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Background: Households affected by HIV/AIDS are at an increased risk for food insecurity and malnutrition. Poor nutrition contributes to more than a third of all deaths associated with infectious diseases among children under 5 years of age in developing countries. With increased household food insecurity, and a greater disease burden associated with HIV/AIDS, the growth of children under five could be impacted, resulting in increased malnutrition for this vulnerable group.Objective: To determine whether there is an association between the type of household (HIV-affected compared with HIV-unaffected) and the nutritional status of children under 5 years of age residing in these households.Methods: The study was set in a Millennium Village Project site in western Kenya and used a cross-sectional design to compare the stunting, wasting, and underweight status among 102 and 99 under-five children living in HIV-affected and -unaffected households, respectively. Height-for-age, weight-for-age, and weight-for-age z-scores were calculated based on the World Health Organization growth standards and compared. Proportions, means, and standard deviations were used to describe the data. The data were analyzed with the use of the chi-square test for comparison of proportions and the independent t-test for comparison of means.Results: Children in HIV-affected households had a significantly higher degree of stunting (height-for-age < -2 SD) than children in unaffected households (25.5% vs. 9.1%, p = .002). The degree of wasting and underweight did not differ significantly between HIV-affected and -unaffected households.Conclusions: Residing in HIV-affected households is associated with stunting in children under 5 years of age. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: Intake of n-3 fatty acids can reduce both fasting and postprandial triglyceride (TG) concentrations in humans as well as in experimental animals, but the mechanisms by which this occurs are not completely known. We investigated in mice the effects of dietary fish oil (a source of n-3 fatty acids) on endogenous TG synthesis and exogenous TG-rich particle removal. METHODS: C57 BL/6J mice were fed for 4 months with three types of high-fat diets (18% fat wt/wt) - soy oil, fish oil and a mixture of soy oil and fish oil (soy/fish) (5:1 wt/wt), and a chow diet with 6% fat from soy oil (wt/wt) served as a control. Plasma TG and apolipoprotein B (apoB) concentrations and lipoprotein lipase (LPL) activity were measured. Triton WR 1339 was used to assess hepatic synthesis of very low density lipoprotein, and intravenous injection of chylomicron-like lipid emulsions was conducted to determine the effects of dietary fish oil n-3 fatty acids on exogenous TG clearance. RESULTS: Both fish and soy/fish oil diets reduced plasma TG levels in fed and fasted states compared to soy oil alone. Plasma pre- and post-heparin LPL activities were significantly higher with fish and soy/fish oil diets than soy oil diet in fed mice. No differences in plasma TG levels and LPL activity were shown among groups of fish oil, soy/fish oil and normal chow diets. Levels of hepatic TG and apoB synthesis were 30-50% and 42% lower in mice fed with the fish oil diet compared to the other three diets. In addition, compared to soy oil diet, fish oil feeding significantly increased blood clearance of chylomicron-like lipid emulsions by 21-26%. CONCLUSIONS: Our data suggest that reduced endogenous TG synthesis, increased LPL activities and more rapid blood clearance of TG-rich particles all distinctly contribute to the TG-lowering effects of fish oil n-3 fatty acids. [ABSTRACT FROM AUTHOR]

Because the mechanisms of (n-3) fatty acid-enriched triglyceride-rich particle [(n-3)-TGRP] uptake are not well characterized, we questioned whether (n-3)-TGRP are removed via "nonclassical" pathways, e.g., pathways other than an LDL receptor and/or involving apolipoprotein E (apoE). Chylomicron-sized model (n-3)-TGRP labeled with [3H]cholesteryl ether were injected into wild-type (WT) and CD36 knockout (CD36-/-) mice at low, nonsaturating and high, saturating doses. Blood clearance of (n-3)-TGRP was determined by calculating fractional catabolic rates. At saturating doses, blood clearance of (n-3)-TGRP was slower in CD36-/- mice relative to WT mice, suggesting that in part CD36 contributes to (n-3)-TGRP uptake. To further examine the potential nonclassical clearance pathways, peritoneal-elicited macrophages from WT and CD36-/- mice were incubated with (n-3)-TGRP in the presence of apoE, lactoferrin, and/or sodium chlorate. Cellular (n-3)-TGRP uptake was measured to test the roles of apoE-mediated pathways and/or proteoglycans. ApoE-mediated pathways compensated in part for defective (n-3)-TGRP uptake in CD36-/- cells. Lactoferrin decreased (n-3)-TGRP uptake in the presence of apoE. Inhibition of cell proteoglycan synthesis by chlorate reduced (n-3)-TGRP uptake in both groups of macrophages, and chlorate effects were independent of apoE. We conclude that although CD36 is involved, it is not the primary contributor to the blood clearance of (n-3)-TGRP. The removal of (n-3)-TGRP likely relies more on nonclassical pathways, such as proteoglycan-mediated pathways. