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Background Most medical educational programs emphasize clinical observation or clinical skill acquisition, fewer focus upon research. The Danish-American Research Exchange (DARE) program, sponsored by the Lundbeck Foundation, is unique in that the medical student initiates biomedical research collaboration between Danish and US medical institutions. To achieve this, Danish medical students (DARE students) conduct binational mentored research projects while based in the United States for 10 months. In addition, DARE students are introduced to interdisciplinary thinking about how to develop ultra-low-cost healthcare interventions through the ‘$10 Challenge’. Methods We conducted a cross-sectional study of DARE alumni over five consecutive years (2015–2020, n = 24). Research metrics included completion of a research project, primary authorship, and co-authorship of publications. The number of publications, prior to and after the DARE program were enumerated. For the first four cohorts, graduation from medical school and acceptance or intention to enter a joint MD-PhD program also were assessed. Two focus groups were conducted using constructivist grounded theory. Discussions were transcribed, redacted, and coded using Dedoose software. Results DARE Medical students were 31.2 years (range 24–35), the majority were women (67%;16/24). The majority (17/24;71%) completed a first author publication in a peer-reviewed journal with a median of 3.9 per DARE alumnus. DARE alumnus reported increased proficiency in biostatistics, epidemiology, coding and public speaking as well as stronger research qualities in creativity, critical thinking, comfort in approaching scientist in both the US and Denmark (p Conclusions Preliminarily, this study suggests that medical students can initiate binational collaboration in medicine. Benefits include research productivity, intention to pursue academic medical careers, as well as positive impacts on motivation. This medical student-initiated research model lays the groundwork for using this model across other country pairs to promote binational collaboration.

Background Malnutrition continues to be a major cause of mortality and morbidity among children in resource limited settings. Children with severe acute malnutrition (SAM) experience severe thymus atrophy, possibly reflecting poor immune function. This immune dysfunction is responsible for the severe infections they experience which lead to mortality. Since their immune dysfunction is not fully understood and there has been a lapse in research in this field, more research is needed. Knowing the correlates of thymus size may help clinicians identify those with more severe atrophy who might have more severe immune impairment. We aimed to describe thymus size and its correlates at admission among children hospitalized with SAM. Methods This cross-sectional study involved children 6-59 months admitted with complicated SAM in Mulago National Referral Hospital. Well-nourished children from same communities were used as a community reference group for thymus size. At admission, thymus size was measured by ultrasound scan. Demographic, clinical and laboratory variables were identified at admission. A linear regression model was used to determine correlates of thymus size among children with SAM. Results Among 388 children with SAM, the mean age was 17±8.5 months and 58% were boys. The mean thymus size was 3.14 (95% CI 2.9; 3.4) cm2 lower than that of the 27 healthy community reference children (1.06 vs 4.2 cm2, p 2 weeks duration of sickness (-0.10; 95% CI -0.19; -0.01). Conclusion The thymus is indeed a barometer for nutrition since all anthropometric measurements and breastfeeding were associated with bigger thymus. The immune benefits of breastfeeding among children with SAM is underscored. Children with longer duration of illness had a smaller thymus gland indicating that infections have a role in the cause or consequence of thymus atrophy.

Background Moderate acute malnutrition (MAM) affects millions of children, increasing their risk of dying from infections. Thymus atrophy may be a marker of malnutrition-associated immunodeficiency, but factors associated with thymus size in children with MAM are unknown, as is the effect of nutritional interventions on thymus size. Methods Thymus size was measured by ultrasound in 279 children in Burkina Faso with MAM, diagnosed by low mid-upper arm circumference (MUAC) and/or low weight-for-length z-score (WLZ), who received 12 weeks treatment with different food supplements as part of a randomized trial. Correlates of thymus size and of changes in thymus size after treatment, and after another 12 weeks of follow-up were identified. Results Thymus size correlated positively with age, anthropometry and blood haemoglobin, and was smaller in children with malaria. Children with malnutrition diagnosed using MUAC had a smaller thymus than children diagnosed based on WLZ. Thymus size increased during and after treatment, similarly across the different food supplement groups. Conclusions In children with MAM, the thymus is smaller in children with anaemia or malaria, and grows with recovery. Assuming that thymus size reflects vulnerability, low MUAC seems to identify more vulnerable children than low WLZ in children with MAM. Impact Thymus atrophy is known to be a marker of the immunodeficiency associated with malnutrition in children.In children with moderate malnutrition, we found the thymus to be smaller in children with anaemia or malaria.Assuming that thymus size reflects vulnerability, low MUAC seems to identify more vulnerable children than low weight for length.Thymus atrophy appears reversible with recovery from malnutrition, with similar growth seen in children randomized to treatment with different nutritional supplements.

