High Traffic Roads and Adverse Birth Outcomes: Comparing Births Upwind and Downwind of the Same Road.

Traffic related air pollution is a major concern for perinatal health. Determining causal associations, however, is difficult since high-traffic areas tend to correspond with lower socioeconomic neighborhoods and other environmental exposures. To overcome confounding, we compared pregnant individuals living downwind and upwind of the same high-traffic road. We leveraged vital statistics data for Texas from 2007-2016 (n=3,570,272 births) and computed hourly wind estimates for residential addresses within 500 m of high-traffic roads (i.e., annual average daily traffic greater than 25,000) (10.9% of births). We matched pregnant individuals predominantly upwind to pregnant neighbors downwind of the same road segment (n=37,631 pairs). Living downwind was associated with an 11.6 gram (95% CI: -18.01, -5.21) decrease in term birth weight. No associations were observed with low term birth weight, preterm birth, or very preterm birth. In distance-stratified models, living downwind within 50 m was associated with a -36.3 gram (95% CI: -67.74, -4.93) decrease in term birth weight and living 51-100m downwind was associated with an odds ratio of 3.68 (95% CI: 1.71, 7.90) for very preterm birth. These results suggest traffic air pollution is associated with adverse birth outcomes, with steep distance decay gradients around major roads.

Roadway construction as a natural experiment to examine air pollution impacts on infant health.

Traffic-related air pollution (TRAP) poses a significant public health risk that is associated with adverse birth outcomes. Large roadway infrastructure projects present a natural experiment to examine how resulting congestion change is associated with adverse birth outcomes for nearby populations. This study is designed to examine the influence of living close to a roadway before, during, and after a construction project using a difference-in-differences design. We integrated data on all large roadway construction projects (defined as widening of existing roads, building new roads, improving bridges, installing intelligent transportation systems, improving intersections, and installing or upgrading traffic signals) in Texas from 2007 to 2016 with Vital Statistic data for all births with residential addresses within 1 km of construction projects. Our outcomes included term low birth weight, term birth weight, preterm birth, and very preterm birth. Using a difference-in-differences design, we included births within 3 years of construction start and 2 years of construction end. In our main model, the exposed group is limited to pregnant individuals residing within 300 m of a construction project, and the control group includes those living within 300-1000 m from a project. We used regression models to estimate the influence of construction on infant health. We included 1,360 large roadway construction projects linked to 408,979 births. During construction, we found that the odds of term low birth weight increased by 19% (95% CI: 1.05, 1.36). However, we saw little evidence of an association for other birth outcomes. Contrary to our hypothesis of decreased TRAP after construction ends, we did not observe consistent improvements post-construction for pregnant individuals living within 300 m. Continued consideration of the influence of traffic congestion programs on birth outcomes is necessary to inform future policy decisions.

Drinking Water Contaminant Concentrations and Birth Outcomes.

Previous research in the US has found negative health effects of contamination when it triggers regulatory violations. An important question is whether levels of contamination that do not trigger a health-based violation impact health. We study the impact of drinking water contamination in community water systems on birth outcomes using drinking water sampling results data in Pennsylvania. We focus on the effects of water contamination for births not exposed to regulatory violations. Our most rigorous specification employs mother fixed effects and finds changing from the 10th to the 90th percentile of water contamination (among births not exposed to regulatory violations) increases low birth weight by 12% and preterm birth by 17%.

Coding long COVID: characterizing a new disease through an ICD-10 lens.

