Applying 3D Models of Giant Salamanders to Explore Form-Function Relationships in Early Digit-Bearing Tetrapods.

Extant salamanders are used as modern analogs of early digit-bearing tetrapods due to general similarities in morphology and ecology, but the study species have been primarily terrestrial and relatively smaller when the earliest digit-bearing tetrapods were aquatic and an order of magnitude larger. Thus, we created a 3D computational model of underwater walking in extant Japanese giant salamanders (Andrias japonicus) using 3D photogrammetry and open-access graphics software (Blender) to broaden the range of testable hypotheses about the incipient stages of terrestrial locomotion. Our 3D model and software protocol represent the initial stages of an open-access pipeline that could serve as a "one-stop-shop" for studying locomotor function, from creating 3D models to analyzing the mechanics of locomotor gaits.

Effects of meteorological and land surface modeling uncertainty on errors in winegrape ET calculated with SIMS.

Unlabelled: Characterization of model errors is important when applying satellite-driven evapotranspiration (ET) models to water resource management problems. This study examines how uncertainty in meteorological forcing data and land surface modeling propagate through to errors in final ET data calculated using the Satellite Irrigation Management Support (SIMS) model, a computationally efficient ET model driven with satellite surface reflectance values. The model is applied to three instrumented winegrape vineyards over the 2017-2020 time period and the spatial and temporal variation in errors are analyzed.

Paediatric Common Infections Pathways: improving antimicrobial stewardship and promoting ambulation for children presenting with common infections to hospitals in the UK and Ireland.

Paediatric common infection pathways have been developed in collaboration between the BSAC and national paediatric groups, addressing the management of cellulitis, lymphadenitis/lymph node abscess, pneumonia/pleural empyema, pyelonephritis, tonsillitis/peritonsillar abscess, otitis media/mastoiditis, pre-septal/post-septal (orbital) cellulitis, and meningitis. Guidance for the management of a child presenting with a petechial/purpuric rash and the infant under 3 months of age with fever is also provided. The aim of these pathways is to support the delivery of high-quality infection management in children presenting to a hospital.

Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel.

Objective: Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn's and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison.

Design: We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases.

Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial.

Background: The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient.

Methods: This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia.

Expression of the iron hormone hepcidin distinguishes different types of anemia in African children.

Childhood anemia is a major global health problem resulting from multiple causes. Iron supplementation addresses iron deficiency anemia but is undesirable for other types of anemia and may exacerbate infections. The peptide hormone hepcidin governs iron absorption; hepcidin transcription is mediated by iron, inflammation, and erythropoietic signals.

Randomised controlled trial of weekly chloroquine to re-establish normal erythron iron flux and haemoglobin recovery in postmalarial anaemia.

Objective: To determine if low-dose weekly chloroquine (CQ) therapy improves recovery from malaria-associated anaemia.

Design: Proof of concept randomised clinical trial.

Setting: West Kiang District, Lower River Region, The Gambia.

FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study.

Background: Recent studies have described relationships between iron status and fibroblast growth factor-23 (FGF23) but the possible confounding effects of inflammation on iron status have not been considered. The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron status and FGF23 whilst correcting for inflammation and c) to assess the relationship between changes in FGF23 and iron status after supplementation.

Study Design And Methodology: Blood samples from an iron supplementation study in children (n=79) were collected at baseline and after 3 months supplementation with iron sulphate.

Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children.

Iron supplementation strategies in the developing world remain controversial because of fears of exacerbating prevalent infectious diseases. Understanding the conditions in which iron will be absorbed and incorporated into erythrocytes is therefore important. We studied Gambian children with either postmalarial or nonmalarial anemia, who were given oral iron supplements daily for 30 days.

Haptoglobin and sickle cell polymorphisms and risk of active trachoma in Gambian children.

Background: Susceptibility and resistance to trachoma, the leading infectious cause of blindness, have been associated with a range of host genetic factors. In vitro studies of the causative organism, Chlamydia trachomatis, demonstrate that iron availability regulates its growth, suggesting that host genes involved in regulating iron status and/or availability may modulate the risk of trachoma. The objective was to investigate whether haptoglobin (Hp) haplotypes constructed from the functional polymorphism (Hp1/Hp2) plus the functional promoter SNPs -61A-C (rs5471) and -101C-G (rs5470), or sickle cell trait (HbAS, rs334) were associated with risk of active trachoma when stratified by age and sex, in rural Gambian children.

