26 research outputs found

    Effects of vitamin D deficiency on neurobehavioural outcomes in children: a systematic review

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    Introduction: Vitamin D plays an important role in brain development in experimental studies; however, the effect of vitamin D deficiency on child development remains inadequately characterized. We aimed to estimate the effects of vitamin D deficiency on neurobehavioural outcomes in children up to 18 years of age. Methods: We searched PubMed, EMBASE, PsycINFO, Scopus, Cochrane Library, Web of Science and Open Grey for published studies up to 10th January 2020. We included all studies that assessed the effects of maternal or child vitamin D status or vitamin D supplementation on neurobehavioural outcomes in children. Study findings were synthesized qualitatively as the high level of heterogeneity in study populations and methodologies precluded a quantitative meta-analysis. Results: Our search identified 5,633 studies, of which 31 studies with 31,375 participants from 18 countries were included in the systematic review. Of the studies identified, one was a randomised controlled trial (RCT) of vitamin D supplementation in children, while 30 were observational. The RCT (n=55) reported a beneficial effect of supplementation with lower doses compared to higher doses of vitamin D on motor development. Twelve mother-child studies (n=17,136) and five studies in children (n=1,091) reported an association between low maternal or child 25-hydroxyvitamin D levels and impaired neurobehavioural outcomes in children, while 15 mother-child studies (n=20,778) and eight studies in children (n=7,496) reported no association. Conclusions: Although animal studies point to an effect of vitamin D deficiency on brain development, there are few studies on the effects of vitamin D deficiency on neurobehavioural outcomes in children and their findings are inconsistent. There is a need for well-conducted, adequately powered studies to further determine these effects in children

    Prevalence and predictors of vitamin D deficiency in young African children.

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    BACKGROUND: Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children. METHODS: We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0-8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses. RESULTS: Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants. CONCLUSIONS: Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa

    Replication Data for: Prevalence of vitamin D deficiency in Africa - a systematic review and meta-analysis

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    This dataset presents information obtained from systematic reviews of published vitamin D prevalence studies. The online searches were conducted on PubMed/MEDLINE, Web of Science, Embase, African Journals Online and African Index Medicus. Studies included in the meta-analyis had measured serum 25-hydroxyvitamin concentrations from healthy participants residing in Africa. The dataset comprises of seven (7) .csv files, one (1) R script for replicating figures and tables reported in the paper and codebook describing each individual file and variables. Variables include: year of publication, first author’s name, sample size, method of recruitment, study design, dates or season of blood sample collection, ethnicity, proportion of males, study country, method of vitamin D measurement, mean vitamin D concentrations and prevalence of vitamin D deficiency.</p

    Deciphering the targets of retroviral protease inhibitors in Plasmodium berghei.

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    Retroviral protease inhibitors (RPIs) such as lopinavir (LP) and saquinavir (SQ) are active against Plasmodium parasites. However, the exact molecular target(s) for these RPIs in the Plasmodium parasites remains poorly understood. We hypothesised that LP and SQ suppress parasite growth through inhibition of aspartyl proteases. Using reverse genetics approach, we embarked on separately generating knockout (KO) parasite lines lacking Plasmepsin 4 (PM4), PM7, PM8, or DNA damage-inducible protein 1 (Ddi1) in the rodent malaria parasite Plasmodium berghei ANKA. We then tested the suppressive profiles of the LP/Ritonavir (LP/RT) and SQ/RT as well as antimalarials; Amodiaquine (AQ) and Piperaquine (PQ) against the KO parasites in the standard 4-day suppressive test. The Ddi1 gene proved refractory to deletion suggesting that the gene is essential for the growth of the asexual blood stage parasites. Our results revealed that deletion of PM4 significantly reduces normal parasite growth rate phenotype (P = 0.003). Unlike PM4_KO parasites which were less susceptible to LP and SQ (P = 0.036, P = 0.030), the suppressive profiles for PM7_KO and PM8_KO parasites were comparable to those for the WT parasites. This finding suggests a potential role of PM4 in the LP and SQ action. On further analysis, modelling and molecular docking studies revealed that both LP and SQ displayed high binding affinities (-6.3 kcal/mol to -10.3 kcal/mol) towards the Plasmodium aspartyl proteases. We concluded that PM4 plays a vital role in assuring asexual stage parasite fitness and might be mediating LP and SQ action. The essential nature of the Ddi1 gene warrants further studies to evaluate its role in the parasite asexual blood stage growth as well as a possible target for the RPIs

    Deciphering the targets of retroviral protease inhibitors in <i>Plasmodium berghei</i> - Fig 1

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    <p><b>PCR genotyping of the knockout (KO) parasites; (A) PM4_KO, (B) PM7_KO, (C) PM8_KO, and the wild-type (WT) control lines.</b> The PCR amplification used three sets of primer pairs; QCR2/GW2 to confirm the presence of the vector, GT/GW1 or GT/GW2 to verify integration of the vector into the parasite genome and QCR1/QCR2 to confirm deletion of the specific genes. The QCR1, QCR2 and GT1 are vector specific primers while GW2 and GW1 primers are standard primers.</p

    Both the LP and SQ exhibited high binding affinity to the PM4 protein.

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    <p>The binding geometries for docking of a single ligand with a single receptor as modelled using the Autodock Vina. The binding energies for LP and SQ to the PM4 were the lowest suggesting better affinity to the protein. The LP and SQ yielded higher binding affinity to both PM7 and PM8 as compared to the known RPIs target; the HIV Aspartic protease (HIV Asp). Both LP and SQ exhibited equal or low binding energy to the essential Ddi1 protein as compared to the HIV Asp.</p

    Deletion of the PM4 gene significantly attenuates the growth of asexual parasites.

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    <p><b>(A).</b> Box plots are showing the percentage parasitaemia in mice infected with the PM4_KO, PM7_KO or PM8_KO parasite line relative to the wild-type (WT) parasite line as measured on day four post parasite inoculation in the standard 4-day suppressive test. <b>(B).</b> Violin plots are showing the distribution of the parasites in mice infected with the PM4_KO, PM7_KO or PM8_KO parasite line relative to the wild-type (WT) parasite line as measured in the standard 4-day suppressive test. The PM4_KO parasites acquired a reduced growth rate phenotype (<i>P</i> = 0. 0.003), while the PM7_KO and PM8_KO parasites lines attained an increased growth rate phenotype.</p
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