A comprehensive bibliometric analysis of global research on the role of acrolein in Alzheimer's disease pathogenesis: involvement of amyloid-beta.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and behavioral decline. Acrolein, an environmental pollutant and endogenous compound, is implicated in AD development. This research employs bibliometric analysis to assess current trends and key areas concerning acrolein-AD interaction. Methods: The Web of Science was used to extensively review literature on acrolein and AD. Relevant data were systematically gathered and analyzed using VOSviewer, CiteSpace, and an online bibliometric tool. Results: We identified 120 English publications in this specialized field across 19 journals. The Journal of Alzheimer's Disease was the most prominent. The primary contributors, both in terms of scientific output and influence, were the USA, the University of Kentucky, and Ramassamy C, representing countries/regions, institutions, and authors, respectively. In this field, the primary focus was on thoroughly studying acrolein, its roles, and its mechanisms in AD utilizing both in vivo and in vitro approaches. A significant portion of the research was based on proteomics, revealing complex molecular processes. The main focuses in the field were "oxidative stress," "lipid peroxidation," "amyloid-beta," and "cognitive impairment." Anticipated future research trajectories focus on the involvement of the internalization pathway, covering key areas such as synaptic dysfunction, metabolism, mechanisms, associations, neuroinflammation, inhibitors, tau phosphorylation, acrolein toxicity, brain infarction, antioxidants, chemistry, drug delivery, and dementia. Our analysis also supported our previous hypothesis that acrolein can interact with amyloid-beta to form a protein adduct leading to AD-like pathology and altering natural immune responses. Conclusion: This study provides a broad and all-encompassing view of the topic, offering valuable insights and guidance to fellow researchers. These emerging directions underscore the continuous exploration of the complexities associated with AD. The analyses and findings aim to enhance our understanding of the intricate relationship between acrolein and AD for future research.

A novel nano-iron supplement versus standard treatment for iron deficiency anaemia in children 6-35 months (IHAT-GUT trial): a double-blind, randomised, placebo-controlled non-inferiority phase II trial in The Gambia.

Background: Iron deficiency anaemia (IDA) is the leading cause of years lost to disability in most sub-Saharan African countries and is especially common in young children. The IHAT-GUT trial assessed the efficacy and safety of a novel nano iron supplement, which is a dietary ferritin analogue termed iron hydroxide adipate tartrate (IHAT), for the treatment of IDA in children under 3 years of age. Methods: In this single-country, randomised, double-blind, parallel, placebo-controlled, non-inferiority Phase II study in The Gambia, children 6-35 months with IDA (7≤Hb < 11 g/dL and ferritin<30 µg/L) were randomly assigned (1:1:1) to receive either IHAT, ferrous sulphate (FeSO4) or placebo daily for 3 months (85 days). The daily iron dose was 12.5 mg Fe equivalent for FeSO4 and the estimated dose with comparable iron-bioavailability for IHAT (20 mg Fe). The primary efficacy endpoint was the composite of haemoglobin response at day 85 and correction of iron deficiency. The non-inferiority margin was 0.1 absolute difference in response probability. The primary safety endpoint was moderate-severe diarrhoea analysed as incidence density and prevalence over the 3 months intervention. Secondary endpoints reported herein include hospitalisation, acute respiratory infection, malaria, treatment failures, iron handling markers, inflammatory markers, longitudinal prevalence of diarrhoea and incidence density of bloody diarrhoea. Main analyses were per-protocol (PP) and intention-to-treat (ITT) analyses. This trial is registered with clinicaltrials.gov (NCT02941081). Findings: Between Nov 2017 and Nov 2018, 642 children were randomised into the study (214 per group) and included in the ITT analysis, the PP population included 582 children. A total of 50/177 (28.2%) children in the IHAT group achieved the primary efficacy endpoint, as compared with 42/190 (22.1%) in the FeSO4 group (OR 1.39, 80% CI 1.01-1.91, PP population) and with 2/186 (1.1%) in the placebo group. Diarrhoea prevalence was similar between groups, with 40/189 (21.2%) children in the IHAT group developing at least one episode of moderate-severe diarrhoea over the 85 days intervention, compared with 47/198 (23.7%) in the FeSO4 group (OR 1.18, 80% CI 0.86-1.62) and 40/195 (20.5%) in the placebo group (OR 0.96, 80% CI 0.7-1.33, PP population). Incidence density of moderate-severe diarrhoea was 2.66 in the IHAT group and 3.42 in the FeSO4 group (RR 0.76, 80% CI 0.59-0.99, CC-ITT population).There were 143/211 (67.8%) children with adverse events (AEs) in the IHAT group, 146/212 (68.9%) in the FeSO4 group and 143/214 (66.8%) in the placebo group. There were overall 213 diarrhoea-related AEs; 35 (28.5%) cases reported in the IHAT group compared with 51 (41.5%) cases in the FeSO4 group and 37 (30.1%) cases in the placebo group. Interpretation: In this first Phase II study conducted in young children with IDA, IHAT showed sufficient non-inferiority compared to standard-of-care FeSO4, in terms of ID correction and haemoglobin response, to warrant a definitive Phase III trial. In addition, IHAT had lower incidence of moderate-severe diarrhoea than FeSO4, with no increased adverse events in comparison with placebo. Funding: The Bill & Melinda Gates Foundation (OPP1140952).