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine weight gain during pregnancy and weight changes postpartum in first-time mothers delivering at or near term. METHODS: At about 2 weeks after delivery, 47 adult, Black and Hispanic women provided information on their prepregnancy weight and height and maximum pregnancy weight. Women reinterviewed at 2 and 6 months after delivery reported their most recent weight measurement and the date of that measurement. This information was used to compute each woman's prepregnancy body mass index, pregnancy weight gain, and weight loss postpartum. Information on infant feeding was also collected at each postpartum visit. RESULTS: About 2/3 of the women and 100% of the overweight and obese women gained excessive weight during pregnancy. Weight gain was most marked in women who started pregnancy overweight or obese. At 2 months postpartum, women were on average almost 18 lb above their prepregnancy weight. No additional maternal weight was lost by 6 months postpartum. Most infants were started on formula by 2 weeks of age. At 2 months of age, 85% were fed formula only and 91% of the infants were on WIC. CONCLUSIONS: Our results demonstrate a need for interventions to help women avoid obesity by regulating their pregnancy weight gain, losing weight for a longer period postpartum, and initiating and maintaining exclusive breast-feeding. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increasing body mass index (BMI) is associated with progressively lower serum HDL-cholesterol concentrations, although the underlying body-composition compartment accounting for this unfavorable lipid change remains uncertain. OBJECTIVE: Because growing evidence favors a role of lean tissue in HDL homeostasis, the hypothesis was tested that non-adipose tissue components of body mass explain the inverse association of HDL cholesterol and BMI. DESIGN: Fasting serum lipid concentrations and body composition [total, subcutaneous, and visceral adipose tissue; adipose tissue-free mass (ATFM); and skeletal muscle by whole-body magnetic resonance imaging and body cell mass by 40K counting) were evaluated in healthy adults. Body-composition compartments were expressed as height2-normalized indexes. RESULTS: An inverse correlation was observed between serum HDL cholesterol and BMI in women (n = 68; R2 = 0.08, P = 0.023) and men (n = 61; R2 = 0.07, P = 0.046). Significant inverse correlations (P = 0.005-0.02) were also observed between HDL cholesterol and nonadipose components (ie, ATFM, skeletal muscle, and body cell mass) but not between HDL cholesterol and any adipose tissue component. The association between HDL cholesterol and ATFM remained significant after serum triacylglycerol was controlled for. When BMI was entered into the HDL cholesterol-ATFM regression model, BMI was not a significant independent variable. The strongest correlate of serum triacylglycerol was visceral adipose tissue (P = 0.002 for both women and men). CONCLUSIONS: Lean tissues and body cell mass appear to account in part for the long-observed inverse association of HDL cholesterol and BMI. These observations suggest a link between nonadipose tissue compartments and the greater cardiovascular risk associated with high BMI. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Dietary fatty acids (FA) are increasingly recognized as major biologic regulators and have properties that relate to health outcomes and disease. The longer chain, more bioactive (n-6) (or omega-6) FA and (n-3) (or omega-3) FA share similar elongation and desaturation enzymes in their conversion from the essential (n-6) FA, linoleic acid, and (n-3) FA, α-linolenic acid (ALA). Conversion from these essential FA is very inefficient. However, now for the (n-3) FA series, soy oil can be enriched with (n-3) stearidonic acid (SDA) to allow for much more efficient conversion to longer chain EPA. EPA and the longer chain DHA possess distinct physical and biological properties that generally impart properties to cells and tissue, which underlie their ability to promote health and prevent disease. Although active in a number of areas of human biology, mechanisms of action of EPA and DHA are perhaps best defined in cardiovascular disease. There is concern that to reach the intake recommendations of EPA and DHA, their supply from cold water fish will be insufficient. Gaps in understanding mechanisms of action of (n-3) FA in a number of health and disease areas as well as optimal sources and intake levels for each need to be defined by further research. Because of the inefficient conversion of ALA, the appearance of SDA in enriched soy oil offers a biologically effective and cost effective approach to providing a sustainable plant source for (n-3) FA in the future. [ABSTRACT FROM AUTHOR]