Children with severe acute malnutrition (SAM) may have impaired intestinal function, which can result in malabsorption, diarrhoea, and poor growth. This study evaluated the gut function of children with SAM using fecal and blood biomarkers and assessed their correlates.A cross-sectional study, nested in a randomized trial (www.isrctn.com, ISRCTN 16454889), was conducted at Mulago hospital, Uganda among subgroups of 400 children with complicated SAM and 30 community controls. Gut function was evaluated by 5 biomarkers: plasma citrulline, fecal myeloperoxidase and fecal neopterin, bacterially derived 16S rRNA gene and internal transcribed Spacer region (ITS) specific for Candida spp. in blood.Compared with controls, children with SAM had lower median plasma citrulline (5.14 vs 27.4 μmol/L, P 0.001), higher median fecal myeloperoxidase (18083 vs 7482 ng/mL, P = 0.001), and fecal neopterin (541 vs 210 nmol/L, P 0.001). A higher blood concentration of 16S rRNA gene copy numbers was observed among children with SAM (95 vs 28 copies/μl, P = 0.05), whereas there was no difference in the blood concentration of Candida-specific ITS fragment.Among those with SAM, plasma citrulline was lower in children with edema, diarrhoea, dermatosis, and plasma C-reactive protein (CRP)10 mg/L. Fecal neopterin was positively correlated with symptoms of fever and cough whereas it was negatively correlated with mid-upper arm circumference (MUAC), weight-for-height z score (WHZ), edema, and dermatosis.Children with complicated SAM seem to have impaired gut function characterized by reduced enterocyte mass, intestinal inflammation, and increased bacterial translocation.

Background: Innovation refers to the process in which individuals or organisations transform ideas into novel products, services or processes. Pharmacy graduates are increasingly expected to have the competencies necessary to find innovative solutions to medicine-related challenges, particularly solutions addressing patient´s need and societal aspects of medicine use.Objective: To describe and discusses the rationale, development, implementation and evaluation of the pharmacy course ‘Contemporary Social Pharmacy’ (CONSOC), and to summarise lessons learned.Methods: Several methods and models were used to develop, run and evaluate the course. The course examination consisted of a written report and an oral presentation and defence of the report. The course was evaluated through a student assessment questionnaire and oral and written feedback from case providers and the teachers.Results: Three selected case reports representing particularly innovative solutions are described. The student evaluations revealed that nine out of 14 course learning objectives were either fully or partly fulfilled, and that what students liked best from the course were the teamwork, the open discussions, the real-world cases and the innovation features. The teachers and case providers also found the course rewarding and extremely positive.Conclusion: Teaching innovation opens up new possibilities for educators and researchers. The CONSOC course introduced several novel components, but the increased complexity of the course also presented challenges to students and faculty alike.

Background Lipid-based nutrient supplements (LNS) and corn–soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. Methods and findings We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks’ supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6–23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2–16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [−0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (−0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. Conclusions In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. Trial registration ISRCTN42569496, In this analysis of secondary trial outcomes, Mette F. Olsen and colleagues show the effects of different supplements on child language and motor skill development., Author summary Why was this study done? Moderate acute malnutrition (MAM) affects more than 33 million children globally with long-term consequences for their development. There has been a call for research on the effects of MAM treatment on functional outcomes, but previous trials have not assessed effects of the treatments on child development. What did the researchers do and find? We conducted a randomised trial of 1,609 children with MAM in Burkina Faso to investigate the effectiveness of supplemental foods, including a comparison of matrix (lipid-based nutrient supplements [LNS] or corn–soy blend [CSB]), soy quality (soy isolate or dehulled soy), and content of milk protein (0%, 20%, or 50% of protein). We assessed child development as gross motor, fine motor, language, and cognitive skills using the Malawi Development Assessment Tool (MDAT). We found that child development improved across intervention groups during the supplementation and continued to improve after the supplementation had ended. Supplements containing milk protein were beneficial for fine motor and language development. Our findings also indicated a benefit of soy isolate over dehulled soy and a benefit of LNS over CSB among boys. What do these findings mean? Previously reported findings from this trial showed that children mainly put on fat-free mass during supplementation. With the data presented here, we show that motor, language, and cognitive development of children also improve during supplementation and that this improvement is sustained post-supplementation. Our results support the use of milk protein in food products, while suggested benefits of soy isolate and LNS merit further investigation. These findings contribute to the needed evidence of supplementation effects on functional outcomes, including child development, and allow better understanding of children’s ability to thrive following MAM treatment.

