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BackgroundLatinx people comprise 18% of the US adult population and a large share of youth and continue to experience inequities that perpetuate health disparities. To engage Latinx people in advocacy for health equity based on this population’s heavy share of smartphone, social media, and Twitter users, Salud America! launched the #SaludTues Tweetchat series. In this paper, we explore the use of #SaludTues to promote advocacy for Latinx health equity. ObjectiveThis study aims to understand how #SaludTues Tweetchats are used to promote dissemination of culturally relevant information on social determinants of health, to determine whether tweetchats serve to drive web traffic to the Salud America! website, and to understand who participates in #SaludTues Tweetchats and what we can learn about the participants. We also aim to share our own experiences and present a step-by-step guide of how tweetchats are planned, developed, promoted, and executed. MethodsWe explored tweetchat data collected between 2014 and 2018 using Symplur and Google Analytics to identify groups of stakeholders and web traffic. Network analysis and mapping tools were also used to derive insights from this series of chats. ResultsWe conducted 187 chats with 24,609 reported users, 177,466 tweets, and more than 1.87 billion impressions using the hashtag #SaludTues during this span, demonstrating effective dissemination of and exposure to culturally relevant information. Traffic to the Salud America! website was higher on Tuesdays than any other day of the week, suggesting that #SaludTues Tweetchats acted effectively as a website traffic–driving tool. Most participants came from advocacy organizations (165/1000, 16.5%) and other health care–related organizations (162/1000, 16.2%), whereas others were unknown users (147/1000, 14.7%) and individual users outside of the health care sector (117/1000, 11.7%). The majority of participants were located in Texas, California, New York, and Florida, all states with high Latinx populations. ConclusionsCarefully planned, culturally relevant tweetchats such as #SaludTues can be a powerful tool for public health practitioners and advocates to engage audiences on Twitter around health issues, advocacy, and policy solutions for Latino health equity. Further information is needed to determine the effect that #SaludTues Tweetchats have on self- and collective efficacy for advocacy in the area of Latino health equity.

Background: Lung transplantation is associated with a high incidence of gastroesophageal reflux disease (GERD). The presence of GERD is considered a risk factor for the subsequent development of obliterative bronchiolitis (OB), and surgical correction of GERD by gastric fundoplication (GF) may be associated with increased freedom from OB. The mechanisms underlying a protective effect from OB remain elusive. The objective of this study was to analyze the flow cytometric properties of BAL cells in patients who have undergone GF early after transplant.Methods: In a single-center lung transplant center, eight patients with GERD who were in the first transplant year underwent GF. Prior to and immediately following GF, BAL cells were analyzed by polychromatic flow cytometry. Spirometry was performed before and after GF.Results: GF was associated with a significant reduction in the frequency of BAL CD8 lymphocytes expressing the intracellular effector marker granzyme B, compared with the pre-GF levels. Twenty-six percent of CD8 cells were granzyme Bhi pre-GF compared with 12% of CD8 cells post-GF (range 8%-50% pre-GF, 2%-24% post-GF, P = .01). In contrast, GF was associated with a significant interval increase in the frequency of CD8 cells with an exhausted phenotype (granzyme Blo, CD127lo, PD1hi) from 12% of CD8 cells pre-GF to 24% post-GF (range 1.7%-24% pre-GF and 11%-47% post-GF, P = .05). No significant changes in spirometry were observed during the study interval.Conclusions: Surgical correction of GF is associated with a decreased frequency of potentially injurious effector CD8 cells in the BAL of lung transplant recipients. [ABSTRACT FROM AUTHOR]

