Effects of food supplementation on cognitive function, cerebral blood flow, and nutritional status in young children at risk of undernutrition: randomized controlled trial.
- 作者列表："Roberts SB","Franceschini MA","Silver RE","Taylor SF","de Sa AB","Có R","Sonco A","Krauss A","Taetzsch A","Webb P","Das SK","Chen CY","Rogers BL","Saltzman E","Lin PY","Schlossman N","Pruzensky W","Balé C","Chui KKH","Muentener P
OBJECTIVE:To assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition. DESIGN:Randomized controlled trial. SETTING:10 villages in Guinea-Bissau. PARTICIPANTS:1059 children aged 15 months to 7 years; children younger than 4 were the primary population. INTERVENTIONS:Supervised isocaloric servings (≈1300 kJ, five mornings each week, 23 weeks) of a new food supplement (NEWSUP, high in plant polyphenols and omega 3 fatty acids, within a wide variety and high fortification of micronutrients, and a high protein content), or a fortified blended food (FBF) used in nutrition programs, or a control meal (traditional rice breakfast). MAIN OUTCOME MEASUREMENTS:The primary outcome was working memory, a core executive function predicting long term academic achievement. Additional outcomes were hemoglobin concentration, growth, body composition, and index of cerebral blood flow (CBFi). In addition to an intention-to-treat analysis, a predefined per protocol analysis was conducted in children who consumed at least 75% of the supplement (820/925, 89%). The primary outcome was assessed by a multivariable Poisson model; other outcomes were assessed by multivariable linear mixed models. RESULTS:Among children younger than 4, randomization to NEWSUP increased working memory compared with the control meal (rate ratio 1.20, 95% confidence interval 1.02 to 1.41, P=0.03), with a larger effect in the per protocol population (1.25, 1.06 to 1.47, P=0.009). NEWSUP also increased hemoglobin concentration among children with anemia (adjusted mean difference 0.65 g/dL, 95% confidence interval 0.23 to 1.07, P=0.003) compared with the control meal, decreased body mass index z score gain (-0.23, -0.43 to -0.02, P=0.03), and increased lean tissue accretion (2.98 cm2, 0.04 to 5.92, P=0.046) with less fat (-5.82 cm2, -11.28 to -0.36, P=0.04) compared with FBF. Additionally, NEWSUP increased CBFi compared with the control meal and FBF in both age groups combined (1.14 mm2/s×10-8, 0.10 to 2.23, P=0.04 for both comparisons). Among children aged 4 and older, NEWSUP had no significant effect on working memory or anemia, but increased lean tissue compared with FBF (4.31 cm2, 0.34 to 8.28, P=0.03). CONCLUSIONS:Childhood undernutrition is associated with long term impairment in cognition. Contrary to current understanding, supplementary feeding for 23 weeks could improve executive function, brain health, and nutritional status in vulnerable young children living in low income countries. Further research is needed to optimize nutritional prescriptions for regenerative improvements in cognitive function, and to test effectiveness in other vulnerable groups. TRIAL REGISTRATION:ClinicalTrials.gov NCT03017209.
目的: 评估食物补充对改善营养不足儿童工作记忆和其他措施 (包括脑血流) 的影响。 设计: 随机对照试验。 背景: 几内亚比绍的10个村庄。 参与者: 1059名15个月至7岁的儿童; 4岁以下的儿童是主要人群。 干预措施: 监督等热量 (≈ 1300千焦，每周5个早晨，23周) 的新食品补充剂 (NEWSUP，高植物多酚和omega -3脂肪酸，广泛种类和高强化微量营养素，高蛋白质含量)，或强化混合食品 (FBF)用于营养计划，或控制餐 (传统米饭早餐)。 主要结果测量: 主要结果是工作记忆，一种预测长期学业成就的核心执行功能。其他结局为血红蛋白浓度、生长、体成分和脑血流指数 (CBFi)。除了意向治疗分析之外，还对摄入至少75% 补充剂 (820/925，89%) 的儿童进行了预先定义的符合方案分析.主要结局通过多变量泊松模型评估; 其他结局通过多变量线性混合模型评估。 结果: 在小于4岁的儿童中，与对照餐相比，随机分组到NEWSUP增加了工作记忆 (率比1.20，95% 置信区间1.02至1.41，P = 0.03)，在每个方案人群中的影响更大 (1.25，1.06至1.47，P = 0.009)。NEWSUP还增加了贫血儿童的血红蛋白浓度 (校正后的平均差0.65g/dL，95% 置信区间0.23至1.07，P = 0.003)，与对照餐相比，体重指数z评分增加减少 (-0.23，-0.43至-0.02，P = 0.03)，和增加的瘦组织增长 (2.98平方厘米，0.04至5.92，P = 0.046) 与FBF相比脂肪较少 (-5.82平方厘米，-11.28至-0.36，P = 0.04)。此外，在两个年龄组中，与对照膳食和FBF相比，NEWSUP增加了CBFi (1.14平方毫米/s × 10-8，0.10至2.23，两组比较P = 0.04)。在4岁及以上儿童中，NEWSUP对工作记忆或贫血没有显著影响，但与FBF相比，瘦组织增加 (4.31平方厘米，0.34至8.28，P = 0.03)。 结论: 儿童营养不足与长期认知障碍有关。与目前的理解相反，23周的补充喂养可以改善低收入国家弱势幼儿的执行功能，大脑健康和营养状况。需要进一步的研究来优化营养处方以再生改善认知功能，并测试其他弱势群体的有效性。 试验注册: clinicaltrials.Gov nct03017209。