Background: Macronutrient and micronutrient deficiencies continue to have a detrimental impact in lower-income countries, with significant costs in morbidity, mortality, and productivity. Food is the primary source of the nutrients needed to sustain life, and it is the essential component that links nutrition, agriculture, and ecology in the econutrition framework.Objective: To present evidence and analysis of food-based approaches for improving nutritional and health outcomes in lower-income countries.Methods: Review of existing literature.Results and Conclusions: The benefits of food-based approaches may include nutritional improvement, food security, cost-effectiveness, sustainability, and human productivity. Food-based approaches require additional inputs, including nutrition education, gender considerations, and agricultural planning. Although some forms of malnutrition can be addressed via supplements, food-based approaches are optimal to achieve sustainable solutions to multiple nutrient deficiencies. [ABSTRACT FROM AUTHOR]

After the symposium 'Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids,' faculty who presented at the conference submitted manuscripts relating to their conference topics, and these are presented in this supplement. The content of these manuscripts was reviewed, and 2 conference calls were convened. The objective was to summarize existing evidence, gaps in evidence, and future research needed to strengthen recommendations for specific intakes of n-3 fatty acids for different conditions relating to cardiovascular disease. The following 2 questions were the main items discussed. What are the roles of n-3 fatty acids in primary versus secondary prevention of coronary heart disease? What are the roles of n-3 fatty acids in hypertriglyceridemia, in the metabolic syndrome and type 2 diabetes, and in sudden cardiac death, cardiac arrhythmias, and vulnerable plaque? Each area was summarized by using 2 general categories: 1) current knowledge for which general consensus exists, and 2) recommendations for research and policy. Additional references for these conclusions can be found in the articles included in the supplement. Copyright © 2008 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Accumulating evidence in both humans and animal models clearly indicates that a group of very-long-chain polyunsaturated fatty acids, the n-3 fatty acids (or omega-3), have distinct and important bioactive properties compared with other groups of fatty acids. n-3 Fatty acids are known to reduce many risk factors associated with several diseases, such as cardiovascular diseases, diabetes, and cancer. The mechanisms whereby n-3 fatty acids affect gene expression are complex and involve multiple processes. As examples, n-3 fatty acids regulate 2 groups of transcription factors, such as sterol-regulatory-element binding proteins and peroxisome proliferator-activated receptors, that are critical for modulating the expression of genes controlling both systemic and tissue-specific lipid homeostasis. Modulation of specific genes by n-3 fatty acids and cross-talk between these genes are responsible for many effects of n-3 fatty acids. Copyright © 2006 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Micronutrients not only benefit women's health during childbearing years and during pregnancy and lactation, but they also have substantial impact on women's health during adolescence and the aging years. Thus, for women, diet quality is important for health today and in the future. Realizing that there are many ways to improve the quality of a diet and to obtain adequate amounts of vitamins and minerals from foods, food-based approaches are still not attaining adequate intakes in most women, both in the United States and worldwide. Efforts are needed to improve diet quality, focusing on the diet as a whole, and not on single vitamins or minerals. However, consideration must be given to fortified foods and/or supplements to insure micronutrient adequacy. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

The benefits of exclusive breastfeeding for health in infants have been widely described. The goal of this study was to determine whether partial breastfeeding has protective effects against enteric infection and associated morbidity in population where early addition of supplementation is common. In this prospective study 238 Bedouin infants were followed from birth to age 18 months. Exclusive breastfeeding was protective against infection and morbidity at ages 0 to 3 months. In the age range of 4 to 6 months, partial versus non breastfeeding was associated with lower rates of infection with Cryptosporidium spp (Odds Ratio OR 0.34, 95% confidence interval CI 0.18; 0.65), and Campylobacter spp (OR 0.58, CI 0.35; 0.98), lower rates of ear infections (OR 0.47, CI 0.24; 0.90) and of asthma (OR 0.33, CI 0.13; 0.81). In older children (10-12 month age range) partial breastfeeding as compared to none, protected against infections with Cryptosporidium spp (OR 0.57, CI 0.36; 0.91) and Giardia lamblia (OR 0.92, CI 0.85; 0.99). In Bedouins, and possibly in other populations, even partial breastfeeding, especially at ages 4 to 6 months offers protection against infection. Thus, encouraging mothers to continue to at least partially breastfeed past age 3 months may help reduce infections and morbidity in infants. