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Common over-the-counter medicines can be an exciting entry point for introducing students to the interesting chemistries that they encounter in their daily lives. In this inquiry-based activity, students are tasked with using a list of given supplies and information about four medications (Aspirin, Tums, Pepto-Bismol, and Tylenol) to design three experiments that will enable them to identify which mystery substance is which medication. This activity introduces students to several chemical concepts, including acid-base reactions, redox reactions, and chelation. Overall, comparing results of pre- and post-activity assessments, students learned about and became more confident in their knowledge of how natural products and metals can be used in medicine and were able to correctly identify their unknown medications. Additionally, a procedure-based activity for extracting bismuth from Pepto-Bismol is included.

Background and Objectives: The utilization of telemedicine has increased dramatically since the onset of the COVID-19 pandemic. In this review, we examined studies published within the past five years that investigated the impact of telemedicine on patient satisfaction. Methods: Four investigators utilized PubMed and Google Scholar to find studies published within the past five years that assessed patient satisfaction with telemedicine in the field of adult primary care, using either the Press Ganey or CAHPS surveys. Studies that compared cost and quality of care between telemedicine and in-patient healthcare were also included to address the secondary aims of this study. Results: A total of 11 studies out of the 405 that were investigated were selected for this review. Five studies found no significant difference in patient satisfaction between telemedicine and in-person medicine, with one of those showing a patient preference for telemedicine. One study demonstrated significantly higher satisfaction with in-person medicine vs. telemedicine. Another study found that most physicians and patients reported no perceived difference in quality of care between telemedicine and in-person visitation. One study found no difference in patient satisfaction with telemedicine between immigrants and non-immigrants. Another study showed that patients have higher satisfaction when using telemedicine with their PCP vs. an unfamiliar provider. Two studies found telemedicine to be cost-effective. Conclusions: Our review concludes that patient satisfaction with telemedicine is not inferior to that with in-person visits. However, further research should be conducted to determine various factors that may affect patient perception and satisfaction.

Abstract Background Domestic and family violence (DFV) is a significant public health issue that poses a high risk to women, globally. Women experiencing DFV have higher rates of healthcare utilisation than women not experiencing DFV. Healthcare services are therefore well placed to address DFV and deliver education and awareness interventions to women. Video interventions are a strategy to deliver education to women, while overcoming barriers such as language, literacy, lack of rapport with clinician, or unwillingness to disclose. The current review will aim to further understand the characteristics, methods of evaluation, and outcomes of DFV video education interventions for perinatal women. Methods The review will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A systematic search will be conducted of the following databases: Medline, Embase, PsycINFO, PsycArticles, Scopus, and Web of Science Core Collection. Two independent reviewers will screen titles and abstracts against the inclusion criteria, followed by a full text screening of eligible articles. A third reviewer will resolve discrepancies. All study types will be included. Only studies published in English will be included. Risk of bias will be assessed using the Quality Assessment with Diverse Studies (QuADS) tool. Data will undergo an aggregate mixed method synthesis informed by The Joanna Briggs Institute, before being analysed using a thematic approach. Discussion This systematic review will provide evidence on best practice for the creation, delivery, and evaluation of DFV video interventions for women in the peripartum. Systematic review registration PROSPERO registration number CRD42023475338.

BackgroundAnxiety and depression in people with epilepsy are common and associated with poor outcomes; yet, they often go untreated due to poor mental health specialist access. Collaborative care is an integrated care model with a strong evidence base in primary care and medical settings, but it has not been evaluated in neurology clinics. Evaluating implementation outcomes when translating evidence-based interventions to new clinical settings to inform future scaling and incorporation into real-world practice is important. ObjectiveThe Collaborative Care for Posttraumatic Epilepsy (CoCarePTE) trial aims to evaluate the effectiveness (improvement in emotional quality of life) and implementation of a collaborative care intervention for people with anxiety or depressive symptoms and posttraumatic epilepsy. MethodsCoCarePTE is a 2-site, randomized, single-blind, hybrid type 1 effectiveness-implementation trial that will randomize 60 adults to receive either neurology-based collaborative care or usual care. Adults receiving neurological care at participating centers with anxiety or depressive symptoms and a history of at least mild traumatic brain injury before epilepsy onset will be enrolled. The collaborative care intervention is a 24-week stepped-care model with video or telephone calls every 2 weeks by a care manager for measurement-based anxiety and depression care, seizure care monitoring, and brief therapy intervention delivery. This is supplemented by antidepressant prescribing recommendations by psychiatrists for neurologists via case conferences and care manager–facilitated team communication. In step 2 of the intervention, individuals with

Abstract We hypothesize that children characterized by deprived factors have poorer health outcomes. We aim to identify clustering of determinants and estimate risk of early childhood diseases. This 1993–2019 longitudinal cohort study combines three Canadian pediatric cohorts and their families. Mothers and children are clustered using latent class analysis (LCA) by 16 indicators in three domains (maternal and newborn; socioeconomic status [SES] and neighbourhood; environmental exposures). Hazard ratios (HR) of childhood asthma, allergic rhinitis (AR), and eczema are quantified with Cox proportional hazard (PH) regression. Rate ratios (RR) of children’s health services use (HSU) are estimated with Poisson regression. Here we report the inclusion of 15,724 mother–child pairs; our LCA identifies four mother-clusters. Classes 1 and 2 mothers are older (30–40 s), non-immigrants with university education, living in high SES neighbourhoods; Class 2 mothers have poorer air quality and less greenspace. Classes 3 and 4 mothers are younger (20–30 s), likely an immigrant/refugee, with high school-to-college education, living in lower SES neighborhoods with poorer air quality and less greenspace. Children’s outcomes differ by Class, in comparison to Class 1. Classes 3 and 4 children have higher risks of asthma (HR 1.24, 95% CI 1.11–1.37 and HR 1.39, 95% CI 1.22–1.59, respectively), and similar higher risks of AR and eczema. Children with AR in Class 3 have 20% higher all-cause physician visits (RR = 1.20, 95% CI 1.10–1.30) and those with eczema have 18% higher all-cause emergency department visits (RR = 1.18, 95% CI 1.09–1.28) and 14% higher all-cause physician visits (RR = 1.14, 95% CI 1.09–1.19). Multifactorial-LCA mother-clusters may characterize associations of children’s health outcomes and care, adjusting for interrelationships.

Abstract Individuals may have a different body odor, when they are sick compared to healthy. In the non-human animal literature, olfactory cues have been shown to predict avoidance of sick individuals. We tested whether the mere experimental activation of the innate immune system in healthy human individuals can make an individuals’ body odor be perceived as more aversive (intense, unpleasant, and disgusting). Following an endotoxin injection (lipopolysaccharide; 0.6 ng/kg) that creates a transient systemic inflammation, individuals smelled more unpleasant compared to a placebo group (saline injection). Behavioral and chemical analyses of the body odor samples suggest that the volatile components of samples from “sick” individuals changed qualitatively rather than quantitatively. Our findings support the hypothesis that odor cues of inflammation in axillary sweat are detectable just a few hours after experimental activation of the innate immune system. As such, they may trigger behavioral avoidance, hence constituting a first line of defense against pathogens of infected conspecifics.