Children with moderate acute malnutrition (MAM) are treated based on low weight-for-length z-score (WLZ), low mid-upper arm circumference (MUAC) or both. This study aimed to assess associations of admission criteria and body composition (BC), to improve treatment of MAM. We undertook a cross-sectional study among 6–23 months old Burkinabe children with MAM. Fat-free (FFM) and fat mass (FM) were determined by deuterium dilution and expressed as FFM (FFMI) and FM index (FMI). Of 1,489 children, 439 (29.5%) were recruited by low MUAC only (MUAC-O), 734 (49.3%) by low WLZ and low MUAC (WLZ-MUAC) and 316 (21.2%) by low WLZ only (WLZ-O). Thus, 1,173 (78.8%) were recruited by low MUAC, with or without low WLZ (ALL-MUAC). After adjustments, WLZ-O had 89 g (95% confidence interval (CI) 5; 172) lower FFM compared to MUAC-O. Similarly, WLZ-O had 0.89 kg/m2 (95% CI 0.77; 1.01) lower FFMI compared to MUAC-O, whereas there was no difference for FMI. However, boys included by WLZ-O compared to MUAC-O had 0.21 kg/m2 (95% CI 0.05; 0.38) higher FMI. In contrast, girls included by WLZ-O had 0.17 (95% CI 0.01; 0.33) kg/m2 lower FMI compared to MUAC-O (interaction, p = 0.002). We found that different criteria for admission into MAM treatment programmes select children with differences in BC, especially FFMI.Trial registration: ISRCTN42569496.

BACKGROUND: Cholesteryl ester storage disease (CESD) is a rare genetic disease. Its symptoms and severity are highly variable. CESD is a systemic disease that can lead to the accumulation of fat and inflammation in the liver, as well as gastrointestinal and cardiovascular disease. The majority of patients require liver transplantation due to decompensated cirrhosis. Enzyme replacement therapy has been approved based on a randomized trial. Our study aims to clinically and genetically evaluate two siblings with CESD who underwent liver transplantation, as well as their first-degree family members. CASE SUMMARY: The siblings were compound heterozygous for the missense variant in LIPA exon 8, c.894G>A, (p.Gln298Gln) and a single base pair deletion, c.482del (p.Asn161Ilefs*19). Analyses of single nucleotide polymorphisms showed variants with an increased risk of fatty liver disease and fibrosis for both patients. Clinically, both patients show signs of recurrence of CESD in the liver after transplantation and additional gastrointestinal and cardiovascular signs of CESD. Three family members who were LIPA heterozygous had a lysosomal acid lipase activity below the reference value. One of these carriers, a seven-year-old boy, was found to have severe dyslipidemia and was subsequently treated with statins. CONCLUSION: Our study underlines that CESD is a multi-organ disease, the progression of which may occur post-liver transplantation. Our findings underline the need for monitoring of complications and assessment of possible further treatment.

Malnutrition impairs cognitive, communication, and motor development, but it is not known how nutrition and health are associated with development in children with moderate acute malnutrition (MAM). We aimed to describe motor and language development of children with MAM and explore its nutrition and health‐related correlates. This cross‐sectional study used baseline data from a nutritional trial in children with MAM aged 6–23 months in Burkina Faso. Motor and language skills were assessed using the Malawi Development Assessment Tool (MDAT). Linear mixed models were used to explore potential correlates of MDAT including socio‐economic status, anthropometry, body composition, whole‐blood polyunsaturated fatty acids (PUFA), haemoglobin (Hb), iron status, and morbidity. We also assessed child and caregiver participation during MDAT procedures and their associations with correlates and development. MDAT data were available for 1.608 children. Mean (95% CI) MDAT z‐scores were −0.39 (−0.45, −0.34) for gross motor, 0.54 (0.48, 0.59) for fine motor, and −0.91 (−0.96, −0.86) for language skills. Children with higher mid‐upper arm circumference, weight‐for‐height, height‐for‐age, fat‐free mass, n‐3 PUFAs, Hb, and iron status had better MDAT z‐scores, whereas children with more fat mass index, anaemia, illness, and inflammation had poorer z‐scores. In addition, children living in larger households or with an unmarried mother had poorer MDAT z‐scores. Associations between morbidity and z‐scores were largely explained by children's poorer participation during MDAT assessment. The identified factors associated with child development may inform interventions needed to stimulate development during or after management of MAM.