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE), resulting from a lack of blood flow and oxygen before or during newborn delivery, is a leading cause of cerebral palsy and neurological disability in children. Therapeutic hypothermia (TH), the current standard of care in HIE, is only beneficial in 1 of 7-8 cases. Therefore, there is a critical need for more efficient treatments. We have previously reported that omega-3 (n-3) fatty acids (FA) carried by triglyceride (TG) lipid emulsions provide neuroprotection after experimental hypoxic-ischemic (HI) injury in neonatal mice. Herein, we propose a novel acute therapeutic approach using an n-3 diglyceride (DG) lipid emulsions. Importantly, n-3 DG preparations had much smaller particle size compared to commercially available or lab-made n-3 TG emulsions. We showed that n-3 DG molecules have the advantage of incorporating at substantially higher levels than n-3 TG into an in vitro model of phospholipid membranes. We also observed that n-3 DG after parenteral administration in neonatal mice reaches the bloodstream more rapidly than n-3 TG. Using neonatal HI brain injury models in mice and rats, we found that n-3 DG emulsions provide superior neuroprotection than n-3 TG emulsions or TH in decreasing brain infarct size. Additionally, we found that n-3 DGs attenuate microgliosis and astrogliosis. Thus, n-3 DG emulsions are a superior, promising, and novel therapy for treating HIE., Competing Interests: Declaration of Competing Interest Richard J Deckelbaum is a founding scientist and scientific advisory board member of DeckTherapeutics Inc., a company that plans to use novel n-3 lipid emulsions to prevent tissue death after ischemic brain injury. Hylde Zirpoli is a scientific advisory board member of DeckTherapeutics Inc. DeckTherapeutics Inc. had no inputs or roles in the experimental design, data analysis and funding of this paper. The other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Traumatic brain injury (TBI) can lead to neurodegenerative diseases such as Alzheimer's disease (AD) through mechanisms that remain incompletely characterized. Similar to AD, TBI models present with cellular metabolic alterations and modulated cleavage of amyloid precursor protein (APP). Specifically, AD and TBI tissues display increases in amyloid-β as well as its precursor, the APP C-terminal fragment of 99 a.a. (C99). Our recent data in cell models of AD indicate that C99, due to its affinity for cholesterol, induces the formation of transient lipid raft domains in the ER known as mitochondria-associated endoplasmic reticulum (ER) membranes ("MAM" domains). The formation of these domains recruits and activates specific lipid metabolic enzymes that regulate cellular cholesterol trafficking and sphingolipid turnover. Increased C99 levels in AD cell models promote MAM formation and significantly modulate cellular lipid homeostasis. Here, these phenotypes were recapitulated in the controlled cortical impact (CCI) model of TBI in adult mice. Specifically, the injured cortex and hippocampus displayed significant increases in C99 and MAM activity, as measured by phospholipid synthesis, sphingomyelinase activity and cholesterol turnover. In addition, our cell type-specific lipidomics analyses revealed significant changes in microglial lipid composition that are consistent with the observed alterations in MAM-resident enzymes. Altogether, we propose that alterations in the regulation of MAM and relevant lipid metabolic pathways could contribute to the epidemiological connection between TBI and AD., (© 2022. The Author(s).)

Background: Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice., Methods: We conducted a 6-country retrospective cohort study among hospitalized women of childbearing age between 1 March 2020 and 31 March 2021. Exposures were (1) pregnancy and (2) a positive SARS-CoV-2 RT-PCR test. The primary outcome for both analyses was intensive care unit (ICU) admission. Secondary outcomes included supplemental oxygen requirement, mechanical ventilation, adverse birth outcomes, and in-hospital mortality. We used log-binomial regression to estimate the effect between pregnancy and SARS-CoV-2 infection. Factors associated with mortality were evaluated using competing-risk proportional subdistribution hazards models., Results: Our analyses included 1315 hospitalized women: 510 pregnant women with SARS-CoV-2, 403 nonpregnant women with SARS-CoV-2, and 402 pregnant women without SARS-CoV-2 infection. Among women with SARS-CoV-2 infection, pregnancy was associated with increased risk for ICU admission (adjusted risk ratio [aRR]: 2.38; 95% CI: 1.42-4.01), oxygen supplementation (aRR: 1.86; 95% CI: 1.44-2.42), and hazard of in-hospital death (adjusted sub-hazard ratio [aSHR]: 2.00; 95% CI: 1.08-3.70). Among pregnant women, SARS-CoV-2 infection increased the risk of ICU admission (aRR: 2.0; 95% CI: 1.20-3.35), oxygen supplementation (aRR: 1.57; 95% CI: 1.17-2.11), and hazard of in-hospital death (aSHR: 5.03; 95% CI: 1.79-14.13)., Conclusions: Among hospitalized women in SSA, both SARS-CoV-2 infection and pregnancy independently increased risks of ICU admission, oxygen supplementation, and death. These data support international recommendations to prioritize COVID-19 vaccination among pregnant women., Competing Interests: Potential conflicts of interest. J. B. N. is an infectious disease internist and epidemiologist and Principal Investigator (PI) of NIH/FIC grant numbers 1R25TW011217-01, 1R21TW011706-01, and 1D43TW010937-01A1; and payment to University of Pittsburgh. N. A. S.