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After the identification of the gamma-ray blazar TXS 0506+056 as the first compelling IceCube neutrino source candidate, we perform a systematic analysis of all high-energy neutrino events satisfying the IceCube realtime trigger criteria. We find one additional known gamma-ray source, the blazar GB6 J1040+0617, in spatial coincidence with a neutrino in this sample. The chance probability of this coincidence is 30% after trial correction. For the first time, we present a systematic study of the gamma-ray flux, spectral and optical variability, and multiwavelength behavior of GB6 J1040+0617 and compare it to TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the Fermi-Large Area Telescope gamma-ray band, being in an active state around the arrival of IceCube-170922A, but in a low state during the archival IceCube neutrino flare in 2014/15. In both cases the spectral shape is statistically compatible (≤2σ) with the average spectrum showing no indication of a significant relative increase of a high-energy component. While the association of GB6 J1040+0617 with the neutrino is consistent with background expectations, the source appears to be a plausible neutrino source candidate based on its energetics and multiwavelength features, namely a bright optical flare and modestly increased gamma-ray activity. Finding one or two neutrinos originating from gamma-ray blazars in the given sample of high-energy neutrinos is consistent with previously derived limits of neutrino emission from gamma-ray blazars, indicating the sources of the majority of cosmic high-energy neutrinos remain unknown.

After the identification of the gamma-ray blazar TXS 0506+056 as the first compelling IceCube neutrino source candidate, we perform a systematic analysis of all high-energy neutrino events satisfying the IceCube realtime trigger criteria. We find one additional known gamma-ray source, the blazar GB6 J1040+0617, in spatial coincidence with a neutrino in this sample. The chance probability of this coincidence is 30% after trial correction. For the first time, we present a systematic study of the gamma-ray flux, spectral and optical variability, and multiwavelength behavior of GB6 J1040+0617 and compare it to TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the Fermi-Large Area Telescope gamma-ray band, being in an active state around the arrival of IceCube-170922A, but in a low state during the archival IceCube neutrino flare in 2014/15. In both cases the spectral shape is statistically compatible (≤2σ) with the average spectrum showing no indication of a significant relative increase of a high-energy component. While the association of GB6 J1040+0617 with the neutrino is consistent with background expectations, the source appears to be a plausible neutrino source candidate based on its energetics and multiwavelength features, namely a bright optical flare and modestly increased gamma-ray activity. Finding one or two neutrinos originating from gamma-ray blazars in the given sample of high-energy neutrinos is consistent with previously derived limits of neutrino emission from gamma-ray blazars, indicating the sources of the majority of cosmic high-energy neutrinos remain unknown.

We present the discovery of PS18kh, a tidal disruption event discovered at the center of SDSS J075654.53+341543.6 (d ≃ 322 Mpc) by the Pan-STARRS Survey for Transients. Our data set includes pre-discovery survey data from Pan-STARRS, the All-sky Automated Survey for Supernovae, and the Asteroid Terrestrial-impact Last Alert System as well as high-cadence, multiwavelength follow-up data from ground-based telescopes and Swift, spanning from 56 days before peak light until 75 days after. The optical/UV emission from PS18kh is well-fit as a blackbody with temperatures ranging from T ≃ 12,000 K to T ≃ 25,000 K and it peaked at a luminosity of L ≃ 8.8 × 1043 erg s-1. PS18kh radiated E = (3.45 ± 0.22) × 1050 erg over the period of observation, with (1.42 ± 0.20) × 1050 erg being released during the rise to peak. Spectra of PS18kh show a changing, boxy/double-peaked Hα emission feature, which becomes more prominent over time. We use models of non-axisymmetric accretion disks to describe the profile of the Hα line and its evolution. We find that at early times the high accretion rate leads the disk to emit a wind which modifies the shape of the line profile and makes it bell-shaped. At late times, the wind becomes optically thin, allowing the non-axisymmetric perturbations to show up in the line profile. The line-emitting portion of the disk extends from r in ∼ 60r g to an outer radius of r out ∼ 1400r g and the perturbations can be represented either as an eccentricity in the outer rings of the disk or as a spiral arm in the inner disk.

Winds arising from galaxies, star clusters, and active galactic nuclei are crucial players in star and galaxy formation, but it has proven remarkably difficult to use observations of them to determine physical properties of interest, particularly mass fluxes. Much of the difficulty stems from a lack of a theory that links a physically realistic model for winds' density, velocity and covering factors to calculations of light emission and absorption. In this paper we provide such a model. We consider a wind launched from a turbulent region with a range of column densities, derive the differential acceleration of gas as a function of column density, and use this result to compute winds' absorption profiles, emission profiles and emission intensity maps in both optically thin and optically thick species. The model is sufficiently simple that all required computations can be done analytically up to straightforward numerical integrals, rendering it suitable for the problem of deriving physical parameters by fitting models to observed data. We show that our model produces realistic absorption and emission profiles for some example cases, and argue that the most promising methods of deducing mass fluxes are based on combinations of absorption lines of different optical depths, or on combining absorption with measurements of molecular line emission. In the second paper in this series, we expand on these ideas by introducing a set of observational diagnostics that are significantly more robust than those commonly in use, and that can be used to obtain improved estimates of wind properties.