Introduction: Genome-wide association studies (GWAS) studies in Alzheimer's disease (AD) demonstrate ancestry-specific loci. Previous studies in the regulatory architecture have only been conducted in Europeans (EUs), thus studies in additional ancestries are needed. Given the prevalence of AD genes expressed in microglia, we initiated our studies in induced pluripotent stem cell (iPSC) -derived microglia., Methods: We created iPSC-derived microglia from 13 individuals of either high Amerindian (AI), African (AF), or EU global ancestry, including both AD and controls. RNA-seq, ATAC-seq, and pathway analyses were compared between ancestries in both AD and non-AD genes., Results: Twelve AD genes were differentially expressed genes (DEGs) and/or accessible between ancestries, including ABI3, CTSB, and MS4A6A. A total of 5% of all genes had differential ancestral expression, but differences in accessibility were less than 1%. The DEGs were enriched in known AD pathways., Discussion: This resource will be valuable in evaluating AD in admixed populations and other neurological disorders and understanding the AD risk differences between populations., Highlights: First comparison of the genomics of AI, AF, and EU microglia. Report differences in expression and accessibility of AD genes between ancestries. Ancestral expression differences are greater than differences in accessibility. Good transcriptome correlation was seen between brain and iPSC-derived microglia. Differentially expressed AD genes were in known AD pathways., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: This study aims to elucidate ancestry-specific changes to the genomic regulatory architecture in induced pluripotent stem cell (iPSC)-derived oligodendroglia, focusing on their implications for Alzheimer's disease (AD). This work addresses the lack of diversity in previous iPSC studies by including ancestries that contribute to African American (European/African) and Hispanic/Latino populations (Amerindian/African/European)., Methods: We generated 12 iPSC lines-four African, four Amerindian, and four European- from both AD patients and non-cognitively impaired individuals, with varying APOE genotypes ( APOE3/3 and APOE4/4 ). These lines were differentiated into neural spheroids containing oligodendrocyte lineage cells. Single-nuclei RNA sequencing and ATAC sequencing were employed to analyze transcriptional and chromatin accessibility profiles, respectively. Differential gene expression, chromatin accessibility, and Hi-C analyses were conducted, followed by pathway analysis to interpret the results., Results: We identified ancestry-specific differences in gene expression and chromatin accessibility. Notably, numerous AD GWAS-associated genes were differentially expressed across ancestries. The largest number of differentially expressed genes (DEGs) were found in European vs. Amerindian and African vs. Amerindian iPSC-derived oligodendrocyte progenitor cells (OPCs). Pathway analysis of APOE4/4 carriers vs APOE3/3 carriers exhibited upregulation of a large number of disease and metabolic pathways in APOE4/4 individuals of all ancestries. Of particular interest was that APOE4/4 carriers had significantly upregulated cholesterol biosynthesis genes relative to APOE3/3 individuals across all ancestries, strongest in iOPCs. Comparison of iOPC and iOL transcriptome data with corresponding human frontal cortex data demonstrated a high correlation (R 2 > 0.85)., Conclusions: This research emphasizes the importance of including diverse ancestries in AD research to uncover critical gene expression differences between populations and ancestries that may influence disease susceptibility and therapeutic interventions. The upregulation of cholesterol biosynthesis genes in APOE4/4 carriers of all three ancestries supports the concept that APOE4 may produce disease effects early in life, which could have therapeutic implications as we move forward towards specific therapy for APOE4 carriers. These findings and the high correlation between brain and iPSC-derived OPC and OL transcriptomes support the relevance of this approach as a model for disease study., Competing Interests: Competing interests The authors declare that they have no competing interests.

APOE ε4 is the strongest genetic risk factor for Alzheimer's disease (AD) with approximately 50% of AD patients carrying at least one APOE ε4 allele. Our group identified a protective interaction between APOE ε4 with the African-specific A allele of rs10423769, which reduces the AD risk effect of APOE ε4 homozygotes by approximately 75%. The protective variant lies 2Mb from APOE in a region of segmental duplications (SD) of chromosome 19 containing a cluster of pregnancy specific beta-1 glycoprotein genes ( PSGs ) and a long non-coding RNA. Using both short and long read sequencing, we demonstrate that rs10423769_A allele lies within a unique single haplotype inside this region of segmental duplication. We identified the protective haplotype in all African ancestry populations studied, including both West and East Africans, suggesting the variant has an old origin. Long-read sequencing identified both structural and DNA methylation differences between the protective rs10423769_A allele and non-protective haplotypes. An expanded variable number tandem repeat (VNTR) containing multiple MEF2 family transcription factor binding motifs was found associated with the protective haplotype (p-value = 2.9e-10). These findings provide novel insights into the mechanisms of this African-origin protective variant for AD in APOE ε4 carriers and supports the importance of including all ancestries in AD research., Competing Interests: Declaration of interests The authors declare no competing interests.

Play is critical to child development. In early childhood, object play evolves from exploratory behavior to complex symbolic play. Engagement during play, particularly joint engagement, is essential for learning and social interaction. Board Certified Behavior Analysts® (BCBAs) who provide early intervention services to young autistic children may experience barriers when designing programming and data collection systems for play and engagement. In this paper, we compare Naturalistic Developmental Behavioral Intervention (NDBI) and Natural Environment Teaching (NET) approaches. Considerations for measuring object play and engagement during naturalistic play routines are presented. We encourage BCBAs to consider simple frequency counts when measuring object play actions and interval recording or rating scales for tracking engagement states. These methods may better accommodate the variability in play and engagement behavior, allow for more flexible play routines, and support a more nuanced analysis of child progress., Competing Interests: Conflict of interestThe authors report no potential conflicts of interest., (© Association for Behavior Analysis International 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes., (© 2024 International League Against Epilepsy.)

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions., (© 2024 International League Against Epilepsy.)