-A. is a clinician-scientist in Pediatric Infectious Diseases and implementation research; she is supported by the NIH National Institute of Child Health and Human Development (NICHD) grant number R01HD089866; by an NIH/FIC award through the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) for the Central and West Africa Implementation Science Alliance (CAWISA) (payment to institution); and by NIH/FIC grant number 1D43TW012280-01. F. S., N. K. S., and A. P. are supported as PIs by NIH/FIC grant number 1R25TW011217-01. A. Z. is PIs of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET; https://www.pandora-id.net) funded by the European Developing Countries Clinical Trial Partnership (EDCTP) and the European Union Horizon 2020 Framework Program for Research and Innovation, paid to institution (University College London, London, UK). R. N. M. reports grants or contracts unrelated to this work, and payment to their institution: NIH/FIC1D43TW010547-01—The African Center for Biostatistical Excellence (ACBE). P. J. R. reports the following grants or contracts unrelated to this work and paid to their institution: 5R01AI075045-12, 5R01AI139179-04, and 5R01AI117001-07. E. R. S. reports a Bill and Melinda Gates Foundation grant for a prospective meta-analysis of COVID-19 in pregnancy, unrelated to this work, and payment to George Washington University. A. B. reports grants or contracts unrelated to this work—NIH: IMPAACT Vice-chair Funding for P1106; and UNITAID: Benefit KIDS funding for PETITE Study. P. A. reports grants or contracts unrelated to this work and paid to the University of Ibadan, Nigeria: NIH/FIC R25 grant number 1R25TW011217-01 to AFREhealth. J. W. N. reports grants paid to the University of Pittsburgh from the NIH to the Pitt-Ohio State Clinical Trials Unit (UM1 AI068636), the University of Pittsburgh Virology Support Laboratory (UM1 AI106701), the I4C Martin Delaney Collaboratory for an HIV Cure (UM1 AI126603), the REACH Martin Delaney Collaboratory for HIV Cure (UM1 AI164565), and from the National Cancer Institute through Leidos contract numbers HHSN261200800001E and 75N91019D00024 USAID; Gilead Sciences, Inc; and Janssen Pharmaceuticals. J. W. N. also reports consulting fees from Gilead Sciences, Inc (Scientific Advisory Board), Accelevir Diagnostics (Consulting Agreement), and Merck (Consulting Agreement); shares from Abound Bio, Inc, share options from Co-Crystal Pharma, Inc, and share options from Infectious Diseases Connect; a consulting agreement with Xi’an Yufan Biotechnologies; and employment with the University of Pittsburgh. M. S. reports grants or contracts unrelated to this work and paid to their institution (MGH-Boston, MA, USA): NIH/NIA R01AG059504-03 and NIH/NHLBI R01 HL141053-04. A.-P. K. reports research support unrelate to this work paid to their institution (South African Medical Research Council): NIH/FIC 1R21TW011706-01-Dolutegravir, Weight Gain and Metabolic Outcomes in South Africa. L. M. reports consulting fees from the World Health Organization on COVID in pregnancy and mother to child SARS-CoV-2 transmission (this contract is now completed); and payment from Virology Education for a talk on SARS-CoV-2 in pregnancy and possibility of mother-to-child SARS-CoV-2 transmission for continuing education sponsored by Virology Education. M. Y. is PI of the NIH/National Institute of Allergy and Infectious Diseases (NIH/NIAID) grant number 5U01AI096299-13 of the Central Africa-International epidemiology to Evaluate AIDS (CA-IeDEA). M. Y. also reports grants or contracts unrelated to this work and paid to their institution: NIH grant numbers 5U01AI096299 (NIAID), R01HD087993 (NICHD), U54CA254568 (National Cancer Institute), and R01HD105526 (NICHD). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol and triglyceride, along with malabsorption of fat and fat-soluble vitamins are characteristic features of these diseases. We summarize the genetic basis of these disorders, provide guidance in their diagnosis and suggest treatment regimens including high dose fat-soluble vitamins as therapeutics. A section on preconception counseling and other special considerations pertaining to pregnancy is included. This information may be useful for patients, caregivers, physicians and insurance agencies involved in the management and support of affected individuals., (Copyright © 2022. Published by Elsevier Inc.)

Importance: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent., Objective: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa., Design, Setting, and Participants: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection., Exposures: Age, sex, preexisting comorbidities, and region of residence., Main Outcomes and Measures: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay., Results: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge., Conclusions and Relevance: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region.