Objective: The chronic impact of acetylcholinesterase inhibitors and other toxicants on Gulf War (GW) veterans' health symptoms is unclear., Methods: Building on reports of adverse neuropsychological outcomes in GW pesticide applicators exposed to pesticides and pyridostigmine bromide, we now report on health symptoms in this group., Results: In adjusted analyses, applicators with high exposures/impact to pesticides reported significantly more symptoms (18/34 symptoms) than applicators with lower exposures/impact and were more likely to meet modified Kansas and CDC Gulf War Illness criteria. The high pyridostigmine bromide exposure/impact group was 3 times more likely to report irregular heart rates. With regard to specific pesticide types, fly baits, pest strips, and delousers were the most associated with increased health symptom reporting., Conclusions: These results suggest that GW veterans with high acetylcholinesterase inhibitor and organochlorine exposures are most at risk for chronic health symptoms., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Importance: Online pharmacies have emerged as stakeholders in abortion care since the US Food and Drug Administration (FDA) relaxed in-person dispensing requirements in 2020. The role of online pharmacies in dispensing abortion medications following the Dobbs v Jackson Women's Health Organization decision on June 24, 2022, is understudied., Objective: To describe medication abortion prescription fulfillment patterns for 1 online pharmacy 1 year before and after the Dobbs v Jackson decision, considering patient, prescriber, and state policy characteristics., Design, Setting, and Participants: This cross-sectional study assesses deidentified medication abortion prescription fulfilment data from 1 online pharmacy. Prescribers sent prescription requests to the online pharmacy, which dispensed abortion medications to patients by mail. The study sample included prescription requests fulfilled by the online pharmacy between June 20, 2021, and June 24, 2023, for patients aged at least 18 years who received the combined medication abortion regimen. Data were analyzed from July 2023 to July 2024., Exposures: The US Supreme Court Dobbs v Jackson decision on June 24, 2022., Main Outcomes and Measures: Patient and prescriber characteristics are described, including patient age, state to which the prescription was sent, medications prescribed, and prescribing prescriber's clinic care modality (in-person only, hybrid [in-person and virtual], and virtual only). States were grouped according to the Guttmacher Institute classification of policy support for abortion (most or very supportive, somewhat supportive, and somewhat restrictive). Fulfillment trends were disaggregated by prescriber modality and state policy environment; 2 states with similar telehealth but differing coverage policies (Illinois and Colorado) were compared., Results: The dataset included 87 942 observations. Most prescriptions were sent to individuals younger than 30 years (57.1%), with a mean (SD) age of 28.7 (6.4) years. Throughout the study period, the greatest volume of prescription requests came from states with most or very supportive policies and from prescribers at virtual-only platforms. More prescriptions were sent in the year after Dobbs v Jackson (daily mean [SD], 88.5 [47.2] prescriptions in March 2022 vs 201.5 [97.5] prescriptions in March 2023) with fulfillment spikes following the Dobbs v Jackson leak on May 2, 2022, and decision on June 24, 2022. State policy contexts mirrored the overall trends, while prescriber modality trends were unique, with a big spike in fulfillment at 12 weeks after the Dobbs v Jackson decision for hybrid clinics compared with in-person-only clinics and telehealth-only platforms, which saw their largest spikes in mean daily prescription fulfillment the week immediately after Dobbs v Jackson. Illinois and Colorado had similar fulfillment trends, with spikes immediately following the Dobbs v Jackson decision and overall higher fulfillment after Dobbs v Jackson, with a daily mean (SD) of 10.5 (7.0) prescriptions in Illinois and 8.8 (5.7) prescriptions in Colorado in March 2022 versus 26.6 (13.6) prescriptions in Illinois and 16.7 (10.1) prescriptions in Colorado in March 2023., Conclusions and Relevance: These findings illustrate the increasingly critical role online pharmacies play in direct-to-patient abortion care provision in the US and the strong linkages between virtual-only prescribers and online pharmacies. These findings suggest that barriers to accessing online pharmacies for abortion care should be removed.

In August 2016, MSI Australia (MSIA) brought to scale a direct-to-patient telehealth medication abortion service. We used MSIA's patient management systems from January 2015 to December 2018 to assess changes in the proportion of abortion patients obtaining care after 13 weeks' gestation, proportion of abortion patients obtaining medication abortion versus procedural abortion and proportion of abortion patients from regional and remote versus metropolitan areas. The proportions of abortion patients obtaining care before 13 weeks' gestational duration and those from regional and remote residents did not change between the pre- and post-periods. We observed an increase in medication abortion use that was greater among those in regional and remote areas than those in metropolitan areas., (© 2024 The Author(s). Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Introduction: Quality abortion care must be person-centered. Although academic literature has focused on full-spectrum and abortion doulas supporting instrumentation abortion (also referred to as procedural abortion) clients, clients undergoing medication abortion remain understudied and may have unique needs. We aimed to understand United States (US) abortion support providers' perceptions of medication abortion clients' support needs by exploring which needs they address, which needs remain unmet, and how remote support provision might help address client needs., Methodology: Between April and October 2018, we conducted 60- to 90-min semi-structured, in-depth interviews by telephone with medication abortion support providers. The interviews focused on their experiences providing support to medication abortion clients in the US. We used a deductive thematic analysis approach., Results: We interviewed 16 abortion support providers affiliated with nine US-based organizations. Six participants provided in-person support to medication abortion clients, five provided remote support, and five provided both remote and in-person support. Both in-person and remote providers described offering support that addressed clients' informational, emotional, physical, spiritual, and logistical needs. Through participant narratives, we identified interwoven benefits and challenges to remote support care provision. Participants highlighted that most medication abortion clients did not have a support provider., Discussion: Participants revealed that abortion support providers, including remote support providers, can be a critical component of high-quality abortion care provision. More work is needed to ensure all abortion clients have access to support services as the abortion landscape in the US continues to evolve., (© 2024 University of Ottawa.)