BACKGROUND: Naming a newly discovered disease is a difficult process; in the context of the COVID-19 pandemic and the existence of post-acute sequelae of SARS-CoV-2 infection (PASC), which includes long COVID, it has proven especially challenging. Disease definitions and assignment of a diagnosis code are often asynchronous and iterative. The clinical definition and our understanding of the underlying mechanisms of long COVID are still in flux, and the deployment of an ICD-10-CM code for long COVID in the USA took nearly 2 years after patients had begun to describe their condition. Here, we leverage the largest publicly available HIPAA-limited dataset about patients with COVID-19 in the US to examine the heterogeneity of adoption and use of U09.9, the ICD-10-CM code for "Post COVID-19 condition, unspecified." METHODS: We undertook a number of analyses to characterize the N3C population with a U09.9 diagnosis code (n = 33,782), including assessing person-level demographics and a number of area-level social determinants of health; diagnoses commonly co-occurring with U09.9, clustered using the Louvain algorithm; and quantifying medications and procedures recorded within 60 days of U09.9 diagnosis. We stratified all analyses by age group in order to discern differing patterns of care across the lifespan. RESULTS: We established the diagnoses most commonly co-occurring with U09.9 and algorithmically clustered them into four major categories: cardiopulmonary, neurological, gastrointestinal, and comorbid conditions. Importantly, we discovered that the population of patients diagnosed with U09.9 is demographically skewed toward female, White, non-Hispanic individuals, as well as individuals living in areas with low poverty and low unemployment. Our results also include a characterization of common procedures and medications associated with U09.9-coded patients. CONCLUSIONS: This work offers insight into potential subtypes and current practice patterns around long COVID and speaks to the existence of disparities in the diagnosis of patients with long COVID. This latter finding in particular requires further research and urgent remediation.

Risk factors associated with post-acute sequelae of SARS-CoV-2: an N3C and NIH RECOVER study.

BACKGROUND: More than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID). The objective is to identify risk factors associated with PASC/long-COVID diagnosis. METHODS: This was a retrospective case-control study including 31 health systems in the United States from the National COVID Cohort Collaborative (N3C). 8,325 individuals with PASC (defined by the presence of the International Classification of Diseases, version 10 code U09.9 or a long-COVID clinic visit) matched to 41,625 controls within the same health system and COVID index date within ± 45 days of the corresponding case's earliest COVID index date. Measurements of risk factors included demographics, comorbidities, treatment and acute characteristics related to COVID-19. Multivariable logistic regression, random forest, and XGBoost were used to determine the associations between risk factors and PASC. RESULTS: Among 8,325 individuals with PASC, the majority were > 50 years of age (56.6%), female (62.8%), and non-Hispanic White (68.6%). In logistic regression, middle-age categories (40 to 69 years; OR ranging from 2.32 to 2.58), female sex (OR 1.4, 95% CI 1.33-1.48), hospitalization associated with COVID-19 (OR 3.8, 95% CI 3.05-4.73), long (8-30 days, OR 1.69, 95% CI 1.31-2.17) or extended hospital stay (30 + days, OR 3.38, 95% CI 2.45-4.67), receipt of mechanical ventilation (OR 1.44, 95% CI 1.18-1.74), and several comorbidities including depression (OR 1.50, 95% CI 1.40-1.60), chronic lung disease (OR 1.63, 95% CI 1.53-1.74), and obesity (OR 1.23, 95% CI 1.16-1.3) were associated with increased likelihood of PASC diagnosis or care at a long-COVID clinic. Characteristics associated with a lower likelihood of PASC diagnosis or care at a long-COVID clinic included younger age (18 to 29 years), male sex, non-Hispanic Black race, and comorbidities such as substance abuse, cardiomyopathy, psychosis, and dementia. More doctors per capita in the county of residence was associated with an increased likelihood of PASC diagnosis or care at a long-COVID clinic. Our findings were consistent in sensitivity analyses using a variety of analytic techniques and approaches to select controls. CONCLUSIONS: This national study identified important risk factors for PASC diagnosis such as middle age, severe COVID-19 disease, and specific comorbidities. Further clinical and epidemiological research is needed to better understand underlying mechanisms and the potential role of vaccines and therapeutics in altering PASC course.

The roles of physician associates and advanced nurse practitioners in the National Health Service in the UK: a scoping review and narrative synthesis.