METHODS::Fanconi anemia (FA) is a recessive disorder that predispose to bone marrow failure and multiple congenital anomalies in affected individuals worldwide. To date, 22 FA genes are known to harbor sequence variations in disease phenotype. Among these, mutations in the FANCA gene are associated with 60% to 70% of FA cases. The aim of the present study was to screen FA cases belonging to consanguineous Pakistani families for selected exons of FANCA gene which are known mutational hotspots for Asian populations. Blood samples were collected from 20 FA cases and 20 controls. RNA was extracted and cDNA was synthesized from blood samples of cases. DNA was extracted from blood samples of cases and ethnically matched healthy controls. Sanger's sequencing of the nine selected exons of FANCA gene in FA cases revealed 19 genetic alterations of which 15 were single nucleotide variants, three were insertions and one was microdeletion. Of the total 19 sequence changes, 13 were novel and six were previously reported. All identified variants were evaluated by computational programs including SIFT, PolyPhen-2 and Mutation taster. Seven out of 20 analyzed patients were carrying homozygous novel sequence variations, predicted to be associated with FA. These disease associated novel variants were not detected in ethnically matched controls and depict genetic heterogeneity of disease.
METHODS::In type 3 von Willebrand disease (VWD3), the most severe form with absent von Willebrand factor (VWF), the bleeding phenotype is variable. Platelet contribution to the hemostatic defect in VWD3 calls upon further studies. We investigated the contribution of platelets to in vitro thrombin generation (TG) and platelet procoagulant activity in VWD3. TG was assessed by calibrated automated thrombogram (CAT) in platelet-poor (PPP) and -rich plasma (PRP) from 9 patients before and in 6 patients also 30 min after receiving their regular VWF therapy. Responsiveness of PPP to FVIII and protein S was also investigated. TG data were compared with routine laboratory variables, rotational thromboelastometry (ROTEM) and platelet expression of P-selectin and phosphatidylserine in flow cytometry. Compared with healthy controls, TG was markedly decreased in VWD3 PPP (peak thrombin was 16% of normal median), but not in PRP (77% of normal median) (p = 0.002). Six out of nine patients (67%) were high responders in their platelet P-selectin, and 5/9 (56%) in phosphatidylserine expression. Replacement therapy improved TG in PPP, while in PRP TG only modestly increased or was unaffected. In PPP, FVIII levels associated with TG and in vitro FVIII-supplemented TG inclined up to threefold. Conversely, a FVIII inhibitory antibody reduced plasma TG in all, but especially in patients with remnant FVIII levels. Inhibition of protein S improved plasma TG, particularly at low FVIII levels. ROTEM failed to detect VWD3.In VWD3, TG is reduced in PPP and regulated by FVIII and protein S, but TG is close to normal in PRP. VWD3 platelets seem to compensate for the FVIII-associated reduction in TG by their exposure of P-selectin and phosphatidylserine.
METHODS:BACKGROUND:The optimal timing of initiating granulocyte-colony stimulating factor following chemotherapy in pediatric patients has not been clearly defined. This study aimed to compare the administration of granulocyte-colony stimulating factor on day 1 versus day 3 postchemotherapy in pediatric patients with Ewing sarcoma. METHOD:A retrospective study of pediatric patients with Ewing sarcoma who received granulocyte-colony stimulating factor following chemotherapy between January 2016 and September 2018 at a comprehensive cancer center. The institution's chemotherapy protocol for Ewing sarcoma was modified in April 2017 to include granulocyte-colony stimulating factor initiation on day 3 instead of day 1 post-chemotherapy. Febrile neutropenia requiring hospitalization, duration of hospital stay, and chemotherapy delay were compared for patients before and after the protocol change. RESULTS:Over the study period, 250 cycles were evaluated with day 1 granulocyte-colony stimulating factor and 221 cycles with day 3 granulocyte-colony stimulating factor. There were no differences between the day 1 and day 3 groups in the number of cycles associated with Febrile neutropenia requiring hospitalization (34 vs. 19, p = 0.086), and the length of Febrile neutropenia-related hospitalization (mean 4 ± 2.1 vs. 4.6 ± 1.8, p = 0.123). However, delay in chemotherapy due to neutropenia was reported in significantly more cycles in the day 1 group, compared to the day 3 group (37 vs. 16, p = 0.01). CONCLUSIONS:Febrile neutropenia resulting in hospital admission and the length of hospital stay was not different between pediatric patients with Ewing sarcoma who received granulocyte-colony stimulating factor on day 1 or day 3 post-chemotherapy. Chemotherapy delay due to neutropenia was higher in patients who received granulocyte-colony stimulating factor on day 1. Larger studies are required to fully determine the impact of delayed initiation of granulocyte-colony stimulating factor.