Iron delocalisation in the pathogenesis of malarial anaemia.

There is consensus that the pathophysiology of malaria-associated anaemia is multifactorial, but the precise mechanisms behind many of the haematological changes during malaria remain unclear. In this review, we attempt to build a composite picture of the pathophysiology of malarial anaemia using evidence from experimental, human and animal studies. We propose that cytokine- and hepcidin-mediated iron delocalisation, a principal mechanism in the anaemia of inflammation, plays an important role in the aetiology of malarial anaemia, and can explain some of the clinical and laboratory findings.

Iron incorporation and post-malaria anaemia.

Background: Iron supplementation is employed to treat post-malarial anaemia in environments where iron deficiency is common. Malaria induces an intense inflammatory reaction that stalls reticulo-endothelial macrophagal iron recycling from haemolysed red blood cells and inhibits oral iron absorption, but the magnitude and duration of these effects are unclear.

Methodology/principal Findings: We examined the red blood cell incorporation of oral administered stable isotopes of iron and compared incorporation between age matched 18 to 36 months old children with either anaemia post-malaria (n = 37) or presumed iron deficiency anaemia alone (n = 36).

Iron metabolism and malaria.

Recent evidence from a large, randomized, controlled trial has suggested that the universal administration of iron to children in malaria-endemic areas is associated with an increase in adverse health outcomes. The purpose of this paper is to summarize the available ecologic and intervention trials related to iron and malaria in children, and to set these against current knowledge of the biology of host-pathogen interactions involving iron metabolism. We conclude that, although not fully consistent, the balance of evidence confirms that administration of iron (usually in combination with folic acid) increases the incidence of malaria when given without prophylaxis and in the absence of universal access to treatment.

Haptoglobin genotype, anaemia and malaria in Gambian children.

Objective: To retest our previous finding that the haptoglobin (Hp) 22 genotype is associated with seasonal anaemia, and to investigate the role of malaria in this effect.

Methods: Haemoglobin (Hb) and peripheral parasitaemia were assessed at pre- and post-malarial season cross-sectional surveys in rural Gambian children aged 10-72 months. Between the surveys, active longitudinal surveillance was conducted to detect febrile episodes.

Effectiveness of an early supplementation scheme of high-dose vitamin A versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial.

Background: Most developing countries have adopted a standard WHO dosing schedule for vitamin A supplementation. However, in 2002 the International Vitamin A Consultative Group (IVACG) Annecy Accord recommended a new high-dose regimen for mothers and infants. Our aim was to test whether the new high-dose regimen of vitamin A supplementation would increase maternal and infant plasma vitamin A, reduce infant Helicobacter pylori infection and nasopharyngeal pneumococcal carriage, and improve infant gut epithelial integrity.

Evaluation of 13C-urea breath test and fecal antigen immunoassay to detect Helicobacter pylori infection in Gambian infants.

Helicobacter pylori colonization was measured by [13C]-urea breath test in 198 Gambian infants and by fecal enzyme-linked immunosorbent assay in 52 of the 198 at ages 2, 5, and 12 months. By 12 months there was good concordance between tests; 33 of 44 (75%) test results were positive by enzyme-linked immunosorbent assay, and 29 of 44 (66%) test results were positive by urea breath test. H.

Host-pathogen interactions: the role of iron.

Iron is essential for both host and pathogen, and complex systems of acquisition and utilization have evolved in competition. Our increasing knowledge of the basic mechanisms of homeostasis and their adaptation during deficiency, overload, and infection indicate that iron is a key regulator of host pathogen interactions. This review concentrated on the clinical and public health aspects of the interaction between the iron acquisition mechanisms of select pathogens of public health importance with host iron homeostasis.

Haplotype association between haptoglobin (Hp2) and Hp promoter SNP (A-61C) may explain previous controversy of haptoglobin and malaria protection.

Background: Malaria is one of the strongest recent selective pressures on the human genome, as evidenced by the high levels of varying haemoglobinopathies in human populations-despite the increased risk of mortality in the homozygous states. Previously, functional polymorphisms of Hp, coded by the co-dominant alleles Hp1 and Hp2, have been variously associated with several infectious diseases, including malaria susceptibility.

Methodology/principal Findings: Risk of a clinical malarial episode over the course of a malarial transmission season was assessed using active surveillance in a cohort of Gambian children aged 10-72 months.