Assessing lead exposure sources at the property scale in Indianapolis

Background and Hypothesis:  Lead (Pb) was phased out of paint and gasoline over 40 years ago due to neurotoxicity in humans, but has persisted in soils and poses a legacy threat to many.  The Indianapolis 46218 zip code has had >10% children exhibiting Pb poisoning. This zip code has had historically high soil Pb levels, and is undergoing redevelopment. We hypothesize that redevelopment will act to re-expose new populations of people to the legacy Pb present in the area.    Experimental Design or Project Methods:  We sampled 5 parks and 7 playgrounds.  Stratified random sampling based on permit type was used to select properties from 25 issued and 25 closed permits from 527 identified demolition permits.  Nearby residential properties were selected, with permission of residents. Samples were taken near the dripline of the house, front yard, and street, or from each quadrant at sites without houses. Samples were dried, crushed, sieved to 150 microns, and assessed using X-Ray Fluorescence.    Results:  Mean Pb levels from driplines (1026 ppm) were significantly higher than streets (p=0.001), parks (p=0.002), yards (p=0.001), and demolition sites (p=0.000).  Pb concentrations for playgrounds had the lowest median lead levels (42 ppm), while dripline samples had the highest (289 ppm).  The EPA standard for children’s play areas is 400 ppm.  Conclusion and Potential Impact:  While all samples from playgrounds were below 400 ppm, children are also likely playing at their homes, where no legislation effectively protects them from potential Pb poisoning and values were found above 400 ppm.  An immediate outcome from this project is the education.  Residents who agreed to testing (n=42) received results of the test and guidelines to prevent Pb poisoning.  More work remains to ensure preventive rather than reactive strategies are employed to protect children’s health

Assessing Lead Exposure Sources at the Property Scale in Indianapolis

Background: Lead (Pb) was phased out of paint and gasoline over 40 years ago due to neurotoxicity in humans, but has persisted in soils and poses a legacy threat to many. The Indianapolis 46218 zip code has had >10% children exhibiting Pb poisoning. This zip code has had historically high soil Pb levels, and is undergoing redevelopment. We hypothesize that redevelopment will act to re-expose new populations of people to the legacy Pb present in the area. Methods: We sampled 5 parks and 7 playgrounds. Stratified random sampling based on permit type was used to select properties from 25 issued and 25 closed permits from 527 identified demolition permits. Nearby residential properties were selected, with permission of residents. Samples were taken near the dripline of the house, front yard, and street, or from each quadrant at sites without houses. Samples were dried, crushed, sieved to 150 microns, and assessed using X-Ray Fluorescence. Results: Mean Pb levels from driplines (1026 ppm) were significantly higher than streets (p=0.001), parks (p=0.002), yards (p=0.001), and demolition sites (p=0.000). Pb concentrations for playgrounds had the lowest median lead levels (42 ppm), while dripline samples had the highest (289 ppm). The EPA standard for children’s play areas is 400 ppm. Conclusion: While all samples from playgrounds were below 400 ppm, children are also likely playing at their homes, where no legislation effectively protects them from potential Pb poisoning and values were found above 400 ppm. An immediate outcome from this project is the education. Residents who agreed to testing (n=42) received results of the test and guidelines to prevent Pb poisoning. More work remains to ensure preventive rather than reactive strategies are employed to protect children’s health

Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples — including Xist, which orchestrates X chromosome inactivation — has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus

LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice

Leishmania spp. are protozoan single-cell parasites that are transmitted to humans by the bite of an infected sand fly, and can cause a wide spectrum of disease, ranging from self-healing skin lesions to potentially fatal systemic infections. Certain species of Leishmania that cause visceral (systemic) disease are a source of significant mortality worldwide. Here, we use a mouse model of visceral Leishmania infection to investigate the effect of a host gene called LXR. The LXRs have demonstrated important functions in both cholesterol regulation and inflammation. These processes, in turn, are closely related to lipid metabolism and the development of atherosclerosis. LXRs have also previously been shown to be involved in protection against other intracellular pathogens that infect macrophages, including certain bacteria. We demonstrate here that LXR is involved in susceptibility to Leishmania, as animals deficient in the LXR gene are much more resistant to infection with the parasite. We also demonstrate that macrophages lacking LXR kill parasites more readily, and make higher levels of nitric oxide (an antimicrobial mediator) and IL-1β (an inflammatory cytokine) in response to Leishmania infection. These results could have important implications in designing therapeutics against this deadly pathogen, as well as other intracellular microbial pathogens

NGF Is an Essential Survival Factor for Bronchial Epithelial Cells during Respiratory Syncytial Virus Infection

