Drug delivery systems for wound healing treatment of upper airway injury.

INTRODUCTION: Endotracheal intubation is a common procedure to maintain an open airway with risks for traumatic injury. Pathological changes resulting from intubation can cause upper airway complications, including vocal fold scarring, laryngotracheal stenosis, and granulomas and present with symptoms such as dysphonia, dysphagia, and dyspnea. Current intubation-related laryngotracheal injury treatment approaches lack standardized guidelines, relying on individual clinician experience, and surgical and medical interventions have limitations and carry risks. AREAS COVERED: The clinical and preclinical therapeutics for wound healing in the upper airway are described. This review discusses the current developments on local drug delivery systems in the upper airway utilizing particle-based delivery systems, including nanoparticles and microparticles, and bulk-based delivery systems, encompassing hydrogels and polymer-based approaches. EXPERT OPINION: Complex laryngotracheal diseases pose challenges for effective treatment, struggling due to the intricate anatomy, limited access, and recurrence. Symptomatic management often requires invasive surgical procedures or medications that are unable to achieve lasting effects. Recent advances in nanotechnology and biocompatible materials provide potential solutions, enabling precise drug delivery, personalization, and extended treatment efficacy. Combining these technologies could lead to groundbreaking treatments for upper airways diseases, significantly improving patients' quality of life. Research and innovation in this field are crucial for further advancements.

Engineering a "detect and destroy" skin probiotic to combat methicillin-resistant Staphylococcus aureus.

The prevalence and virulence of pathogens such as methicillin-resistant Staphylococcus (S.) aureus (MRSA), which can cause recurrent skin infections, are of significant clinical concern. Prolonged antibiotic exposure to treat or decolonize S. aureus contributes to development of antibiotic resistance, as well as depletion of the microbiome, and its numerous beneficial functions. We hypothesized an engineered skin probiotic with the ability to selectively deliver antimicrobials only in the presence of the target organism could provide local bioremediation of pathogen colonization. We constructed a biosensing S. epidermidis capable of detecting the presence of S. aureus quorum sensing autoinducer peptide and producing lysostaphin in response. Here, we demonstrate in vitro activity of this biosensor and present and discuss challenges to deployment of this and other engineered topical skin probiotics.

Combination of STING and TLR 7/8 Agonists as Vaccine Adjuvants for Cancer Immunotherapy.

Immunostimulatory adjuvants that potently activate antigen-presenting cells and (in turn) prime cytotoxic T cells are a key component of anticancer vaccines. In this study, we investigated a multi-adjuvant approach combining a TLR 7/8 agonist (522) and a STING agonist (DMXAA) to promote enhanced antigen cross-presentation, stimulate specific antitumor T-cell responses, and provide improved anticancer efficacy. In vitro experiments using bone marrow-derived dendritic cells (BMDCs) confirmed enhanced activation with the 522-DMXAA combination based on both co-stimulatory molecule expression and pro-inflammatory cytokine secretion. The immunization of mice with vaccines comprising both 522 and DMXAA resulted in greater antitumor efficacy in B16F10 melanoma and MB49 bladder tumor models relative to mono-agonist vaccines. Flow cytometry-based analysis of immune cells from immunized mice revealed the significant activation of antigen-presenting cells, increased numbers of activated and Ag-specific CD8+ T cells in the spleen and lymph nodes, modest NK cell activation, and an overall reduction in CD206+ macrophages. These results were supported by an increase in the levels of IFN-γ and a reduction in IL-10 levels in the sera. Taken together, these findings demonstrate the potential of the TLR7/8 and STING agonist combination as vaccine adjuvants to activate both innate and adaptive immune responses.

Associations of the skin, oral and gut microbiome with aging, frailty and infection risk reservoirs in older adults.