BACKGROUND: Mid-level practitioners (MLPs), including physician associates (PAs) and advanced nurse practitioners (ANPs), have emerged to address workforce shortages in the UK and perform specific roles in relation to population needs. This has resulted in new ways of working and changes to established professional hierarchies. We conducted a study to investigate the career development, competencies, effectiveness, perceptions, and regulation of PAs and ANPs, with the aim of understanding ways to effectively integrate MLPs into the NHS workforce. METHODS: We conducted a systematic scoping review following PRISMA guidelines. Embase, Medline, the Cochrane database, Pubmed, and CINAHL databases were searched, using terms relating to PAs and ANPs in the UK. A total of 128 studies (60 on PAs and 68 on ANPs) were included in the final analysis. A narrative synthesis, guided by the pre-defined themes and emerging themes, was conducted to bring together the findings. RESULTS: PAs are educated on a medical model with basic medical skills but lack formal professional regulation and do not have prescribing rights. ANPs are educated on a nurse model with enhanced skills that depend on roles within specific specialities, and their governance is mostly employer-led. PAs are primarily employed in secondary care. ANPs are employed widely in both primary and secondary care. No defined career progression exists for PAs. In contrast, becoming an ANP is a form of career progression within nursing. Both roles were regarded as cost-effective in comparison to doctors performing simple tasks. PAs were less understood compared to ANPs and received a mixed reception from colleagues, which sometimes undermined their professional identity, whereas ANPs were mostly welcomed by colleagues. CONCLUSIONS: Potential ways to better integrate PAs and ANPs into the NHS workforce include further initiatives by regulatory bodies and the NHS to create more awareness and clearer role definitions for MLPs, outline potential for career progression, offer transparency with regard to remuneration, and introduction of prescribing rights. Future research might include more cadres of MLPs and explore the international literature.

Coroner county systems are associated with a higher likelihood of unclassified drug overdoses compared to medical examiner county systems.

Background: There is a striking geographic variation in drug overdose deaths without a specific drug recorded, many of which likely involve opioids. Knowledge of the reasons underlying this variation is limited.Objectives: We sought to understand the role of medicolegal death investigation (MDI) systems in unclassified drug overdose mortality.Methods: This is an observational study of 2014 and 2018 fatal drug overdoses and U.S. county-level MDI system type (coroner vs medical examiner). Mortality data are from the CDC's National Center for Health Statistics. We estimated multivariable logistic regressions to quantify associations between MDI system type and several outcome variables: whether the drug overdose was unclassified and whether involvement of any opioid, synthetic opioid, methadone, and heroin was recorded (vs unclassified), for 2014 (N = 46,996) and 2018 (N = 67,359).Results: In 2018, drug overdose deaths occurring in coroner counties were almost four times more likely to be unclassified (OR 3.87, 95% CI 2.32, 6.46) compared to medical examiner counties. These odds ratios are twice as large as in 2014 (difference statistically significant, P < .001), indicating that medical examiner counties are improving identification of opioids in drug overdoses faster than coroner counties.Conclusions: Accurate reporting of drug overdose deaths depends on MDI systems. When developing state policies and local interventions aimed to decrease opioid overdose mortality, decision-makers should understand the role their MDI system is playing in underestimating the extent of the opioid overdose crisis. Improvements to state and county MDI systems are desirable if accurate reporting and appropriate policy response are to be achieved.

Institutional Postacute Care Use May Help Reduce Readmissions for Ischemic Stroke Patients.

OBJECTIVES: Readmissions for Medicare patients initially admitted for stroke are common and costly. Rehabilitation in an institutional postacute care (PAC) setting is an evidence-based component of recovery for stroke. Under current Medicare payment reforms, care coordination across hospitals and PAC providers is key to improving quality and efficiency of care. We examined the causal impact of institutional PAC use on 30-day readmission rates for Medicare fee-for-service patients initially admitted for ischemic stroke. DATA SOURCES: The 2010-2016 Medicare Provider Analysis and Review files. RESEARCH DESIGN: We used the method of instrumental variable (IV) analysis to control for unobserved differences in the types of patients admitted to each PAC facility. We chose the distance from the patient's residence to the closest institutional PAC provider and the number of PAC providers of each type within a county where the patient resides as IVs. PRINCIPAL FINDINGS: In the naive model, an increase in institutional PAC use was significantly associated with an increase in 30-day readmission by 0.03 percentage points. However, using IV analysis to control for endogeneity bias, an increase in institutional PAC use was associated with a decrease in 30-day readmission rate by 0.19 percentage points. Our findings indicate that reducing institutional PAC use among patients typically requiring rehabilitation in institutional settings for recovery may potentially lead to adverse postdischarge outcomes that require rehospitalization. Thus, payment incentives to reduce institutional PAC use should be balanced with postdischarge outcomes among ischemic stroke patients.

The Effect of Medicare Shared Savings Program on Readmissions and Variations by Race/Ethnicity and Payer Status (December 9, 2020).