Background Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplements (LNSs) or corn-soy blends (CSBs) but little is known about the impact of these supplements on hemoglobin, iron status, and inflammation. Objective The objective of this study was to investigate the impact of supplementary foods for treatment of MAM on hemoglobin, iron status, inflammation, and malaria. Design A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6-23 mo with MAM received 500 kcal/d as LNS or CSB, containing either dehulled soy (DS) or soy isolate (SI) and different quantities of dry skimmed milk (0%, 20% or 50% of total protein) for 12 wk. The trial was double-blind with regard to quality of soy and quantity of milk, but not matrix (CSB compared to LNS). Hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), serum C-reactive protein (CRP), serum α1-acid glycoprotein (AGP), and malaria antigens were measured at inclusion and after supplementation. Results Between September 2013 and August 2014, 1609 children were enrolled. Among these, 61 (3.8%) were lost to follow-up. During the 12-wk supplementation period, prevalence of anemia, low SF adjusted for inflammation (SFAI), elevated sTfR, and iron-deficiency anemia decreased by 16.9, 8.7, 12.6 and 10.5 percentage points. Children who received LNS compared to CSB had higher hemoglobin (2 g/L; 95% CI: 1, 4 g/L), SFAI (4.2 µg/L; 95% CI: 2.9, 5.5 µg/L), and CRP (0.8 mg/L; 95% CI: 0.4, 1.2 mg/L) and lower sTfR (-0.9 mg/L, 95% CI: -1.3, -0.6 mg/L) after the intervention. Replacing DS with SI or increasing milk content did not affect hemoglobin, SFAI, sTfR, or CRP. Conclusion Supplementation with LNS compared to CSB led to better hemoglobin and iron status, but overall prevalence of anemia remained high. The higher concentrations of acute-phase proteins in children who received LNSs requires further investigation. This trial was registered at www.controlled-trials.com as ISRCTN42569496.

The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9 and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11% of the relationship between excessive sugar-sweetened beverage consumption and obesity. Shorter leukocyte telomere length may be an indicator of future obesity risk in high-risk populations as it is particularly sensitive to damage from oxidative stress exposure, including those from sugar-sweetened beverages.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BACKGROUND: Childhood obesity is increasing especially in Latinos and early intervention is essential to prevent later obesity complications. METHODS: Latino children (n=201) recruited at two San Francisco hospitals were assessed at birth including infant anthropometrics and feeding practices and followed to age 9 with annual anthropometric assessments. We evaluated the relationship between perinatal risk factors and obesity at age 9 and chronic obesity (obesity at both 5 and 9 years). RESULTS: Higher birthweight (odds ratio (OR) 2.48, 95% confidence interval (CI) 1.06-5.81) and maternal pre-pregnancy body mass index (BMI) (OR 1.09, 95%CI 1.00-1.18) were associated with increased risk for obesity at 9 years. Higher maternal pre-pregnancy BMI (OR 1.10, 95%CI 1.01-1.20) was associated with chronic obesity. Additionally, prenatal depression symptoms were protective (OR 0.33, 95%CI 0.11-0.94) against chronic obesity. We found no association between maternal age and education, exclusive breastfeeding at 4-6 weeks, rapid infant weight gain, and obesity or chronic obesity. DISCUSSION: Perinatal risk factors for obesity including higher birthweight and maternal pre-pregnancy BMI persisted until age 9, whereas, other variables significant at age 5 in our cohort and other populations including exclusive breastfeeding and rapid infant weight gain were no longer associated with increased risk.

Pediatric liver disease (PLD) is a major cause of severe morbidity and prolonged hospitalizations in children. Stratifying patients in terms of prognosis remains challenging. The limited knowledge about molecular mechanisms causing and accompanying PLD remains the main obstacle in a search for reliable prognostic biomarkers. A systematic search of MEDLINE via PubMed and Embase via OVID was conducted on studies published between August 2007 and August 2017. Molecular markers with a prognostic potential in terms of survival, need for liver transplantation or disease progression/regression were selected. In general, identified studies were single center smaller case-control studies or case series with a low level of evidence and a high risk of bias. Only 23 studies comprising 898 patients could be included, mostly focusing on biliary atresia, non-alcoholic fatty liver disease, viral hepatitis, and LT; and markers related to morphogenesis and fibrosis. Furthermore, molecular markers in metabolic pathways and inflammation shown to be relevant, however requiring further validation. Hence, further biological and clinical studies are needed to gain greater molecular insight into PLD.