Diagnostic evaluation of a patient with dizziness or vertigo is complicated by a lack of standardized nomenclature, significant overlap in symptom descriptions, and the subjective nature of the patient's symptoms. Although dizziness is an imprecise term often used by patients to describe a feeling of being off-balance, in many cases dizziness can be subcategorized based on symptomatology as vertigo (false sense of motion or spinning), disequilibrium (imbalance with gait instability), presyncope (nearly fainting or blacking out), or lightheadedness (nonspecific). As such, current diagnostic paradigms focus on timing, triggers, and associated symptoms rather than subjective descriptions of dizziness type. Regardless, these factors complicate the selection of appropriate diagnostic imaging in patients presenting with dizziness or vertigo. This document serves to aid providers in this selection by using a framework of definable clinical variants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Alcohol use is pervasive in the Caribbean; however, the prevalence and correlates of alcohol use and drinking problems in the elderly have not been extensively studied., Methods: Data were obtained from the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study, a cohort study of Caribbean people from Puerto Rico, Barbados, Trinidad, and Tobago, and the U.S. Virgin Islands, collected between 2013 and 2018 (baseline study sample, ages 60+, n = 811). Descriptive statistics were used to compare the differences in drinking status (current vs. former vs. never), alcohol problems (Cut-down, Annoyed, Guilty, and Eye-opener (CAGE) scale score ≥2 vs. <2), and binge drinking days (0 days vs. 1-2 days vs. ≥3 days) across sample characteristics. Logistic regression analyses estimated the association of these alcohol measures with sociodemographic (e.g., sex), psychological (depression), and cultural (e.g., religion) correlates., Results: Thirty-six percent were 70 + years of age, 64 % were female, and 41 % had less than a high school education. Alcohol problems (≥2 CAGE score) was 21 %. Binge drinking ≥3 days was 30.6 %. Never attending religious services (vs. attending once a week or more) was associated with almost three times higher odds of alcohol problems (adjusted Odds Ratio: OR = 2.88, 95 % CI = 1.02, 8.15) four times higher odds of increasing binge drinking days (aOR = 4.04, 95 % CI = 1.11, 14.96). College education was protective against both the outcomes., Conclusion: We provide current estimates of alcohol problems among elderly Eastern Caribbean people. Among the sociodemographic, psychological, and cultural correlates examined, religious attendance was significant. Replicate longitudinal studies using DSM-5 alcohol dependence are recommended., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified to be pivotal regulators of genome structure and gene expression. To investigate the regulatory roles of lncRNAs in P. falciparum we explore the intergenic lncRNA distribution in nuclear and cytoplasmic subcellular locations. Using nascent RNA expression profiles, we identify a total of 1768 lncRNAs, of which 718 (~41%) are novels in P. falciparum. The subcellular localization and stage-specific expression of several putative lncRNAs are validated using RNA-FISH. Additionally, the genome-wide occupancy of several candidate nuclear lncRNAs is explored using ChIRP. The results reveal that lncRNA occupancy sites are focal and sequence-specific with a particular enrichment for several parasite-specific gene families, including those involved in pathogenesis and sexual differentiation. Genomic and phenotypic analysis of one specific lncRNA demonstrate its importance in sexual differentiation and reproduction. Our findings bring a new level of insight into the role of lncRNAs in pathogenicity, gene regulation and sexual differentiation, opening new avenues for targeted therapeutic strategies against the deadly malaria parasite., (© 2023. Springer Nature Limited.)

Neutrinos remain mysterious. As an example, enhanced self-interactions (νSI), which would have broad implications, are allowed. At the high neutrino densities within core-collapse supernovae, νSI should be important, but robust observables have been lacking. We show that νSI make neutrinos form a tightly coupled fluid that expands under relativistic hydrodynamics. The outflow becomes either a burst or a steady-state wind; which occurs here is uncertain. Though the diffusive environment where neutrinos are produced may make a wind more likely, further work is needed to determine when each case is realized. In the burst-outflow case, νSI increase the duration of the neutrino signal, and even a simple analysis of SN 1987A data has powerful sensitivity. For the wind-outflow case, we outline several promising ideas that may lead to new observables. Combined, these results are important steps toward solving the 35-year-old puzzle of how νSI affect supernovae.

Defects in intestinal epithelial tight junctions (TJs) allow paracellular permeation of noxious luminal antigens and are important pathogenic factors in inflammatory bowel disease (IBD). We show that alpha-tocopherylquinone (TQ), a quinone-structured oxidation product of vitamin E, consistently enhances the intestinal TJ barrier by increasing barrier-forming claudin-3 (CLDN3) and reducing channel-forming CLDN2 in Caco-2 cell monolayers (in vitro), mouse models (in vivo), and surgically resected human colons (ex vivo). TQ reduces colonic permeability and ameliorates colitis symptoms in multiple colitis models. TQ, bifunctionally, activates both aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. Genetic deletion studies reveal that TQ-induced AhR activation transcriptionally increases CLDN3 via xenobiotic response element (XRE) in the CLDN3 promoter. Conversely, TQ suppresses CLDN2 expression via Nrf2-mediated STAT3 inhibition. TQ offers a naturally occurring, non-toxic intervention for enhancement of the intestinal TJ barrier and adjunct therapeutics to treat intestinal inflammation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The human malaria parasites, including Plasmodium falciparum, persist as a major cause of global morbidity and mortality. The recent stalling of progress toward malaria elimination substantiates a need for novel interventions. Controlled gene expression is central to the parasite's numerous life cycle transformations and adaptation. With few specific transcription factors (TFs) identified, crucial roles for chromatin states and epigenetics in parasite transcription have become evident. Although many chromatin-modifying enzymes are known, less is known about which factors mediate their impacts on transcriptional variation. Like those of higher eukaryotes, long noncoding RNAs (lncRNAs) have recently been shown to have integral roles in parasite gene regulation. This review aims to summarize recent developments and key findings on the role of lncRNAs in P. falciparum., Competing Interests: Declaration of interests The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Although studies have documented challenges people encounter when attempting to access abortion care in the United States, there is little research on the perspectives and experiences of foreign-born individuals, who may encounter unique barriers to accessing care. Since lack of data may be due to difficulty recruiting this population, we explored the feasibility of using social media to recruit foreign-born individuals who have sought an abortion into interviews to share their abortion experiences. Our target population was limited to English and Spanish-speakers due to budget constraints. As this recruitment method was unsuccessful, we attempted to recruit our target population through the crowdsourcing website, Amazon Mechanical Turk (mTurk) to take a one-time survey on their abortion experience. Both online recruitment methods yielded a significant number of fraudulent responses. Although we aimed to collaborate with organizations that work closely with immigrant populations, they were unavailable to assist with recruitment efforts at the time of the study. Future abortion research utilizing online methods to recruit foreign-born populations should consider incorporating information on their target populations' use of online platforms as well as cultural views on abortion in order to develop effective recruitment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zuniga, Ragosta and Thompson.)