Background: Menstrual Regulation (MR) has been legal in Bangladesh since 1979 in an effort to reduce maternal mortality from unsafe abortion care. However, access to high-quality and patient-centered MR care remains a challenge. This analysis aimed to explore what clients know before going into care and the experience itself across a variety of service delivery sites where MR care is available., Methods: We conducted 26 qualitative semi-structured interviews with MR clients who were recruited from three different service delivery sites in Dhaka, Bangladesh from January to March 2019. Interviews explored client expectations and beliefs about MR care, the experience of the care they received, and their perception of the quality of that care. We conducted a thematic content analysis using a priori and emergent codes., Results: Clients overall lacked knowledge about MR care and held fears about the damage to their bodies after receiving care. Despite their fears, roughly half the clients held positive expectations about the care they would receive. Call center clients felt the most prepared by their provider about what to expect during their MR care. During counseling sessions, providers at in-facility locations reinforced the perception of risk of future fertility as a result of MR and commonly questioned clients on their need for MR services. Some even attempted to dissuade nulliparous women from getting the care. Clients received this type of questioning throughout their time at the facilities, not just from their medical providers. The majority of clients perceived their care as good and rationalized these comments from their providers as coming from a caring place. However, a handful of clients did report bad care and negative feelings about their interactions with providers and other clinical staff., Conclusion: Providers and clinical staff can play a key role in shaping the experience of clients accessing MR care. Training on accurate knowledge about the safety and effectiveness of MR, and the importance of client communication could help improve client knowledge and person-centered quality of MR care., (© 2024. The Author(s).)

Background: Little research has been completed on the correlation between cystic fibrosis (CF) modulator therapy and its effect on respiratory cultures in CF patients. This study evaluated the effect of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory colonization with Pseudomonas aeruginosa., Methods: This single center, IRB approved, retrospective chart review compared patient data two years immediately prior to ETI initiation with patient data two years post-initiation from January 2017-December 2022. Patients were included in the study if they were at least 18 years old with a diagnosis of CF and had at least one month of ETI dispensed, at least one sputum culture obtained, and were currently on ETI. Those who had not been seen since ETI initiation or received a bilateral lung transplant were excluded. The primary outcome was rate of patients with respiratory colonization post-ETI. Colonization was defined as two or more positive P. aeruginosa cultures in a 12-month period. Decolonization was defined as three consecutive negative P. aeruginosa cultures after previous colonization. Key secondary outcomes included average time to discontinuation of mucolytic therapy and relative risk of pulmonary exacerbation., Results: A significant reduction (p<0.001) in colonization with P. aeruginosa was observed with 49 patients in the pre-ETI group compared to 25 in the post-ETI group meeting the definition of colonization (n=79). Average time to discontinuation of mucolytic therapy was 14 months (p=0.002). Relative risk of pulmonary exacerbation was 4.80 (p<0.001)., Conclusions: ETI use resulted in reduced colonization with P. aeruginosa, discontinuation of mucolytic therapy, and decreased frequency of pulmonary exacerbation., Competing Interests: Declaration of competing interest Authors have no conflict of interest specifically related to this manuscript., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Introduction: Addressing social determinants of health (SDOH) is fundamental to improving health outcomes. At a student-run free clinic, we developed a screening process to understand the SDOH needs and resource utilization of Milwaukee's uninsured population., Methods: In this cross-sectional study, we screened adult patients without health insurance ( N = 238) for nine traditional SDOH needs as well as their access to dental and mental health care between October 2021 and October 2022. Patients were surveyed at intervals greater than or equal to 30 days. We assessed correlations between SDOH needs and trends in patient-reported resource usefulness., Results: Access to dental care (64.7%) and health insurance (51.3%) were the most frequently endorsed needs. We found significant correlations ( P ≤ 0.05) between various SDOH needs. Notably, mental health access needs significantly correlated with dental ( r = 0.41; 95% CI = 0.19, 0.63), medications ( r = 0.51; 95% CI = 0.30, 0.72), utilities ( r = 0.39; 95% CI = 0.17, 0.61), and food insecurity ( r = 0.42; 95% CI = 0.19, 0.64). Food-housing ( r = 0.55; 95% CI = 0.32, 0.78), housing-medications ( r = 0.58; 95% CI = 0.35, 0.81), and medications-food ( r = 0.53; 95% CI = 0.32, 0.74) were significantly correlated with each other. Longitudinal assessment of patient-reported usefulness informed changes in the resources offered., Conclusions: Understanding prominent SDOH needs can inform resource offerings and interventions, addressing root causes that burden under-resourced patients. In this study, patient-reported data about resource usefulness prompted the curation of new resources and volunteer roles. This proof-of-concept study shows how longitudinally tracking SDOH needs at low-resource clinics can inform psychosocial resources., Competing Interests: The authors of this manuscript affirm that there are no conflicts of interest to disclose regarding the content of this work. We have no financial, personal, or professional relationships with individuals or organizations that could inappropriately influence or bias our research., (© The Author(s) 2024.)