Background Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplement (LNS) or corn-soy blend (CSB). We assessed the effectiveness of (a) matrix, i.e., LNS or CSB, (b) soy quality, i.e., soy isolate (SI) or dehulled soy (DS), and (c) percentage of total protein from dry skimmed milk, i.e., 0%, 20%, or 50%, in increasing fat-free tissue accretion. Methods and findings Between September 9, 2013, and August 29, 2014, a randomised 2 × 2 × 3 factorial trial recruited 6- to 23-month-old children with MAM in Burkina Faso. The intervention comprised 12 weeks of food supplementation providing 500 kcal/day as LNS or CSB, each containing SI or DS, and 0%, 20%, or 50% of protein from milk. Fat-free mass (FFM) was assessed by deuterium dilution technique. By dividing FFM by length squared, the primary outcome was expressed independent of length as FFM index (FFMI) accretion over 12 weeks. Other outcomes comprised recovery rate and additional anthropometric measures. Of 1,609 children, 4 died, 61 were lost to follow-up, and 119 were transferred out due to supplementation being switched to non-experimental products. No children developed allergic reaction. At inclusion, 95% were breastfed, mean (SD) weight was 6.91 kg (0.93), with 83.5% (5.5) FFM. In the whole cohort, weight increased 0.90 kg (95% CI 0.88, 0.93; p < 0.01) comprising 93.5% (95% CI 89.5, 97.3) FFM. As compared to children who received CSB, FFMI accretion was increased by 0.083 kg/m2 (95% CI 0.003, 0.163; p = 0.042) in those who received LNS. In contrast, SI did not increase FFMI compared to DS (mean difference 0.038 kg/m2; 95% CI −0.041, 0.118; p = 0.35), irrespective of matrix. Having 20% milk protein was associated with 0.097 kg/m2 (95% CI −0.002, 0.196) greater FFMI accretion than having 0% milk protein, although this difference was not significant (p = 0.055), and there was no effect of 50% milk protein (0.049 kg/m2; 95% CI −0.047, 0.146; p = 0.32). There was no effect modification by season, admission criteria, or baseline FFMI, stunting, inflammation, or breastfeeding (p > 0.05). LNS compared to CSB resulted in 128 g (95% CI 67, 190; p < 0.01) greater weight gain if both contained SI, but there was no difference between LNS and CSB if both contained DS (mean difference 22 g; 95% CI −40, 84; p = 0.49) (interaction p = 0.017). Accordingly, SI compared to DS increased weight by 89 g (95% CI 27, 150; p = 0.005) when combined with LNS, but not when combined with CSB. A limitation of this and other food supplementation trials is that it is not possible to collect reliable data on individual adherence. Conclusions Based on this study, children with MAM mainly gain fat-free tissue when rehabilitated. Nevertheless, LNS yields more fat-free tissue and higher recovery rates than CSB. Moreover, current LNSs with DS may be improved by shifting to SI. The role of milk relative to soy merits further research. Trial registration ISRCTN registry ISRCTN42569496, Malnourished children accrue more fat free tissue with lipid-based food supplements compared to corn-soy blend ones, as revealed in a trial in Burkina Faso led by Christian Fabiansen, Author summary Why was this study done? Moderate acute malnutrition (MAM) is widespread among children in low-income countries and is a risk factor for morbidity, severe acute malnutrition, and death. WHO recommends more research on food supplements for children with MAM. Currently, there is no consensus on either the effectiveness of lipid-nutrient supplement (LNS) compared to corn-soy blend (CSB), or on the role of key factors like milk and soy. There is concern that children receiving LNS might accumulate too much fat tissue. What did the researchers do and find? In a large randomised trial of 1,609 children with MAM, conducted in a humanitarian setting in Burkina Faso, we investigated the effectiveness of key factors in supplemental foods, namely (a) the matrix (LNS versus CSB), (b) the soy quality (soy isolate versus dehulled soy), and (c) the level of dry skimmed milk. We evaluated body composition to assess the quality of weight gain, and used fat-free mass tissue accretion as our primary outcome. Fat-free tissue accretion as well as recovery from MAM were both higher when using LNS compared to CSB. Children given LNS did not put on excessive fat. What do these findings mean? Our findings support a wider use of LNS in the treatment of children with MAM. A switch to LNS would lead to greater gain of fat-free tissue and recovery, and would benefit millions of children.