OBJECTIVE: Accountable care organizations in the Medicare Shared Savings Program (MSSP) in the United States attempt to reduce cost and improve quality for their patients by improving care coordination across care settings. We examined the impact of hospital participation in the MSSP on 30-day readmissions for several groups of Medicare inpatients, and by race/ethnicity and payer status. MAIN DATA SOURCE: A 2010-2016 Medicare Provider Analysis and Review files. RESEARCH DESIGN: With propensity score matched sample of MSSP and non-MSSP-participating hospitals, patient-level linear probability models with difference-in-differences approach were used to compare the changes in readmission rates for Medicare fee-for-service patients initially admitted for ischemic stroke, hip fracture, or total joint arthroplasty in MSSP-participating hospitals with non-MSSP-participating hospitals as well as to compare the changes in disparities in readmission rates over time. PRINCIPAL FINDINGS: Hospital participation in MSSP was associated with further reduced readmission rate by 1.1 percentage points (95% confidence interval: -0.02 to 0.00, P<0.05) and 1.5 percentage points (95% confidence interval: -0.03 to 0.00, P=0.08) for ischemic stroke and hip fracture cohorts, respectively, compared with non-MSSP-participating hospitals, after the third year of hospital participation in the MSSP. There was no evidence that MSSP had an impact on racial/ethnic disparities, but increased disparity by payer status (dual vs. Medicare-only) was observed. These findings together suggest that MSSP accountable care organizations may take at least 3 years to achieve reduced readmissions and may increase disparities by payer status.

Acute myocardial infarction associated with unconventional natural gas development: A natural experiment.

BACKGROUND: Whereas it is plausible that unconventional natural gas development (UNGD) may adversely affect cardiovascular health, little is currently known. We investigate whether UNGD is associated with acute myocardial infarction (AMI). METHODS: In this observational study leveraging the natural experiment generated by New York's ban on hydraulic fracturing, we analyzed the relationship between age- and sex-specific county-level AMI hospitalization and mortality rates and three UNGD drilling measures. This longitudinal panel analysis compares Pennsylvania and New York counties on the Marcellus Shale observed over 2005-2014 (N = 2840 county-year-quarters). RESULTS: A hundred cumulative wells is associated with 0.26 more hospitalizations per 10,000 males 45-54y.o. (95% CI 0.07,0.46), 0.40 more hospitalizations per 10,000 males 65-74y.o. (95% CI 0.09,0.71), 0.47 more hospitalizations per 10,000 females 65-74y.o. (95% CI 0.18,0.77) and 1.11 more hospitalizations per 10,000 females 75y.o.+ (95% CI 0.39,1.82), translating into 1.4-2.8% increases. One additional well per square mile is associated with 2.63 more hospitalizations per 10,000 males 45-54y.o. (95% CI 0.67,4.59) and 9.7 hospitalizations per 10,000 females 75y.o.+ (95% CI 1.92,17.42), 25.8% and 24.2% increases, respectively. As for mortality rates, a hundred cumulative wells is associated with an increase of 0.09 deaths per 10,000 males 45-54y.o. (95% CI 0.02,0.16), a 5.3% increase. CONCLUSIONS: Cumulative UNGD is associated with increased AMI hospitalization rates among middle-aged men, older men and older women as well as with increased AMI mortality among middle-aged men. Our findings lend support for increased awareness about cardiovascular risks of UNGD and scaled-up AMI prevention as well as suggest that bans on hydraulic fracturing can be protective for public health.

Fatal opioid overdoses in the U.S. declined more than reported between 2017 and 2018.

Background: In U.S. death records, many drug overdoses do not have classified drug involvement, which challenges surveillance of opioid overdoses across time and space.Objective: To estimate the 2017-2018 change in opioid overdose deaths that accounts for probable opioid involvement in unclassified drug overdose deaths.Methods: In this retrospective design study, data on all drug overdose decedents from 2017-2018 in the U.S. were used to calculate the year-to-year change in known opioid overdoses, predict opioid involvement in unclassified drug overdoses, and estimate the year-to-year change in corrected opioid overdoses, which include both known and predicted opioid deaths. We used the Multiple Cause of Death (MCOD) data from CDC.Results: We estimated that the decrease in the age-adjusted opioid overdose death rate from 2017-2018 was 7.0%. There is a striking variation across states. Age-adjusted opioid overdose death rates decreased by 9.9% in Ohio and more than 5.0% in other Appalachian states (Pennsylvania, West Virginia, Kentucky), while they increased by 6.8% in Delaware.Conclusions: Our models suggest that opioid overdose-related mortality declined from 2017 to 2018 at a higher rate than reported (7.0% versus than the reported 2.0%), potentially indicating that clinical efforts and federal, state, and local government policies designed to control the epidemic have been effective in most states. Our local area estimates can be used by researchers, policy-makers and public health officials to assess effectiveness of state policies and interventions in smaller jurisdictions implemented in response to the crisis.