Acute Kidney Injury Among Children Likely Associated with Diethylene Glycol-Contaminated Medications - The Gambia, June-September 2022.

On July 26, 2022, a pediatric nephrologist alerted The Gambia's Ministry of Health (MoH) to a cluster of cases of acute kidney injury (AKI) among young children at the country's sole teaching hospital, and on August 23, 2022, MoH requested assistance from CDC. CDC epidemiologists arrived in The Gambia, a West African country, on September 16 to assist MoH in characterizing the illness, describing the epidemiology, and identifying potential causal factors and their sources. Investigators reviewed medical records and interviewed caregivers to characterize patients' symptoms and identify exposures. The preliminary investigation suggested that various contaminated syrup-based children's medications contributed to the AKI outbreak. During the investigation, MoH recalled implicated medications from a single international manufacturer. Continued efforts to strengthen pharmaceutical quality control and event-based public health surveillance are needed to help prevent future medication-related outbreaks.

Hepcidin-guided screen-and-treat interventions for young children with iron-deficiency anaemia in The Gambia: an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial.

BACKGROUND: Iron deficiency is the most prevalent nutritional disorder worldwide. Iron supplementation has modest efficacy, causes gastrointestinal side-effects that limit compliance, and has been associated with serious adverse outcomes in children across low-income settings. We aimed to compare two hepcidin-guided screen-and-treat regimens designed to reduce overall iron dosage by targeting its administration to periods when children were safe and ready to receive iron supplementation, with WHO's recommendation of universal iron supplementation. METHODS: We conducted an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial in 12 rural communities across The Gambia. Eligible participants were children aged 6-23 months with anaemia. Participants were randomly assigned (1:1:1) to either the WHO recommended regimen of one sachet of multiple micronutrient powder (MMP) daily containing 12·0 mg iron as encapsulated ferrous fumarate (control group); to MMP with 12·0 mg per day iron for the next 7 days if plasma hepcidin concentration was less than 5·5 µg/L, or to MMP without iron for the next 7 days if plasma hepcidin concentration was at least 5·5 µg/L (12 mg screen-and-treat group); or to MMP with 6·0 mg per day iron for the next 7 days if plasma hepcidin concentration was less than 5·5 µg/L, or to MMP without iron for the next 7 days if plasma hepcidin concentration was at least 5·5 µg/L (6 mg screen-and-treat group). Randomisation was done by use of a permuted block design (block size of 9), with stratification by haemoglobin and age, using computer-generated numbers. Participants and the research team (except for the data manager) were masked to group allocation. The primary outcome was haemoglobin concentration, with a non-inferiority margin of -5 g/L. A per-protocol analysis, including only children who had consumed at least 90% of the supplements (ie, supplement intake on ≥75 days during the study), was done to assess non-inferiority of the primary outcome at day 84 using a one-sided t test adjusted for multiple comparisons. Safety was assessed by use of ex-vivo growth tests of Plasmodium falciparum in erythrocytes and three species of sentinel bacteria in plasma samples from participants. This trial is registered with the ISRCTN registry, ISRCTN07210906. FINDINGS: Between April 23, 2014, and Aug 7, 2015, we prescreened 783 children, of whom 407 were enrolled into the study: 135 were randomly assigned to the control group, 136 to the 12 mg screen-and-treat group, and 136 to the 6 mg screen-and-treat group. 345 (85%) children were included in the per-protocol population: 115 in the control group, 116 in the 12 mg screen-and-treat group, and 114 in the 6 mg screen-and-treat group. Directly observed adherence was high across all groups (control group 94·8%, 12 mg screen-and-treat group 95·3%, and 6 mg screen-and-treat group 95·0%). 82 days of iron supplementation increased mean haemoglobin concentration by 7·7 g/L (95% CI 3·2 to 12·2) in the control group. Both screen-and-treat regimens were significantly less efficacious at improving haemoglobin (-5·6 g/L [98·3% CI -9·9 to -1·3] in the 12 mg screen-and-treat group and -7·8 g/L [98·3% CI -12·2 to -3·5] in the 6 mg screen-and-treat group) and neither regimen met the preset non-inferiority margin of -5 g/L. The 12 mg screen-and-treat regimen reduced iron dosage to 6·1 mg per day and the 6 mg screen-and-treat regimen reduced dosage to 3·0 mg per day. 580 adverse events were observed in 316 participants, of which eight were serious adverse events requiring hospitalisation mainly due to diarrhoeal disease (one [1%] participant in the control group, three [2%] in the 12 mg screen-and-treat group, and four [3%] in the 6 mg screen-and-treat group). The most common causes of non-serious adverse events (n=572) were diarrhoea (145 events [25%]), upper respiratory tract infections (194 [34%]), lower respiratory tract infections (62 [11%]), and skin infections (122 [21%]). No adverse events were deemed to be related to the study interventions. INTERPRETATION: The hepcidin-guided screen-and-treat strategy to target iron administration succeeded in reducing overall iron dosage, but was considerably less efficacious at increasing haemoglobin and combating iron deficiency and anaemia than was WHO's standard of care, and showed no differences in morbidity or safety outcomes. FUNDING: Bill & Melinda Gates Foundation and UK Medical Research Council.