Severe acute malnutrition (SAM) has been associated with low polyunsaturated fatty acid (PUFA) status. However, investigations regarding PUFA status and correlates in children with moderate acute malnutrition (MAM) from low-income countries are scarce. The aim of this study was to describe whole-blood PUFA levels in children with moderate acute malnutrition (MAM) and to identify correlates of PUFAs. We conducted a cross-sectional study using baseline data from a prospective nutritional intervention trial among 1609 children with MAM aged 6–23 months in Burkina Faso,West Africa. Whole-blood PUFAs were measured by gas chromatography and expressed as percent of total whole-blood fatty acids (FA%). Potential correlates of PUFAs including infection, inflammation, hemoglobin, anthropometry (difference between children diagnosed as having MAM based on low mid-upper-arm-circumference (MUAC) only, low MUAC and weight-for-height z-score (WHZ), or low WHZ only) and diet were assessed by linear regression adjusted for age and sex. Children with MAM had low concentrations of whole-blood PUFAs, particularly n-3 PUFAs. Moreover, children diagnosed with MAM based only on low MUAC had 0.32 (95% confidence interval (CI), 0.14; 0.50) and 0.40 (95% CI, 0.16; 0.63) FA% lower arachidonic acid (AA) than those recruited based on both low WHZ as well as low MUAC and those recruited with low WHZ only, respectively. Infection and inflammation were associated with low levels of all long-chain (LC)-PUFAs, while hemoglobin was positively associated with whole-blood LC-PUFAs. While PUFA deficiency was not a general problem, overall whole-blood PUFA concentrations, especially of n-3 PUFAs, were low. Infection, inflammation, hemoglobin, anthropometry and diet were correlates of PUFAs concentrations in children with MAM. The trial is registered at http://www.isrctn.com ( ISRCTN42569496 ).

We determined the predictors of mortality among children admitted with severe acute malnutrition (SAM). This was a prospective study nested in a randomized trial among 6–59-month-old children admitted with SAM. Socio-demographic and medical history data were collected using questionnaires and clinical examination, anthropometry and laboratory tests were performed. They were monitored daily until discharge or death during hospitalization while receiving care according to national guidelines. Predictors of death were assessed using Cox regression. Of 400 children, 9.8% (n = 39) died during hospitalization. Predictors of mortality included diarrhoea at admission [hazard ratio [HR] 2.19, 95% confidence interval (CI): 1.06; 4.51], lack of appetite [HR 4.50, 95% CI: 1.76; 11.50], suspected sepsis [HR 2.23, 95% CI: 1.18; 4.24] and skin ulcers [HR 4.23, 95% CI: 1.26; 4.17]. Chest indrawing [HR 5.0, 95% CI: 1.53; 16.3], oxygen saturation below 94% [HR 3.92, 95% CI: 1.42; 10.83] and confirmed HIV infection [HR 3.62, 95% CI: 1.69; 7.77] also predicted higher mortality. Infections were major contributors to mortality. This underscores the need for improved prevention and management of these infections among children with severe malnutrition.

BACKGROUND: Biomarkers of iron status are affected by inflammation. In order to interpret them in individuals with inflammation, the use of correction factors (CFs) has been proposed.OBJECTIVE: The objective of this study was to investigate the use of regression models as an alternative to the CF approach.METHODS: Morbidity data were collected during clinical examinations with morbidity recalls in a cross-sectional study in children aged 6-23 mo with moderate acute malnutrition. C-reactive protein (CRP), α1-acid glycoprotein (AGP), serum ferritin (SF), and soluble transferrin receptor (sTfR) were measured in serum. Generalized additive, quadratic, and linear models were used to model the relation between SF and sTfR as outcomes and CRP and AGP as categorical variables (model 1; equivalent to the CF approach), CRP and AGP as continuous variables (model 2), or CRP and AGP as continuous variables and morbidity covariates (model 3) as predictors. The predictive performance of the models was compared with the use of 10-fold crossvalidation and quantified with the use of root mean square errors (RMSEs). SF and sTfR were adjusted with the use of regression coefficients from linear models.RESULTS: Crossvalidation revealed no advantage to using generalized additive or quadratic models over linear models in terms of the RMSE. Linear model 3 performed better than models 2 and 1. Furthermore, we found no difference in CFs for adjusting SF and those from a previous meta-analysis. Adjustment of SF and sTfR with the use of the best-performing model led to a 17% point increase and CONCLUSION: Regression analysis is an alternative to adjust SF and may be preferable in research settings, because it can take morbidity and severity of inflammation into account. In clinical settings, the CF approach may be more practical. There is no benefit from adjusting sTfR. This trial was registered at www.controlled-trials.com as ISRCTN42569496.

The objective of this study was to evaluate, within the context of a randomized controlled trial of product effectiveness, the acceptability of new formulations of six corn-soy blended flours (CSB) and six lipid-based nutrient supplements (LNS) with different quantities of milk and qualities of soy for the treatment of children with moderate acute malnutrition (MAM). Our study included 1546 children aged 6-23 months and involved questionnaires after one month of supplementation home visits and interviews with a sub-sample of 20 trial participants and their caretakers, and nine focus group discussion. All 12 products were well accepted in terms of organoleptic qualities and received good ratings. However, LNS were more appreciated by caretakers and children. Additionally, an effect of soy isolate was detected on child appreciation where products with high milk content also received better ratings. CSB were not consumed as readily; 33.9% (n = 257) of children receiving CSB were reported to have leftovers compared to 17.3% (n = 134) of children receiving LNS (p=