Collaborative healthcare education programmes for continuing professional education in low and middle-income countries: A Best Evidence Medical Education (BEME) systematic review. BEME Guide No. 65.

BACKGROUND: Large discrepancies exist between standards of healthcare provision in high-income (HICs) and low and middle-income countries (LMICs). The root cause is often financial, resulting in poor infrastructure and under-resourced education and healthcare systems. Continuing professional education (CPE) programmes improve staff knowledge, skills, retention, and practice, but remain costly and rare in low-resource settings. One potential solution involves healthcare education collaborations between institutions in HICs and LMICs to provide culturally appropriate CPE in LMICs. To be effective, educational partnerships must address the challenges arising from differences in cultural norms, language, available technology and organisational structures within collaborating countries. METHODS: Seven databases and other sources were systematically searched on 7 July 2020 for relevant studies. Citations, abstracts, and studies were screened and consensus was reached on which to include within the review. 54 studies were assessed regarding the type of educational programme involved, the nature of HIC/LMIC collaboration and quality of the study design. RESULTS: Studies varied greatly regarding the types and numbers of healthcare professionals involved, pedagogical and delivery methods, and the ways in which collaboration was undertaken. Barriers and enablers of collaboration were identified and discussed. The key findings were: 1. The methodological quality of reporting in the studies was generally poor. 2. The way in which HIC/LMIC healthcare education collaboration is undertaken varies according to many factors, including what is to be delivered, the learner group, the context, and the resources available. 3. Western bias was a major barrier. 4. The key to developing successful collaborations was the quality, nature, and duration of the relationships between those involved. CONCLUSION: This review provides insights into factors that underpin successful HIC/LMIC healthcare CPE collaborations and outlines inequities and quality issues in reporting.

Consent in the time of COVID-19.

The COVID-19 pandemic crisis has necessitated widespread adaptation of revised treatment regimens for both urgent and routine medical problems in patients with and without COVID-19. Some of these alternative treatments maybe second-best. Treatments that are known to be superior might not be appropriate to deliver during a pandemic when consideration must be given to distributive justice and protection of patients and their medical teams as well the importance given to individual benefit and autonomy. What is required of the doctor discussing these alternative, potentially inferior treatments and seeking consent to proceed? Should doctors share information about unavailable but standard treatment alternatives when seeking consent? There are arguments in defence of non-disclosure; information about unavailable treatments may not aid a patient to weigh up options that are available to them. There might be justified concern about distress for patients who are informed that they are receiving second-best therapies. However, we argue that doctors should tailor information according to the needs of the individual patient. For most patients that will include a nuanced discussion about treatments that would be considered in other times but currently unavailable. That will sometimes be a difficult conversation, and require clinicians to be frank about limited resources and necessary rationing. However, transparency and honesty will usually be the best policy.

Twelve tips for undertaking a focused systematic review in medical education.

The exponential growth of the systematic review methodology within health has been mirrored within medical education, allowing large numbers of publications on a topic to be synthesized to guide researchers and teachers. The robust, transparent and reproducible search methodologies employed offer scholarly rigor. The scope and scale of many reviews in education have only been matched by the size of the commitment needed to complete them and occasional lack of utility of reports. As such, we have noticed a growth in reviews across journals in the field that have questions that are more focused in scope. The authors propose 12 tips for performing a focused review in the right settings for the right reasons and discuss why such "focused reviews" may be more beneficial in those circumstances. Focused reviews allow researchers to formulate answers to specific local issues that have explicit utility of findings. Such reviews are equipped to identify what works for specific groups in specific circumstances and even question how and why this may occur. An additional impact of a focused approach can be a rapid turnaround. This article explains the purpose and benefits of focused review and provides guidance on how to produce them.

