Publications

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  1. Neonatal IL-4 exposure decreases adipogenesis of male rats into adulthood

    The cytokine interleukin 4 (IL-4) can increase beige adipogenesis in adult rodents. However, neonatal animals use a distinct adipocyte precursor compartment for adipogenesis as compared with adults. In this study, we address whether IL-4 can induce persistent effects on adipose tissue when administered subcutaneously in the interscapular region during the neonatal period in Sprague-Dawley rats. We injected IL-4 into neonatal male rats during postnatal days 1-6, followed by analysis of adipose...
  2. Correction to: Incentivizing appropriate malaria case management in the private sector: a study protocol for two linked cluster randomized controlled trials to evaluate provider- and client-focused interventions in western Kenya and Lagos, Nigeria

    No abstract
  3. The Role of Adipocyte Precursors in Development and Obesity

    Maintenance of adipocyte precursors is critical for regulating metabolism and preventing obesity related disease. These precursors have been immortalized and studied in cellular models as well as-more recently-in animal models. However, little is known about adipocyte precursors from animals of different ages. Most research has focused on adipocyte precursors during obesity. This review goes over the most recent reports of adipocyte precursors during development and in adulthood. Some of these...
  4. Cerebrospinal fluid pterins, pterin-dependent neurotransmitters, and mortality in pediatric cerebral malaria

    CONCLUSION: Despite low systemic BH4, CSF BH4 was elevated and associated with increased odds of survival in CM. Coma in malaria is not explained by deficiency of BH4-dependent neurotransmitters. Elevated CSF neopterin was 100% sensitive for CM diagnosis, and warrants further assessment of its clinical utility for ruling out CM in malaria-endemic areas.
  5. Immune dysfunction in developmental programming of type 2 diabetes mellitus

    Intrauterine growth restriction (IUGR) is a common complication of pregnancy and increases the risk of the offspring developing type 2 diabetes mellitus (T2DM) later in life. Alterations in the immune system are implicated in the pathogenesis of IUGR-induced T2DM. The development of the fetal immune system is a delicate balance as it must remain tolerant of maternal antigens whilst also preparing for the post-birth environment. In addition, the fetal immune system is susceptible to an altered...
  6. Incentivizing appropriate malaria case management in the private sector: a study protocol for two linked cluster randomized controlled trials to evaluate provider- and client-focused interventions in western Kenya and Lagos, Nigeria

    CONCLUSIONS: If our study demonstrates that malaria case management can be improved in the retail sector, it could reduce overconsumption of ACTs and enhance targeting of publicly funded treatment reimbursements, lowering the economic barrier to appropriate diagnosis and treatment for patients with malaria.
  7. Exposure to high fructose corn syrup during adolescence in the mouse alters hepatic metabolism and the microbiome in a sex-specific manner

    KEY POINTS: The prevalence of obesity and non-alcoholic fatty liver disease in children is dramatically increasing at the same time as consumption of foods with a high sugar content. Intake of high fructose corn syrup (HFCS) is a possible aetiology as it is thought to be more lipogenic than glucose. In a mouse model, HFCS intake during adolescence increased fat mass and hepatic lipid levels in male and female mice. However, only males showed impaired glucose tolerance. Multiple metabolites...
  8. Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta

    Placental insufficiency is implicated in spontaneous preterm birth (SPTB) associated with intrauterine inflammation. We hypothesized that intrauterine inflammation leads to deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy ultimately resulting in SPTB. Using a mouse model of intrauterine inflammation that leads to preterm delivery, we performed RNA-seq and metabolomics studies to assess how intrauterine inflammation alters gene expression...
  9. Subsidise the test, the treatment or both? Results of an individually randomised controlled trial of the management of suspected malaria fevers in the retail sector in western Kenya

    CONCLUSION: Test dependent ACT subsidies may contribute to ACT targeting. However, in this context, high confidence in the accuracy of RDTs and reliable supplies of RDTs and ACTs likely played a greater role in testing uptake and adherence to test results.
  10. Transcriptomic and Quantitative Proteomic Profiling Reveals Signaling Pathways Critical for Pancreatic Islet Maturation

    Pancreatic β-cell dysfunction and reduced insulin secretion play a key role in the pathogenesis of diabetes. Fetal and neonatal islets are functionally immature and have blunted glucose responsiveness and decreased insulin secretion in response to stimuli and are far more proliferative. However, the mechanisms underlying functional immaturity are not well understood. Pancreatic islets are composed of a mixture of different cell types, and the microenvironment of islets and interactions between...
  11. Statistical properties of Continuous Composite Outcomes: Implications for clinical trial design

    Statistical efficiency can be gained in clinical trials by using composites of time-to-event outcomes when the individual component outcomes have low event rates. However, the utility of continuous composite outcome measures is not as clear. Efficiency can be either gained or lost by using a continuous composite outcome measure depending on several factors, including the strength of correlation between the component outcomes and the size of the treatment effect on each component. In this article...
  12. Environmental and Aerosolized Severe Acute Respiratory Syndrome Coronavirus 2 Among Hospitalized Coronavirus Disease 2019 Patients