BACKGROUND: Morbidity plays an important role in the development of and recovery from malnutrition. Morbidity in children with moderate acute malnutrition (MAM) has not been described in detail and it is unclear how morbidity compares to serum levels of acute phase proteins (APPs) which indicate systemic inflammation and which can impede response to therapeutic nutritional interventions. The objective of this study was to describe morbidity in children with MAM and to assess to what extent maternally reported and clinically diagnosed morbidity explain the variation in APPs. METHODS: A cross-sectional sub study was conducted as part of a nutrition intervention trial among 6–23 months old children with MAM residing in Burkina Faso. Morbidity data collection at baseline included 2 week maternal recalls and physical examinations. Multivariate ANCOVA models were used to explore the associations between morbidity and C-reactive protein (CRP) as well as α1-acid glycoprotein (AGP). These models were also used to determine to what extent morbidity explains variation in APPs. RESULTS: In the 2 weeks prior to the study inclusion visit, 38 % of children were ill according to mothers. Furthermore, 71.8 % of children had a symptom or infection identified during the physical examination and 24.2 and 66.4 % of children had elevated CRP and AGP, respectively. Among children without any identified symptom or illness at the inclusion visit, 10.7 and 46.5 % had elevated CRP and AGP, respectively. History of fever as well as nurse-documented fever, malaria, respiratory tract infections and skin infections were associated with higher levels of both APPs. History of cough and diarrhoea at the inclusion visit was associated with higher α1-acid glycoprotein only. Overall, morbidity data only explained a small amount of the variation in APP levels (adjusted R2 below 0.2 in all tested models). CONCLUSION: Morbidity among children with MAM in this setting is common, but maternal reports and clinical examination explained only a small proportion of the variation in APPs, indicating a presence of subclinical inflammation. We recommend further research into the causes of this subclinical inflammation as it could affect nutritional status and success of MAM treatment. TRIAL REGISTRATION: The trial was registered in the International Standard Randomised Controlled Trial Number Register (ISRCTN42569496).

Background Severe acute malnutrition is a serious public health problem, and a challenge to clinicians. Why some children with malnutrition develop oedema (kwashiorkor) is not well understood. The objective of this study was to investigate socio-demographic, dietary and clinical correlates of oedema, in children hospitalised with severe acute malnutrition. Methods We recruited children with severe acute malnutrition admitted to Mulago Hospital, Uganda. Data was collected using questionnaires, clinical examination and measurement of blood haemoglobin, plasma c-reactive protein and α1-acid glycoprotein. Correlates of oedema were identified using multiple logistic regression analysis. Results Of 120 children included, 77 (64%) presented with oedematous malnutrition. Oedematous children were slightly older (17.7 vs. 15.0 months, p = 0.006). After adjustment for age and sex, oedematous children were less likely to be breastfed (odds ratio (OR): 0.19, 95%-confidence interval (CI): 0.06; 0.59), to be HIV-infected (OR: 0.10, CI: 0.03; 0.41), to report cough (OR: 0.33, CI: 0.13; 0.82) and fever (OR: 0.22, CI: 0.09; 0.51), and to have axillary temperature > 37.5°C (OR: 0.28 CI: 0.11; 0.68). Household dietary diversity score was lower in children with oedema (OR: 0.58, CI: 0.40; 85). No association was found with plasma levels of acute phase proteins, household food insecurity or birth weight. Conclusion Children with oedematous malnutrition were less likely to be breastfed, less likely to have HIV infection and had fewer symptoms of other infections. Dietary diversity was lower in households of children who presented with oedema. Future research may confirm whether a causal relationship exists between these factors and nutritional oedema. Electronic supplementary material The online version of this article (doi:10.1186/s12887-015-0341-8) contains supplementary material, which is available to authorized users.

Interleukin-10 (IL-10) is described as a cytokine that exerts immune downregulating actions. In this regard, our study indicates that IL-10 activity on human saphenous veins is coupled to nitric oxide (NO) release. We demonstrated this phenomenon by using in vitro real-time amperometric measurement of NO levels in explanted human saphenous veins after IL-10 exposure. IL-10-induced NO release can inhibit the adherence of monocytes (75.7 +/- 15 cells/600 microm2 of endothelial surface) and granulocytes (65 +/- 18 cells/600 microm2 of endothelial surface) from control values (250-300 cells/600 microm2 of endothelial surface; p < 0.005). This inhibition is directly sensitive to NO synthase inhibition. The specificity of the IL-10 effects is shown by its sensitivity to antibody. In vivo measurement of IL-10 levels during and after cardiopulmonary bypass surgery indicated that they are higher at 6 h after skin closure (1,400 pg/ml) compared with levels found during surgery (300 pg/ml). We surmise that the postsurgical increase of IL-10 levels may be an immunoregulatory attempt to downregulate the diffuse inflammation that has been shown to be associated with cardiopulmonary bypass surgery.