The overturn of Roe v. Wade has resulted in fewer rights and resources for people seeking abortion care, particularly in the South. The Hyde Amendment has historically restricted abortion access for those enrolled in Medicaid. We argue here that its guarantees of minimum abortion coverage should be leveraged to offset harms where possible.

Objectives: We assessed the safety and effectiveness of direct-to-patient telehealth provision of medication abortion in Australia., Study Design: We included all medication abortions (January 2017-December 2018) from Marie Stopes Australia's patient management and adverse event reporting systems. We defined effectiveness as whether the patient had a continuing pregnancy, incomplete abortion, and/or subsequent vacuum aspiration or procedural abortion and safety as whether the patient experienced any adverse event., Results: Direct-to-patient telehealth was more effective than in-clinic provision (97.2% vs 95.4%). The proportion of adverse events did not differ between groups., Conclusions: This direct-to-patient telehealth service is safe and effective., (Copyright © 2022. Published by Elsevier Inc.)

Aim: To elicit preferences for pharmacogenomic (PGx) testing in polypharmacy patients. Materials & methods: A face-to-face discrete choice experiment survey was designed and administered to adult polypharmacy patients recruited at a local retail pharmacy in Albuquerque (NM, USA). Results: A total of 128 eligible polypharmacy patients completed the discrete choice experiment survey and significantly preferred a PGx test with lower cost, better confidentiality and higher certainty of identifying best medication/dose and side effects and one that can be used to advocate for their treatment needs (all p < 0.01). Conclusion: This is the first study eliciting preferences for PGx testing among polypharmacy patients. The study found most polypharmacy patients were willing to take a PGx test and their preferences were mostly influenced by test cost.

Background: In the site-to-site telehealth for medication abortion model, patients visit a health center to meet with a remote clinician using telehealth technology. This model is safe, effective, and acceptable to patients and providers. The objective of this study was to document the experiences of patients and providers using telehealth for medication abortion in Planned Parenthood health centers across different geographical contexts in the United States., Methods: We conducted in-depth interviews with Planned Parenthood medication abortion patients who either met with a clinician at the clinic via telehealth or in-person about their experiences receiving care. We also interviewed Planned Parenthood staff members about their experiences implementing telehealth for medication abortion at their health center., Results: We interviewed 29 patients who received care at Planned Parenthood health centers in five states. Both telehealth and in-person patients described positive interactions with health center staff and clinicians. The vast majority of telehealth patients said that they felt comfortable speaking with the clinician over telehealth and had no trouble using the telehealth technology. We interviewed 12 providers, including clinicians and administrative staff, who worked in seven states. Providers largely thought that telehealth for medication abortion expanded access to medication abortion., Conclusions: Across different locations, our findings indicate that patients found telehealth for medication abortion services to be highly acceptable and providers found that telehealth services may help improve medication abortion access. As the use of telehealth for medication abortion expands, future research should include additional measures of quality to ensure that services are acceptable across different identities and experiences, including age, race, gender, and income level., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://mhealth.amegroups.com/article/view/10.21037/mhealth-22-12/coif). After the completion of this study, JWS served as a consultant to an independent US-abortion provider. In this capacity she provided technical assistance with data analysis regarding the effects of implementation of a telemedicine for medication abortion care model on service delivery patterns. TAT, Principal Investigator of this study, reports that all payments from the anonymous grant that supported this research were made to the primary institution and used solely for research costs, including travel to meetings to present on work broadly related to telehealth for medication abortion but not specific to this manuscript. DG has received payment from Lawyering Project and Planned Parenthood Federation of America for his role as an expert witness in legal cases challenging laws that limit the use of telemedicine in abortion care. The other authors have no conflicts of interest to declare., (2022 mHealth. All rights reserved.)

Objectives. To quantify the impact of telemedicine for medication abortion (TMAB) expansion or ban removal on abortion accessibility. Methods. We included 1091 facilities from the 2018 Advancing New Standards in Reproductive Health facility database and Planned Parenthood Web site, among which 241 did not offer abortion as sites for TMAB expansion. Accessibility was defined as the proportion of reproductive-aged women living within a 30-, 60-, or 90-minute drive time from an abortion-providing facility. We calculated accessibility differences between 3 scenarios: (1) facilities offering abortion in 2018 (reference), (2) the reference scenario in addition to all facilities in states without TMAB bans (TMAB expansion), and (3) all facilities (TMAB ban removal). We also stratified by state and urban-rural status. Results. In 2018, 65%, 81%, and 89% of women lived within a 30-, 60-, or 90-minute drive time from an abortion-providing facility, respectively. Expansion and ban removal expanded abortion accessibility relative to the current accessibility scenario (range: 1.25-5.66 percentage points). Women in rural blocks experienced greater increases in accessibility than those in urban blocks. Conclusions. TMAB program and policy changes could expand abortion accessibility to an additional 3.5 million reproductive-aged women. Public Health Implications. Our findings can inform where to invest resources to improve abortion accessibility. ( Am J Public Health . 2022;112(8):1202-1211. https://doi.org/10.2105/AJPH.2022.306876).