BackgroundThe HEALing Communities Study (HCS) included health campaigns as part of a community-engaged intervention to reduce opioid-related overdose deaths in 67 highly impacted communities across Kentucky, Massachusetts, New York, and Ohio. Five campaigns were developed with community input to provide information on opioid use disorder (OUD) and overdose prevention, reduce stigma, and build demand for evidence-based practices (EBPs). An evaluation examined the recognition of campaign messages about naloxone and whether stigma and efficacy beliefs regarding OUD treatment and naloxone changed in HCS intervention communities.MethodsData were collected through surveys offered on Facebook/Instagram to members of communities participating in the HCS intervention and wait-list control communities.ResultsParticipants in HCS intervention communities reported a reduction in stigma regarding OUD and increased efficacy beliefs regarding naloxone associated with recognition of campaign messages. However, this finding is cautiously interpreted as there was no clear evidence for recognition differences between the treatment/control conditions.ConclusionStudy findings indicate associations between campaign message recognition and positive outcomes. Results also highlight possible challenges concerning evaluations of social media campaigns using conventional evaluation techniques.Trial registrationClinicalTrials.gov NCT04111939.

BackgroundPersons who inject drugs (PWID) may be unengaged with healthcare services and face an elevated risk of severe morbidity and mortality associated with COVID-19 due to chronic diseases and structural inequities. However, data on COVID-19 vaccine uptake, particularly booster vaccination, among PWID are limited. We examined COVID-19 vaccine uptake and factors associated with booster vaccination among PWID in New York City (NYC).MethodsWe recruited PWID using respondent-driven sampling from October 2021 to November 2023 in a survey that included HIV and SARS-CoV-2 antibodies testing. The questionnaire included demographics, COVID-19 vaccination and attitudes, and drug use behaviors.ResultsOf 436 PWID, 80% received at least one COVID-19 vaccine dose. Among individuals who received at least one COVID-19 vaccine dose, 95% were fully vaccinated. After excluding participants recruited before booster authorization for general adults started in NYC, and those who had never received an initial vaccination, 41% reported having received a COVID-19 booster vaccine dose. COVID-19 booster vaccination was significantly associated with having a high school diploma or GED (adjusted odds ratio (aOR) 1.93; 95% confidence interval (CI) 1.09, 3.48), ever received the hepatitis A/B vaccine (aOR 2.23; 95% CI 1.27, 3.96), main drug use other than heroin/speedball, fentanyl and stimulants (aOR 14.4; 95% CI 2.32, 280), number of non-fatal overdoses (aOR 0.35; 95% CI 0.16, 0.70), and mean vaccination attitude score (aOR 0.94; 95% CI 0.89, 0.98).ConclusionsWe found a suboptimal level of COVID-19 booster vaccination among PWID, which was consistent with the rates observed in the general population in NYC and the U.S. Community-based interventions are needed to improve COVID-19 booster vaccination access and uptake among PWID. Attitudes towards vaccination were significant predictors of both primary and booster vaccination uptake. Outreach efforts focusing on improving attitudes towards vaccination and educational programs are essential for reducing hesitancy and increasing booster vaccination uptake among PWID.

BackgroundThe prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) is between 50-70%. Prior systematic reviews demonstrated that PWID have similar direct acting antiviral treatment outcomes compared to non-PWID; however, reviews have not examined treatment outcomes by housing status. Given the links between housing and health, identifying gaps in HCV treatment can guide future interventions.MethodsWe conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched six databases for articles from 2014 onward. Two reviewers conducted title/abstract screenings, full-text review, and data extraction. We extracted effect measures for treatment initiation, adherence, completion, success, and reinfection by housing status. Studies underwent quality and certainty assessments, and we performed meta-analyses as appropriate.ResultsOur search yielded 473 studies, eight of which met inclusion criteria. Only the treatment initiation outcome had sufficient measures for meta-analysis. Using a random-effects model, we found those with unstable housing had 0.40 (0.26, 0.62) times the odds of initiating treatment compared to those with stable housing. Other outcomes were not amenable for meta-analysis due to a limited number of studies or differing outcome definitions.ConclusionsAmong PWID, unstable housing appears to be a barrier to HCV treatment initiation; however, the existing data is limited for treatment initiation and the other outcomes we examined. There is a need for more informative studies to better understand HCV treatment among those with unstable housing. Specifically, future studies should better define housing status beyond a binary, static measure to capture the nuances and complexity of housing and its subsequent impact on HCV treatment. Additionally, researchers should meaningfully consider whether the outcome(s) of interest are being accurately measured for individuals experiencing unstable housing.

Abstract Background: Community advisory boards (CABs) are an established approach to ensuring research reflects community priorities. This paper examines two CABs that are part of the HEALing Communities Study which aims to reduce overdose mortality. This analysis aimed to understand CAB members’ expectations, experiences, and perspectives on CAB structure, communication, facilitation, and effectiveness during the first year of an almost fully remote CAB implementation. Current literature exploring these perspectives is limited. Methods: We collected qualitative and survey data simultaneously from members (n = 53) of two sites’ CABs in the first 9 months of CAB development. The survey assessed trust, communication, and relations; we also conducted 32 semi-structured interviews. We analyzed the survey results descriptively. The qualitative data were analyzed using a deductive codebook based on the RE-AIM PRISM framework. Themes were drawn from the combined qualitative data and triangulated with survey results to further enrich the findings. Results: CAB members expressed strong commitment to overall study goals and valued the representation of occupational sectors. The qualitative data described a dissonance between CAB members’ commitment to the mission and unmet expectations for influencing the study within an advisory role. Survey results indicated lower satisfaction with the research teams’ ability to create a mutually beneficial process, clear communication, and sharing of power. Conclusion: Building a CAB on a remote platform, within a study utilizing a community engagement strategy, still presents challenges to fully realizing the potential of a CAB. These findings can inform more effective operationalizing of community-engaged research through enhanced CAB engagement.

Abstract Previous immunological studies in the eastern USA have failed to establish a direct connection between Paleoamericans and extinct megafauna species. The lack of physical evidence for the presence of extinct megafauna begs the question, did early Paleoamericans regularly hunt or scavenge these animals, or were some megafauna already extinct? In this study of 120 Paleoamerican stone tools from across North and South Carolina, we investigate this question using crossover immunoelectrophoresis (CIEP). We find immunological support for the exploitation of extant and extinct megafauna, including Proboscidea, Equidae, and Bovidae (possibly Bison antiquus), on Clovis points and scrapers, as well as possible early Paleoamerican Haw River points. Post-Clovis points tested positive for Equidae and Bovidae but not Proboscidea. Microwear results are consistent with projectile usage, butchery, fresh- and dry hide scraping, the use of ochre-coated dry hides for hafting, and dry hide sheath wear. This study represents the first direct evidence of the exploitation of extinct megafauna by Clovis and other Paleoamerican cultures in the Carolinas and more broadly, across the eastern United States, where there is generally poor to non-existent faunal preservation. Future CIEP analysis of stone tools may provide evidence on the timing and demography of megafaunal collapse leading to eventual extinction.

