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1.
N Engl J Med ; 385(11): 982-995, 2021 09 09.
Article in English | MEDLINE | ID: mdl-34496174

ABSTRACT

BACKGROUND: Universal provision of iron supplements (drops or syrup) or multiple micronutrient powders to young children in low-to-middle-income countries where anemia is prevalent is recommended by the World Health Organization and widely implemented. The functional benefits and safety of these interventions are unclear. METHODS: We conducted a three-group, double-blind, double-dummy, individually randomized, placebo-controlled trial to assess the immediate and medium-term benefits and risks of 3 months of daily supplementation with iron syrup or iron-containing multiple micronutrient powders, as compared with placebo, in 8-month-old children in rural Bangladesh. The primary outcome was cognitive development, as assessed by the cognitive composite score on the Bayley Scales of Infant and Toddler Development, third edition, immediately after completion of the assigned 3-month regimen; scores range from 55 to 145, with higher scores indicating better cognitive performance. Secondary outcomes included the cognitive composite score at 9 months after completion of the assigned regimen; behavioral, language, and motor development, as well as growth and hematologic markers, immediately after completion and at 9 months after completion; and safety. RESULTS: We randomly assigned 3300 infants to receive iron syrup (1101 infants), multiple micronutrient powders (1099), or placebo (1100) daily. After completion of the assigned 3-month regimen, no apparent effect on the cognitive composite score was observed with iron syrup as compared with placebo (mean between-group difference in change in score from baseline, -0.30 points; 95% confidence interval [CI], -1.08 to 0.48) or with multiple micronutrient powders as compared with placebo (mean between-group difference in change in score from baseline, 0.23 points; 95% CI, -0.55 to 1.00). No apparent effect on any other developmental or growth outcome was observed immediately after completion of the assigned regimen or at 9 months after completion. At 9 months after completion of the assigned regimen, the prevalences of anemia, iron deficiency, and iron deficiency anemia increased in all three trial groups but remained lower among the children who received iron syrup or multiple micronutrient powders than among those who received placebo. The risk of serious adverse events and incidence of symptoms of infection were similar in the three trial groups. CONCLUSIONS: In this trial involving infants in Bangladesh, 3 months of daily supplementation with iron syrup or multiple micronutrient powders did not appear to have an effect on child development or other functional outcomes as compared with placebo. (Funded by the National Health and Medical Research Council of Australia; BRISC Australian New Zealand Clinical Trials Registry number, ACTRN12617000660381.).


Subject(s)
Anemia, Iron-Deficiency/drug therapy , Child Development/drug effects , Dietary Supplements , Micronutrients/therapeutic use , Anemia, Iron-Deficiency/prevention & control , Bangladesh , Cognition/drug effects , Double-Blind Method , Female , Hemoglobins/analysis , Humans , Infant , Language Development , Male , Rural Population
2.
J Anim Sci ; 96(10): 4063-4075, 2018 Sep 29.
Article in English | MEDLINE | ID: mdl-30265318

ABSTRACT

Genomic selection using high-density single-nucleotide polymorphism (SNP) markers is used in dairy and beef cattle breeds to accurately estimate genomic breeding values and accelerate genetic improvement by enabling selection of animals with high genetic merit. This genome-wide association study (GWAS) aimed to identify genetic variants associated with beef fatty-acid composition (FAC) traits and to evaluate the accuracy of genomic predictions (GPs) for those traits using genomic best linear unbiased prediction (GBLUP), pedigree BLUP (PBLUP), and BayesR models. Samples of the longissimus dorsi muscle of 965 thirty-month-old Hanwoo steers (progeny of 73 proven bulls) were used to investigate 14 FAC traits. Animals were genotyped or imputed using two bovine SNP platforms (50K and 777K), and after quality control, 38,715 (50K) and 633,448 (777K) SNPs were subjected to GWAS and GP study using a cross-validation scheme. SNP-based heritability estimates were moderate to high (0.25 to 0.47) for all studied traits, with some exceptions for polyunsaturated fatty acids. Association analysis revealed that 19 SNPs in BTA19 (98.7 kb) were significantly associated (P < 7.89 × 10-8) with C14:0 and C18:1n-9; these SNPs were in the fatty-acid synthase (FASN) and coiled-coil domain-containing 57 (CCDC57) genes. BayesR analysis revealed that 0.41 to 0.78% of the total SNPs (n = 2,571 to 4,904) explained almost all of the genetic variance; the majority of the SNPs (>99%) had negligible effects, suggesting that the FAC traits were polygenic. Genome partitioning analysis indicated mostly nonlinear and weak correlations between the variance explained by each chromosome and its length, which also reflected the considerable contributions of relatively few genes. The prediction accuracy of breeding values for FAC traits varied from low to high (0.25 to 0.57); the estimates using the GBLUP and BayesR methods were superior to those obtained by the PBLUP method. The BayesR method performed similarly to GBLUP for most of the studied traits but substantially better for those traits that were controlled by SNPs with large effects; this was supported by the GWAS results. In addition, the predictive abilities of the 50K and 777K SNP arrays were almost similar; thus, both are suitable for GP in Hanwoo cattle. In conclusion, this study provides important insight into the genetic architecture and predictive ability of FAC traits in Hanwoo cattle. Our findings could be used in selection and breeding programs to promote production of meat with enhanced nutritional value.


