Assessment of blood levels of heavy metals including lead and manganese in healthy children living in the Katanga settlement of Kampala, Uganda.

BACKGROUND: Exposure to environmental heavy metals is common among African children. Although many of these metals are known neurotoxicants, to date, monitoring of this exposure is limited, even in countries such as Uganda that are undergoing rapid industrialization. An assessment of the burden and potential causes of metal exposure is a critical first step in gauging the public health burden of metal exposure and in guiding its elimination. METHODS: In May 2016, we enrolled 100 children between the ages of 6 and 59 months living in the Katanga urban settlement of Kampala, Uganda. We measured whole blood concentrations of antimony, arsenic, barium, cadmium, cesium, chromium, cobalt, copper, lead, manganese, nickel, selenium, and zinc. Applying reference cutoffs, we identified metals whose prevalence of elevated blood concentrations was > 10%. We also administered an environmental questionnaire to each child's caregiver to assess potential exposures, including source of drinking water, cooking location and fuel, materials used for roof, walls, and floor, and proximity to potential pollution sources such as main roads, garbage landfills, and fuel stations. We compared log-transformed blood metal concentrations by exposure category, using t-test for dichotomous comparisons and ANOVA for comparisons of three categories, using Tukeys test to adjust for multiple comparisons. RESULTS: The prevalence of high blood levels was elevated for six of the metals: antimony (99%), copper (12%), cadmium (17%), cobalt (19.2%), lead (97%), and manganese (36.4%). Higher blood manganese was significantly associated with having cement walls (p = 0.04) or floors (p = 0.04). Cadmium was greater among children who attended school (< 0.01), and cobalt was higher among children who lived near a garbage landfill (p = 0.01). CONCLUSIONS: Heavy metal exposure is prevalent in the Katanga settlement and may limit neurodevelopment of children living there. Future studies are needed to definitively identify the sources of exposure and to correct potential nutritional deficiencies that may worsen metal absorption

Deletion of Trim28 in committed adipocytes promotes obesity but preserves glucose tolerance.

The effective storage of lipids in white adipose tissue (WAT) critically impacts whole body energy homeostasis. Many genes have been implicated in WAT lipid metabolism, including tripartite motif containing 28 (Trim28), a gene proposed to primarily influence adiposity via epigenetic mechanisms in embryonic development. However, in the current study we demonstrate that mice with deletion of Trim28 specifically in committed adipocytes, also develop obesity similar to global Trim28 deletion models, highlighting a post-developmental role for Trim28. These effects were exacerbated in female mice, contributing to the growing notion that Trim28 is a sex-specific regulator of obesity. Mechanistically, this phenotype involves alterations in lipolysis and triglyceride metabolism, explained in part by loss of Klf14 expression, a gene previously demonstrated to modulate adipocyte size and body composition in a sex-specific manner. Thus, these findings provide evidence that Trim28 is a bona fide, sex specific regulator of post-developmental adiposity and WAT function

Prevalence of plasmodium falciparum in active conflict areas of eastern Burma: a summary of cross-sectional data

BACKGROUND: Burma records the highest number of malaria deaths in southeast Asia and may represent a reservoir of infection for its neighbors, but the burden of disease and magnitude of transmission among border populations of Burma remains unknown. METHODS: Plasmodium falciparum (Pf) parasitemia was detected using a HRP-II antigen based rapid test (Paracheck-Pf(R)). Pf prevalence was estimated from screenings conducted in 49 villages participating in a malaria control program, and four retrospective mortality cluster surveys encompassing a sampling frame of more than 220,000. Crude odds ratios were calculated to evaluate Pf prevalence by age, sex, and dry vs. rainy season. RESULTS: 9,796 rapid tests were performed among 28,410 villagers in malaria program areas through four years (2003: 8.4%, 95% CI: 8.3 - 8.6; 2004: 7.1%, 95% CI: 6.9 - 7.3; 2005:10.5%, 95% CI: 9.3 - 11.8 and 2006: 9.3%, 95% CI: 8.2 - 10.6). Children under 5 (OR = 1.99; 95% CI: 1.93 - 2.06) and those 5 to 14 years (OR = 2.24, 95% CI: 2.18 - 2.29) were more likely to be positive than adults. Prevalence was slightly higher among females (OR = 1.04, 95% CI: 1.02 - 1.06) and in the rainy season (OR = 1.48, 95% CI: 1.16 - 1.88). Among 5,538 rapid tests conducted in four cluster surveys, 10.2% were positive (range 6.3%, 95% CI: 3.9 - 8.8; to 12.4%, 95% CI: 9.4 - 15.4). CONCLUSION: Prevalence of plasmodium falciparum in conflict areas of eastern Burma is higher than rates reported among populations in neighboring Thailand, particularly among children. This population serves as a large reservoir of infection that contributes to a high disease burden within Burma and likely constitutes a source of infection for neighboring regions

Cross-reactive monoclonal antibodies to multiple HIV-1 subtype and SIVcpz envelope glycoproteins

The extraordinarily high level of genetic variation of HIV-1 env genes poses a challenge to obtain antibodies that cross-react with multiple subtype Env glycoproteins. To determine if cross-reactive monoclonal antibodies (mAbs) to highly conserved epitopes in HIV-1 envelope glycoproteins can be induced, we immunized mice with wild-type or consensus HIV-1 Env proteins and characterized a panel of ten mAbs that reacted with varying breadth to subtypes A, B, C, D, F, G, CRF01_AE and a highly divergent SIVcpzUS Env proteins by ELISA and Western blot analysis. Two mAbs (3B3 and 16H3) cross–reacted with all tested Env proteins, including SIVcpzUS Env. Surface plasmon resonance analyses showed both 3B3 and 16H3 bound Env proteins with high affinity. However, neither neutralized primary HIV-1 pseudoviruses. These data indicate that broadly-reactive non-neutralizing monoclonal antibodies can be elicited, but that the conserved epitopes that they recognize are not present on functional virion trimers. Nonetheless, such mAbs represent valuable reagents to study the biochemistry and structural biology of Env protein oligomers