Key Clinical Message Diastrophic dysplasia (DTD) is caused by biallelic pathogenic variants in the SLC26A2 gene. We report the case of a 49‐year‐old female with DTD and esophageal stenosis. This broadens the phenotypic spectrum in adult patients with DTD and raises awareness of extra‐skeletal manifestations that could develop in later stages of life.

Abstract Deep venous thrombosis and residual thrombus burden correlates with circulating IL-6 levels in humans. To investigate the cellular source and role of IL-6 in thrombus resolution, Wild type C57BL/6J (WT), and IL-6−/− mice underwent induction of VT via inferior vena cava (IVC) stenosis or stasis. Vein wall (VW) and thrombus were analyzed by western blot, immunohistochemistry, and flow cytometry. Adoptive transfer of WT bone marrow derived monocytes was performed into IL6-/- mice to assess for rescue. Cultured BMDMs from WT and IL-6−/− mice underwent quantitative real time PCR and immunoblotting for fibrinolytic factors and matrix metalloproteinase activity. No differences in baseline coagulation function or platelet function were found between WT and IL-6−/− mice. VW and thrombus IL-6 and IL-6 leukocyte-specific receptor CD126 were elevated in a time-dependent fashion in both VT models. Ly6Clo Mo/MØ were the predominant leukocyte source of IL-6. IL-6−/− mice demonstrated larger, non-resolving stasis thrombi with less neovascularization, despite a similar number of monocytes/macrophages (Mo/MØ). Adoptive transfer of WT BMDM into IL-6−/− mice undergoing stasis VT resulted in phenotype rescue. Human specimens of endophlebectomized tissue showed co-staining of Monocyte and IL-6 receptor. Thrombosis matrix analysis revealed significantly increased thrombus fibronectin and collagen in IL-6−/− mice. MMP9 activity in vitro depended on endogenous IL-6 expression in Mo/MØ, and IL-6−/− mice exhibited stunted matrix metalloproteinase activity. Lack of IL-6 signaling impairs thrombus resolution potentially via dysregulation of MMP-9 leading to impaired thrombus recanalization and resolution. Restoring or augmenting monocyte-mediated IL-6 signaling in IL-6 deficient or normal subjects, respectively, may represent a non-anticoagulant target to improve thrombus resolution.

Morphological traits have often been used to predict diet and trophic position of species across many animal groups. Variation in gut size of closely related animals is known to be a good predictor of dietary habits. Species that are more herbivorous or that persist on low-quality diets often have larger stomachs than their carnivorous counterparts. This same pattern exists in crabs and in most species, individuals exhibit external markings on the dorsal side of their carapace that appear to align with the position and size of their gut. We hypothesized that these external markings could be used as an accurate estimate of the crab’s cardiac stomach size, allowing an approximation of crab dietary strategies without the need to sacrifice and dissect individual animals. We used literature values for mean diet and standardized external gut size markings taken from crab photographs across 50 species to show that percent herbivory in the diet increases non-linearly across species of brachyuran crab with the external estimate of gut size. We also used data from dissections in four species to show that external gut markings were positively correlated with gut sizes, though the strength of this correlation differed across species. We conclude that when rough approximations of diet quality such as percent herbivory will suffice, measuring external carapace markings in crabs presents a quick, free, non-lethal alternative to dissections. Our results also provide important insights into tradeoffs that occur in crab morphology and have implications for crab evolution.

Abstract Vector control strategies are among the most effective measures to combat mosquito-borne diseases, such as malaria. These strategies work by altering the mosquito age structure through increased mortality of the older female mosquitoes that transmit pathogens. However, methods to monitor changes to mosquito age structure are currently inadequate for programmatic implementation. Female mosquitoes generally mate a single time soon after emergence and draw down spermatozoa reserves with each oviposition cycle. Here, we demonstrate that measuring spermatozoa quantity in female Anopheles mosquitoes is an effective approach to assess mosquito age. Using multiplexed qPCR targeted at male spermatozoa, we show that Y-linked genes in female mosquitoes are exclusively found in the spermatheca, the organ that houses spermatozoa, and the quantity of these gene sequences significantly declines with age. The method can accurately identify mosquitoes more than 10 days old and thus old enough to potentially transmit pathogens harbored in the salivary glands during blood feeding. Furthermore, mosquito populations that differ by 10% in daily survivorship have a high likelihood of being distinguished using modest sample sizes, making this approach scalable for assessing the efficacy of vector intervention control programs.

Abstract Vitrified, or “frozen”, donor eggs can either be fertilized and cultured for fresh transfer (group 1), or fertilized and cryopreserved for transfer in a “frozen embryo transfer” cycle (group 2). This study compared the pregnancy rates between the two groups. Frozen donor egg cycles (N = 1213) were analyzed at the World Egg Bank. The outcome studied was clinical pregnancy rate. Cycles included only single embryo transfers (ET) without preimplantation genetic testing (PGT). A total of 600 cycles met the inclusion criteria. Group 1 included 409 cycles and group 2 had 191 cycles. There was no statistical significance in clinical pregnancy rate between the two groups (38.63% vs 32.46%, p = 0.14). Mean embryo age was higher in group 2 (5.1 vs. 5.4 days, p

Abstract Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season.

Acceptance of the COVID-19 vaccination becomes more critical as new variants continue to evolve and the United States (US) attempts to move from pandemic response to management and control. COVID-19 stands out in the unique way it has polarized patients and generated sustained vaccine hesitancy over time. We sought to understand differences in perceptions and acceptance of COVID-19 vaccination between vaccine hesitant and non-hesitant patients, with the goal of informing communication and implementation strategies to increase uptake of COVID-19 vaccines in Veteran and non-Veteran communities. This qualitative study used interview data from focus groups conducted by the Department of Veterans Affairs (VA) and the University of Utah; all focus groups were conducted using the same script March-July 2021. Groups included forty-six United States Veterans receiving care at 28 VA facilities across the country and 166 non-Veterans across Utah for a total of 36 one-hour focus groups. We identified perceptions and attitudes toward COVID-19 vaccination through qualitative analysis of focus group participant remarks, grouping connections with identified themes within domains developed based on the questions asked in the focus group guide. Responses suggest participant attitudes toward the COVID-19 vaccine were shaped primarily by vaccine attitude changes over time, impacted by perceived vaccine benefits, risks, differing sources of vaccine information and political ideology. Veterans appeared more polarized, being either largely non-hesitant, or hesitant, whereas non-Veterans had a wider range of hesitancy, with more participants identifying minor doubts and concerns about receiving the vaccine, or simply being altogether unsure about receiving it. Development of COVID-19 vaccine communication strategies in Veteran and non-Veteran communities should anticipate incongruous sources of information and explicitly target community differences in perceptions of risks and benefits associated with the vaccine to generate candid discussions and repair individuals' trust. We believe this could accelerate vaccine acceptance over time.