We previously demonstrated that mutation of sarA in Staphylococcus aureus limits biofilm formation, cytotoxicity for osteoblasts and osteoclasts, and virulence in osteomyelitis, and that all of these phenotypes can be attributed to the increased production of extracellular proteases. Here we extend these studies to assess the individual importance of these proteases alone and in combination with each other using the methicillin-resistant USA300 strain LAC, the methicillin-susceptible USA200 strain UAMS-1, and isogenic sarA mutants that were also unable to produce aureolysin (Aur), staphopain A (ScpA), staphylococcal serine protease A (subsp.), staphopain B (SspB), and the staphylococcal serine protease-like proteins A-F (SplA-F). Biofilm formation was restored in LAC and UAMS-1 sarA mutants by subsequent mutation of aur and scpA , while mutation of aur had the greatest impact on cytotoxicity to mammalian cells, particularly with conditioned medium (CM) from the more cytotoxic strain LAC. However, SDS-PAGE and western blot analysis of CM confirmed that mutation of sspAB was also required to mimic the phenotype of sarA mutants unable to produce any extracellular proteases. Nevertheless, in a murine model of post-traumatic osteomyelitis, mutation of aur and scpA had the greatest impact on restoring the virulence of LAC and UAMS-1 sarA mutants, with concurrent mutation of sspAB and the spl operon having relatively little effect. These results demonstrate that the increased production of Aur and ScpA in combination with each other is a primary determinant of the reduced virulence of S. aureus sarA mutants in diverse clinical isolates including both methicillin-resistant and methicillin-susceptible strains.IMPORTANCEPrevious work established that SarA plays a primary role in limiting the production of extracellular proteases to prevent them from limiting the abundance of S. aureus virulence factors. Eliminating the production of all 10 extracellular proteases in the methicillin-resistant strain LAC has also been shown to enhance virulence in a murine sepsis model, and this has been attributed to the specific proteases Aur and ScpA. The importance of this work lies in our demonstration that the increased production of these same proteases largely accounts for the decreased virulence of sarA mutants in a murine model of post-traumatic osteomyelitis not only in LAC but also in the methicillin-susceptible human osteomyelitis isolate UAMS-1. This confirms that sarA -mediated repression of Aur and ScpA production plays a critical role in the posttranslational regulation of S. aureus virulence factors in diverse clinical isolates and diverse forms of S. aureus infection., Competing Interests: The authors declare no conflict of interest.

Purpose: In a previous study, we documented that the Intravitreal injections (IVIs) of bevacizumab in rats caused a retinal inflammatory response. We now study whether the IVI of other humanized anti-VEGF: ranibizumab and aflibercept also cause an inflammatory reaction in the rat retina and if it depends on the dose administered. Finally, we study whether this reaction affects retinal ganglion cell (RGC) survival., Methods: Albino Sprague-Dawley rats received a single IVI of 5 µL of PBS or ranibizumab or aflibercept at the concentration used in clinical practice (10 µg/µL or 40 µg/µL) or at a lower concentration (0.38 µg/µL and 1.5 µg/µL) calculated to obtain within the rat eye the same concentration as in the human eye in clinical practice. Others received a single 5 µL IVI of a polyclonal goat anti-rat VEGF (0.015 µg/µL) or of vehicle (PBS). Animals were processed 7 days or 1 month later. Retinal whole mounts were immunolabeled for the detection of microglial, macroglial, RGCs, and intrinsically photosensitive RGCs (ipRGCs). Fluorescence and confocal microscopy were used to examine retinal changes, and RGCs and ipRGCs were quantified automatically or semiautomatically, respectively., Results: All the injected substances including the PBS induced detectable side effects, namely, retinal microglial cell activation and retinal astrocyte hypertrophy. However, there was a greater microglial and macroglial response when the higher concentrations of ranibizumab and aflibercept were injected than when PBS, the antibody anti-rat VEGF and the lower concentrations of ranibizumab or aflibercept were injected. The higher concentration of ranibizumab and aflibercept resulted also in significant RGC death, but did not cause appreciable ipRGC death., Conclusions: The IVI of all the substances had some retinal inflammatory effects. The IVI of humanized anti-VEGF to rats at high doses cause important side effects: severe inflammation and RGC death, but not ipRGC death.