Intensive insulin therapy in critically ill patients reduces morbidity and mortality. The current study elucidates whether acute hyperinsulinemia per se could attenuate the systemic cytokine response and improve neutrophil function during endotoxin (lipopolysaccharide)-induced systemic inflammation in a porcine model.Pigs were anesthetized, mechanically ventilated, randomized into four groups, and followed for 570 min: group 1 (anesthesia solely, n = 10), group 2 (hyperinsulinemic euglycemic clamp [HEC], n = 9), group 3 (lipopolysaccharide, n = 10), group 4 (lipopolysaccharide-HEC, n = 9). Groups 3 and 4 were given a 180-min infusion of lipopolysaccharide (total, 10 microg/kg). Groups 2 and 4 were clamped (p-glucose: 5 mM/l, insulin 0.6 mU.kg(-1).min(-1)) throughout the study period. Changes in pulmonary and hemodynamic function, circulating cytokines, free fatty acids, glucagon, and neutrophil chemotaxis were monitored.Tumor necrosis factor alpha and interleukin 6 were significantly reduced in the lipopolysaccharide-HEC group compared with the lipopolysaccharide group (both P = 0.04). In the lipopolysaccharide-HEC group, the glucagon response was diminished compared with the lipopolysaccharide group (P0.05). Serum free fatty acid concentrations were decreased in animals exposed to HEC. Animals receiving lipopolysaccharide showed an increase in pulmonary pressure (P0.001), but otherwise, there were no major changes in pulmonary or hemodynamic function. Neutrophil function was impaired after lipopolysaccharide administration.Hyperinsulinemia concomitant with normoglycemia reduces plasma concentrations of tumor necrosis factor alpha and the catabolic hormone glucagon in lipopolysaccharide-induced systemic inflammation in pigs. The finding strongly supports the role of insulin as an antiinflammatory hormone. Whether the effect to some extent operates via a reduced free fatty acid concentration is unsettled.

Objective. To characterize early risk factors of moderate/severe hepatotoxicity in a pediatric population with acetaminophen overdose, due to suicide attempt, admitted to a general secondary-level pediatric department. Methods. A retrospective case study of 107 patients, 11 to 15 years old. Results. There was a highly significant relationship between the number of episodes of prehospital vomiting and several elevated hepatologically relevant biochemical parameters, for example, maximum aspartate aminotransferase ( P = .0001). The duration of the latency time before initiation of N-acetylcysteine treatment was significantly related to the elevation of several hepatologically relevant biochemical parameters (eg, maximum γ-glutamyl transferase; P = .0001). Patients suffering from illness prior to their suicide attempt had significantly greater elevations of their hepatologically relevant biochemical parameters, for example, maximum alanine aminotransferase ( P = .01) levels than healthy patients. Conclusion. By use of risk factors, it is possible to identify pediatric patients at increased risk of moderate/severe hepatotoxicity at an early stage of admission.

A Dinka-tribesman came to Marial Lou Hospital, South Sudan, in 2005. He experienced severe discomfort from a Dracunculus Medinensis (Guinea worm) emerging from his perineum (see Figures 1 and ​and2).2). The 80-cm-long parasite was successfully extracted. Figure 1. Dracunculus Medinensis emerging from patient's perineum. This figure appears in color at www.ajtmh.org. Figure 2. Dracunculus Medinensis emerging from patient's perineum. This figure appears in color at www.ajtmh.org. Persons get Dracunculiasis by drinking water containing water fleas harboring the larvae of the worm. The larvae are released into the water by the adult worm that emerges through the skin of infected people. Eighty percent of cases today exist in South Sudan. Sudan's civil war officially ended in 2005 after decades of fighting. Following the peace agreement the Southern Sudan Guinea Worm Eradication Program was created in 2006, counting thousands of village volunteers and health staff. The same year an increase of 270% (> 20,000 cases) occurred because of prior underreporting.1 In the first 6 months of 2009 only 1,188 cases were reported. New episodes of violence in South Sudan pose the greatest challenge for again giving Dracunculiasis the upper hand. In the first half of 2009, 23 incidents of insecurity were reported to disrupt program operations.2 Widespread violence will make coherent surveillance and provision of safe drinking water impossible leaving sporadic treatment to medical humanitarian organizations. Keeping peace contains the hope not only of preventing cases but altogether eradicating Dracunculiasis.