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Piloting a Developmental Screening Tool Adapted for East African Children

The study is about Piloting a Developmental Screening Tool Adapted for East African ChildrenThere is a need for developmental screening that is easily administered in resource-poor settings. We hypothesized that known risk factors would predict failed developmental screening on an adapted screening tool in East African children living in poverty. The sample included 100 healthy Ugandan children aged 6–59 months. We adapted a parent-reported developmental screener based on the Child Development Review chart. The primary outcome was failure to meet age-appropriate milestones for any developmental domain. Venous blood was analyzed for lead, and caregivers completed a demographics questionnaire. We used multivariate logistic regression models to determine if elevated blood lead and stunting predicted failure on the screener, controlling for maternal education level, age in months past the lower bound of the child’s developmental age group, and absence of home electricity. In the sample, 14% (n = 14) of children failed one or more milestones on the screener. Lead levels or stunting did not predict failing the screener after controlling for covariates. Though this tool was feasibly administered, it did not demonstrate preliminary construct validity and is not yet recommended for screening in high-risk populations. Future research should include a larger sample size and cognitive interviews to ensure it is contextually relevant

Association of Prenatal and Perinatal Exposures to Particulate Matter With Changes in Hemoglobin A1c Levels in Children Aged 4 to 6 Years.

Importance: Environmental risk factors for childhood type 2 diabetes, an increasing global problem, are understudied. Air pollution exposure has been reported to be a risk factor for this condition. Objective: To examine the association between prenatal and perinatal exposures to fine particulate matter with a diameter less than 2.5 μm (PM2.5) and changes in hemoglobin A1c (HbA1c), a measure of glycated hemoglobin and marker of glucose dysregulation, in children aged 4 to 7 years. Design, Setting, and Participants: The Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) study, a birth cohort study conducted in Mexico City, Mexico, recruited pregnant women from July 3, 2007, to February 21, 2011, through public health maternity clinics. The present analysis includes 365 mother-child pairs followed up until the child was approximately 7 years of age. This study included data from only study visits at approximately 4 to 5 years (visit 1) and 6 to 7 years (visit 2) post partum because HbA1c levels were not measured in earlier visits. The data were analyzed from March 11, 2018, to May 3, 2019. Exposures: Daily PM2.5 exposure estimates at participants\u27 home addresses from 4 weeks prior to mothers\u27 date of last menstrual period (LMP), a marker of the beginning of pregnancy, to 12 weeks after the due date. Exposure was estimated from satellite measurements and calibrated against ground PM2.5 measurements, land use, and meteorological variables. Main Outcomes and Measures: Outcomes included HbA1c levels at 4 to 5 years and 6 to 7 years of age, and the change in the level from the former age group to the latter. Results: The sample included 365 children, of whom 184 (50.4%) were girls. The mean (range) age of the children was 4.8 (4.0-6.4) years at visit 1, and 6.7 (6.0-9.7) years at visit 2. At the time of delivery, the mean (range) age of the mothers was 27.7 (18.3-44.4) years, with a mean (range) prepregnancy body mass index of 26.4 (18.5-43.5). The mean (SD) prenatal PM2.5 exposure (22.4 μg/m3 [2.7 μg/m3]) was associated with an annual increase in HbA1c levels of 0.25% (95% CI, 0.004%-0.50%) from age 4 to 5 years to 6 to 7 years compared with exposure at 12 μg/m3, the national regulatory standard in Mexico. Sex-specific effect estimates were statistically significant for girls (β = 0.21%; 95% CI, 0.10% to 0.32%) but not for boys (β = 0.31%; 95% CI, -0.09% to 0.72%). The statistically significant windows of exposure were from week 28 to 50.6 after the mother\u27s LMP for the overall cohort and from week 11 to the end of the study period for girls. Lower HbA1c levels were observed at age 4 to 5 years in girls (β = -0.72%; 95% CI, -1.31% to -0.13%, exposure window from week 16 to 37.3) and boys (β = -0.98%; 95% CI, -1.70% to -0.26%, exposure window from the beginning of the study period to week 32.7), but no significant association was found in the overall cohort (β = -0.13%; 95% CI, -1.27% to 1.01%). There was no significant association between PM2.5 exposure and HbA1c level at age 6 to 7 years in any group. Conclusions and Relevance: The findings of this study suggest that prenatal and perinatal exposures to PM2.5 are associated with changes in HbA1c, which are indicative of glucose dysregulation, in early childhood. Further research is needed because this finding may represent a risk factor for childhood or adolescent diabetes

Piloting a Developmental Screening Tool Adapted for East African Children.

There is a need for developmental screening that is easily administered in resource-poor settings. We hypothesized that known risk factors would predict failed developmental screening on an adapted screening tool in East African children living in poverty. The sample included 100 healthy Ugandan children aged 6⁻59 months. We adapted a parent-reported developmental screener based on the Child Development Review chart. The primary outcome was failure to meet age-appropriate milestones for any developmental domain. Venous blood was analyzed for lead, and caregivers completed a demographics questionnaire. We used multivariate logistic regression models to determine if elevated blood lead and stunting predicted failure on the screener, controlling for maternal education level, age in months past the lower bound of the child\u27s developmental age group, and absence of home electricity. In the sample, 14%