Older adults represent a vulnerable population with elevated risk for numerous morbidities. To explore the association of the microbiome with aging and age-related susceptibilities including frailty and infectious disease risk, we conducted a longitudinal study of the skin, oral, and gut microbiota in 47 community- or skilled nursing facility-dwelling older adults vs. younger adults. We found that microbiome changes were not associated with chronological age so much as frailty: we identified prominent changes in microbiome features associated with susceptibility to pathogen colonization and disease risk, including diversity, stability, heterogeneity, and biogeographic determinism, which were moreover associated with a loss of Cutibacterium (C.) acnes in the skin microbiome. Strikingly, the skin microbiota were also the primary reservoir for antimicrobial resistance, clinically important pathobionts, and nosocomial strains, suggesting a potential role particularly for the skin microbiome in disease risk and dissemination of multidrug resistant pathogens.

Snakebite victim profiles and treatment-seeking behaviors in two regions of Kenya: results from a health demographic surveillance system.

INTRODUCTION: Snakebites are a major cause of permanent injury and death among poor, rural populations in developing countries, including those in East Africa. This research characterizes snakebite incidence, risk factors, and subsequent health-seeking behaviors in two regions of Kenya using a mixed methods approach. METHODS: As a part of regular activities of a health demographic surveillance system, household-level survey on snakebite incidence was conducted in two areas of Kenya: Kwale along the Kenyan Coast and Mbita on Lake Victoria. If someone in the home was reported to have been bitten in the 5 years previous to the visit, a survey instrument was administered. The survey gathered contextual information on the bite, treatment-seeking behavior and clinical manifestations. To obtain deeper, contextual information, respondents were also asked to narrate the bite incident, subsequent behavior and outcomes. RESULTS: 8775 and 9206 households were surveyed in Kwale and Mbita, respectively. Out of these, 453 (5.17%) and 92 (1.00%) households reported that at least one person had been bitten by a snake in the past 5 years. Deaths from snakebites were rare (4.04%), but patterns of treatment seeking varied. Treatment at formal care facilities were sought for 50.8% and at traditional healers for 53.3%. 18.4% sought treatment from both sources. Victims who delayed receiving treatment from a formal facility were more likely to have consulted a traditional healer (OR 8.8995% CI [3.83, 20.64]). Delays in treatment seeking were associated with significantly increased odds of having a severe outcome, including death, paralysis or loss of consciousness (OR 3.47 95% CI [1.56; 7.70]). CONCLUSION: Snakebite incidence and outcomes vary by region in Kenya, and treatment-seeking behaviors are complex. Work needs to be done to better characterize the spatial distribution of snakebite incidence in Kenya and efforts need to be made to ensure that victims have sufficient access to effective treatments to prevent death and serious injury.

Ambient air pollution and non-communicable respiratory illness in sub-Saharan Africa: a systematic review of the literature.

INTRODUCTION: Aerosol pollutants are known to raise the risk of development of non-communicable respiratory diseases (NCRDs) such as asthma, chronic bronchitis, chronic obstructive pulmonary disease, and allergic rhinitis. Sub-Saharan Africa's rapid pace of urbanization, economic expansion, and population growth raise concerns of increasing incidence of NCRDs. This research characterizes the state of research on pollution and NCRDs in the 46 countries of Sub-Saharan Africa (SSA). This research systematically reviewed the literature on studies of asthma; chronic bronchitis; allergic rhinitis; and air pollutants such as particulate matter, ozone, NOx, and sulfuric oxide. METHODS: We searched three major databases (PubMed, Web of Science, and Scopus) using the key words "asthma", "chronic bronchitis", "allergic rhinitis", and "COPD" with "carbon monoxide (CO)", "sulfuric oxide (SO)", "ozone (O3)", "nitrogen dioxide (NO2)", and "particulate matter (PM)", restricting the search to the 46 countries that comprise SSA. Only papers published in scholarly journals with a defined health outcome in individuals and which tested associations with explicitly measured or modelled air exposures were considered for inclusion. All candidate papers were entered into a database for review. RESULTS: We found a total of 362 unique research papers in the initial search of the three databases. Among these, 14 met the inclusion criteria. These papers comprised studies from just five countries. Nine papers were from South Africa; two from Malawi; and one each from Ghana, Namibia, and Nigeria. Most studies were cross-sectional. Exposures to ambient air pollutants were measured using spectrometry and chromatography. Some studies created composite measures of air pollution using a range of data layers. NCRD outcomes were measured by self-reported health status and measures of lung function (spirometry). Populations of interest were primarily schoolchildren, though a few studies focused on secondary school students and adults. CONCLUSIONS: The paucity of research on NCRDs and ambient air pollutant exposures is pronounced within the African continent. While capacity to measure air quality in SSA is high, studies targeting NCRDs should work to draw attention to questions of outdoor air pollution and health. As the climate changes and SSA economies expand and countries urbanize, these questions will become increasingly important.