Wildlife disease surveillance and monitoring poses unique challenges when assessing rates of population vaccination, immunity, or infection prevalence. Non-invasively detected biomarkers can help reduce risk to both animal and field personnel during wildlife disease management activities. In this study, we investigated the utility of fecal microbiome data collected from captive striped skunks (Mephitis mephitis) in predicting rabies virus vaccination and infection status. We sequenced the hypervariable region 4 (V4) of the bacterial 16S gene and estimated alpha and beta diversity across timepoints in three groups of skunks: vaccination then rabies virus infection, sham vaccination then rabies virus infection, and rabies virus infected without vaccination. Alpha diversity did not differ among treatment groups but beta diversity between treatments was statistically significant. The phyla Firmicutes and Proteobacteria were dominant among all samples. Using Random Forests, we identified operational taxonomic units (OTUs) that greatly influenced classification of fecal samples into treatment groups. Each of these OTUs was correlated with fecal volatile organic compounds detected from the samples for companion treatment groups in another study. This research is the first to highlight striped skunk microbiome biodiversity as a vaccination biomarker which pushes the frontier on alternative methods for surveillance and monitoring of vaccination and disease in wildlife populations.

Literature is limited regarding the COVID-19 pandemic's impact on health services use in younger Canadian populations with asthma. We utilized health administrative databases from January 2019-December 2021 for a population-based cross-sectional study to identify Ontario residents 0-25 years old with physician-diagnosed asthma and calculate rates of healthcare use. Multivariable negative binomial regression analysis was used to adjust for confounders. We included 716,690 children and young adults ≤25 years. There was a sharp increase of ICS and SABA prescription rates at the start of the pandemic (March 2020) of 61.7% and 54.6%, respectively. Monthly virtual physician visit rates increased from zero to 0.23 per 100 asthma population during the pandemic. After adjusting for potential confounders, rate ratios (RR) with 95% confidence intervals (CI) showed that the pandemic was associated with significant decrease in hospital admissions (RR = 0.21, 95% CI: 0.18-0.24), emergency department visits (RR = 0.35, 95% CI: 0.34-0.37), and physician visits (RR = 0.61, 95% CI: 0.60-0.61). ICS and SABA prescriptions filled also significantly decreased during the pandemic (RR = 0.58, 95% CI: 0.57-0.60 and RR = 0.47, 95% CI: 0.46-0.48, respectively). This Canadian population-based asthma study demonstrated a dramatic decline in physician and emergency department visits, hospitalizations, and medication prescriptions filled during the COVID-19 pandemic. An extensive evaluation of the factors contributing to an 80% reduction in the risk of hospitalization may inform post-pandemic asthma management.

Abstract This study assesses attitudes towards COVID-19 vaccination and the predictive value of COVID-VAC, a novel scale, among adults in the four largest US metropolitan areas and nationally. A 36-item survey of 6037 Americans was conducted in mid-April 2021. The study reports factors for COVID-19 vaccine acceptance among: (1) already vaccinated; (2) unvaccinated but willing to accept a vaccine; and (3) unvaccinated and unwilling to vaccinate. More than 20% were unwilling to vaccinate, expressing concerns about vaccine efficacy and safety and questioning the disease’s severity. Poverty, working outside of the home and conservative political views are predictors of unwillingness. Conversely, those who either personally tested positive for COVID-19, or had a family member who did so, were more likely to accept vaccination. Majorities of all respondents supported vaccination mandates for employees and university students. Respondents preferred to receive vaccines in their doctor´s office. Lower income and conservative ideology, but not race, were strongly associated with vaccine unwillingness. The predictive value of COVID-VAC was demonstrated. While vaccination mandates are likely to be accepted, additional effective, targeted interventions to increase vaccine uptake are needed urgently.

We compared the characteristics of hospitalized and nonhospitalized patients who had coronavirus disease in Atlanta, Georgia, USA. We found that risk for hospitalization increased with a patient’s age and number of concurrent conditions. We also found a potential association between hospitalization and high hemoglobin A1c levels in persons with diabetes.

Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a channelopathy which can lead to fatal ventricular arrhythmias. The diagnosis can be challenging due to a wide variety of clinical presentations. In this case, we describe the unusual presentation and subsequent workup of a young patient who was ultimately diagnosed with CPVT.

Yaws is a chronic infection that affects mainly the skin, bone and cartilage and spreads mostly between children. The new approval of a medication as treatment in 2012 has revived eradication efforts and now only few known localized foci of infection remain. The World Health Organization strategy mandates an initial round of total community treatment (TCT) with single-dose azithromycin followed either by further TCT or by total targeted treatment (TTT), an active case-finding and treatment of cases and their contacts. We develop the compartmental ODE model of yaws transmission and treatment for these scenarios. We solve for disease-free and endemic equilibria and also perform the stability analysis. We calibrate the model and validate its predictions on the data from Lihir Island in Papua New Guinea. We demonstrate that TTT strategy is efficient in preventing outbreaks but, due to the presence of asymptomatic latent cases, TTT will not eliminate yaws within a reasonable time frame. To achieve the 2030 eradication target, TCT should be applied instead.

Recent Global Initiative for Asthma (GINA) recommendations reduce the role of short-acting β2-agonist (SABA) premised on the associated exacerbation risk. The widely accepted SABA risk profile is based on limited data described 30 years ago. This GINA paradigm shift demands an examination of SABA risks in a modern therapeutic era. Recent studies confirm that SABA overuse is common and associated with adverse outcomes. This study aimed to determine associations between SABA use, all-cause mortality and asthma exacerbations in an older North American asthma population. In this population-based cohort study, individuals with prevalent asthma (2006–2015) aged ≥65 years, eligible for provincial drug coverage, were included. Annual SABA canisters filled (0, 1–2, 3–5, ≥6) was the primary exposure. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazard regression, adjusted for confounders. There were 59 533 asthma individuals; 14% overused SABA (≥3 canisters annually). Compared to those who used

Ecological restoration frequently involves the addition of native plants, but the effectiveness (in terms of plant growth, plant survival, and cost) of using seeds versus container plants has not been studied in many plant communities. It is also not known if plant success would vary by species or based on functional traits. To answer these questions, we added several shrub species to a coastal sage scrub restoration site as seeds or as seedlings in a randomized block design. We measured percent cover, density, species richness, size, survival, and costs. Over the two years of the study, shrubs added to the site as seeds grew more and continued to have greater density than plants added from containers. Seeded plots also had greater native species richness than planted plots. However, shrubs from containers had higher survival rates, and percent cover was comparable between the planted and seeded treatments. Responses varied by species depending on functional traits, with deep-rooted evergreen species establishing better from container plants. Our cost analysis showed that it is more expensive to use container plants than seed, with most of the costs attributed to labor and supplies needed to grow plants. Our measurements of shrub density, survival, species richness, and growth in two years in our experimental plots lead us to conclude that coastal sage scrub restoration with seeds is optimal for increasing density and species richness with limited funds, yet the addition of some species from container plants may be necessary if key species are desired as part of the project objectives.