Unconventional natural gas development and pediatric asthma hospitalizations in Pennsylvania.

BACKGROUND: Pediatric asthma is a common chronic condition that can be exacerbated by environmental exposures, and unconventional natural gas development (UNGD) has been associated with decreased community air quality. This study aims to quantify the association between UNGD and pediatric asthma hospitalizations. METHODS: We compare pediatric asthma hospitalizations among zip codes with and without exposure to UNGD between 2003 and 2014 using a difference-in-differences panel analysis. Our UNGD exposure metrics include cumulative and contemporaneous drilling as well as reported air emissions by site. RESULTS: We observed consistently elevated odds of hospitalizations in the top tertile of pediatric patients exposed to unconventional drilling compared with their unexposed peers. During the same quarter a well was drilled, we find a 25% increase (95% CI: 1.07, 1.47) in the odds of being hospitalized for asthma. Ever-establishment of an UNGD well within a zip code was associated with a 1.19 (95% CI: 1.04, 1.36) increased odds of a pediatric asthma hospitalization. Our results further demonstrate that increasing specific air emissions from UNGD sites are associated with increased risks of pediatric asthma hospitalizations (e.g. 2,2,4-trimethylpentane, formaldehyde, x-hexane). These results hold across multiple age groups and sensitivity analyses. CONCLUSIONS: Community-level UNGD exposure metrics were associated with increased odds of pediatric asthma-related hospitalization among young children and adolescents. This study provides evidence that additional regulations may be necessary to protect children's respiratory health from UNGD activities.

Bundling of Reimbursement for Inferior Vena Cava Filter Placement Resulted in Significantly Decreased Utilization between 2012 and 2014.

BACKGROUND: On January 1, 2012, reimbursement for inferior vena cava filters (IVCFs) became bundled by the Centers for Medicare and Medicaid Services. This resulted in ICVF placement (CPT code 37191) now yielding 4.71 relative value units (RVUs), a decrease from 15.6 RVUs for placement and associated procedures (CPT codes 37620, 36010, 75825-26, 75940-26). Our hypothesis was that IVCF utilization would decrease in response to this change as other procedures had done once they had become bundled. METHODS: Including data from 2010 to 2011 (before bundling) and 2012 to 2014 (after bundling), we utilized 5% inpatient, outpatient, and carrier files of Medicare limited data sets and analyzed IVCF utilization before and after bundling across specialty types, controlling for total diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) (ICD-9 codes 453.xx and 415.xx, respectively) and placement location. RESULTS: In 2010 and 2011, the rates/10,000 DVT/PE diagnoses were 918 and 1,052, respectively (average 985). In 2012, 2013, and 2014, rates were 987, 877, and 605, respectively (average 823). Comparing each year individually, there is a significant difference (P < 0.0001) with 2012, 2013, and 2014 having lower rates of ICVF utilization. Comparing averages in the 2010-2011 and 2012-2014 groups, there is also a significant decrease in utilization after bundling (P < 0.0001). CONCLUSIONS: Following the bundling of reimbursement for IVCF placement, procedural utilization decreased significantly. More data from subsequent years will be needed to show if this decrease utilization continues to persist.

Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter.

The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the role of GSK3 in production of IL-10 by subsets of CD4(+) T helper cells. Treatment of naive murine CD4(+) T cells with GSK3 inhibitors did not affect their production of IL-10. However, treatment of Th1 and Th2 cells with GSK3 inhibitors dramatically increased production of IL-10. GSK3 inhibition also led to upregulation of IL-10 among Th1, Th2, and Th17 subsets isolated from human blood. The encephalitogenic potential of GSK3 inhibitor treated murine Th1 cells was significantly reduced in adoptive transfer experiments by an IL-10-dependent mechanism. Analysis of the murine IL-10 promoter in response to inhibition of GSK3 in Th1 cells showed modification to a transcriptionally active state indicated by changes in histone H3 acetylation and methylation. Additionally, GSK3 inhibition increased expression of the transcription factors c-Maf, Nfil3, and GATA3, correlating with the increase in IL-10. These findings are important in the context of autoimmune disease since they show that it is possible to reprogram disease-causing cells through GSK3 inhibition.