Long-Term PM2.5 Exposure Is Associated with Symptoms of Acute Respiratory Infections among Children under Five Years of Age in Kenya, 2014.

Introduction: Short-term exposures to air pollutants such as particulate matter (PM) have been associated with increased risk for symptoms of acute respiratory infections (ARIs). Less well understood is how long-term exposures to fine PM (PM2.5) might increase risk of ARIs and their symptoms. This research uses georeferenced Demographic Health Survey (DHS) data from Kenya (2014) along with a remote sensing based raster of PM2.5 concentrations to test associations between PM2.5 exposure and ARI symptoms in children for up to 12 monthly lags. Methods: Predicted PM2.5 concentrations were extracted from raster of monthly averages for latitude/longitude locations of survey clusters. These data and other environmental and demographic data were used in a logistic regression model of ARI symptoms within a distributed lag nonlinear modeling framework (DLNM) to test lag associations of PM2.5 exposure with binary presence/absence of ARI symptoms in the previous two weeks. Results: Out of 7036 children under five for whom data were available, 46.8% reported ARI symptoms in the previous two weeks. Exposure to PM2.5 within the same month and as an average for the previous 12 months was 18.31 and 22.1 µg/m3, respectively, far in excess of guidelines set by the World Health Organization. One-year average PM2.5 exposure was higher for children who experienced ARI symptoms compared with children who did not (22.4 vs. 21.8 µg/m3, p < 0.0001.) Logistic regression models using the DLNM framework indicated that while PM exposure was not significantly associated with ARI symptoms for early lags, exposure to high concentrations of PM2.5 (90th percentile) was associated with elevated odds for ARI symptoms along a gradient of lag exposure time even when controlling for age, sex, types of cooking fuels, and precipitation. Conclusions: Long-term exposure to high concentrations of PM2.5 may increase risk for acute respiratory problems in small children. However, more work should be carried out to increase capacity to accurately measure air pollutants in emerging economies such as Kenya.

Impact of the COVID-19 pandemic on temporal patterns of mental health and substance abuse related mortality in Michigan: An interrupted time series analysis.

Background: The emergence of SARS-CoV2 (COVID-19) had wide impacts to health and mortality and prompted unprecedented containment efforts. The full impact of the COVID-19 pandemic and resulting responses on mental health and substance abuse related mortality are unknown. Methods: We obtained records for deaths from suicide, alcohol related liver failure, and overdose from the Michigan Department of Health and Human Services (MDHHS) for 2006 to 2020. We compared mortality within sex, age, marital, racial and urban/rural groups using basic statistical methods. We compared standardized mean daily mortality incidence before and after the onset of the pandemic using t-tests. We used an interrupted time series approach, using generalized additive Poisson regression models with smoothed components for time to assess differences in mortality trends before and after the onset of the pandemic within demographic groups. Findings: There were 19,365 suicides, 8,790 deaths from alcohol related liver failure, and 21,778 fatal drug overdoses. Compared with 2019, suicides in 2020 declined by 17.6%, overdose mortality declined by 22.5%-while alcohol deaths increased by 12.4%. Crude comparisons suggested that there were significant declines in suicides for white people, people 18 to 65 and increases for rural decedents, overdoses increased for Black people, females and married/widowed people, and alcohol mortality increased for nearly all groups. ITS models, however, suggested increased suicide mortality for rural residents, significantly increased alcohol related mortality for people ≥65 and increased overdose mortality in men. Interpretation: The onset of the pandemic was associated with mixed patterns of mortality between suicide, alcohol and overdose deaths. Patterns varied within demographic groups, suggesting that impacts varied among different groups, particularly racial and marital groups. Funding: This work was supported by the United States National Institute of Environmental Health Sciences [K99/R00ES026198] and their Michigan Center on Lifestage Environmental Exposures and Disease [grant number P30ES017885]; and the Institute for Global Biological Change at the University of Michigan.