Health Care Consumption, Psychiatric Diagnoses, and Pharmacotherapy 1 and 2 Years Before and After Newly Diagnosed HIV: A Case-Control Study Nested in The Greater Stockholm HIV Cohort Study.

OBJECTIVE: We compare individuals with newly diagnosed HIV with sex-, age-, and socioeconomic status-matched HIV-negative controls, with the aim of studying the frequency of health care visits, the types of clinics visited, registered diagnoses, and psychopharmacotherapy. METHODS: The data were collected through the Stockholm Region administrative database (Stockholm Regional Health Care Data Warehouse) for men and women (people) living with newly diagnosed HIV (PLWH) in their medical records (930 men, 450 women) and controls. The odds ratios (ORs) with 99% confidence intervals (CIs) for psychiatric comorbidities and relevant pharmacotherapies were calculated during the 2011-2018 period. RESULTS: Substance use disorder was higher in PLWH than in controls, before and after newly diagnosed HIV in men (OR = 1 year before 4.36 [99% CI = 2.00-9.5] and OR = 1 year after 5.16 [99% CI = 2.65-10.08]) and women (OR = 1 year before 6.05 [99% CI = 1.89-19.40] and OR = 1 year after 5.24 [99% CI = 1.69-16.32]). Health care contacts and psychiatric disorders were more common in cases than controls 1 and 2 years after diagnosis, particularly for depression in men 1 year after HIV (OR = 3.14, 99% CI = 2.11-4.67), which was not found in women (1 year OR = 0.94, 99% CI = 0.50-1.77). CONCLUSIONS: Before newly diagnosed HIV, PLWH have the same level of psychiatric diagnoses as their controls, except for substance use disorder. Psychiatric problems are more common in PLWH than in their controls after newly diagnosed HIV.

Gut microbiomes from Gambian infants reveal the development of a non-industrialized Prevotella-based trophic network.

Distinct bacterial trophic networks exist in the gut microbiota of individuals in industrialized and non-industrialized countries. In particular, non-industrialized gut microbiomes tend to be enriched with Prevotella species. To study the development of these Prevotella-rich compositions, we investigated the gut microbiota of children aged between 7 and 37 months living in rural Gambia (616 children, 1,389 stool samples, stratified by 3-month age groups). These infants, who typically eat a high-fibre, low-protein diet, were part of a double-blind, randomized iron intervention trial (NCT02941081) and here we report the secondary outcome. We found that child age was the largest discriminating factor between samples and that anthropometric indices (collection time points, season, geographic collection site, and iron supplementation) did not significantly influence the gut microbiome. Prevotella copri, Faecalibacterium prausnitzii and Prevotella stercorea were, on average, the most abundant species in these 1,389 samples (35%, 11% and 7%, respectively). Distinct bacterial trophic network clusters were identified, centred around either P. stercorea or F. prausnitzii and were found to develop steadily with age, whereas P. copri, independently of other species, rapidly became dominant after weaning. This dataset, set within a critical gut microbial developmental time frame, provides insights into the development of Prevotella-rich gut microbiomes, which are typically understudied and are underrepresented in western populations.

