (BMI), mean arterial pressure (MAP), glucose (HbA1c), and lipid levels (TC to HDL ratio). We conducted mixed regression analyses to assess intervention effects by cardiometabolic risk profile, and Wilcoxon signed-rank tests to evaluate longitudinal changes in the high-risk subpopulation. Results: We found a significant intervention effect on MVPA during school hours for physically inactive children, and among active as well as inactive girls. In contrast, the intervention lowered HbA1c and TC to HDL ratio only in children with glucose or lipid values within the norm, respectively. At follow-up, the intervention effects were not maintained in at-risk children, who showed a decline in MVPA, and an increase in BMI-for-age, MAP, HbA1c and TC to HDL ratio. Conclusion: We conclude that schools are key settings in which to promote PA and improve health; however, structural changes are necessary to ensure that effective interventions reach marginalized school populations and achieve sustainable impact.


Subject(s)
COVID-19 , Hypertension , Noncommunicable Diseases , Female , Humans , Child , South Africa/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Follow-Up Studies , Glycated Hemoglobin , Overweight , Pandemics , Exercise , Glucose , Hypertension/epidemiology , Hypertension/prevention & control , Lipids
16.
Article in English | MEDLINE | ID: mdl-36674182

ABSTRACT

This study aimed to establish the prevalence of underweight, overweight and obesity, the level of moderate-to-vigorous physical activity (MVPA) and the association thereof among vulnerable children from low-income communities in South Africa. Cross-sectional data were collected from 916 children (467 boys and 449 girls) aged 8-13 years (x̄ = 10.4 ± 1.2 years) attending eight low-income schools in Gqeberha, South Africa. Measured outcomes included accelerometery-measured physical activity (PA), weight, height and body mass index (BMI). Analysis of variance was used to determine the mean difference of total MVPA stratified by sex and BMI classification. Overall, 13% of the cohort were underweight, 19% were overweight/obese and 64% engaged in 60 min of MVPA per day. Girls presented nearly twice the odds of being overweight or obese than boys (95% CI: 1.40-2.77). Underweight to normal-weight children (boys: OR = 3.89, 95% CI: 2.18-6.93; girls: OR = 1.78, 95% CI: 1.13-2.80) were more likely to engage in 60 min/day of MVPA than overweight to obese children. There is an inverse association between BMI categories and theduration of MVPA achieved per day. Special attention should be aimed at increasing awareness of healthy nutrition and promoting a variety of PA, especially among girls and children with excess weight.


Subject(s)
Overweight , Pediatric Obesity , Male , Female , Humans , Child , Body Mass Index , Cross-Sectional Studies , Overweight/epidemiology , Thinness/epidemiology , South Africa/epidemiology , Exercise , Body Weight
17.
PLoS Negl Trop Dis ; 17(10): e0011664, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37831637

ABSTRACT

BACKGROUND/AIM: School-aged children in low- and middle-income countries carry the highest burden of intestinal helminth infections, such as soil-transmitted helminths (STH). STH infections have been associated with negative consequences for child physical and cognitive development and wellbeing. With the epidemiological transition and rise in cardiovascular disease (CVD), studies have shown that helminth infections may influence glucose metabolism by preventing obesity. Thus, the aim of this study was to determine the association of STH infections in schoolchildren from Gqeberha, focusing on physical activity, physical fitness, and clustered CVD risk score. METHODS: This cross-sectional study involved 680 schoolchildren (356 girls and 324 boys; mean age 8.19 years, SD±1.4) from disadvantaged communities in Gqeberha (formerly, Port Elizabeth), South Africa. Stool samples were collected and examined for STH infections using the Kato-Katz method. Physical activity (accelerometer) and physical fitness (grip strength, 20 m shuttle run) were measured using standard procedures. Furthermore, anthropometry, blood pressure, as well as glycated haemoglobin and lipid profile from capillary blood samples were assessed. We employed one-way ANOVAs to identify the associations of STH infections in terms of species and infection intensity with physical activity, physical fitness, and clustered CVD risk score. RESULTS: We found a low STH infection prevalence (7.2%) in our study, with participants infected with at least one intestinal helminth species. In comparison to their non-infected peers, children infected with STH had lower mean grip strength scores, but higher mean VO2max estimation and higher levels of MVPA (p < .001). When considering type and intensity of infection, a positive association of A. lumbricoides infection and MVPA was found. In contrast, light T. trichiura-infected children had significantly lower grip strength scores compared to non and heavily-infected children. VO2max and MVPA were positively associated with light T. trichiura infection. No significant association between the clustered CVD risk score and infection with any STH species was evident. CONCLUSIONS: STH-infected children had lower grip strength scores than their non-infected peers, yet, achieved higher VO2max and MVPA scores. Our study highlights that the type and intensity of STH infection is relevant in understanding the disease burden of STH infections on children's health. The findings of our study must be interpreted cautiously due to the low infection rate, and more research is needed in samples with higher prevalence rates or case-control designs.