Environmental and Economic Impacts of Localizing Food Systems: The Case of Dairy Supply Chains in the Northeastern United States.

We developed and evaluated an empirical model of the U.S. dairy supply chain with a high degree of spatial and product disaggregation to assess the impacts of increasing localization of the northeast region's fluid milk supply on food miles, supply chain costs, greenhouse gas and criteria pollutant emissions, economic activity, and employment. Evaluation included comparison to regional production values and sensitivity analysis of demand and unit cost assumptions. Our analysis compares a baseline to two localization scenarios based on state boundaries and multiple-state subregions. Localization scenarios increased total distances fluid milk traveled by 7-15%, overall supply chain costs by 1-2%, and emissions of greenhouse gases (CO2 equivalent) criteria pollutants such as oxides of nitrogen and particulate matter smaller than 2.5 µm associated with fluid milk transportation by 7-15% per month. The impacts of localization on employment and economic activity are positive, but changes are small on a percentage basis. Our analyses indicate that the definition used for localization has an impact on outcomes and that efforts to localize food systems may benefit from a more systems-oriented approach.

Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle.

PIKfyve (FYVE domain-containing phosphatidylinositol 3-phosphate 5-kinase), the lipid kinase that phosphorylates PtdIns3P to PtdIns(3,5)P2, has been implicated in insulin-stimulated glucose uptake. We investigated whether PIKfyve could also be involved in contraction/AMPK (AMP-activated protein kinase)-stimulated glucose uptake in skeletal muscle. Incubation of rat epitrochlearis muscles with YM201636, a selective PIKfyve inhibitor, reduced contraction- and AICAriboside (5-amino-4-imidazolecarboxamide riboside)-stimulated glucose uptake. Consistently, PIKfyve knockdown in C2C12 myotubes reduced AICAriboside-stimulated glucose transport. Furthermore, muscle contraction increased PtdIns(3,5)P2 levels and PIKfyve phosphorylation. AMPK phosphorylated PIKfyve at Ser307 both in vitro and in intact cells. Following subcellular fractionation, PIKfyve recovery in a crude intracellular membrane fraction was increased in contracting versus resting muscles. Also in opossum kidney cells, wild-type, but not S307A mutant, PIKfyve was recruited to endosomal vesicles in response to AMPK activation. We propose that PIKfyve activity is required for the stimulation of skeletal muscle glucose uptake by contraction/AMPK activation. PIKfyve is a new AMPK substrate whose phosphorylation at Ser307 could promote PIKfyve translocation to endosomes for PtdIns(3,5)P2 synthesis to facilitate GLUT4 (glucose transporter 4) translocation.

Influence of Community Determinants on Barriers and Facilitators to COVID-19 Vaccine Uptake: Regional Stakeholders' Perspectives.

Our study objective was to explore possible pathways by which neighborhood-level characteristics drive COVID-19 vaccination among communities experiencing health inequity and disparities. To do so, we conducted semi-structured qualitative interviews with stakeholders in the Finger Lakes region of New York between November 2022 through January 2023. Using a pre-developed interview guide informed by the Health Belief Model, we elicited county health commissioner, medical professional and community-health partner's perspectives regarding the impact community determinants have on shaping barriers to and facilitators of COVID-19 vaccine uptake, as well as recommended solutions for ensuring health equity in future vaccination efforts. Fifteen stakeholders were interviewed, of which 40% were county health commissioners, 27% hospital executives and 33% community-health organization partners. We identified diverse perceived and logistical barriers to COVID-19 vaccination that emerged as sub-themes including perceived risks outweighing the benefits of vaccination, concerns of vaccine safety, distrust stemming from changing scientific knowledge surrounding the vaccines, mistrust of the medical system, and challenges with transportation to and registering for vaccine appointments. Stakeholders reported these barriers were linked to the racial diversity, poverty, political conservatism, and availability of health care of the communities where they reported these were experienced. Notable solutions for improving equitable vaccination included facilitating structural access to vaccination and engaging community trusted messengers. Perceived and experienced barriers to COVID-19 vaccination may differ based upon the social, racial and economic composition of neighboring communities. Strategies for ensuring health equity in future vaccination campaigns should specifically target prevalent barriers based upon the community composition.