We previously demonstrated that MgrA, SarA, SarR, SarS, SarZ, and Rot bind at least three of the four promoters associated with genes encoding primary extracellular proteases in Staphylococcus aureus (Aur, ScpA, SspA/SspB, SplA-F). We also showed that mutation of sarA results in a greater increase in protease production, and decrease in biofilm formation, than mutation of the loci encoding any of these other proteins. However, these conclusions were based on in vitro studies. Thus, the goal of the experiments reported here was to determine the relative impact of the regulatory loci encoding these proteins in vivo . To this end, we compared the virulence of mgrA , sarA , sarR , sarS , sarZ , and rot mutants in a murine osteomyelitis model. Mutants were generated in the methicillin-resistant USA300 strain LAC and the methicillin-sensitive USA200 strain UAMS-1, which was isolated directly from the bone of an osteomyelitis patient during surgical debridement. Mutation of mgrA and rot limited virulence to a statistically significant extent in UAMS-1, but not in LAC, while the sarA mutant exhibited reduced virulence in both strains. The reduced virulence of the sarA mutant was correlated with reduced cytotoxicity for osteoblasts and osteoclasts, reduced biofilm formation, and reduced sensitivity to the antimicrobial peptide indolicidin, all of which were directly attributable to increased protease production in both LAC and UAMS-1. These results illustrate the importance of considering diverse clinical isolates when evaluating the impact of regulatory mutations on virulence and demonstrate the significance of SarA in limiting protease production in vivo in S. aureus .

Objective: This qualitative study aimed to identify person-centred domains that would contribute to the definition and measurement of abortion quality of care based on the perceptions, experiences and priorities of people seeking abortion., Methods: We conducted interviews with people seeking abortion aged 15-41 who obtained care in Argentina, Bangladesh, Ethiopia or Nigeria. Participants were recruited from hospitals, clinics, pharmacies, call centres and accompaniment models. We conducted thematic analysis and quantified key domains of quality identified by the participants., Results: We identified six themes that contributed to high-quality abortion care from the clients' perspective, with particular focus on interpersonal dynamics. These themes emerged as participants described their abortion experience, reflected on their interactions with providers and defined good and bad care. The six themes included (1) kindness and respect, (2) information exchange, (3) emotional support, (4) attentive care throughout the process, (5) privacy and confidentiality and (6) prepared for and able to cope with pain., Conclusions: People seeking abortion across multiple country contexts and among various care models have confirmed the importance of interpersonal care in quality. These findings provide guidance on six priority areas which could be used to sharpen the definition of abortion quality, improve measurement, and design interventions to improve quality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Despite the benefits of goals-of-care (GOC) communication, many hospitalized individuals never communicate their goals or preferences to clinicians., Objective: To assess whether a GOC video intervention delivered by palliative care educators (PCEs) increased the rate of GOC documentation., Design, Setting, and Participants: This pragmatic, stepped-wedge cluster randomized clinical trial included patients aged 65 years or older admitted to 1 of 14 units at 2 urban hospitals in New York and Boston from July 1, 2021, to October 31, 2022., Intervention: The intervention involved PCEs (social workers and nurses trained in GOC communication) facilitating GOC conversations with patients and/or their decision-makers using a library of brief, certified video decision aids available in 29 languages. Patients in the control period received usual care., Main Outcome and Measures: The primary outcome was GOC documentation, which included any documentation of a goals conversation, limitation of life-sustaining treatment, palliative care, hospice, or time-limited trials and was obtained by natural language processing., Results: A total of 10 802 patients (mean [SD] age, 78 [8] years; 51.6% male) were admitted to 1 of 14 hospital units. Goals-of-care documentation during the intervention phase occurred among 3744 of 6023 patients (62.2%) compared with 2396 of 4779 patients (50.1%) in the usual care phase (P < .001). Proportions of documented GOC discussions for Black or African American individuals (865 of 1376 [62.9%] vs 596 of 1125 [53.0%]), Hispanic or Latino individuals (311 of 548 [56.8%] vs 218 of 451 [48.3%]), non-English speakers (586 of 1059 [55.3%] vs 405 of 863 [46.9%]), and people living with Alzheimer disease and related dementias (520 of 681 [76.4%] vs 355 of 570 [62.3%]) were greater during the intervention phase compared with the usual care phase., Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of older adults, a GOC video intervention delivered by PCEs resulted in higher rates of GOC documentation compared with usual care, including among Black or African American individuals, Hispanic or Latino individuals, non-English speakers, and people living with Alzheimer disease and related dementias. The findings suggest that this form of patient-centered care delivery may be a beneficial decision support tool., Trial Registration: ClinicalTrials.gov Identifier: NCT04857060.

Here, we present the complete chloroplast genome sequence of Toxicodendron diversilobum, western poison oak, from Pacific Grove, California. The genome is 159,543 bp in length, contains 133 genes, and has a high level of gene synteny to other species of Toxicodendron .