Aquaporin 4 is absent from astrocytes in the rodent optic nerve head, despite high expression in the retina and myelinated optic nerve. The purpose of this study was to quantify regional aquaporin channel expression in astrocytes of the porcine and human mouse optic nerve (ON). Ocular tissue sections were immunolabeled for aquaporins 1(AQP1), 4(AQP4), and 9(AQP9), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP) and alpha-dystroglycan (αDG) for their presence in retina, lamina, myelin transition zone (MTZ, region just posterior to lamina) and myelinated ON (MON). Semi- quantification of AQP4 labeling & real-time quantitative PCR (qPCR) data were analyzed in retina and ON tissue. Porcine and control human eyes had abundant AQP4 in Müller cells, retinal astrocytes, and myelinated ON (MON), but minimal expression in the lamina cribrosa. AQP1 and AQP9 were present in retina, but not in the lamina. Immunolabeling of GFAP and αDG was similar in lamina, myelin transition zone (MTZ) and MON regions. Semi-quantitative AQP4 labeling was at background level in lamina, increasing in the MTZ, and highest in the MON (lamina vs MTZ, MON; p≤0.05, p≤0.01, respectively). Expression of AQP4 mRNA was minimal in lamina and substantial in MTZ and MON, while GFAP mRNA expression was uniform among the lamina, MTZ, and MON regions. Western blot assay showed AQP4 protein expression in the MON samples, but none was detected in the lamina tissue. The minimal presence of AQP4 in the lamina is a specific regional phenotype of astrocytes in the mammalian optic nerve head.

Objective This study will add to existing literature by examining the impact of smoke-free legislation in outdoor areas among children with asthma. We aimed to examine the effect of the 2015 Smoke-Free Ontario Act (SFOA) amendment, which prohibited smoking on patios, playgrounds and sports fields, on health services use (HSU) rates in children with asthma.Methods We conducted a population-based open cohort study using health administrative data from the province of Ontario, Canada. Each year, all Ontario residents aged 0–18 years with physician diagnosed asthma were included in the study. Annual rates of HSU (emergency department (ED) visits, hospitalisations and physician office visits) for asthma and asthma-related conditions (eg, bronchitis, allergic rhinitis, influenza and pneumonia) were calculated. Interrupted time-series analysis, accounting for seasonality, was used to estimate changes in HSU following the 2015 SFOA.Results The study population ranged from 618 957 individuals in 2010 to 498 812 in 2018. An estimated average increase in ED visits for asthma in infants aged 0–1 years of 0.42 per 100 individuals (95% CI: 0.09 to 0.75) and a 57% relative increase corresponding to the 2015 SFOA was observed. A significant decrease in ED visits for asthma-related conditions of 0.19 per 100 individuals (95% CI: −0.37 to –0.01) and a 22% relative decrease corresponding to the 2015 SFOA was observed.Conclusion Based on the observed positive effect of restricting smoking on patios, playgrounds and sports fields on respiratory morbidity in children with asthma, other jurisdictions globally should consider implementing similar smoke-free policies.

Abstract Data from dietary intervention studies suggest that intake of (−)-epicatechin mediates beneficial vascular effects in humans. However, population-based investigations are required to evaluate associations between habitual intake and health and these studies rely on accurate estimates of intake, which nutritional biomarkers can provide. Here, we evaluate a series of structurally related (−)-epicatechin metabolites (SREM), particularly (−)-epicatechin-3′-glucuronide, (−)-epicatechin-3′-sulfate and 3′-O-methyl-(−)-epicatechin-5-sulfate (SREMB), as flavan-3-ol and (−)-epicatechin intake. SREMB in urine proved to be a specific indicator of (−)-epicatechin intake, showing also a strong correlation with the amount of (−)-epicatechin ingested (R2: 0.86 (95% CI 0.8l; 0.92). The median recovery of (−)-epicatechin as SREMB in 24 h urine was 10% (IQR 7–13%) and we found SREMB in the majority of participants of EPIC Norfolk (83% of 24,341) with a mean concentration of 2.4 ± 3.2 µmol/L. Our results show that SREMB are suitable as biomarker of (−)-epicatechin intake. According to evaluation criteria from IARC and the Institute of Medicine, the results obtained support use of SREMB as a recovery biomarker to estimate actual intake of (−)-epicatechin.

Species distribution models are useful for identifying the ecological characteristics that may limit a species' geographic range and for inferring patterns of speciation. Here, we test a hypothesis of niche conservatism across evolutionary time in a group of manakins (Aves: Pipridae), with a focus on Chiroxiphia boliviana, and examine the degree of ecological differentiation with other Chiroxiphia and Antilophia manakins. We tested whether allopatric sister species were more or less similar in environmental space than expected given their phylogenetic distances, which would suggest, respectively, ecological niche conservatism over time or ecologically mediated selection (i.e. niche divergence). We modeled the distribution of nine manakin taxa (C. boliviana, C. caudata, C. lanceolata, C. linearis, C. p. pareola, C. p. regina, C. p. napensis, Antilophia galeata and A. bokermanni) using Maxent. We first performed models for each taxon and compared them. To test our hypothesis we followed three approaches: (1) we tested whether C. boliviana could predict the distribution of the other manakin taxa and vice versa; (2) we compared the ecological niches by using metrics of niche overlap, niche equivalency and niche similarity; and (3) lastly, we tested whether niche differentiation corresponded to phylogenetic distances calculated from two recent phylogenies. All models had high training and test AUC values. Mean AUC ratios were high (>0.8) for most taxa, indicating performance better than random. Results suggested niche conservatism, and high niche overlap and equivalency between C. boliviana and C. caudata, but we found very low values between C. boliviana and the rest of the taxa. We found a negative, but not significant, relationship between niche overlap and phylogenetic distance, suggesting an increase in ecological differentiation and niche divergence over evolutionary time. Overall, we give some insights into the evolution of C. boliviana, proposing that ecological selection may have influenced its speciation.

PurposeTo study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null).MethodsC57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression, and transport block were also analyzed.ResultsB6 mice had abundant AQP4 expression in Müller cells, astrocytes of retina and myelinated ON (MON), but minimal AQP4in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p = 0.42) and axonal transport blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6).ConclusionLack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.