Objective: Investigate the theory that chronic exertional compartment syndrome (CECS) results from venous outflow obstruction due to functional muscular compression. Chronic exertional compartment syndrome occurs when increased pressure within a muscle compartment produces pain and/or neurologic symptoms. The exact etiology of CECS is unknown, leading to inconsistent diagnostic and treatment plans., Study Design: Retrospective case series., Setting: Private practice and sports medicine., Patients: Two hundred eighty-four patients with exercise-induced lower leg pain. Twenty-two patients lost to follow-up., Interventions: Leg vasculature was evaluated using stress computed tomography angiography (CTA) and MVP Flex to identify areas of functional venous compression. All patients then underwent targeted botulinum toxin treatment. Posttreatment follow-up imaging was performed using stress CTA in 197 patients., Main Outcome Measures: Presence of functional venous compression on stress CTA. Symptom reduction and normalization of venous flow after targeted botulinum toxin injections., Results: Baseline imaging demonstrated CECS and functional venous obstruction with replication of symptoms in 260 of 284 patients [91.5% ± 3.2% (95% CI)]. Four weeks after treatment, 227 of 284 patients [79.9% ± 4.7% (95% CI)] described reduced/resolved symptoms with activity. One hundred fifty-five of the 197 patients [78.7% ± 5.7% (95% CI)] reimaged with stress CTA demonstrated resolved/reduced venous outflow obstruction. Twenty-two patients were lost to follow-up, and 35 patients had persistent symptoms., Conclusion: Chronic exertional compartment syndrome results from venous outflow obstruction due to functional muscular compression. Understanding the cause of CECS will allow the development of more precise and successful treatment plans. Based on our findings, treatment should be directed at the sites of venous compression., Competing Interests: Conflicts of Interest: Patent, Ownership—MVP Flex, Patent—MVP Treatment, (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: While abortion care is widely legal in Australia, access to care is often poor. Many Australians must travel long distances or interstate to access abortion care, while others face stigma when seeking care. Telehealth-at-home medical abortion is a potential solution to these challenges. In this study, we compared the experience of accessing an abortion via telehealth-at-home to accessing care in-clinic., Methods: Over a 20-month period, we surveyed patients who received medical abortion services at Marie Stopes Australia via the telehealth-at-home service or in-clinic. We conducted bivariate analyses to assess differences in reported acceptability and accessibility by delivery model., Results: In total, 389 patients were included in the study: 216 who received medical abortion services in-clinic and 173 through the telehealth-at-home service. Telehealth-at-home and in-clinic patients reported similarly high levels of acceptability: satisfaction with the service (82% vs 82%), provider interaction (93% vs 84%), and recommending the service to a friend (73% vs 72%). Only 1% of telehealth-at-home patients reported that they would have preferred to be in the same room as the provider. While median time between discovering the pregnancy to first contact with a clinic was similar between groups, median time from first contact to taking the first abortion medication was 7 days longer for telehealth-at-home patients versus in-clinic patients (14 days (IQR 9-21) vs 7 days (IQR 4-14); p<0.01)., Conclusion: The telehealth-at-home medical abortion service has the potential to address some of the challenges with provision of abortion care in Australia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many people seeking abortion encounter financial difficulties that delay or prevent them from accessing care. Although some patients qualify for Medicaid (a public program that can help cover health care costs), laws in some states restrict the use of Medicaid for abortion care. In 2017, Illinois passed House Bill 40 (HB-40), which allowed patients with Medicaid to receive coverage for their abortion. This study aimed to understand how HB-40 affected abortion affordability from the perspectives of individuals that work directly or indirectly with abortion patients or facilities providing abortion care., Methods: We conducted interviews with clinicians and administrators from facilities that provided abortion services; staff from organizations that provided resources to abortion providers or patients; and individuals at organizations involved in the passage and/or implementation of HB-40. Interviews were audio-recorded and transcribed. We created codes based on the interview guides, coded each transcript using the web application Dedoose, and summarized findings by code., Results: Interviews were conducted with 38 participants. Participants reflected that HB-40 seemed to remove a significant financial barrier for Medicaid recipients and improve the experience for patients seeking abortion care. Participants also described how the law led to a shift in resource allocation, allowing financial support to be directed towards uninsured patients. Some participants thought HB-40 might contribute to a reduction in abortion stigma. Despite the perceived positive impacts of the law, participants noted a lack of public knowledge about HB-40, as well as confusing or cumbersome insurance-related processes, could diminish the law's impact. Participants also highlighted persisting barriers to abortion utilization for minors, recent and undocumented immigrants, and people residing in rural areas, even after the passage of HB-40., Conclusions: HB-40 was perceived to improve the affordability of abortion. However, participants identified additional obstacles to abortion care in Illinois that weakened the impact of HB-40 for patients and required further action, Findings suggest that policymakers must also consider how insurance coverage can be disrupted by other legal barriers for historically excluded populations and ensure clear information on Medicaid enrollment and abortion coverage is widely disseminated., (© 2022. The Author(s).)

Telehealth, one of the newest health innovations, has been promoted as a tool to enhance access to health care services in ways that center patient needs. However, integrating telehealth within an inequitable health system undermines its potential. This perspective highlights policies and practices that foster structural inequities and names their impact on the use and acceptability of telehealth for medication abortion among specific communities of color. Communities of color have a higher prevalence of abortion use but face many barriers, including financial and geographic barriers, to abortion access. Preliminary evidence on telehealth for medication abortion shows that it is highly acceptable, accommodating of patient needs, and may allow patients to access abortion care at earlier gestational ages. However, evidence during the COVID-19 pandemic shows that utilization of telehealth is lower among communities of color. We describe how systemic barriers, including regulations on or laws banning telehealth for medication abortion, disinvestments in digital access, and restrictions on public insurance coverage, could perpetuate lower utilization of telehealth for medication abortion care among communities of color. We call for systems changes that will remove these barriers and make this health care innovation available to all who may desire it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thompson, Northcraft and Carrión.)