Subject(s)
Cattle/genetics , Fatty Acids/metabolism , Genome-Wide Association Study/veterinary , Genomics , Multifactorial Inheritance , Polymorphism, Single Nucleotide/genetics , Animals , Breeding , Cattle/physiology , Female , Genotype , Linkage Disequilibrium , Male , Oligonucleotide Array Sequence Analysis/veterinary , Pedigree , Phenotype
3.
Front Genet ; 9: 217, 2018.
Article in English | MEDLINE | ID: mdl-29988410

ABSTRACT

Quantitative traits are usually controlled by numerous genomic variants with small individual effects, and variances associated with those traits are explained in a continuous manner. However, the relative contributions of genomic regions to observed genetic variations have not been well explored using sequence level single nucleotide polymorphism (SNP) information. Here, imputed sequence level SNP data (11,278,153 SNPs) of 2109 Hanwoo steers (Korean native cattle) were partitioned according to functional annotation, chromosome, and minor allele frequency (MAF). Genomic relationship matrices (GRMs) were constructed for each classified region and fitted in the model both separately and together for carcass weight (CWT), eye muscle area (EMA), backfat thickness (BFT), and marbling score (MS) traits. A genome-wide association study (GWAS) was performed to identify significantly associated variants in genic and exon regions using a linear mixed model, and the genetic contribution of each exonic SNP was determined using a Bayesian mixture model. Considering all SNPs together, the heritability estimates for CWT, EMA, BFT, and MS were 0.57 ± 0.05, 0.46 ± 0.05, 0.45 ± 0.05, and 0.49 ± 0.05, respectively, which reflected substantial genomic contributions. Joint analysis revealed that the variance explained by each chromosome was proportional to its physical length with weak linear relationships for all traits. Moreover, genomic variances explained by functional category and MAF class differed greatly among the traits studied in joint analysis. For example, exon regions had larger contributions for BFT (0.13 ± 0.08) and MS (0.22 ± 0.08), whereas intron and intergenic regions explained most of the total genomic variances for CWT and EMA (0.22 ± 0.09-0.32 ± 0.11). Considering different functional classes of exon regions and the per SNP contribution revealed the largest proportion of genetic variance was attributable to synonymous variants. GWAS detected 206 and 27 SNPs in genic and exon regions, respectively, on BTA4, BTA6, and BTA14 that were significantly associated with CWT and EMA. These SNPs were harbored by 31 candidate genes, among which TOX, FAM184B, PPARGC1A, PRKDC, LCORL, and COL1A2 were noteworthy. BayesR analysis found that most SNPs (>93%) had very small effects and the 4.02-6.92% that had larger effects (10-4 × σA2 , 10-3 × σA2 , and 10-2 × σA2 ) explained most of the total genetic variance, confirming polygenic components of the traits studied.

4.
Article in English | MEDLINE | ID: mdl-17952795

ABSTRACT

This was a cross-sectional study under taken to explore the socioeconomic perspective of the arsenicosis problem, carried out in arsenic contaminated Upazillas where at least 100 arsenicosis patients had been identified. Two of the Upazillas with significant arsenic mitigation intervention and three of the Upazillas with limited interventions were selected for the study. Seven hundred fifty respondents were included in the study from 25 villages of the 5 Upazillas. Arsenicosis became a serious problem for the affected communities. Majority (71.31%) of respondents obtained their drinking water from tubewells, almost one third (29%) of the respondents still knowingly using arsenic contaminated water. Primary reason identified for this practice was distance of safe water source. Majority (58.6%) of the respondents said to face economic and 17.9% said to face social problem of varied range. Patients of lower income group were particularly more likely to face economic problems (P< .001) as well as social problem (P< .01). About half (50.7%) of the arsenicosis patients faced difficulty whilst receiving treatment, particularly female patients were more likely to face problem than male (P< .05). Several concerns also were surfaced regarding the heath care service provider particularly to the women patients, some of which are: long waiting time for receiving treatment (15%), discrimination in service delivery (10.7%) and inadequate separate facility for female patients (14.3%). Moreover the issues of financial burden raised by the respondents seem to have emerged as significant in terms of health care access. Access to Health service was particularly difficult for poor patients, as they often had to face problems associated with accessing service like, non availability of medicines in the hospitals (50.7%), traveling long distance (26.7%), purchasing medicine in most cases (32.4%) etc. Their dissatisfaction was compounded by negligent behavior of health care staff and nature of treatment provided. Furthermore length of time needed for reversal of symptoms led to loosing faith on efficacy of treatment, which cascades to negligence of patient's part in seeking health care. Women are less likely to get treatment for arsenicosis than men (P< .01). As there appear to be specific difficulties for women particularly for poor women in accessing health care, social and cultural values make it difficult for them to attend to their own health needs and to travel to service providers. Study findings suggest that a significant proportion (79.9%) of arsenicosis patient was found to access alternative health care. This includes; Homeopath, village doctors, Kabiraj and local pharmacists. Respondents in high intervention Upazillas were significantly more likely to get treatment (P< .05), to face fewer problems and to be satisfied with the facility (P< .001). Provision of safe water options, periodic screening of water source for arsenic, availability of trained doctor, regular availability of medicine, doorstep treatment, follow up on severe patients were the suggestions came from community for improvement.


Subject(s)
Arsenic/analysis , Keratosis/epidemiology , Melanosis/epidemiology , Water Pollutants, Chemical/poisoning , Adolescent , Adult , Aged , Bangladesh/epidemiology , Cross-Sectional Studies , Environmental Monitoring/economics , Environmental Monitoring/statistics & numerical data , Epidemiological Monitoring , Female , Health Care Costs , Health Services Needs and Demand , Humans , Keratosis/economics , Keratosis/prevention & control , Male , Melanosis/economics , Melanosis/prevention & control , Middle Aged , Socioeconomic Factors , Water Pollutants, Chemical/analysis
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