Background: Mental health care is a top clinical concern for modern Puerto Rico, especially given a dramatically changing economic landscape paired with recurrent natural disasters. Youth are particularly at-risk due to long-term impacts of toxic stress and adverse childhood experiences on health and development., Objectives: Here we present a novel clinician-community-educator-scientist partnership to address Puerto Rican youth mental well-being and wellness. We deployed pilot health workshops within the Boys & Girls Clubs of Puerto Rico to build youth mental health conceptual understanding and competencies in stress recognition and management. The work in progress herein evaluates acceptability and feasibility of our curricular model., Methods: Dialogue with community stakeholders guided curricular design of workshops for youth ages 6 to 13 and older. Prior to implementation, educators and volunteers attended a 1-day training on educational strategies. Workshop success was evaluated using qualitative approaches (i.e., narrative feedback, educator and volunteer reflections, youth Talking Drawings) to assess youth engagement, youth conceptual health understanding, and educator/volunteer impressions of feasibility and impact., Results: Initial findings indicate high acceptability and feasibility of our curricular model. Youth engagement and enthusiasm were noted in educator feedback and continue to be sustained post-workshop. Preliminary analysis shows accompanying increases in youth conceptual mental health understanding, particularly for 6- to 12-year-olds in recognition of stress and healthy coping mechanisms. Reciprocal gains were observed for volunteers., Conclusions: Activities have evolved into a formal partnership called Semilla, which features expanded analysis of mental well-being and wellness outcomes. Our collaborative model continues to engage Puerto Rican youth in the science of their well-being.

Introduction: Disrespect and abuse are components of poor quality abortion care. This analysis aimed to understand negative experiences of care from perspectives of abortion clients in public and private facilities in Ethiopia., Study Design: We conducted 23 in-depth interviews with people who obtained abortion care in Addis Ababa, Ethiopia as well as Aksum and Mekele in Tigray State, Ethiopia. The interviews were coded using a priori and emergent codes and we conducted thematic analysis to understand negative interactions with providers from participant's perspectives., Results: Participants experienced denial of abortion services along their pathway to care and attempts by providers to dissuade them prior to providing an abortion. Underlying both the denial and the dissuasion were reports of disrespect and condemnation from providers. Participants described how providers doubted or forced them to justify their reasons for having an abortion, stigmatized them for seeking multiple abortions or later abortions, and ascribed misinformation about abortion safety. Despite reports of denial, dissuasion, and disrespect, abortion clients generally felt that providers had their best interest at heart and were grateful for having access to an abortion., Conclusions: Participants in Ethiopia experienced providers as gatekeepers to legal abortion services, facing disrespect and judgment at facilities where they sought care. Interventions aimed at increasing awareness of abortion laws such that clients understand their rights and values clarification interventions for providers could help reduce barriers to accessing care and improve the quality of abortion services., 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., (© 2022 Bercu, Jacobson, Gebrehanna, Ramirez, Katz, Filippa and Baum.)

Introduction: Despite the known benefit to patients and families, discussions about goals, values and preferences for medical care in advancing serious illness often do not occur. Many system and clinician factors, such as patient and clinician reticence and shortage of specialty palliative care teams, contribute to this lack of communication. To address this gap, we designed an intervention to promote goals-of-care conversations and palliative care referrals in the hospital setting by using trained palliative care educators and video decision aids. This paper presents the rationale, design and methods for a trial aimed at addressing barriers to goals-of-care conversations for hospitalised adults aged 65 and older and those with Alzheimer's disease and related Dementias, regardless of age., Methods and Analysis: The Video Image about Decisions to Improve Ethical Outcomes with Palliative Care Educators is a pragmatic stepped wedge, cluster randomised controlled trial, which aims to improve and extend goals-of-care conversations in the hospital setting with palliative care educators trained in serious illness communication and video decision aids. The primary outcome is the proportion of patients with goals-of-care documentation in the electronic health record. We estimate that over 9000 patients will be included., Ethics and Dissemination: The Institutional Review Board (IRB) at Boston Medical Center will serve as the single IRB of record for all regulatory and ethical aspects of this trial. BMC Protocol Number: H-41482. Findings will be presented at national meetings and in publications. This trial is registered at ClinicalTrials.gov., Trial Registration Number: NCT04857060; ClinicalTrials.gov., Competing Interests: Competing interests: Dr. Angelo Volandes has a financial interest in ACP Decisions, a non-profit organisation developing advance care planning video decision support tools. Dr. Volandes’ interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflict-of-interest policies. Aretha Delight Davis is an employee of ACPD and the spouse of Angelo Volandes. No other disclosures to report., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mutations in the Lamin A/C ( LMNA ) gene are responsible for about 6% of all familial dilated cardiomyopathy (DCM) cases which tend to present at a young age and follow a fulminant course., Methods: We report a 47-year-old DCM patient with severely impaired left ventricular ejection fraction and NYHA functional class IV despite optimal heart failure treatment. Whole-exome sequencing revealed an LMNA E161K missense mutation as the pathogenetic cause for DCM in this patient. We generated a patient-specific LMNA -knock in ( LMNA -KI) in vitro model using mES cells., Results: Beta adrenergic stimulation of cardiomyocytes derived from LMNA -KI mES cells resulted in augmented mTOR signaling and increased dysregulation of action potentials, which could be effectively prevented by the mTOR-inhibitor rapamycin. A cardiac biopsy confirmed strong activation of the mTOR-signaling pathway in the patient. An off-label treatment with oral rapamycin was initiated and resulted in an improvement in left ventricular ejection fraction (27.8% to 44.5%), NT-BNP (8120 ng/L to 2210 ng/L) and NYHA functional class., Conclusion: We have successfully generated the first in vitro model to recapitulate a patient-specific LMNA E161K mutation which leads to a severe form of DCM. The model may serve as a template for individualized and specific treatment of heart failure.