Most studies of abortion access have recruited participants from abortion clinics, thereby missing people for whom barriers to care were insurmountable. Consequently, research may underestimate the nature and scope of barriers that exist. We aimed to recruit participants who had considered, but failed to obtain, an abortion using three online platforms, and to evaluate the feasibility of collecting data on their abortion-seeking experiences in a multi-modal online study. In 2018, we recruited participants for this feasibility study from Facebook, Google Ads, and Reddit for an online survey about experiences seeking abortion care in the United States; we additionally conducted in-depth interviews among a subset of survey participants. We completed descriptive analyses of survey data, and thematic analyses of interview data. Recruitment results have been previously published. For the primary outcomes of this analysis, over one month, we succeeded in capturing data on abortion-seeking experiences from 66 individuals who were not currently pregnant and reported not having obtained an abortion, nor visited an abortion facility, despite feeling that abortion could have been the best option for a recent pregnancy. A subset of survey respondents (n = 14) completed in-depth interviews. Results highlighted multiple, reinforcing barriers to abortion care, including legal restrictions such as gestational limits and waiting periods that exacerbated financial and other burdens, logistical and informational barriers, as well as barriers to abortion care less frequently reported in the literature, such as a preference for medication abortion. These findings support the use of online recruitment to identify and survey an understudied population about their abortion-seeking experiences. Further, findings contribute to a more complete understanding of the full range of barriers to abortion care that people experience in the United States, and how these barriers intersect to not just delay, but to prevent people from obtaining abortion., Competing Interests: The authors have declared that no competing interests exist.

Chronic HIV-1 infection results in the sustained disruption of gut homeostasis culminating in alterations in microbial communities (dysbiosis) and increased microbial translocation. Major questions remain on how interactions between translocating microbes and gut immune cells impact HIV-1-associated gut pathogenesis. We previously reported that in vitro exposure of human gut cells to enteric commensal bacteria upregulated the serine protease and cytotoxic marker Granzyme B (GZB) in CD4 T cells, and GZB expression was further increased in HIV-1-infected CD4 T cells. To determine if these in vitro findings extend in vivo , we evaluated the frequencies of GZB + CD4 T cells in colon biopsies and peripheral blood of untreated, chronically infected people with HIV-1 (PWH). Colon and blood GZB + CD4 T cells were found at significantly higher frequencies in PWH. Colon, but not blood, GZB + CD4 T cell frequencies were associated with gut and systemic T cell activation and Prevotella species abundance. In vitro , commensal bacteria upregulated GZB more readily in gut versus blood or tonsil-derived CD4 T cells, particularly in inflammatory T helper 17 cells. Bacteria-induced GZB expression in gut CD4 T cells required the presence of accessory cells, the IL-2 pathway and in part, MHC Class II. Overall, we demonstrate that GZB + CD4 T cells are prevalent in the colon during chronic HIV-1 infection and may emerge following interactions with translocated bacteria in an IL-2 and MHC Class II-dependent manner. Associations between GZB + CD4 T cells, dysbiosis and T cell activation suggest that GZB + CD4 T cells may contribute to gut HIV-1 pathogenesis.

Introduction: The use of small interfering RNA (siRNA) gene silencing is a promising therapeutic option as it does not impose selective pressure on bacteria that is often associated with the development of resistance. The study assessed the effect of siRNA targeted to sarA and agrA in S. aureus and the relationship between the transcriptional response, biofilm formation and pathogenicity., Methodology: siRNAs designed against agrA and sarA were electroporated into methicillin-resistant and methicillin-susceptible S. aureus strains. mRNA levels, growth kinetics, biofilm formation and minimal inhibitory concentration were measured. Efficacy of siRNA in bacteria was assessed using survival assays in a C. elegans model. Differences in gene expression before and after siRNA treatment were anaysed using the paired t-test, while the log rank test was used to assess the significance of any difference among survival rates of nematodes., Results: Biofilm formation decreased significantly in siRNA treated strains and growth rates of siRNA treated strains were significantly higher compared to untreated strains. We observed significant decreases in the transcriptional response in siRNA treated strains, with concomitant significant increases in the lifespan of C. elegans worms exposed to siRNA-treated versus untreated strains., Conclusions: siRNA targeted to agrA and sarA lowered mRNA transcription and pathogenicity of S. aureus., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Terissa Alexas Thompson, Paul Dean Brown.)

In Australia, there are many barriers to abortion, particularly for women living in regional, rural and remote areas. Telehealth provision of medical abortion is safe, effective and acceptable to patients and providers. In 2015, Marie Stopes Australia (MSA) launched an at-home telehealth model for medical abortion to which GPs could refer. Between April and November of 2017, we interviewed 20 GPs who referred patients to MSA's telehealth-at-home abortion service to better understand their experiences and perspectives regarding telehealth-at-home abortion. We found that there was widespread support and recognition of the benefits of telehealth-at-home abortion in increasing access to abortion and reducing travel and costs. However, the GPs interviewed lacked knowledge and understanding of the processes involved in medical abortion, and many were unaware of the availability of telehealth as an option until a patient requested a referral. The GPs interviewed called for increased communication between telehealth-at-home abortion providers and GPs. Increasing GP familiarity with medical abortion and awareness of the availability of telehealth-at-home abortion may assist people in accessing safe, effective medical abortion.