A type IVB pilin influences twitching motility and in vitro adhesion to epithelial cells in Burkholderia pseudomallei.

Type IV pili are involved in adhesion, twitching motility, aggregation, biofilm formation and virulence in a variety of Gram-negative bacteria. Burkholderia pseudomallei, the causative agent of melioidosis and a Tier 1 biological select agent, is a Gram-negative bacterium with eight type IV pili-associated loci (TFP1 to TFP8). Most have not been fully characterized. In this study, we investigated BPSS2185, an uncharacterized TFP8 gene that encodes a type IVB pilus protein subunit. Using genetic deletion and complementation analysis in B. pseudomallei JW270, we demonstrate that BPSS2185 plays an important role in twitching motility and adhesion to A549 human alveolar epithelial cells. Compared to JW270, the JW270 ΔBPSS2185 mutant failed to display twitching motility and did not adhere to the epithelial cells. These phenotypes were partially reversed by the complementation of BPSS2185 in the mutant strain. The study also shows that BPSS2185 is expressed only during the onset of mature biofilm formation and at the dispersal of a biofilm, suggesting that the motility characteristic is required to form a biofilm. Our study is the first to suggest that the BPSS2185 gene in TFP8 contributes to twitching motility, adhesion and biofilm formation, indicating that the gene may contribute to B. pseudomallei virulence.

Optimizing Rehabilitation and Return to Sport in Athletes With Anterior Knee Pain Using a Biomechanical Perspective.

Anterior knee pain represents one of the most common athletic knee conditions and arguably also one of the most complex. The patellofemoral joint is at the center of several forces, and alterations in any of these force vectors due to muscular imbalance, soft-tissue tightness or laxity, and altered functional movement patterns can all combine to create a painful anterior knee. While typically anterior knee pain is not a surgical entity, the orthopaedic surgeon with an understanding of these biomechanical intricacies is best positioned to provide comprehensive evidence-based care for the patient with anterior knee pain. LEVEL OF EVIDENCE: V, expert opinion.

Toll-like receptor 7 and 8 imidazoquinoline-based agonist/antagonist pairs.

Toll-like receptors (TLRs) 7 and 8 are key targets in the development of immunomodulatory drugs for treating infectious disease, cancer, and autoimmune disorders. These receptors can adopt both agonist and antagonist binding conformations that switch the receptor signal on or off to the downstream production of cytokines. In this study, we examined the effect of simple isomeric substitutions to the C2-butyl group of two imidazoquinoline agonists and evaluated the activity of these analogs using both TLR7 and TLR8 reporter cells and cytokine induction assays. Results are presented showing the C2-isobutyl and C2-cyclopropylmethyl isomers are both mixed TLR7/8 competitive antagonists of the parent agonist [4-Amino-1-(4-(aminomethyl)benzyl)-2-butyl-7-methoxycarbonyl-1H-imidazo[4,5-c]quinoline], indicating the conformation of the dimeric receptor complex is highly sensitive to steric perturbations to the ligand binding pocket. This observation is consistent with prior work demonstrating TLR7 and TLR8 activity is directly correlated to C2-alkyl substitutions that project into a hydrophobic pocket at the dimer interface of the receptor. The close structural relationship of the agonist/antagonist pairs identified here highlights the importance of this pocket in tipping the balance between the agonist and antagonist binding states of the receptor which may have significant ramifications to the design of imidazoquinoline-based immunomodulatory agents.

Indoor apparent temperature, cognition, and daytime sleepiness among low-income adults in a temperate climate.