Relationship between Quality of Nursing Work Life and Uniformed Nurses' Attitudes and Practices Related to COVID-19 in the Philippines: A Cross-Sectional Study.

(1) Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. Uniformed nurses have played a critical role during the COVID-19 pandemic in the Philippines; however, uptake of literature is limited. This study assessed the relationship between quality of nursing work life (QNWL) and nurses' attitudes and practices during the COVID-19 pandemic. (2) Methods: A descriptive cross-sectional design was used. Participants were recruited from four government hospitals in the Manila metropolitan area of the Philippines. Participants completed three questionnaires in an online survey: a demographic questionnaire, a QNWL questionnaire, and the attitude and practices toward COVID-19 questionnaire. Descriptive statistics, an independent t-test, a one-way analysis of variance, the Pearson correlation coefficient, and hierarchical linear regression were applied for data analysis. (3) Results: The mean age of the participants was 29 years. Most of the participants were single women who were not certified in their specialties. A total of QNWL scores were high, indicating that the participants displayed favorable attitudes and practices in relation to COVID-19. A statistically significant relationship was observed between QNWL, specialty certification, and practices related to COVID-19. Practices related to COVID-19 were a significant predictor of QNWL and one of its subscales, work design. (4) Conclusion: Young adult uniformed nurses in the Philippines have assumed numerous responsibilities during the COVID-19 pandemic. Providing these frontline nurses with comprehensive specialized education and training is crucial.

Interactions between fecal gut microbiome, enteric pathogens, and energy regulating hormones among acutely malnourished rural Gambian children.

BACKGROUND: The specific roles that gut microbiota, known pathogens, and host energy-regulating hormones play in the pathogenesis of non-edematous severe acute malnutrition (marasmus SAM) and moderate acute malnutrition (MAM) during outpatient nutritional rehabilitation are yet to be explored. METHODS: We applied an ensemble of sample-specific (intra- and inter-modality) association networks to gain deeper insights into the pathogenesis of acute malnutrition and its severity among children under 5 years of age in rural Gambia, where marasmus SAM is most prevalent. FINDINGS: Children with marasmus SAM have distinct microbiome characteristics and biologically-relevant multimodal biomarkers not observed among children with moderate acute malnutrition. Marasmus SAM was characterized by lower microbial richness and biomass, significant enrichments in Enterobacteriaceae, altered interactions between specific Enterobacteriaceae and key energy regulating hormones and their receptors. INTERPRETATION: Our findings suggest that marasmus SAM is characterized by the collapse of a complex system with nested interactions and key associations between the gut microbiome, enteric pathogens, and energy regulating hormones.  Further exploration of these systems will help inform innovative preventive and therapeutic interventions. FUNDING: The work was supported by the UK Medical Research Council (MRC; MC-A760-5QX00) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement; Bill and Melinda Gates Foundation (OPP 1066932) and the National Institute of Medical Research (NIMR), UK. This network analysis was supported by NIH U54GH009824 [CLD] and NSF OCE-1558453 [CLD].

Anti-apoptotic and pro-survival effect of exercise training on early aged hypertensive rat cerebral cortex.

The anti-apoptotic and pro-survival effects of exercise training were evaluated on the early aged hypertensive rat cerebral cortex. The brain tissues were analysed from ten sedentary male Wistar Kyoto normotensive rats (WKY), ten sedentary spontaneously 12 month early aged hypertensive rats (SHR), and ten hypertensive rats undergoing treadmill exercise training (60 min/day, 5 days/week) for 12 weeks (SHR-EX). TUNEL-positive apoptotic cells, the expression levels of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) (caspase-independent apoptotic pathway), Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain, active caspase-8 and active caspase-3 (Fas-mediated apoptotic pathways) as well as t-Bid, Bax, Bak, Bad, cytochrome c, active caspase 9 and active caspase-3 (mitochondria-mediated apoptotic pathways) were reduced in SHR-EX compared with SHR. Pro-survival Bcl2, Bcl-xL, p-Bad, 14-3-3, insulin-like growth factor (IGF)-1, pPI3K/PI3K, and pAKT/AKT were significantly increased in SHR-EX compared to those in SHR. Exercise training suppressed neural EndoG/AIF-related caspase-independent, Fas/FasL-mediated caspase-dependent, mitochondria-mediated caspase-dependent apoptotic pathways as well as enhanced Bcl-2 family-related and IGF-1-related pro-survival pathways in the early aged hypertensive cerebral cortex. These findings indicated new therapeutic effects of exercise training on preventing early aged hypertension-induced neural apoptosis in cerebral cortex.