An important function of the gut microbiome is the fermentation of non-digestible dietary fibers into short chain fatty acids (SCFAs). The three primary SCFAs: acetate, propionate, and butyrate, are key mediators of metabolism and immune cell function in the gut mucosa. We previously demonstrated that butyrate at high concentrations decreased human gut lamina propria (LP) CD4 T cell activation in response to enteric bacteria exposure in vitro. However, to date, the mechanism by which butyrate alters human gut LP CD4 T cell activation remains unknown. In this current study, we sought to better understand how exposure to SCFAs across a concentration range impacted human gut LP CD4 T cell function and activation. LP CD4 T cells were directly activated with T cell receptor (TCR) beads in vitro in the presence of a physiologic concentration range of each of the primary SCFAs. Exposure to butyrate potently inhibited CD4 T cell activation, proliferation, and cytokine (IFNγ, IL-17) production in a concentration dependent manner. Butyrate decreased the proliferation and cytokine production of T helper (Th) 1, Th17 and Th22 cells, with differences noted in the sensitivity of LP versus peripheral blood Th cells to butyrate's effects. Higher concentrations of propionate and acetate relative to butyrate were required to inhibit CD4 T cell activation and proliferation. Butyrate directly increased the acetylation of both unstimulated and TCR-stimulated CD4 T cells, and apicidin, a Class I histone deacetylase inhibitor, phenocopied butyrate's effects on CD4 T cell proliferation and activation. GPR43 agonism phenocopied butyrate's effect on CD4 T cell proliferation whereas a GPR109a agonist did not. Our findings indicate that butyrate decreases in vitro human gut LP CD4 T cell activation, proliferation, and inflammatory cytokine production more potently than other SCFAs, likely through butyrate's ability to increase histone acetylation, and potentially via signaling through GPR43. These findings have relevance in furthering our understanding of how perturbations of the gut microbiome alter local immune responses in the gut mucosa., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Most U.S. states have one or more pregnancy-specific alcohol or drug policies. However, research evidence indicates that some of these policies lead to increases in adverse birth outcomes, including low-birthweight and preterm birth. We offer explanations for why these ineffective policies related to pregnant people's use of alcohol and drugs in the U.S. exist, including: abortion politics; racism and the 'War on Drugs'; the design and application of scientific evidence; and lack of a pro-active vision. We propose alternative processes and concepts to guide strategies for developing new policy approaches that will support the health and well-being of pregnant people who use alcohol and drugs and their children. Processes include: involving people most affected by pregnancy-specific alcohol and drug policies in developing alternative policy and practice approaches as well as future research initiatives. Additionally, we propose that research funding support the development of policies and practices that bolster health and well-being rather than primarily documenting the harms of different substances. Concepts include accepting that policies adopted in response to pregnant people's use of alcohol and drugs cause harms and working to do better, as well as connecting to efforts that re-envision the child welfare system in the U.S.

Medicaid is the largest publicly funded health insurance program in the United States, covering 76 million individuals as of August 2020. Research shows that Medicaid improves health and healthcare access on a variety of indicators. Abortion is a common reproductive health service in the United States. However, Medicaid coverage of abortion varies by state; with 34 states and the District of Columbia limiting themselves to a federal policy that only permits coverage under cases of incest, rape, or life endangerment. With 75% of abortion patients earning low incomes, Medicaid coverage of this service is particularly salient to abortion access. In this commentary, we describe the complexities of Medicaid coverage and reimbursement of abortion in the United States and the implications of this complexity. Further, we consider the potential impact of changes in abortion provision, including increasing provision of medication abortion and the use of healthcare delivery models such as telemedicine for medication abortion, on Medicaid coverage and reimbursement. Finally, we provide a few policy and practice recommendations for abortion coverage now and in the future., (Copyright © 2021. Published by Elsevier Inc.)

Group 3 innate lymphoid cells (ILC3s) in the gut mucosa have long been thought to be noncytotoxic lymphocytes that are critical for homeostasis of intestinal epithelial cells through secretion of IL-22. Recent work using human tonsillar cells demonstrated that ILC3s exposed to exogenous inflammatory cytokines for a long period of time acquired expression of granzyme B, suggesting that under pathological conditions ILC3s may become cytotoxic. We hypothesized that inflammation associated with bacterial exposure might trigger granzyme B expression in gut ILC3s. To test this, we exposed human colon lamina propria mononuclear cells to a panel of enteric bacteria. We found that the Gram-negative commensal and pathogenic bacteria induced granzyme B expression in a subset of ILC3s that were distinct from IL-22-producing ILC3s. A fraction of granzyme B + ILC3s coexpressed the cytolytic protein perforin. Granzyme B expression was mediated, in part, by IL-15 produced upon exposure to bacteria. ILC3s coexpressing all three IL-15R subunits (IL15Rα/β/γ) increased following bacterial stimulation, potentially allowing for cis presentation of IL-15 during bacterial exposure. Additionally, a large frequency of colonic myeloid dendritic cells expressed IL-15Rα, implicating myeloid dendritic cells in trans presentation of IL-15 to ILC3s. Tonsillar ILC3s minimally expressed granzyme B when exposed to the same bacteria or to rIL-15. Overall, these data establish the novel, to our knowledge, finding that human colonic ILC3s can express granzyme B in response to a subset of enteric bacteria through a process mediated by IL-15. These observations raise new questions about the multifunctional role of human gut ILC3s., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Objective: On January 1, 2018, Illinois became the first Midwestern state to cover abortion care for Medicaid enrollees. This study describes state implementation of the policy, the impact on abortion providers, and lessons learned., Study Design: We documented abortion providers' perspectives on the service delivery consequences of Medicaid coverage for abortion in Illinois. We conducted in-depth interviews with clinicians and administrators (N = 23) from 15 Illinois clinics, including clinics that provided other services and those primarily providing abortion. We conducted interviews in person or by phone between April and October 2019. They lasted ≤100 minutes, were audio-recorded, transcribed, and coded in Dedoose. We developed code summaries to identify salient themes across interviews., Results: All participants supported the law and expected benefits to patients. Many struggled to implement the policy because of difficulties obtaining certification to bill the state Medicaid program, confusing and cumbersome paperwork requirements, reimbursement delays, confusing claim denials, and uncertain protocols for Medicaid patients covered under the exceptions defined by the Hyde Amendment. Nearly all participants expressed concern that low reimbursement rates were insufficient to cover costs. Implementation was easier for multiservice clinics and those nested in larger institutions. Several clinics closed during implementation; one clinic opened. Clinics leveraged internal resources, external funding, and technical assistance to ensure that Medicaid enrollees could receive care without costs., Conclusions: Implementing Medicaid coverage for abortion requires proactive and responsive state institutions, improvements to reimbursement processes, and adequate reimbursement rates. In Illinois, successful implementation depended on clinic adaptability, external support, and advocacy., Implications: Our research suggests that successful, sustainable implementation of Medicaid coverage for abortion depends on state policies that allow clinics to enroll patients, process claims in 30 to 90 days, and receive reimbursements covering the cost of care. Without these measures, ensuring immediate patient access may depend upon clinics mobilizing resources and external transitional support., (Copyright © 2021. Published by Elsevier Inc.)