Bioactive ingredients for infant formula have been sought to reduce disparities in health outcomes between breastfed and formula-fed infants. Traditional food safety methodologies have limited ability to assess some bioactive ingredients. It is difficult to assess the effects of nutrition on the infant immune system because of coincident developmental adaptations to birth, establishment of the microbiome and introduction to solid foods, and perinatal environmental factors. An expert panel was convened to review information on immune system development published since the 2004 Institute of Medicine report on evaluating the safety of new infant formula ingredients and to recommend measurements that demonstrate the safety of bioactive ingredients intended for that use. Panel members participated in a 2-d virtual symposium in November 2020 and in follow-up discussions throughout early 2021. Key topics included identification of immune system endpoints from nutritional intervention studies, effects of human milk feeding and human milk substances on infant health outcomes, ontologic development of the infant immune system, and microbial influences on tolerance. The panel explored how "nonnormal" conditions such as preterm birth, allergy, and genetic disorders could help define developmental immune markers for healthy term infants. With consideration of breastfed infants as a reference, ensuring proper control groups, and attention to numerous potential confounders, the panel recommended a set of standard clinical endpoints including growth, response to vaccination, infection and other adverse effects related to inflammation, and allergy and atopic diseases. It compiled a set of candidate markers to characterize stereotypical patterns of immune system development during infancy, but absence of reference ranges, variability in methods and populations, and unreliability of individual markers to predict disease prevented the panel from including many markers as safety endpoints. The panel's findings and recommendations are applicable for industry, regulatory, and academic settings, and will inform safety assessments for immunomodulatory ingredients in foods besides infant formula., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background & Aims: Medium-chain triglycerides (TG) (MCT) and fish oil (FO) TG are incorporated as the core TG component into intravenous (IV) lipid emulsions for infusion in parenteral nutrition. Bolus injections of IV emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. However, intravascular metabolism and organ delivery of acute IV injection of emulsions containing both MCT and FO are not fully defined, nor have they been characterized across common experimental animal models. We characterized and compared blood clearance kinetics and organ distribution of bolus injections of MCT/FO emulsions among different animal species. We also examined whether sex differences or feeding status can affect catabolic properties of MCT/FO lipid emulsions., Design: Blood clearance rates of lipid emulsions with specific TG composition were compared in rats IV injected with [3H]cholesteryl hexadecyl ether labeled pure n-6 long-chain (LCT) and n-3 FO TG lipid emulsions, or emulsions containing MCT and FO at different ratios (wt/wt), which include 8:2 (80% MCT: 20% FO), 5:4:1 (50% MCT: 40% LCT: 10% FO) and SMOF (30% LCT: 30% MCT: 25% olive oil: 10% FO). Dose-response effects (0.016 mg-1.6 mg TG/g body weight) of the MCT/FO 8:2 emulsions on blood clearance properties and organ delivery were determined in both mice and rats. Blood clearance kinetics and organ uptake of MCT/FO 8:2 emulsions were compared between male and female rats and between fed and fasted rats. Changes in plasma lipid profiles after acute injections of MCT/FO 8:2 lipid emulsion at different doses (0.043, 0.133, and 0.4 mg TG/g body weight) were characterized in non-human primates (Cynomolgus monkeys)., Results: MCT/FO 8:2 emulsion was cleared faster in rats when compared with other emulsions with different TG contents. Mice had faster blood clearance and higher fractional catabolic rates (FCR) when compared with the rats injected with MCT/FO 8:2 emulsions regardless of the injected doses. Mice and rats had similar plasma TG and free fatty acid (FFA) levels after low- or high-dose injections of the MCT/FO emulsion. Tissue distribution of the MCT/FO 8:2 lipid emulsion are comparable between mice and rats, where liver had the highest uptake per recovered dose among all organs (>60%). Feeding status and sex differences did not alter the blood clearance rate of the MCT/FO 8:2 emulsion in rats. In a nonhuman primate model, dose-response increases in plasma TG and FFA were observed after IV injection of MCT/FO 8:2 emulsions within the 1st 10 min., Conclusion: A lipid emulsion containing both MCT and FO TG is cleared rapidly in blood and readily available for organ uptake in rodent and primate animal models. Characterization of the blood clearance properties of the MCT/FO 8:2 emulsion administered in various animal models may provide further insight into the safety and efficacy profiles for future therapeutic use of bolus injections of MCT/FO emulsions in humans., Competing Interests: Conflicts of interest R.J.D. is a founding scientist and member of the scientific advisory board of DeckTherapeutics, Inc., a company developing diglyceride lipid emulsions to prevent tissue death after ischemic organ injuries. R.J.D. is an inventor on Columbia University assigned patents on omega-3 rich diglyceride emulsions