Mapping survey of schistosomiasis and soil-transmitted helminthiases towards mass drug administration in The Gambia.

BACKGROUND: A national mapping survey of schistosomiasis (SCH) and soil-transmitted helminthiases (STH) was conducted in The Gambia in May, 2015. The survey aimed at establishing endemicity of schistosomiasis and soil-transmitted helminthiases to inform decisions on program planning and implementation of mass drug administration (MDA). METHODOLOGY/PRINCIPAL FINDINGS: A cross-section of 10,434 eligible school aged children (SAC), aged 7 to 14 years old were enrolled in the survey. The participants were randomly sampled from 209 schools countrywide using N/50, where N = total eligible children per school. Stool, and urine samples were provided by each child and examined for schistosomiasis and soil-transmitted helminthic infections using double Kato-Katz, urine filtration, dipstick techniques and CCA rapid test kits. Data were managed using online LINKS system enabling real-time data availability and access. Epi Info version 3.5.3 and health mapper version 4.3.2 were used to generate outputs of endemicity and distribution. Descriptions of mapped districts for MDA eligibility and frequency were done with reference to WHO PC strategy recommendations. Mapping results indicated that nationally, the prevalence of schistosomiasis (SCH) and soil-transmitted helminthiases (STH) was 4.3% and 2.5% respectively. In terms of distribution STH are more common in Western Region One (WR1) at 4.1% prevalence, then Lower River Region (LRR) 3.6%, and Western Region Two (WR2) 3.0%. In contrast, SCH indicated much higher prevalence in Central River Region (CRR) at a rate of 14.2%. This is within medium prevalence range, and is followed by Upper River Region (URR) at 9.4%, which is within low prevalence range. At the district level, schistosomiasis prevalence seems to be highest in Niani district (22%) in CRR. Banjul island, the capital city, seems to have the highest prevalence of STH (up to 55%), followed by Kombo South with 22% prevalence. Schistosoma haematobium characterised by haematuria, was the most dominant infection of schistosomiasis discovered followed by Schistosoma mansoni which reported in 0.1% of infections. Out of 42 districts mapped 14, or 38%, of them are co-endemic for soil-transmitted helminthiases (ascariasis, trichuriasis, and hook-worm infections) and schistosomiasis (S. haematobium and S. mansoni). CONCLUSIONS: We identified that 24/42(57%) districts mapped in The Gambia are endemic for schistosomiasis expressing the need for preventive chemotherapy. Twenty (47%) of the districts mapped are endemic for STH. However, only two STH endemic districts namely Banjul (55%) and Kombo South (22%) were within rates eligible for mass drug administration.

Association of Two Indices of Insulin Resistance Marker with Abnormal Liver Function Tests: A Cross-Sectional Population Study in Taiwanese Adults.

Background and objectives: Insulin resistance (IR) is frequently associated with chronic low-grade inflammation and has an important role as a mediator in the development of liver disease. Thus, this study aimed to explore the relationship between two indexes of IR and abnormal liver function parameters. Materials and Methods: This cross-sectional study obtained data of 41,510 men and 92,357 women aged ≥30 years from a private health screening institute in Taiwan. Two IR indexes namely triglyceride-glucose (TyG) index and triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio were used to examine their relationship to predict abnormal liver function parameters (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP)). Results: Positive trend was shown for the association of TyG index in the highest quintile (Q5) and risk of high AST (OR = 1.45, 95% CI: 1.33-1.57), high ALT (OR = 1.85, 95% CI: 1.73-1.97), high GGT (OR = 2.04, 95% CI: 1.93-2.15), and high ALP (OR = 1.13, 95% CI: 1.07-1.19) compared with the median quintile (Q3) in the fully adjusted model. Similarly, participants in the Q5 of the TG/HDL-C ratio were associated with 1.38 (95% CI: 1.27-1.49), 1.71 (95% CI: 1.61-1.82), 1.75 (95% CI: 1.66-1.84), and 1.21 (1.16-1.27) odds for having high AST, ALT, GGT, and ALP respectively. The AUC (95% CI) value of the TyG index for predicting high AST, high ALT, and high GGT was 0.699 (0.692-0.705), 0.738 (0.734-0.742), and 0.752 (0.749-0.755), respectively. Meanwhile, the AUC (95% CI) of the TG/HDL-C ratio for predicting high AST, high ALT, and high GGT was 0.680 (0.673-0.686), 0.738 (0.734-0.742), 0.734 (0.731-0.738), respectively. Conclusions: Our study supported that the TyG index and TG/HDL-C ratio may be useful as non-invasive methods to predict the existence of impaired liver function in the early stage.