    During April and May 2020, we studied 20 patients hospitalized with coronavirus disease 2019 (COVID-19), their hospital rooms (fomites and aerosols), and their close contacts for molecular and culture evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among >400 samples, we found molecular evidence of virus in most sample types, especially the nasopharyngeal (NP), saliva, and fecal samples, but the prevalence of molecular positivity among fomites and aerosols was low. The...
  13. Paternal bisphenol A exposure in mice impairs glucose tolerance in female offspring

    Humans are ubiquitously exposed bisphenol A (BPA), and epidemiological studies show a positive association between BPA exposure and diabetes risk, but the impact of parental exposure on offspring diabetes risk in humans is unknown. Our previous studies in mice show disruption of metabolic health upon maternal BPA exposure. The current study was undertaken to determine whether exposure in fathers causes adverse metabolic consequences in offspring. Male C57BL/6 J mice were exposed to BPA in the...
  14. A multiple baseline study of a brief alcohol reduction and family engagement intervention for fathers in Kenya

    CONCLUSION: Results provide preliminary evidence that a BA-MI intervention developed for lay providers may reduce alcohol use and improve family outcomes among men in Kenya. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
  15. Maternal and neonatal response to COVID-19

    The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to maternal and newborn health has yet to be determined. Several reports suggest pregnancy does not typically increase the severity of maternal disease; however, cases of preeclampsia and preterm birth have been infrequently reported. Reports of placental infection and vertical transmission are rare. Interestingly, despite lack of SARS-CoV-2 placenta infection, there are several reports of significant abnormalities in...
  16. Environmental bioaerosol surveillance as an early warning system for pathogen detection in North Carolina swine farms: A pilot study

    Disease outbreaks can readily threaten swine production operations sometimes resulting in large economic losses. Pathogen surveillance in swine farms can be an effective approach for the early identification of new disease threats and the mitigation of transmission before broad dissemination among a herd occurs. Non-invasive environmental bioaerosol sampling could be an effective and affordable approach for conducting routine surveillance in farms, providing an additional tool for farmers to...
  17. Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats

    Intrauterine growth retardation (IUGR), which induces epigenetic modifications and permanent changes in gene expression, has been associated with the development of type 2 diabetes. Using a rat model of IUGR, we performed ChIP-Seq to identify and map genome-wide histone modifications and gene dysregulation in islets from 2- and 10-week rats. IUGR induced significant changes in the enrichment of H3K4me3, H3K27me3, and H3K27Ac marks in both 2-wk and 10-wk islets, which were correlated with...
  18. The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth

    The placenta is metabolically active and supports the growth of the fetus. We hypothesize that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may result in spontaneous preterm birth (SPTB). To explore this hypothesis, we performed a nested cased control study of metabolomic signatures in placentas from women with SPTB (36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation). To control for the effects of gestational...
  19. Reducing Th2 inflammation through neutralizing IL-4 antibody rescues myelination in IUGR rat brain

    CONCLUSIONS: In this study, we have identified inflammation as a factor in the decrease in myelin seen in an animal model of IUGR. IL-4, an inflammatory protein often thought to be protective in the adult, is specifically increased, and treatment of these animals to prevent this increase ameliorates white matter damage. Our results suggest that the immune system plays a role in IUGR that is different in the perinatal period than in the adult and preventing this exaggerated Th2 response may be a...
  20. Correction to: Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  21. Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study

    In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor...
  22. High Risk of Influenza Virus Infection Among Swine Workers: Examining a Dynamic Cohort in China

    CONCLUSIONS: While some of the observed increased risk against swine viruses may have been explained by exposure to human influenza strains, study data suggest that even with elevated preexisting antibodies, swine-exposed workers were at high risk of infection with enzootic swine influenza A viruses.
  23. Effect of parental origin of damaging variants in pro-angiogenic genes on fetal growth in patients with congenital heart defects: Data and analyses

    The placenta is a highly vascular structure composed of both maternal and fetal elements. We have determined that damaging variants in genes responsible for the positive regulation of angiogenesis (PRA) (GO:0045766) that are inherited by the fetus impair fetal growth and placental function in pregnancies involving critical congenital cardiac defects (Russell et al., 2019). In this dataset, we present the specific genetic variants identified, describe the parental origin of each variant where...
  24. Environmental neglect: endocrine disruptors as underappreciated but potentially modifiable diabetes risk factors

    Type 2 diabetes prevalence is increasing dramatically across the globe, imposing a tremendous toll on individuals and healthcare systems. Reversing these trends requires comprehensive approaches to address both classical and emerging diabetes risk factors. Recently, environmental toxicants acting as endocrine-disrupting chemicals (EDCs) have emerged as novel metabolic disease risk factors. EDCs implicated in diabetes pathogenesis include various inorganic and organic molecules of both natural...
  25. Damaging Variants in Proangiogenic Genes Impair Growth in Fetuses with Cardiac Defects