The burden of temperature-associated mortality and hospital visits is significant, but temperature's effects on non-emergency health outcomes is less clear. This burden is potentially greater in low-income households unable to afford efficient heating and cooling. We examined short-term associations between indoor temperatures and cognitive function and daytime sleepiness in low-income residents of Detroit, Michigan. Apparent temperature (AT, based on temperature and humidity) was recorded hourly in 34 participant homes between July 2019-March 2020. Between July-October 2019, 18 participants were administered word list immediate (WLL) and delayed (WLD) recall tests (10-point scales) and the Epworth Sleepiness Scale (24-point scale) 2-4 times. We applied longitudinal models with nonlinear distributed lags of temperature up to 7 days prior to testing. Indoor temperatures ranged 8-34°C overall and 15-34°C on survey days. We observed a 0.4 (95% CI: 0.0, 0.7) point increase in WLL and 0.4 (95% CI: 0.0, 0.9) point increase in WLD scores per 2°C increase in AT. Results suggested decreasing sleepiness scores with decreasing nighttime AT below 22°C. Low-income Detroit residents experience uncomfortably high and low indoor temperatures. Indoor temperature may influence cognitive function and sleepiness, although we did not observe deleterious effects of higher temperatures.

Seasonal calibration of the end-cretaceous Chicxulub impact event.

The end-Cretaceous Chicxulub impact triggered Earth's last mass-extinction, extinguishing ~ 75% of species diversity and facilitating a global ecological shift to mammal-dominated biomes. Temporal details of the impact event on a fine scale (hour-to-day), important to understanding the early trajectory of mass-extinction, have largely eluded previous studies. This study employs histological and histo-isotopic analyses of fossil fish that were coeval with a unique impact-triggered mass-death assemblage from the Cretaceous-Paleogene (KPg) boundary in North Dakota (USA). Patterns of growth history, including periodicity of ẟ18O and ẟ13C and growth band morphology, plus corroborating data from fish ontogeny and seasonal insect behavior, reveal that the impact occurred during boreal Spring/Summer, shortly after the spawning season for fish and most continental taxa. The severity and taxonomic symmetry of response to global natural hazards are influenced by the season during which they occur, suggesting that post-impact perturbations could have exerted a selective force that was exacerbated by seasonal timing. Data from this study can also provide vital hindsight into patterns of extant biotic response to global-scale hazards that are relevant to both current and future biomes.

An urban-to-rural continuum of malaria risk: new analytic approaches characterize patterns in Malawi.

BACKGROUND: The urban-rural designation has been an important risk factor in infectious disease epidemiology. Many studies rely on a politically determined dichotomization of rural versus urban spaces, which fails to capture the complex mosaic of infrastructural, social and environmental factors driving risk. Such evaluation is especially important for Plasmodium transmission and malaria disease. To improve targeting of anti-malarial interventions, a continuous composite measure of urbanicity using spatially-referenced data was developed to evaluate household-level malaria risk from a house-to-house survey of children in Malawi. METHODS: Children from 7564 households from eight districts throughout Malawi were tested for presence of Plasmodium parasites through finger-prick blood sampling and slide microscopy. A survey questionnaire was administered and latitude and longitude coordinates were recorded for each household. Distances from households to features associated with high and low levels of development (health facilities, roads, rivers, lakes) and population density were used to produce a principal component analysis (PCA)-based composite measure for all centroid locations of a fine geo-spatial grid covering Malawi. Regression methods were used to test associations of the urbanicity measure against Plasmodium infection status and to predict parasitaemia risk for all locations in Malawi. RESULTS: Infection probability declined with increasing urbanicity. The new urbanicity metric was more predictive than either a governmentally defined rural/urban dichotomous variable or a population density variable. One reason for this was that 23% of cells within politically defined rural areas exhibited lower risk, more like those normally associated with "urban" locations. CONCLUSIONS: In addition to increasing predictive power, the new continuous urbanicity metric provided a clearer mechanistic understanding than the dichotomous urban/rural designations. Such designations often ignore urban-like, low-risk pockets within traditionally rural areas, as were found in Malawi, along with rural-like, potentially high-risk environments within urban areas. This method of characterizing urbanicity can be applied to other infectious disease processes in rapidly urbanizing contexts.

Molecular analysis of the 2012 Bundibugyo virus disease outbreak.