ObjectiveTo test in mice with a double mutation of the ApoE gene (ApoE-/-) whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy attenuates the impact of SCI.MethodsApoE-/- mice were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (70 k-dynes). Sham animals underwent all surgical procedures, excluding injury. Injured animals were randomized to 2 groups: SCI or SCI+Salsalate [120 mg/Kg/day i.p.]. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI, and body mass was recorded. At sacrifice, heart and aorta were harvested intact, fixed in 10% buffered formalin, cleaned and cut longitudinally for en face preparation. The aortic tree was stained with oil-red-O (ORO). AD lesion histomorphometry was calculated from the proportional area of ORO. Plasma total cholesterol, triglycerides and proatherogenic inflammatory cytokines (PAIC's) were analyzed.ResultsAD lesion in the aortic arch progressively increased in ApoE-/-, significant at 24- and 28-weeks. AD in SCI is significantly greater at 24- and 28-weeks compared to time-controlled ApoE-/-. Salsalate treatment attenuates the SCI-induced increase at these time points. Body mass in all SCI groups are significantly reduced compared to time-controlled ApoE-/-. Cholesterol and triglycerides are significantly higher with SCI by 24- and 28-weeks, compared to ApoE-/-, and Salsalate reduces the SCI-induced effect on cholesterol. PAIC's interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL-5) are significantly greater with SCI compared to ApoE-/- at varying timepoints. Salsalate confers a marginal reducing effect on PAIC's by 28-weeks compared to SCI. Regression models determine that each PAIC is a significant and positive predictor of lesion. (p's ConclusionsSCI accelerates aortic AD and associated risk factors, and anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes. PAIC's IL-1β, IL-6, TNFα, MCP-1, and CCL-5 may be effective predictors of AD.

Recent avian influenza infection outbreaks have resulted in global biosecurity and economic concerns. Mallards are asymptomatic for the disease and can potentially spread AI along migratory bird flyways. In a previous study, trained mice correctly discriminated the health status of individual ducks on the basis of fecal odors when feces from post-infection periods were paired with feces from pre-infection periods. Chemical analyses indicated that avian influenza infection was associated with a marked increase of acetoin (3-hydroxy-2-butanone) in feces. In the current study, domesticated male ferrets (Mustela putorius furo) were trained to display a specific conditioned response (i.e. active scratch alert) in response to a marked increase of acetoin in a presentation of an acetoin:1-octen-3-ol solution. Ferrets rapidly generalized this learned response to the odor of irradiated feces from avian influenza infected mallards. These results suggest that a trained mammalian biosensor could be employed in an avian influenza surveillance program.

Outbreaks of avian influenza virus (AIV) infection included the spread of highly pathogenic AIV in commercial poultry and backyard flocks in the spring of 2015. This resulted in estimated losses of more than $8.5 million from federal government expenditures, $1.6 billion from direct losses to produces arising from destroyed turkey and chicken egg production, and economy-wide indirect costs of $3.3 billion from impacts on retailers and the food service industries. Additionally, these outbreaks resulted in the death or depopulation of nearly 50 million domestic birds. Domesticated male ferrets (Mustela putorius furo) were trained to display a specific conditioned behavior (i.e. active scratch alert) in response to feces from AIV-infected mallards in comparison to feces from healthy ducks. In order to establish that ferrets were identifying samples based on odors associated with infection, additional experiments controlled for potentially confounding effects, such as: individual duck identity, housing and feed, inoculation concentration, and day of sample collection (post-infection). A final experiment revealed that trained ferrets could detect AIV infection status even in the presence of samples from mallards inoculated with Newcastle disease virus or infectious laryngotracheitis virus. These results indicate that mammalian biodetectors are capable of discriminating the specific odors emitted from the feces of non-infected versus AIV infected mallards, suggesting that the health status of waterfowl can be evaluated non-invasively for AIV infection via monitoring of volatile fecal metabolites. Furthermore, in situ monitoring using trained biodetectors may be an effective tool for assessing population health.

Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment. The backs of 14 women were treated with ablative fractional laser (Fraxel®) and 4 mm punch biopsies were collected from an untreated site and at the treated sites 1, 3, 7, 14, 21 and 28 days after the single treatment. In addition, in order to understand the effect that multiple fractional laser treatments have on skin rejuvenation, several sites were treated sequentially with either 1, 2, 3, or 4 treatments (with 28 days between treatments) followed by the collection of 4 mm punch biopsies. RNA was extracted from the biopsies, analyzed using Affymetrix U219 chips and gene expression was compared between untreated and treated sites. We observed dramatic changes in gene expression as early as 1 day after fractional laser treatment with changes remaining elevated even after 1 month. Analysis of individual genes demonstrated significant and time related changes in inflammatory, epidermal, and dermal genes, with dermal genes linked to extracellular matrix formation changing at later time points following fractional laser treatment. When comparing the age-related changes in skin gene expression to those induced by fractional laser, it was observed that fractional laser treatment reverses many of the changes in the aging gene expression. Finally, multiple fractional laser treatments, which cover different regions of a treatment area, resulted in a sustained or increased dermal remodeling response, with many genes either differentially regulated or continuously upregulated, supporting previous observations that maximal skin rejuvenation requires multiple fractional laser treatments. In conclusion, fractional laser treatment of human skin activates a number of biological processes involved in wound healing and tissue regeneration.

Introduction Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterise, and potentially contain new and emerging influenza strains at both an individual and population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population.Methods and analysis Starting in the 2018–2019 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modelling platforms are in development to characterise the regional spread of influenza and other respiratory pathogens.Ethics and dissemination The study was approved by the University of Washington’s Institutional Review Board (STUDY00006181). Results will be disseminated through talks at conferences, peer-reviewed publications and on the study website (www.seattleflu.org).

PurposeTo delineate responses of optic nerve head astrocytes to sustained intraocular pressure (IOP) elevation in mice.MethodsWe elevated IOP for 1 day to 6 weeks by intracameral microbead injection in 4 strains of mice. Astrocyte alterations were studied by transmission electron microscopy (TEM) including immunogold molecular localization, and by laser scanning microscopy (LSM) with immunofluorescence for integrin β1, α-dystroglycan, and glial fibrillary acidic protein (GFAP). Astrocyte proliferation and apoptosis were quantified by Ki67 and TUNEL labeling, respectively.ResultsAstrocytes in normal optic nerve head expressed integrin β1 and α-dystroglycan by LSM and TEM immunogold labeling at electron dense junctional complexes that were found only on cell membrane zones bordering their basement membranes (BM) at the peripapillary sclera (PPS) and optic nerve head capillaries. At 1-3 days after IOP elevation, abnormal extracellular spaces appeared between astrocytes near PPS, and axonal vesical and mitochondrial accumulation indicated axonal transport blockade. By 1 week, abnormal spaces increased, new collagen formation occurred, and astrocytes separated from their BM, leaving cell membrane fragments. Electron dense junctional complexes separated or were absent at the BM. Astrocyte proliferation was modest during the first week, while only occasional apoptotic astrocytes were observed by TEM and TUNEL.ConclusionsAstrocytes normally exhibit junctions with their BM which are disrupted by extended IOP elevation. Responses include reorientation of cell processes, new collagen formation, and cell proliferation.