    CONCLUSIONS: Damaging variants in proangiogenic genes may impact placental function and are associated with impaired fetal growth in pregnancies involving a fetus with congenital heart defect.
  26. A CACE for assessing non-compliance: Addressing non-compliance in randomised controlled trials

    No abstract
  27. Dysregulation of Neuronal Genes by Fetal-Neonatal Iron Deficiency Anemia Is Associated with Altered DNA Methylation in the Rat Hippocampus

    Early-life iron deficiency results in long-term abnormalities in cognitive function and affective behavior in adulthood. In preclinical models, these effects have been associated with long-term dysregulation of key neuronal genes. While limited evidence suggests histone methylation as an epigenetic mechanism underlying gene dysregulation, the role of DNA methylation remains unknown. To determine whether DNA methylation is a potential mechanism by which early-life iron deficiency induces gene...
  28. Use of clinical algorithms and rapid influenza testing to manage influenza-like illness: a cost-effectiveness analysis in Sri Lanka

    CONCLUSION: Clinical prediction tools and targeted rapid influenza testing may be cost-saving strategies in Sri Lanka when accounting for the societal cost of antimicrobial resistance.
  29. Perceptions of chest pain and healthcare seeking behavior for chest pain in northern Tanzania: A community-based survey

    CONCLUSIONS: There is little community awareness of cardiac causes of chest pain in northern Tanzania, and most adults reported that they would not present to a hospital for this symptom. There is an urgent need for educational interventions to address this knowledge deficit and guide appropriate care-seeking behavior.
  30. Knowledge of myocardial infarction symptoms and perceptions of self-risk in Tanzania

    CONCLUSIONS: In northern Tanzania, knowledge of myocardial infarction symptoms is poor among all segments of the population and only a minority of residents perceive themselves to be at risk of this disease. Educational interventions regarding ischemic heart disease are urgently needed.
  31. Transgenerational effects of maternal bisphenol A exposure on offspring metabolic health - Erratum

    No abstract
  32. Self-medication with non-prescribed pharmaceutical agents in an area of low malaria transmission in northern Tanzania: a community-based survey

    CONCLUSIONS: Self-treatment with antimicrobials in an area of low malaria transmission intensity was uncommon and self-treatment with antihypertensives and antihyperglycemics was rare.
  33. Transgenerational effects of maternal bisphenol: a exposure on offspring metabolic health

    Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2)...
  34. A Randomized Trial of an Online Risk Reduction Intervention for Young Black MSM

    HealthMpowerment.org (HMP), is a mobile optimized, online intervention to reduce sexual risk behaviors among HIV-positive and HIV-negative young Black men who have sex with men (BMSM) by providing information and resources, fostering social support, and including game-based elements. A randomized controlled trial with 474 young BMSM compared HMP to an information-only control website. The rate of self-reported condomless anal intercourse (CAI) at 3-months was 32% lower in the intervention group...
  35. Oxidative Stress, Intrauterine Growth Restriction, and Developmental Programming of Type 2 Diabetes

    Intrauterine growth restriction (IUGR) leads to reduced birth weight and the development of metabolic diseases such as Type 2 diabetes in adulthood. Mitochondria dysfunction and oxidative stress are commonly found in key tissues (pancreatic islets, liver, and skeletal muscle) of IUGR individuals. In this review, we explore the role of oxidative stress in IUGR-associated diabetes etiology.
  36. A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes

    Use of oral agents to treat gestational diabetes mellitus remains controversial. Recent recommendations from the Society for Maternal-Fetal Medicine assert that metformin may be a safe first-line alternative to insulin for gestational diabetes mellitus treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of metformin use during pregnancy. Fetal concentrations of metformin are equal to maternal, and metformin can inhibit growth, suppress...
  37. Mice exposed to bisphenol A exhibit depressive-like behavior with neurotransmitter and neuroactive steroid dysfunction

    Fetal exposure to endocrine disrupting chemicals (EDCs) has been associated with adverse neurobehavioral outcomes across the lifespan and can persist across multiple generations of offspring. However, the underlying mechanisms driving these changes are not well understood. We investigated the molecular perturbations associated with EDC-induced behavioral changes in first (F1) and second (F2) filial generations, using the model EDC bisphenol A (BPA). C57BL/6J dams were exposed to BPA from...
  38. Adverse effects of small for gestational age differ by gestational week among very preterm infants

    CONCLUSION: The excess risk for neonatal morbidity and mortality associated with being born SGA varies by adverse outcome and gestational age.
  39. Offspring sex impacts DNA methylation and gene expression in placentae from women with diabetes during pregnancy

    CONCLUSIONS/INTERPRETATION: These findings begin to explain mechanisms responsible for the increased risk for obesity and type 2 diabetes in offspring of mothers with DDP.
  40. The impact of the maternal-foetal environment on outcomes of surgery for congenital heart disease in neonates

    CONCLUSIONS: An impaired MFE is common in pregnancies in which the foetus has congenital heart disease. After cardiac surgery in neonates, the presence of an impaired MFE was associated with lower survival at 36 months of age for the entire cohort and for the subgroup with hypoplastic left heart syndrome.