Hepcidin mediates hypoferremia and reduces the growth potential of bacteria in the immediate post-natal period in human neonates.

Septicemia is a leading cause of death among neonates in low-income settings, a situation that is deteriorating due to high levels of antimicrobial resistance. Novel interventions are urgently needed. Iron stimulates the growth of most bacteria and hypoferremia induced by the acute phase response is a key element of innate immunity. Cord blood, which has high levels of hemoglobin, iron and transferrin saturation, has hitherto been used as a proxy for the iron status of neonates. We investigated hepcidin-mediated redistribution of iron in the immediate post-natal period and tested the effect of the observed hypoferremia on the growth of pathogens frequently associated with neonatal sepsis. Healthy, vaginally delivered neonates were enrolled in a cohort study at a single center in rural Gambia (N = 120). Cord blood and two further blood samples up to 96 hours of age were analyzed for markers of iron metabolism. Samples pooled by transferrin saturation were used to conduct ex-vivo growth assays with Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli and Klebsiella pneumonia. A profound reduction in transferrin saturation occurred within the first 12 h of life, from high mean levels in cord blood (47.6% (95% CI 43.7-51.5%)) to levels at the lower end of the normal reference range by 24 h of age (24.4% (21.2-27.6%)). These levels remained suppressed to 48 h of age with some recovery by 96 h. Reductions in serum iron were associated with high hepcidin and IL-6 levels. Ex-vivo growth of all sentinel pathogens was strongly associated with serum transferrin saturation. These results suggest the possibility that the hypoferremia could be augmented (e.g. by mini-hepcidins) as a novel therapeutic option that would not be vulnerable to antimicrobial resistance. Trial registration: The original trial in which this study was nested is registered at ISRCTN, number 93854442.

Respiratory infections drive hepcidin-mediated blockade of iron absorption leading to iron deficiency anemia in African children.

Iron deficiency anemia (IDA) is the most prevalent nutritional condition worldwide. We studied the contribution of hepcidin-mediated iron blockade to IDA in African children. We measured hepcidin and hemoglobin weekly, and hematological, inflammatory, and iron biomarkers at baseline, 7 weeks, and 12 weeks in 407 anemic (hemoglobin < 11 g/dl), otherwise healthy Gambian children (6 to 27 months). Each child maintained remarkably constant hepcidin levels (P < 0.0001 for between-child variance), with half consistently maintaining levels that indicate physiological blockade of iron absorption. Hepcidin was strongly predicted by nurse-ascribed adverse events with dominant signals from respiratory infections and fevers (all P < 0.0001). Diarrhea and fecal calprotectin were not associated with hepcidin. In multivariate analysis, C-reactive protein was the dominant predictor of hepcidin and contributed to iron blockade even at very low levels. We conclude that even low-grade inflammation, especially associated with respiratory infections, contributes to IDA in African children.

A novel nano-iron supplement to safely combat iron deficiency and anaemia in young children: The IHAT-GUT double-blind, randomised, placebo-controlled trial protocol.

Background: Iron deficiency and its associated anaemia (IDA) are the leading forms of micronutrient malnutrition worldwide. Here we describe the rationale and design of the first clinical trial evaluating the efficacy and safety of an innovative nano iron supplement, iron hydroxide adipate tartrate (IHAT), for the treatment of IDA in young children (IHAT-GUT trial). Oral iron is often ineffective due to poor absorption and/or gastrointestinal adverse effects. IHAT is novel since it is effectively absorbed whilst remaining nanoparticulate in the gut, therefore should enable supplementation with fewer symptoms. Methods: IHAT-GUT is a three-arm, double-blind, randomised, placebo-controlled phase II trial conducted in Gambian children 6-35 months of age. The intervention consists of a 12-week supplementation with either IHAT, ferrous sulphate (both at doses bioequivalent to 12.5 mg Fe/day) or placebo. The trial aims to include 705 children with IDA who will be randomly assigned (1:1:1) to each arm. The primary objectives are to test non-inferiority of IHAT in relation to ferrous sulphate at treating IDA, and to test superiority of IHAT in relation to ferrous sulphate and non-inferiority in relation to placebo in terms of diarrhoea incidence and prevalence. Secondary objectives are mechanistic assessments, to test whether IHAT reduces the burden of enteric pathogens, morbidity, and intestinal inflammation, and that it does not cause detrimental changes to the gut microbiome, particularly in relation to Lactobacillaceae, Bifidobacteriaceae and Enterobacteriaceae. Discussion: This trial will test the hypothesis that supplementation with IHAT eliminates iron deficiency and improves haemoglobin levels without inducing gastrointestinal adverse effects. If shown to be the case, this would open the possibility for further testing and use of IHAT as a novel iron source for micronutrient intervention strategies in resource-poor countries, with the ultimate aim to help reduce the IDA global burden. Registration: This trial is registered at clinicaltrials.gov ( NCT02941081).