as potential agents for cytoprotection of different organs after ischemic injury. Y.A.C. is founder and director of Nutrition Lipid Developments, SPRL, a company that aims to develop novel lipid emulsions for therapeutic applications. The other authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Therapeutic hypothermia (HT) is a currently accepted treatment for neonatal asphyxia and is a promising strategy in adult stroke therapy. We previously reported that acute administration of docosahexaenoic acid (DHA) triglyceride emulsion (tri-DHA) protects against hypoxic-ischemic (HI) injury in neonatal mice. We questioned if co-treatment with HT and tri-DHA would achieve synergic effects in protecting the brain from HI injury. Neonatal mice (10-day old) subjected to HI injury were placed in temperature-controlled chambers for 4 h of either HT (rectal temperature 31-32°C) or normothermia (NT, rectal temperature 37°C). Mice were treated with tri-DHA (0.375 g tri-DHA/kg bw, two injections) before and 1 h after initiation of HT. We observed that HT, beginning immediately after HI injury, reduced brain infarct volume similarly to tri-DHA treatment (~50%). Further, HT delayed 2 h post-HI injury provided neuroprotection (% infarct volume: 31.4 ± 4.1 vs. 18.8 ± 4.6 HT), while 4 h delayed HT did not protect against HI insult (% infarct volume: 30.7 ± 5.0 vs. 31.3 ± 5.6 HT). HT plus tri-DHA combination treatment beginning at 0 or 2 h after HI injury did not further reduce infarct volumes compared to HT alone. Our results indicate that HT offers similar degrees of neuroprotection against HI injury compared to tri-DHA treatment. HT can only be provided in tertiary care centers, requires intense monitoring and can have adverse effects. In contrast, tri-DHA treatment may be advantageous in providing a feasible and effective strategy in patients after HI injury., Competing Interests: RD is a founding scientist and member of the scientific advisory board of DeckTherapeutics, Inc. (DT), a company that plans to use novel n-3 lipid emulsions to prevent tissue death after ischemic brain injury. The plans for DT do not overlap with any of the data presented in this paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Manual Kollareth, Zirpoli, Ten and Deckelbaum.)

Mitochondria-related cell death pathways play a major role in ischemic brain injury. Thus, mitochondrial "protective" molecules could be considered for new therapeutic regimens. We recently reported that acute administration of docosahexaenoic acid (DHA) triglyceride lipid emulsion, immediately after hypoxic-ischemic (HI) insult, markedly attenuated brain infarct size. This was associated with an early change of DHA-derived specialized pro-resolving mediator (SPM) profiles. Specifically, DHA treatment induced a 50% increase of neuroprotectin D1 (NPD1) levels in ischemic brain. Based on these findings, we questioned if direct administration of NPD1 after HI injury also affords neuroprotection, and if so, by what mechanisms. Using HI insult to mimic ischemic stroke in neonatal mice, we observed that acute intraperitoneal injection of NPD1 immediately after HI injury prevented the expansion of the ischemic core by ~40% and improved coordination and motor abilities compared to the control group. At 7 days after HI injury, NPD1 treatment decreased ipsilateral hemisphere atrophy and preserved motor functions in wire-holding and bridge-crossing tests compared to control littermates. Brain mitochondria, isolated at 4 h after reperfusion from mice treated with NPD1, showed an increase in the capacity to buffer calcium after HI injury, as result of the preservation of mitochondrial membranes. Further, NPD1 induced a reduction of mitochondrial BAX translocation and oligomerization, attenuated cytochrome C release and decreased AIF nuclear translocation. To confirm whether NPD1 acts as BAX inhibitor, we evaluated NPD1 action co-administrated with a pro-apoptotic agent, staurosporine, using mouse embryonic fibroblasts as in vitro model of apoptosis. NPD1 exposure markedly decreased mitochondria-mediated apoptosis, blocking BAX translocation from cytosol to mitochondria and subsequently reducing caspase-3 activation. Our findings provide novel evidence that the neuroprotective action of NPD1 is elicited rapidly in the first few hours after ischemic injury and is associated with both preserved mitochondrial membrane structure and reduced BAX mitochondrial translocation and activation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We recently reported that acute injection of docosahexaenoic acid (DHA) triglyceride emulsions (tri-DHA) conferred neuroprotection after hypoxic-ischemic (HI) injury in a neonatal mouse stroke model. We showed that exogenous DHA increased concentrations of DHA in brain mitochondria as well as DHA-derived specialized pro-resolving mediator (SPM) levels in the brain. The objective of the present study was to investigate the distribution of emulsion particles and changes in plasma lipid profiles after tri-DHA injection in naïve mice and in animals subjected to HI injury. We also examined whether tri-DHA injection would change DHA- and eicosapentaenoic acid (EPA)-derived SPM levels in the brain. To address this, neonatal (10-day-old) naïve and HI mice were injected with radiolabeled tri-DHA emulsion (0.375 g tri-DHA/kg bw), and blood clearance and tissue distribution were analyzed. Among all the organs assayed, the lowest uptake of emulsion particles was in the brain (<0.4% recovered dose) in both naïve and HI mice, while