Background: Overall expression of neurotrophins in the respiratory tract is upregulated in infants infected by the respiratory syncytial virus (RSV), but it is unclear where (structural vs. inflammatory cells, upper vs. lower airways) and why, these changes occur. We analyzed systematically the expression of neurotrophic factors and receptors following RSV infection of human nasal, tracheal, and bronchial epithelial cells, and tested the hypothesis that neurotrophins work as innate survival factors for infected respiratory epithelia. Methodology: Expression of neurotrophic factors (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF) and receptors (trkA, trkB, p75) was analyzed at the protein level by immunofluorescence and flow cytometry and at the mRNA level by real-time PCR. Targeted siRNA was utilized to blunt NGF expression, and its effect on virus-induced apoptosis/ necrosis was evaluated by flow cytometry following annexin V/7-AAD staining. Principal Findings: RSV infection was more efficient in cells from more distal (bronchial) vs. more proximal origin. In bronchial cells, RSV infection induced transcript and protein overexpression of NGF and its high-affinity receptor trkA, with concomitant downregulation of the low-affinity p75 NTR. In contrast, tracheal cells exhibited an increase in BDNF, trkA and trkB, and nasal cells increased only trkA. RSV-infected bronchial cells transfected with NGF-specific siRNA exhibited decreased trkA and increased p75 NTR expression. Furthermore, the survival of bronchial epithelial cells was dramaticall

The effects of acute CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college students

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to examine the effect of acute and prolonged (4-weeks) ingestion of a supplement designed to improve reaction time and subjective measures of alertness, energy, fatigue, and focus compared to placebo.</p> <p>Methods</p> <p>Nineteen physically-active subjects (17 men and 2 women) were randomly assigned to a group that either consumed a supplement (21.1 ± 0.6 years; body mass: 80.6 ± 9.4 kg) or placebo (21.3 ± 0.8 years; body mass: 83.4 ± 18.5 kg). During the initial testing session (T1), subjects were provided 1.5 g of the supplement (CRAM; α-glycerophosphocholine, choline bitartrate, phosphatidylserine, vitamins B3, B6, and B12, folic acid, L-tyrosine, anhydrous caffeine, acetyl-L-carnitine, and naringin) or a placebo (PL), and rested quietly for 10-minutes before completing a questionnaire on subjective feelings of energy, fatigue, alertness and focus (PRE). Subjects then performed a 4-minute quickness and reaction test followed by a 10-min bout of exhaustive exercise. The questionnaire and reaction testing sequence was then repeated (POST). Subjects reported back to the lab (T2) following 4-weeks of supplementation and repeated the testing sequence.</p> <p>Results</p> <p>Reaction time significantly declined (p = 0.050) between PRE and POST at T1 in subjects consuming PL, while subjects under CRAM supplementation were able to maintain (p = 0.114) their performance. Significant performance declines were seen in both groups from PRE to POST at T2. Elevations in fatigue were seen for CRAM at both T1 and T2 (p = 0.001 and p = 0.000, respectively), but only at T2 for PL (p = 0.029). Subjects in CRAM maintained focus between PRE and POST during both T1 and T2 trials (p = 0.152 and p = 0.082, respectively), whereas significant declines in focus were observed between PRE and POST in PL at both trials (p = 0.037 and p = 0.014, respectively). No difference in alertness was seen at T1 between PRE and POST for CRAM (p = 0.083), but a significant decline was recorded at T2 (p = 0.005). Alertness was significantly lower at POST at both T1 and T2 for PL (p = 0.040 and p = 0.33, respectively). No differences in any of these subjective measures were seen between the groups at any time point.</p> <p>Conclusion</p> <p>Results indicate that acute ingestion of CRAM can maintain reaction time, and subjective feelings of focus and alertness to both visual and auditory stimuli in healthy college students following exhaustive exercise. However, some habituation may occur following 4-weeks of supplementation.</p

Co-habiting amphibian species harbor unique skin bacterial communities in wild populations

Although all plant and animal species harbor microbial symbionts, we know surprisingly little about the specificity of microbial communities to their hosts. Few studies have compared the microbiomes of different species of animals, and fewer still have examined animals in the wild. We sampled four pond habitats in Colorado, USA, where multiple amphibian species were present. In total, 32 amphibian individuals were sampled from three different species including northern leopard frogs (Lithobates pipiens), western chorus frogs (Pseudacris triseriata) and tiger salamanders (Ambystoma tigrinum). We compared the diversity and composition of the bacterial communities on the skin of the collected individuals via barcoded pyrosequencing of the 16S rRNA gene. Dominant bacterial phyla included Acidobacteria, Actinobacteria, Bacteriodetes, Cyanobacteria, Firmicutes and Proteobacteria. In total, we found members of 18 bacterial phyla, comparable to the taxonomic diversity typically found on human skin. Levels of bacterial diversity varied strongly across species: L. pipiens had the highest diversity; A. tigrinum the lowest. Host species was a highly significant predictor of bacterial community similarity, and co-habitation within the same pond was not significant, highlighting that the skin-associated bacterial communities do not simply reflect those bacterial communities found in their surrounding environments. Innate species differences thus appear to regulate the structure of skin bacterial communities on amphibians. In light of recent discoveries that some bacteria on amphibian skin have antifungal activity, our finding suggests that host-specific bacteria may have a role in the species-specific resistance to fungal pathogens

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I(2) = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care