Hormonal Correlates and Predictors of Nutritional Recovery in Malnourished African Children.

Background: Malnourished children show variable growth responses to nutritional rehabilitation. We aimed to investigate whether these differences could be explained by variations in growth and energy-regulating hormones. Methods: Quasi-experimental study: Children aged 6-24 months in rural Gambia were recruited to controls if weight-for-height z-score (WHZ) > -2 (n = 22), moderate acute malnutrition if WHZ < -2 and > -3 (n = 18) or severe acute malnutrition if WHZ < -3 (n = 20). Plasma hormone and salivary CRP levels were determined by ELISA. Results: In univariable analyses, increases in weight-for-age z-score (WAZ) in malnourished children were positively correlated with insulin (F-ratio 7.8, p = 0.006), C-peptide (F-ratio 12.2, p < 0.001) and cortisol (F-ratio 5.0, p = 0.03). In multivariable analysis, only baseline C-peptide (F-ratio 7.6, p = 0.009) predicted the changes in WAZ over 28 days of interventions. Conclusion: In rural Gambian, malnourished children, although it cannot be used in isolation, baseline C-peptide was a predictor of future response to rehabilitation.

HIV-infection and psychiatric illnesses - A double edged sword that threatens the vision of a contained epidemic: The Greater Stockholm HIV Cohort Study.

CONTEXT: The Greater Stockholm HIV Cohort Study is an initiative to provide longitudinal information regarding the health of people living with HIV. OBJECTIVE: Our aim was to explore the prevalence of HIV and its association with psychiatric co-morbidities. DESIGN, SETTING AND PARTICIPANTS: All patients with a recorded diagnosis of HIV (any position of the ICD-10 codes B20-B24) were identified during the period 2007-2014 and related to the total population in Stockholm by January 1, 2015, N = 2.21 million. The age at diagnosis, gender, and first occurrence of an HIV diagnosis was recorded. Analyses were done by age and gender. Prevalence of psychiatric co-morbidities amongst HIV patients were recorded. MAIN OUTCOME MEASURES: Age-adjusted odds ratios with 95% confidence intervals were calculated with logistic regression for prevalent psychiatric co-morbidities in HIV infected individuals compared to the prevalence in the general population. RESULTS: The total prevalence of HIV was 0.16%; females 0.10% (n = 1134) and males 0.21% (n = 2448). HIV-infected people were more frequently diagnosed with psychiatric illnesses and drug abuse. In females and males with HIV-diagnosis respectively, drug dependence disorder was 7.5 (7.76% vs 1.04%) and 5.1 (10.17% vs 1.98%) times higher, psychotic disorders were 6.3 (2.65% vs 0.42%) and 2.9 (1.43% vs 0.49%) times higher, bipolar disorder was 2.5 (1.41% vs 0.57%) and 3 (1.02% vs 0.34%) times higher, depression diagnosis was 1.5 (8.47% vs 5.82%) and 3.4 (10.17% vs 2.97%) higher, trauma-related disorder was 1.5 (6.00% vs 4.10%) respectively 2.9 (4.45% vs 1.56%) times higher, anxiety disorder was 1.2 (6.88% vs 5.72%) and 2.2 (6.54% vs 2.93%) times higher than in their non-infected peers. CONCLUSION: Despite effective ART, many individuals with HIV have an impaired mental health and a history of drug abuse that may threaten the vision of a contained epidemic.

Oral iron acutely elevates bacterial growth in human serum.

Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses.

Enteric pathogens of food sellers in rural Gambia with incidental finding of Myxobolus species (Protozoa: Myxozoa).