Subject(s)
Cardiovascular Diseases , Helminthiasis , Helminths , Male , Child , Female , Animals , Humans , Soil/parasitology , South Africa/epidemiology , Cross-Sectional Studies , Cardiovascular Diseases/epidemiology , Helminthiasis/complications , Helminthiasis/epidemiology , Helminthiasis/parasitology , Physical Fitness , Exercise , Prevalence , Feces/parasitology
18.
RNA ; 16(6): 1138-45, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20430858

ABSTRACT

The genomic termini of RNA viruses contain essential cis-acting signals for such diverse functions as packaging, genome translation, mRNA transcription, and RNA replication, and thus preservation of their sequence integrity is critical for virus viability. Sequence alteration can arise due to cellular mechanisms that add or remove nucleotides from terminal regions, or, alternatively, from introduction of sequence errors through nucleotide misincorporation by the error-prone viral RNA-dependent RNA polymerase (RdRp). To preserve template function, many RNA viruses utilize repair mechanisms to prevent accumulation of terminal alterations. Here we show that Bunyamwera virus (BUNV), the prototype of the Bunyaviridae family of segmented negative-sense RNA viruses, also can repair its genomic termini. When an intact nontranslated region (NTR) was added to the anti-genomic 3' end, it was precisely removed, to restore both length and RNA synthesis function of the wild-type template. Furthermore, when nucleotides were removed from the anti-genome 3' end, and replaced with a duplicate and intact NTR, both the external NTR were removed, and the missing nucleotides were restored, thus, indicating that the BUNV RdRp can both remove and add nucleotides to the template. We show that the mechanism for repair of terminal extensions is likely that of internal entry of the viral RdRp during genome synthesis. Possible mechanisms for repair of terminal deletions are discussed.


Subject(s)
Bunyamwera virus/genetics , Genome, Viral , RNA, Viral/biosynthesis , RNA, Viral/genetics , Transcription, Genetic , Animals , Cell Line , Cricetinae , Kidney/virology , Luciferases/genetics , Open Reading Frames , Plasmids , RNA Viruses/genetics , RNA, Messenger/genetics , RNA, Untranslated/genetics , Renilla/enzymology , Renilla/genetics , Sequence Deletion
19.
Nutrients ; 14(13)2022 Jun 23.
Article in English | MEDLINE | ID: mdl-35807790

ABSTRACT

Executive functions (EFs) are essential for optimal academic development. Appropriate nutrition and physical activity (PA) have been shown to facilitate optimal cognitive development. Therefore, this study examined whether a 12-week school-based PA and multi-micronutrient supplementation (MMNS) intervention would improve cognitive and academic performance. A cluster-randomized controlled trial (RCT) was conducted. Children from four schools located in a peri-urban area of South Africa were randomly assigned to (i) PA + MMNS, (ii) PA + placebo, (iii) MMNS or (iv) placebo. Information processing and inhibitory control were measured with a computerized Flanker task. End-of-year results provided insight into academic achievement. Anthropometric measures were used to determine nutritional status. Data were analyzed with linear mixed-models, adjusting for baseline scores, school classes and age; 932 children (458 girls (49.1%), Mage (mean age) = 8.42 ± 1.94 years) completed baseline and post-intervention assessments. Cognitive performance improved among all four groups, with no significant group × time effects. For academic achievement, there was no significant interaction effect between the combined intervention group and placebo. We encourage future studies in this neglected area in order to determine the most optimal design of school-based nutrition and PA programs to enhance overall cognitive performance.


Subject(s)
Academic Performance , Micronutrients , Child , Cognition , Exercise , Female , Humans , South Africa
20.
Talanta Open ; 6: 100166, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36406953

ABSTRACT

In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic and disparities of vaccination coverage in low-and middle-income countries, it is vital to adopt a widespread testing and screening programme, combined with contact tracing, to monitor and effectively control the infection dispersion in areas where medical resources are limited. This work presents a lab-on-a-chip device, namely 'IFAST-LAMP-CRISPR', as an affordable, rapid and high-precision molecular diagnostic means for detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The herein proposed 'sample-to-answer' platform integrates RNA extraction, amplification and molecular detection with lateral flow readout in one device. The microscale dimensions of the device containing immiscible liquids, coupled with the use of silica paramagnetic beads and guanidine hydrochloride, streamline sample preparation (including RNA extraction, concentration and purification) in 15 min with minimal hands-on steps. The pre-amplification in combination with CRISPR-Cas12a detection assays targeting the nucleoprotein (N) gene achieved visual identification of ≥ 470 copies mL-1 genomic SARS-CoV-2 samples in 45 min. On-chip assays showed the ability to isolate and detect SARS-CoV-2 RNA from 100 genome copies mL-1 of replication-deficient viral particles in 1 h. This simple, affordable and integrated platform demonstrated a visual, faster, and yet specificity- and sensitivity-comparable alternative to the costly gold-standard reverse transcription-polymerase chain reaction (RT-PCR) assay, requiring only a simple heating source. Initial testing illustrates the platform viability both on nasopharyngeal swab and saliva samples collected using the easily accessible Swan-brand cigarette filter, providing a complete workflow for COVID-19 diagnostics in low-resource settings.

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