Bundibugyo virus (BDBV) is one of four ebolaviruses known to cause disease in humans. Bundibugyo virus disease (BVD) outbreaks occurred in 2007-2008 in Bundibugyo District, Uganda, and in 2012 in Isiro, Province Orientale, Democratic Republic of the Congo. The 2012 BVD outbreak resulted in 38 laboratory-confirmed cases of human infection, 13 of whom died. However, only 4 BDBV specimens from the 2012 outbreak have been sequenced. Here, we provide BDBV sequences from seven additional patients. Analysis of the molecular epidemiology and evolutionary dynamics of the 2012 outbreak with these additional isolates challenges the current hypothesis that the outbreak was the result of a single spillover event. In addition, one patient record indicates that BDBV's initial emergence in Isiro occurred 50 days earlier than previously accepted. Collectively, this work demonstrates how retrospective sequencing can be used to elucidate outbreak origins and provide epidemiological contexts to a medically relevant pathogen.

Automated Electronic Health Record-Based Tool for Identification of Patients With Metastatic Disease to Facilitate Clinical Trial Patient Ascertainment.

PURPOSE: To facilitate identification of clinical trial participation candidates, we developed a machine learning tool that automates the determination of a patient's metastatic status, on the basis of unstructured electronic health record (EHR) data. METHODS: This tool scans EHR documents, extracting text snippet features surrounding key words (such as metastatic, progression, and local). A regularized logistic regression model was trained and used to classify patients across five metastatic categories: highly likely and likely positive, highly likely and likely negative, and unknown. Using a real-world oncology database of patients with solid tumors with manually abstracted information as reference, we calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We validated the performance in a real-world data set, evaluating accuracy gains upon additional user review of tool's outputs after integration into clinic workflows. RESULTS: In the training data set (N = 66,532), the model sensitivity and specificity (% [95% CI]) were 82.4 [81.9 to 83.0] and 95.5 [95.3 to 96.7], respectively; the PPV was 89.3 [88.8 to 90.0], and the NPV was 94.0 [93.8 to 94.2]. In the validation sample (n = 200 from five distinct care sites), after user review of model outputs, values increased to 97.1 [85.1 to 99.9] for sensitivity, 98.2 [94.8 to 99.6] for specificity, 91.9 [78.1 to 98.3] for PPV, and 99.4 [96.6 to 100.0] for NPV. The model assigned 163 of 200 patients to the highly likely categories. The error prevalence was 4% before and 2% after user review. CONCLUSION: This tool infers metastatic status from unstructured EHR data with high accuracy and high confidence in more than 75% of cases, without requiring additional manual review. By enabling efficient characterization of metastatic status, this tool could mitigate a key barrier for patient ascertainment and clinical trial participation in community clinics.

Presence of dogs and proximity to a wildlife reserve increase household level risk of tungiasis in Kwale, Kenya.

INTRODUCTION: Tungiasis is a ectopic skin disease caused by some species of fleas in the Tunga genus, most notably T. penetrans. The disease afflicts poor and marginalized communities in developing countries. Transmission of tungiasis comprises a complex web of factors including domesticated animals and wildlife. This research explores animal and environmental risk factors for tungiasis in an area adjacent to a wildlife reserve in Kwale, Kenya. METHODS: A two-stage complex sampling strategy was used. Households were selected from three areas in and around Kwale Town, Kenya, an area close to the Kenyan Coast. Households were listed as positive if at least one member had tungiasis. Each household was administered a questionnaire regarding tungiasis behaviors, domesticated animal assets, and wild animal species that frequent the peridomiciliary area. Associations of household tungiasis were tests with household and environmental variables using regression methods. RESULTS: The study included 319 households. Of these, 41 (12.85%) were found to have at least one person who had signs of tungiasis. There were 295 (92.48%) households that possessed at least one species of domesticated animal. It was reported that wildlife regularly come into the vicinity of the home 90.59% of households. Presence of dogs around the home (OR 3.85; 95% CI 1.84; 8.11) and proximity to the park were associated with increased risk for tungiasis infestation in humans in a multivariate regression model. CONCLUSIONS: Human tungiasis is a complex disease associated with domesticated and wild animals. Canines in particular appear to be important determinants of household level risk.