the liver had the highest uptake. Tri-DHA administration increased DHA concentrations in plasma lysophosphatidylcholine and non-esterified fatty acids. Additionally, treatment with tri-DHA after HI injury significantly elevated the levels of DHA-derived SPMs and monohydroxy-containing DHA-derived products in the brain. Further, tri-DHA administration increased resolvin E2 (RvE2, 5S,18R-dihydroxy-eicosa-6E,8Z,11Z,14Z,16E-pentaenoic acid) and monohydroxy-containing EPA-derived products in the brain. These results suggest that the transfer of DHA through plasma lipid pools plays an important role in DHA brain transport in neonatal mice subjected to HI injury. Furthermore, increases in EPA and EPA-derived SPMs following tri-DHA injection demonstrate interlinked metabolism of these two fatty acids. Hence, changes in both EPA and DHA profile patterns need to be considered when studying the protective effects of DHA after HI brain injury. Our results highlight the need for further investigation to differentiate the effects of DHA from EPA on neuroprotective pathways following HI damage. Such information could contribute to the development of specific DHA-EPA formulations to improve clinical endpoints and modulate potential biomarkers in ischemic brain injury., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This article reviews novel approaches for omega-3 fatty acid (FA) therapeutics and the linked molecular mechanisms in cardiovascular and central nervous system (CNS) diseases. In vitro and in vivo research studies indicate that omega-3 FAs affect synergic mechanisms that include modulation of cell membrane fluidity, regulation of intracellular signaling pathways, and production of bioactive mediators. We compare how chronic and acute treatments with omega-3 FAs differentially trigger pathways of protection in heart, brain, and spinal cord injuries. We also summarize recent omega-3 FA randomized clinical trials and meta-analyses and discuss possible reasons for controversial results, with suggestions on improving the study design for future clinical trials. Acute treatment with omega-3 FAs offers a novel approach for preserving cardiac and neurological functions, and the combinations of acute treatment with chronic administration of omega-3 FAs might represent an additional therapeutic strategy for ameliorating adverse cardiovascular and CNS outcomes.

Background: In 1996 and in 2006, Palestine initiated salt iodization and multiple micronutrient fortification of wheat flour, respectively as a strategy to prevent deficiencies of these nutrients. In 2009, we assessed the impact of these interventions on the health and nutritional status of schoolchildren residing in the West Bank., Methods: We surveyed a sample of 22 schools run by the UN Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) and the Palestinian Government. We randomly selected students from the first (mean age 6.7 years [SD 0.5]), sixth (11.8 years [0.6]), and ninth grades (14.8 years [0.6]). Data were obtained from 1484 (99%) of 1500 students planned for enrollment., Results: Our results suggest that iodine intake appears adequate and there was essentially no iodine deficiency. As to the status of other micronutrients, the main nutritional micronutrient risks for schoolchildren in the West Bank continue to be low serum levels of iron, zinc, and vitamin B-12; folate levels were seemingly high. The overall prevalence of anemia was 9.6%, but there were pockets of anemia in certain districts. Almost 42% of the anemia in our sample was explained by iron deficiency. There were significant differences in iron deficiency between girls and boys, 29.5% vs. 15.7%, respectively ( p  = 0.0001). There were no cases of lead toxicity in the studied sample., Conclusions: Wheat flour and salt fortification has had a major influence on improving the micronutrient status of Palestinian children, for some but not all micronutrients. The recommended key blood and biochemical parameters to be incorporated in the surveillance system are iron, zinc, and vitamin B12., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75-80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk. Whole-exome genotyping was performed in three independent cohorts from disparate regions of the world, for a total of 1520 genotyped subjects. Cohort 1 (MTA (Multimodal Treatment study of children with ADHD) sample, 371 subjects) was analyzed as the discovery cohort, while cohorts 2 (Paisa sample, 298 subjects) and 3 (US sample, 851 subjects) were used for replication. A set of 58 genes was manually curated based on their roles in sphingolipid metabolism. A targeted exploration for association between ADHD and 137 markers encoding for common and rare potentially functional allelic variants in this set of genes was performed in the screening cohort. Single- and multi-locus additive, dominant and recessive linear mixed-effect models were used. During discovery, we found statistically significant associations between ADHD and variants in eight genes (GALC, CERS6, SMPD1, SMPDL3B, CERS2, FADS3, ELOVL5, and CERK). Successful local replication for associations with variants in GALC, SMPD1, and CERS6 was demonstrated in both replication cohorts. Variants rs35785620, rs143078230, rs398607, and rs1805078, associated with ADHD in the discovery or replication cohorts, correspond to missense mutations with predicted deleterious effects. Expression quantitative trait loci analysis revealed an association between rs398607 and increased GALC expression in the cerebellum.