BackgroundUnderstanding public perceptions of government responses to COVID-19 may foster improved public cooperation. Trust in government and population risk of exposure may influence public perception of the response. Other population-level characteristics, such as country socio-economic development, COVID-19 morbidity and mortality, and degree of democratic government, may influence perception.Methods and findingsWe developed a novel ten-item instrument that asks respondents to rate key aspects of their government's response to the pandemic (COVID-SCORE). We examined whether the results varied by gender, age group, education level, and monthly income. We also examined the internal and external validity of the index using appropriate predefined variables. To test for dimensionality of the results, we used a principal component analysis (PCA) for the ten survey items. We found that Cronbach's alpha was 0.92 and that the first component of the PCA explained 60% of variance with the remaining factors having eigenvalues below 1, strongly indicating that the tool is both reliable and unidimensional. Based on responses from 13,426 people randomly selected from the general population in 19 countries, the mean national scores ranged from 35.76 (Ecuador) to 80.48 (China) out of a maximum of 100 points. Heterogeneity in responses was observed across age, gender, education and income with the greatest amount of heterogeneity observed between countries. National scores correlated with respondents' reported levels of trust in government and with country-level COVID-19 mortality rates.ConclusionsThe COVID-SCORE survey instrument demonstrated satisfactory validity. It may help governments more effectively engage constituents in current and future efforts to control COVID-19. Additional country-specific assessment should be undertaken to measure trends over time and the public perceptions of key aspects of government responses in other countries.

Abstract Body odors change with health status and the odors of sick animals can induce avoidance behaviors in healthy conspecifics. Exposure to sickness odors might also alter the physiology of healthy conspecifics and modify the odors they produce. We hypothesized that exposure to odors of sick (but non-infectious) animals would alter the odors of healthy cagemates. To induce sickness, we injected mice with a bacterial endotoxin, lipopolysaccharide. We used behavioral odor discrimination assays and analytical chemistry techniques followed by predictive classification modeling to ask about differences in volatile odorants produced by two types of healthy mice: those cohoused with healthy conspecifics and those cohoused with sick conspecifics. Mice trained in Y-maze behavioral assays to discriminate between the odors of healthy versus sick mice also discriminated between the odors of healthy mice cohoused with sick conspecifics and odors of healthy mice cohoused with healthy conspecifics. Chemical analyses paired with statistical modeling revealed a parallel phenomenon. Urine volatiles of healthy mice cohoused with sick partners were more likely to be classified as those of sick rather than healthy mice based on discriminant model predictions. Sickness-related odors could have cascading effects on neuroendocrine or immune responses of healthy conspecifics, and could affect individual behaviors, social dynamics, and pathogen spread.

The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species’ geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation.

Objectives Hidradenitis suppurativa (HS) causes substantial morbidity and quality-of-life impairment. We examined demographic/clinical characteristics of patients with HS and treatment patterns, prevalence and healthcare resource utilisation/expenditures related to HS in the real-world.Design Retrospective claims data of MarketScan Commercial, Medicare Supplemental and Medicaid databases (2009–2014).Setting USA.Participants Patients aged ≥12 years with ≥3 non-diagnostic outpatient or inpatient claims with an HS diagnosis code and ≥12 months continuous enrolment with medical and pharmacy benefits before (preindex) and after (postindex) the earliest diagnosis of HS (index) were included.Results There were 11 325 Commercial/Medicare patients (mean age 37.4 years) and 5164 Medicaid patients (mean age 28.3 years). HS was more common in Medicaid than Commercial/Medicare patients (0.301% and 0.098%, respectively, in 2014). Cellulitis and psychiatric disorders were the most common comorbidities and oral antibiotics and narcotics were the most frequently prescribed drugs preindex, with ≥10% increase postindex in both populations. HS-related inpatient costs decreased while outpatient costs increased from preindex to postindex. Medicaid patients had several risk factors that may be associated with poor outcomes (eg, high rates of prescription pain medication use, comorbidities, drug discontinuation/interruption/holiday, emergency department (ED) visits and hospitalisation).Conclusions Commercial/Medicare and Medicaid HS beneficiaries experience high comorbidity burden but use different treatment modalities to manage HS. Results suggest a substantial unmet need exists among this patient population, with Medicaid patients experiencing a particularly high burden of disease and expensive healthcare resource utilisation.

Introduction Clinical trials and systematic reviews of trials involving vitamin D supplementation have mainly focused on defining the optimal amount of vitamin D dosage. However, the comparative effectiveness of different dosing schedules (ie, daily vs bolus dosing schedule) has been largely unexplored; and currently, there is no consensus regarding the optimal vitamin D dosing schedule. Our objective is to conduct a systematic review and network meta-analysis (NMA) to evaluate the comparative effectiveness and safety of steady (eg, daily, weekly) and intermittent high-dose (eg, monthly, yearly) vitamin D dosing schedules; and to determine the effectiveness of the various dosing schedules and combinations of treatments.Methods and analysis We will conduct a systematic search and review of literature from major medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) involving studies that compare vitamin D supplementation alone or in combination with calcium. Only randomised controlled trials (RCTs) will be considered. We will, however, consider various settings (eg, community, institutional care) and study designs (eg, cluster RCTs, cross-over trials). Our primary outcomes include falls and fractures including hip-fracture and non-vertebral fractures. Secondary outcomes will include muscle strength, physical performance, gait and mobility limitation. A Bayesian NMA will be conducted, and the results will be presented in the form of treatment effect estimates and ranking probabilities, with corresponding CIs. Pairwise meta-analysis will also be conducted for studies reporting head-to-head comparisons. Subgroup analysis will be performed with respect to pre-determined subgroups; including vitamin D status as measured by serum 25-hydroxyvitamin D levels, age and follow-up time. Sensitivity analysis will also be performed with respect to risk of bias.Ethics and dissemination This study is a systematic review and meta-analysis of published RCTs; therefore, no ethical approval is required. Results will be disseminated through open access peer-reviewed publications.Systematic review registration PROSPERO CRD42018112662.

To accelerate scientific progress on remote tree classification—as well as biodiversity and ecology sampling—The National Institute of Science and Technology created a community-based competition where scientists were invited to contribute informatics methods for classifying tree species and genus using crown-level images of trees. We classified tree species and genus at the pixel level using hyperspectral and LiDAR observations. We compared three algorithms that have been implemented extensively across a broad range of research applications: support vector machines, random forests, and multilayer perceptron. At the pixel level, the multilayer perceptron algorithm classified species or genus with high accuracy (92.7% and 95.9%, respectively) on the training data and performed better than the other two algorithms (85.8–93.5%). This indicates promise for the use of the multilayer perceptron (MLP) algorithm for tree-species classification based on hyperspectral and LiDAR observations and coincides with a growing body of research in which neural network-based algorithms outperform other types of classification algorithm for machine vision. To aggregate patterns across the images, we used an ensemble approach that averages the pixel-level outputs of the MLP algorithm to classify species at the crown level. The average accuracy of these classifications on the test set was 68.8% for the nine species.