Recurrent Home Flooding in Detroit, MI 2012-2020: Results of a Household Survey.

Household flooding has wide ranging social, economic and public health impacts particularly for people in resource poor communities. The determinants and public health outcomes of recurrent home flooding in urban contexts, however, are not well understood. A household survey was used to assess neighborhood and household level determinants of recurrent home flooding in Detroit, MI. Survey activities were conducted from 2012 to 2020. Researchers collected information on past flooding, housing conditions and public health outcomes. Using the locations of homes, a "hot spot" analysis of flooding was performed to find areas of high and low risk. Survey data were linked to environmental and neighborhood data and associations were tested using regression methods. 4803 households participated in the survey. Flooding information was available for 3842 homes. Among these, 2085 (54.26%) reported experiencing pluvial flooding. Rental occupied units were more likely to report flooding than owner occupied homes (Odd ratio (OR) 1.72 [95% Confidence interval (CI) 1.49, 1.98]). Housing conditions such as poor roof quality and cracks in basement walls influenced home flooding risk. Homes located in census tracts with increased percentages of owner occupied units (vs. rentals) had a lower odds of flooding (OR 0.92 [95% (CI) 0.86, 0.98]). Household factors were found the be more predictive of flooding than neighborhood factors in both univariate and multivariate analyses. Flooding and housing conditions associated with home flooding were associated with asthma cases. Recurrent home flooding is far more prevalent than previously thought. Programs that support recovery and which focus on home improvement to prevent flooding, particularly by landlords, might benefit the public health. These results draw awareness and urgency to problems of urban flooding and public health in other areas of the country confronting the compounding challenges of aging infrastructure, disinvestment and climate change.

Short-term exposures to atmospheric evergreen, deciduous, grass, and ragweed aeroallergens and the risk of suicide in Ohio, 2007-2015: Exploring disparities by age, gender, and education level.

BACKGROUND: Seasonal trends in suicide mortality are observed worldwide, potentially aligning with the seasonal release of aeroallergens. However, only a handful of studies have examined whether aeroallergens increase the risk of suicide, with inconclusive results thus far. The goal of this study was to use a time-stratified case-crossover design to test associations of speciated aeroallergens (evergreen, deciduous, grass, and ragweed) with suicide deaths in Ohio, USA (2007-2015). METHODS: Residential addresses for 12,646 persons who died by suicide were linked with environmental data at the 4-25 km grid scale including atmospheric aeroallergen concentrations, maximum temperature, sunlight, particulate matter <2.5 µm, and ozone. A case-crossover design was used to examine same-day and 7-day cumulative lag effects on suicide. Analyses were stratified by age group, gender, and educational level. RESULTS: In general, associations were null between aeroallergens and suicide. Stratified analyses revealed a relationship between grass pollen and same-day suicide for women (OR = 3.84; 95% CI = 1.44, 10.22) and those with a high school degree or less (OR = 2.03; 95% CI = 1.18, 3.49). CONCLUSIONS: While aeroallergens were generally not significantly related to suicide in this sample, these findings provide suggestive evidence for an acute relationship of grass pollen with suicide for women and those with lower education levels. Further research is warranted to determine whether susceptibility to speciated aeroallergens may be driven by underlying biological mechanisms or variation in exposure levels.

Genomic features of humoral immunity support tolerance model in Egyptian rousette bats.

Bats asymptomatically harbor many viruses that can cause severe human diseases. The Egyptian rousette bat (ERB) is the only known reservoir for Marburgviruses and Sosuga virus, making it an exceptional animal model to study antiviral mechanisms in an asymptomatic host. With this goal in mind, we constructed and annotated the immunoglobulin heavy chain locus, finding an expansion on immunoglobulin variable genes associated with protective human antibodies to different viruses. We also annotated two functional and distinct immunoglobulin epsilon genes and four distinctive functional immunoglobulin gamma genes. We described the Fc receptor repertoire in ERBs, including features that may affect activation potential, and discovered the lack of evolutionary conserved short pentraxins. These findings reinforce the hypothesis that a differential threshold of regulation and/or absence of key immune mediators may promote tolerance and decrease inflammation in ERBs.