Enregisterment of English Borrowing as an Advertising “voice” in French Advertisements

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Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial.

ObjectivesTo evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children.Study designIn total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression.ResultsAt baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P < .001), with no impact on stunting (37.1%-41.3% across the groups, P = .37). The micronutrient powder reduced iron deficiency by 44%-55% compared with other groups (P < .001), with no overall impact on anemia (P = .14). Micronutrient powder tended to reduce anemia by 11%-16% among children who were anemic at baseline (P = .06).ConclusionsDespite improving zinc status, preventive zinc and micronutrient powder had no impact on growth. The micronutrient powder improved iron status and tended to reduce anemia among the subset of previously anemic children.Trial registrationClinicalTrials.govNCT02428647

Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial.

BACKGROUND:Zinc deficiency impairs immune function and is common among children in South-East Asia. OBJECTIVES:The effect of zinc supplementation on immune function in young Laotian children was investigated. METHODS:Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration). RESULTS:T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL, P = 0.012). CONCLUSIONS:Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647

Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B ₁₂ status among young Laotian children:a randomized controlled trial

PURPOSE: To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B(12) status among young Laotian children. METHODS: Children (n = 1704) aged 6–23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin B(12) along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B(12) concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline. RESULTS: There was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B(12) concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B(12) deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p < 0.001), and correspondingly, the prevalence of folate deficiency was significantly lower in the MNP group (1.6% vs 17.4%; p = 0.015). CONCLUSIONS: Compared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B(12) status in young Laotian children. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov (NCT02428647) on April 29 2015

INTERACTIONS BETWEEN MALARIA AND IRON OR VITAMIN A STATUS IN RURAL ZAMBIAN CHILDREN

Background and objectives Evidence regarding the bidirectional interactions between iron or vitamin A status and malaria remains inconclusive. We assessed the longitudinal associations between iron (defined by ferritin) or vitamin A (defined by retinol) and malaria, assessed 6 months later by microscopy. Additionally, the changes in ferritin, soluble transferrin receptor (sTfR) and retinol during malaria and/or inflammation (AGP >1 g/L) were estimated. Design We included 1024 children, 4-8 years old from Mkushi District, Zambia, participating in a 6-month trial, designed to evaluate the efficacy of a provitamin A intervention. We analyzed baseline (August, 2013) and endline (March, 2014) survey data, collected in the low and high malaria transmission seasons respectively. We estimated incidence rate ratios (IRR) comparing endline malaria risk across baseline iron or vitamin A status using, modified Poisson regression, controlling for inflammatory changes in the indicators of iron and vitamin A at baseline. Results Inflammation alone was associated with changes of up to 66% in ferritin, up to 12% in sTfR, and up to -13% in serum retinol relative to their respective reference groups. Malaria with inflammation was associated with changes of up to 280% in ferritin, up to 40% in sTfR and up to -36% in retinol. After controlling for baseline inflammation, the IRR, comparing the low (0.7-1.05 µmol/L) and adequate (>1.05 µmol/L) vitamin A groups to the deficient group (75 µg/L) ferritin groups, relative to the deficient group (<12/15 µg/L depending on age), were 2.49 (95% CI: 0.97-6.40) and 3.27 (95% CI: 1.21-8.81) respectively. Conclusion Our data suggests that vitamin A adequacy may protect against malaria, whereas iron adequacy beyond some threshold may increase malaria risk. Our results also suggest that the concurrent assessment of malaria, in addition to inflammation, may enhance the interpretation of retinol, ferritin and sTfR in endemic regions

Prospect of reprogramming replication licensing for cancer drug development

Eukaryotic chromosomal DNA replication is preceded by replication licensing which involves the identification of the origin of replication by origin recognition complex (ORC). The ORC loads pre-replication complexes (pre-RCs) through a series of tightly regulated mechanisms where the ORC interacts with Cdc6 to recruit cdt1-MCM2-7 complexes to the origin of replication. In eukaryotes, adherence to regulatory mechanisms of the replication program is required to ensure that all daughter cells carry the exact copy of genetic material as the parent cell. Failure of which leads to the development of genome instability syndromes like cancer, diabetes, etc. In an event of such occurrence, preventing cells from carrying the defaulted genetic material and passing it to other cells hinges on the regulation of chromosomal DNA replication. Thus, understanding the mechanisms underpinning chromosomal DNA replication and particularly replication licensing can expose druggable enzymes, effector molecules, and secondary messengers that can be targeted for diagnosis and therapeutic purposes. Effectively drugging these molecular markers to reprogram pre-replication events can be used to control the fate of chromosomal DNA replication for the treatment of genome instability disorders and in this case, cancer. This review discusses available knowledge of replication licensing in the contest of molecular drug discovery for the treatment of cancer

INTERACTIONS BETWEEN MALARIA AND IRON OR VITAMIN A STATUS IN RURAL ZAMBIAN CHILDREN

Background and objectives Evidence regarding the bidirectional interactions between iron or vitamin A status and malaria remains inconclusive. We assessed the longitudinal associations between iron (defined by ferritin) or vitamin A (defined by retinol) and malaria, assessed 6 months later by microscopy. Additionally, the changes in ferritin, soluble transferrin receptor (sTfR) and retinol during malaria and/or inflammation (AGP >1 g/L) were estimated. Design We included 1024 children, 4-8 years old from Mkushi District, Zambia, participating in a 6-month trial, designed to evaluate the efficacy of a provitamin A intervention. We analyzed baseline (August, 2013) and endline (March, 2014) survey data, collected in the low and high malaria transmission seasons respectively. We estimated incidence rate ratios (IRR) comparing endline malaria risk across baseline iron or vitamin A status using, modified Poisson regression, controlling for inflammatory changes in the indicators of iron and vitamin A at baseline. Results Inflammation alone was associated with changes of up to 66% in ferritin, up to 12% in sTfR, and up to -13% in serum retinol relative to their respective reference groups. Malaria with inflammation was associated with changes of up to 280% in ferritin, up to 40% in sTfR and up to -36% in retinol. After controlling for baseline inflammation, the IRR, comparing the low (0.7-1.05 µmol/L) and adequate (>1.05 µmol/L) vitamin A groups to the deficient group (75 µg/L) ferritin groups, relative to the deficient group (<12/15 µg/L depending on age), were 2.49 (95% CI: 0.97-6.40) and 3.27 (95% CI: 1.21-8.81) respectively. Conclusion Our data suggests that vitamin A adequacy may protect against malaria, whereas iron adequacy beyond some threshold may increase malaria risk. Our results also suggest that the concurrent assessment of malaria, in addition to inflammation, may enhance the interpretation of retinol, ferritin and sTfR in endemic regions