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output.

We have previously shown that endoplasmic reticulum stress (ER stress) represses the PTEN inducible kinase 1 (PINK1) in lung type II alveolar epithelial cells (AECII) reducing mitophagy and increasing the susceptibility to lung fibrosis. Although increased circulating mitochondrial DNA (mtDNA) has been reported in chronic lung diseases, the contribution of mitophagy in the modulation of mitochondrial DAMP release and activation of profibrotic responses is unknown. In this study, we show that ER stress and PINK1 deficiency in AECII led to mitochondrial stress with significant oxidation and damage of mtDNA and subsequent extracellular release. Extracellular mtDNA was recognized by TLR9 in AECII by an endocytic-dependent pathway. PINK1 deficiency-dependent mtDNA release promoted activation of TLR9 and triggered secretion of the profibrotic factor TGF-β which was rescued by PINK1 overexpression. Enhanced mtDNA oxidation and damage were found in aging and IPF human lungs and, in concordance, levels of circulating mtDNA were significantly elevated in plasma and bronchoalveolar lavage (BAL) from patients with IPF. Free mtDNA was found elevated in other ILDs with low expression of PINK1 including hypersensitivity pneumonitis and autoimmune interstitial lung diseases. These results support a role for PINK1 mediated mitophagy in the attenuation of mitochondrial damage associated molecular patterns (DAMP) release and control of TGF-β mediated profibrotic responses.

ABSTRACT IMPACT: Our data reveal a histone modifying enzyme involved in regulating inflammation that may be a novel target for treating non-healing diabetic wounds. OBJECTIVES/GOALS: We investigate molecular mechanisms that regulate the inflammatory phenotype of macrophages in normal and diabetic wound healing. Our goal is to identify novel pathways that may be used to better treat diabetic patients with non-healing wounds. METHODS/STUDY POPULATION: We utilize normal and transgenic murine models on standard chow or high-diet to identify chromatin modifying enzymes involved in regulating macrophage function during wound healing. We validate our murine studies with human blood monocytes or wound macrophages from diabetic patients undergoing limb amputation surgery. RESULTS/ANTICIPATED RESULTS: We have identified the histone methyltransferase SETDB2 as a regulator inflammation in normal and diabetic wound macrophages. We found that SETDB2 was dependent on IFNβ singaling and that both IFNβ and Setdb2 expression were impaired in diabetic wound macrophages. Further, we show that SETDB2 regulates inflammatory response and immune cell trafficking pathways. We also show that SETDB2 genomic localization is dependent on *NFκΒ deposition of the promoter. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results indicate that SETDB2 is a regulator of macrophage plasticity and that SETDB2 expression is impaired in diabetic wound macrophages leading to hyper-inflammatory response and delayed wound healing. These data provide a novel potential therapeutic pathway for treating non-healing diabetic wounds.

Debilitating neurodegenerative conditions with metabolic origins affect millions of individuals worldwide. Still, for most of these neurometabolic disorders there are neither cures nor disease-modifying therapies, and novel animal models are needed for elucidation of disease pathology and identification of potential therapeutic agents. To date, metabolic neurodegenerative disease has been modeled in animals with only limited success, in part because existing models constitute analyses of single mutants and have thus overlooked potential redundancy within metabolic gene pathways associated with disease. Here, we present the first analysis of a very-long-chain acyl-CoA synthetase (ACS) double mutant. We show that the Drosophila bubblegum (bgm) and double bubble (dbb) genes have overlapping functions, and that the consequences of double knockout of both bubblegum and double bubble in the fly brain are profound, affecting behavior and brain morphology, and providing the best paradigm to date for an animal model of adrenoleukodystrophy (ALD), a fatal childhood neurodegenerative disease associated with the accumulation of very-long-chain fatty acids. Using this more fully penetrant model of disease to interrogate brain morphology at the level of electron microscopy, we show that dysregulation of fatty acid metabolism via disruption of ACS function in vivo is causal of neurodegenerative pathologies that are evident in both neuronal cells and their supporting cell populations, and leads ultimately to lytic cell death in affected areas of the brain. Finally, in an extension of our model system to the study of human disease, we describe our identification of an individual with leukodystrophy who harbors a rare mutation in SLC27a6 (encoding a very-long-chain ACS), a human homolog of bgm and dbb.

Terrestrial tardigrades, commonly known as “water bears”, are part of a phylum of microscopic, aquatic invertebrates famous for cryptobiosis and space travel, but little is known about their modes of dispersal on Earth. Wind is assumed, but not truly demonstrated, to be the major method of global dispersal. Yet, some water bear distribution patterns cannot be explained by patterns of prevailing winds. Mammals and birds have been proposed as potential animal vectors. Importantly, most nearctic-neotropical migrant birds move north and south, with many crossing the equator, whereas prevailing winds move west to east or east to west but do not cross the equator. When multiplied by billions of birds over tens of millions of years, if the ectozoochory of tardigrades by birds is true then both regional and intercontinental patterns can be better explained. To test for the potential role of birds in tardigrade dispersal, the nests of 10 species for birds were examined. Seventy percent of nests were positive for tardigrades, demonstrating that some birds are in a position for transference. The carcasses of eight birds (six species) found dead from window strikes and a Sandhill Crane (Grus canadensis) found dead during routine surveys were also examined. Of the birds examined, 66% yielded tardigrades from two classes, three orders, and five species, including juveniles, adults, and eggs, suggesting that many bird species are potential vectors for many species of tardigrades. Our data support the hypothesis of avian-mediated long distance dispersal of tardigrades and provide evidence that further investigation is warranted.

Little is known about the capacity of lower vertebrates to experience itch. A screen of itch-inducing compounds (pruritogens) in zebrafish larvae yielded a single pruritogen, the TLR7 agonist imiquimod, that elicited a somatosensory neuron response. Imiquimod induced itch-like behaviors in zebrafish distinct from those induced by the noxious TRPA1 agonist, allyl isothiocyanate. In the zebrafish, imiquimod-evoked somatosensory neuronal responses and behaviors were entirely dependent upon TRPA1, while in the mouse TRPA1 was required for the direct activation of somatosensory neurons and partially responsible for behaviors elicited by this pruritogen. Imiquimod was found to be a direct but weak TRPA1 agonist that activated a subset of TRPA1 expressing neurons. Imiquimod-responsive TRPA1 expressing neurons were significantly more sensitive to noxious stimuli than other TRPA1 expressing neurons. Together, these results suggest a model for selective itch via activation of a specialized subpopulation of somatosensory neurons with a heightened sensitivity to noxious stimuli.