Objective(s): Telemedicine for medication abortion (teleMAB) is safe and effective, yet little is known about how its introduction affects service delivery. We assessed changes in service delivery patterns 1 year after introducing teleMAB at Planned Parenthood in 2 U.S. states., Study Design: Retrospective records analysis using electronic health record data from Planned Parenthood health centers in Montana and Nevada from 2015 to 2018. We included all patients receiving medication or aspiration abortion in the year before and after introducing site-to-site teleMAB. Outcomes included: the proportion of medication abortions (vs. aspiration); gestational age at abortion; time to appointment; and distance traveled. We compared outcomes pre- and postimplementation using χ 2 , t tests, and Mann-Whitney U tests., Results: We analyzed data for 3,038 abortions: 1,314 pre- and 1,724 postimplementation. In Montana, the proportion of medication abortions increased postimplementation (60% vs. 65%, p = 0.04). Mean gestational age was similar: 58 versus 57 days (p = 0.35). Mean time to appointment decreased (14 vs. 12 days, p < 0.0001), as did one-way distance traveled by patients (134 vs. 115 miles, p = 0.03). In Nevada, where Planned Parenthood only provided medication abortion, total medication abortions increased (461 vs. 735). Mean gestational age remained stable (51 vs. 51 days, p = 0.33), as did time to appointment (8 vs. 8 days, p = 0.76). Mean one-way distance traveled was 47 miles in the preperiod versus 34 miles in the postperiod (p = 0.22)., Conclusion(s): Medication abortion increased after the introduction of telemedicine in both states, though we cannot account for abortions performed by other providers. Telemedicine has the potential to improve access to medication abortion., Implications: Telemedicine has the potential to improve or maintain access to medication abortion and should be taken to scale where feasible. Continued efforts are needed to mitigate or reverse policy restrictions on telemedicine for medication abortion., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In the United States, abortion access is restricted by numerous logistical, financial, social, and policy barriers. Most studies on abortion-seeking experiences in the United States have recruited participants from abortion clinics. However, clinic-based recruitment strategies fail to capture the experiences of people who consider an abortion but do not make it to an abortion clinic. Research indicates that many people search for abortion information on the web; however, web-based recruitment remains underutilized in abortion research., Objective: This study aims to establish the feasibility of using Facebook, Google Ads, and Reddit as recruitment platforms for a study on abortion-seeking experiences in the United States., Methods: From August to September 2018, we posted recruitment advertisements for a survey about abortion-seeking experiences through Facebook, Google Ads, and Reddit. Eligible participants were US residents aged 15-49 years who had been pregnant in the past 5 years and had considered abortion for a pregnancy in this period but did not abort. For each platform, we recorded staff time to develop advertisements and manage recruitment, as well as costs related to advertisement buys and social marketing firm support. We summarized the number of views and clicks for each advertisement where possible, and we calculated metrics related to cost per recruited participant and recruitment rate by week for each platform. We assessed differences across platforms using the chi-square and Kruskal-Wallis tests., Results: Overall, study advertisements received 77,464 views in the 1-month period (from Facebook and Google; information not available for Reddit) and 2808 study page views. After clicking on the advertisements, there were 1254 initiations of the eligibility screening survey, which resulted in 98 eligible survey participants (75 recruited from Facebook, 14 from Google Ads, and 9 from Reddit). The cost for each eligible participant in each platform was US $49.48 for Facebook, US $265.93 for Google Ads, and US $182.78 for Reddit. A total of 84% (66/79) of those who screened eligible from Facebook completed the short survey compared with 73% (8/11) of those who screened eligible from Reddit and 13% (7/53) of those who screened eligible from Google Ads., Conclusions: These results suggest that Facebook advertisements may be the most time- and cost-effective strategy to recruit people who considered but did not obtain an abortion in the United States. Adapting and implementing Facebook-based recruitment strategies for research on abortion access could facilitate a more complete understanding of the barriers to abortion care in the United States., (©Heidi Moseson, Alexandra Wollum, Jane W Seymour, Carmela Zuniga, Terri-Ann Thompson, Caitlin Gerdts. Originally published in JMIR Formative Research (http://formative.jmir.org), 24.02.2021.)

Background: The etiology of the low-level chronic inflammatory state associated with aging is likely multifactorial, but a number of animal and human studies have implicated a functional decline of the gastrointestinal immune system as a potential driver. Gut tissue-resident memory T cells play critical roles in mediating protective immunity and in maintaining gut homeostasis, yet few studies have investigated the effect of aging on human gut T cell immunity. To determine if aging impacted CD4 T cell immunity in the human large intestine, we utilized multi-color flow cytometry to measure colonic lamina propria (LP) CD4 T cell frequencies and immune-modulatory marker expression in younger (mean ± SEM: 38 ± 1.5 yrs) and older (77 ± 1.6 yrs) adults. To determine cellular specificity, we evaluated colon LP CD8 T cell frequency and phenotype in the same donors. To probe tissue specificity, we evaluated the same panel of markers in peripheral blood (PB) CD4 T cells in a separate cohort of similarly aged persons., Results: Frequencies of colonic CD4 T cells as a fraction of total LP mononuclear cells were higher in older persons whereas absolute numbers of colonic LP CD4 T cells per gram of tissue were similar in both age groups. LP CD4 T cells from older versus younger persons exhibited reduced CTLA-4, PD-1 and Ki67 expression. Levels of Bcl-2, CD57, CD25 and percentages of activated CD38 + HLA-DR + CD4 T cells were similar in both age groups. In memory PB CD4 T cells, older age was only associated with increased CD57 expression. Significant age effects for LP CD8 T cells were only observed for CTLA-4 expression, with lower levels of expression observed on cells from older adults., Conclusions: Greater age was associated with reduced expression of the co-inhibitory receptors CTLA-4 and PD-1 on LP CD4 T cells. Colonic LP CD8 T cells from older persons also displayed reduced CTLA-4 expression. These age-associated profiles were not observed in older PB memory CD4 T cells. The decline in co-inhibitory receptor expression on colonic LP T cells may contribute to local and systemic inflammation via a reduced ability to limit ongoing T cell responses to enteric microbial challenge.