BACKGROUND: Ongoing surveillance of enteric pathogens of public health significance among casual food sellers is undertaken in many resource-limited countries. We report the results of a survey in Kiang West province, The Gambia, and provide an exemplar methodology for such surveys in resource-limited laboratories. METHODS: Unpreserved, unrefrigerated stool samples were subjected to Salmonella, Shigella and agar plate culture for rhabditoid nematodes. Direct microscopy, formalin-ethyl acetate concentration and iron-hematoxylin staining was performed later, following preservation. RESULTS: Of 128 specimens received, no Shigella spp. was recovered, while four serovars of non-typhoidal Salmonella enterica, including Chandans, were isolated. Pathogenic parasitic infections were Necator americanus 10/128 (7.8%), Strongyloides stercoralis 3/128 (2.8%), Blastocystis species 45/128 (35.1%), Entamoeba histolytica complex 19/128 (14.8%) and Giardia intestinalis 4/128 (3.1%). A single case each of Hymenolepis diminuta and S. mansoni infection were detected. In one participant, myxozoan spores identical to those of Myxobolus species were found. CONCLUSIONS: Rare parasitoses and serovars of Salmonella enterica may occur relatively commonly in rural Africa. This paper describes intestinal pathogens found in a cohort of food sellers in such a setting. Furthermore, it describes two parasites rarely recovered from humans and demonstrates the need for methods other than microscopy to detect S. stercoralis infections.

Prevalence, incidence, mortality and co-morbidities amongst human immunodeficiency virus (HIV) patients in Stockholm County, Sweden - the Greater Stockholm HIV Cohort Study.

Our aim was to study the prevalence and incidence of patients with human immunodeficiency virus (HIV) in the general population in Stockholm, Sweden. We also aimed to study mortality among individuals with HIV and to explore co-morbidities. The study population included all living persons who resided in Stockholm County, Sweden, as of 31 December 2012 (N = 2,212,435). Information on all consultations between 2007 and 2012 was obtained from primary health care, specialist outpatient care and inpatient care. Analyses were done by age and gender. All patients with a recorded diagnosis of HIV were included. The prevalence of HIV was calculated using 2012 data. The prevalence of HIV in Stockholm area as per end of December 2012 was as low as 0.1% in females and 0.2% in males, and the annual incidence of HIV continued to decline over the years. In recent years, cancers, diabetes and hypertension were about as common in individuals with HIV as in the general population. Males with HIV had 3- to 4-fold higher age-adjusted odds of being diagnosed with depression and 3-fold higher odds of anxiety disorders and women had 1.6 to 2-fold higher age-adjusted odds of depression and anxiety disorders, than males and females in the general population, respectively. The relatively good somatic health observed in this study could be attributed to nearly optimal HIV therapy in Sweden. The mental health of HIV patients was significantly worse than that in the general population and needs further attention.

Trypanosomosis in The Gambia: prevalence in working horses and donkeys detected by whole genome amplification and PCR, and evidence for interactions between trypanosome species.

BACKGROUND: The Gambia has an increasing population of equidae largely used for agriculture and transportation. A review of cases at The Gambian Horse and Donkey Trust (GHDT) indicated that a common reason for presentation is a poorly defined medical condition often attributed to trypanosomosis. There are few reports describing the prevalence or the range of clinical signs associated with infection with different species of trypanosomes in horses and donkeys, but given the importance of these animals, the role of trypanosomosis requires investigation. RESULTS: In total 241 animals from the Central River Division in The Gambia (183 horses and 58 donkeys) were screened using Whole Genome Amplification (WGA) followed by trypanosome species identification using polymerase chain reaction (PCR). The results indicated overall trypanosome prevalence of 91%; with an infection rate of 31% for Trypanosoma congolense Savannah, 87% for Trypanosoma vivax and 18% for Trypanosoma brucei sp. Multiple species were present in 43% of infections. Microscopy had a good specificity (100%) and positive predictive value (100%) for trypanosome detection, but the sensitivity (20%) and negative predictive value (10.5%) were low relative to PCR-based diagnosis. Infection with T congolense showed the greatest negative effect on packed cell volume (PCV), while infection with T. brucei sp also had a significant, although lesser, negative effect on PCV. In addition, cases positive by microscopy were associated with significantly lower PCV. However, concurrent infection with T. vivax appeared to cause less effect on PCV, compared to animals infected with T. congolense alone. CONCLUSION: The prevalence of Trypanosomosis was high in both horses and donkeys. Infection with T. congolense appeared to have the greatest clinical significance, while T. vivax infection may be of limited clinical significance in this population. Indeed, there is evidence of T. vivax co-infection ameliorating the pathology caused by T. congolense. WGA and PCR allowed a more comprehensive analysis of field infections with the detection of infections below the threshold of microscopy, and provided indications of interactions between parasite species that would otherwise remain undetected. The study raises important questions about the epidemiology of trypanosome infection in relation to disease that require a full scale longitudinal analysis.