Introduction: Little is known about how people who have abortions describe high-quality interpersonal care in Argentina. This qualitative study aimed to understand preferences and priorities in their interactions with providers., Study Design: We conducted 24 in-depth interviews with people who obtained abortions at a comprehensive reproductive health clinic or with support from a feminist accompaniment group in Buenos Aires and Neuquén, Argentina. We iteratively coded transcripts using a thematic analysis approach based on interpersonal domains present in current quality of care frameworks., Results: Participants described high-quality abortion care as feeling acompañamiento and contención from their providers - terms that imply receiving kind, caring, compassionate and emotionally supportive care throughout their abortion. They described four key elements of interpersonal interactions: attentive communication from providers and accompaniers, clear and understandable information provision, non-judgmental support, and individualized options for pain management., Conclusions: People obtaining abortions in Argentina consistently identified receiving compassionate and supportive care throughout an abortion as a key aspect of care. The findings have implications for incorporating people's perspectives in the development of care guidelines, training of providers, and monitoring and improving of services. This is particularly important as the government of Argentina prepares to expand legal access to abortion., (© 2022. The Author(s).)

Three healthy adolescents presented with myocarditis confirmed on cardiac magnetic resonance imaging after receiving Pfizer-BioNTech COVID-19 vaccine. All patients were hemodynamically stable and had good short-term outcomes. Long-term outcomes are yet to be determined. Larger studies are needed to determine whether an association between Pfizer-BioNTech COVID-19 vaccine and myocarditis exists., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Pediatric Cardiology.)

This qualitative study aimed to examine how abortion clients in Nigeria perceive abortion and explore the role their beliefs and fears play in their care-seeking experiences and interactions with providers. Abortion is severely legally restricted in Nigeria but remains common. We conducted in-depth interviews with 25 people who obtained abortion services through three distinct models of care. We coded interview transcripts and conducted thematic analysis. Clients perceived negative attitudes toward abortion in their communities, though clients' own beliefs were more nuanced. Clients recounted a range of fears, and nearly all mentioned worrying that they might die as a result of their abortion. Despite their concerns, clients relied on social networks and word-of-mouth recommendations to identify providers they perceived as trustworthy and safe. Kind and non-judgmental treatment, clear instructions, open communication, and reassurance of privacy and confidentiality by providers alleviated client fears and helped clients feel supported throughout their abortion process. Within restrictive contexts, the mobilization of information networks, provision of high-quality care through innovative models, and personalization of care to individual needs can assuage fears and contribute to reducing stigma and increasing access to safe abortion services., Competing Interests: The authors have declared that no competing interests exist.

Using the USA300, methicillin-resistant Staphylococcus aureus strain LAC, we previously examined the impact of regulatory mutations implicated in biofilm formation on protease production and virulence in a murine sepsis model. Here we examined the impact of these mutations in the USA200, methicillin-sensitive strain UAMS-1. Mutation of agr, mgrA, rot, sarA and sigB attenuated the virulence of UAMS-1. A common characteristic of codY, rot, sigB , and sarA mutants was increased protease production, with mutation of rot having the least impact followed by mutation of codY, sigB and sarA , respectively. Protein A was undetectable in conditioned medium from all four mutants, while extracellular nuclease was only present in the proteolytically cleaved NucA form. The abundance of high molecular weight proteins was reduced in all four mutants. Biofilm formation was reduced in codY, sarA and sigB mutants, but not in the rot mutant. Eliminating protease production partially reversed these phenotypes and enhanced biofilm formation. This was also true in LAC codY, rot, sarA and sigB mutants. Eliminating protease production enhanced the virulence of LAC and UAMS-1 sarA, sigB and rot mutants in a murine sepsis model but did not significantly impact the virulence of the codY mutant in either strain. Nevertheless, these results demonstrate that repressing protease production plays an important role in defining critical phenotypes in diverse clinical isolates of S. aureus and that Rot, SigB and SarA play critical roles in this regard.

Background: This study aims to report postoperative complications of chest wall reconstructions due to resections of primary or secondary neoplasms in a South American cancer institution and their association with prosthesis reconstruction., Materials and Methods: We retrospectively reviewed clinical records of patients with primary or secondary chest wall neoplasms who underwent resection and reconstruction between November 2008 and October 2018 at the Instituto Nacional de Cancerología, Bogota, Colombia., Results: A total of 77 patients were analyzed, 50 were women (64.9%), and the median age was 45.8 years. There were 22(28.6%) sternal resections and 55(71.4%) costal resections. Prosthetic material was used in 14(18.2%) sternal and 37(48.1%) costal reconstructions. There were 26(33.7%) early postoperative complications and 16(20.8%) reinterventions. Infections were observed in 12(15.6%) patients and 4(5.2%) patients developed respiratory complications. 33.3% of all the early infections were presented in patients with methyl methacrylate (MMA) reconstructions and the same percentage in those with titanium plates. There were six (7.8%) late complications and five were related to prosthetic material extrusion, all required prosthetic material removal. The mean overall survival was 77,3 months (SD = 8 months), and 1-year and 5-year overall survival was 85% and 61%, respectively., Conclusions: Infections were the more frequent postoperative complications in chest wall reconstructions. The use of either MMA or titanium plates was not related to early postoperative complications, although MMA reconstructions developed higher late complications and required prosthetic material removal., (© 2021. Société Internationale de Chirurgie.)

Evolution of practical resistance is the main threat to the sustainability of transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt crops). Monitoring of resistance to Cry and Vip3A proteins produced by Bt crops is critical to mitigate the development of resistance. Currently, Cry/Vip3A resistance allele monitoring is based on bioassays with larvae from inbreeding field-collected moths. As an alternative, DNA-based monitoring tools should increase sensitivity and reduce overall costs compared to bioassay-based screening methods. Here, we evaluated targeted sequencing as a method allowing detection of known and novel candidate resistance alleles to Cry proteins. As a model, we sequenced a Cry1F receptor gene ( SfABCC2 ) in fall armyworm ( Spodoptera frugiperda ) moths from Puerto Rico, a location reporting continued practical field resistance to Cry1F-producing corn. Targeted sequencing detected a previously reported Cry1F resistance allele ( SfABCC2mut ), in addition to a resistance allele originally described in S. frugiperda populations from Brazil. Moreover, targeted sequencing detected mutations in SfABCC2 as novel candidate resistance alleles. These results support further development of targeted sequencing for monitoring resistance to Bt crops and provide unexpected evidence for common resistance alleles in S. frugiperda from Brazil and Puerto Rico.

We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

Mutation of purR was previously shown to enhance the virulence of Staphylococcus aureus in a murine sepsis model, and this cannot be fully explained by increased expression of genes within the purine biosynthesis pathway. Rather, the increased production of specific S. aureus virulence factors, including alpha toxin and the fibronectin-binding proteins, was shown to play an important role. Mutation of purR was also shown previously to result in increased abundance of SarA. Here, we demonstrate by transposon sequencing that mutation of purR in the USA300 strain LAC increases fitness in a biofilm while mutation of sarA has the opposite effect. Therefore, we assessed the impact of sarA on reported purR -associated phenotypes by characterizing isogenic purR , sarA , and sarA/purR mutants. The results confirmed that mutation of purR results in increased abundance of alpha toxin, protein A, the fibronectin-binding proteins, and SarA, decreased production of extracellular proteases, an increased capacity to form a biofilm, and increased virulence in an osteomyelitis model. Mutation of sarA had the opposite effects on all of these phenotypes and, other than bacterial burdens in the bone, all of the phenotypes of sarA / purR mutants were comparable to those of sarA mutants. Limiting the production of extracellular proteases reversed all of the phenotypes of sarA mutants and most of those of sarA/purR mutants. We conclude that a critical component defining the virulence of a purR mutant is the enhanced production of SarA, which limits protease production to an extent that promotes the accumulation of critical S. aureus virulence factors., (Copyright © 2021 American Society for Microbiology.)

Background: The fall armyworm (Spodoptera frugiperda (J.E. Smith)) is a highly polyphagous agricultural pest with long-distance migratory behavior threatening food security worldwide. This pest has a host range of > 80 plant species, but two host strains are recognized based on their association with corn (C-strain) or rice and smaller grasses (R-strain). The population genomics of the United States (USA) fall armyworm remains poorly characterized to date despite its agricultural threat., Results: In this study, the population structure and genetic diversity in 55 S. frugiperda samples from Argentina, Brazil, Kenya, Puerto Rico and USA were surveyed to further our understanding of whole genome nuclear diversity. Comparisons at the genomic level suggest a panmictic S. frugiperda population, with only a minor reduction in gene flow between the two overwintering populations in the continental USA, also corresponding to distinct host strains at the mitochondrial level. Two maternal lines were detected from analysis of mitochondrial genomes. We found members from the Eastern Hemisphere interspersed within both continental USA overwintering subpopulations, suggesting multiple individuals were likely introduced to Africa., Conclusions: Our research is the largest diverse collection of United States S. frugiperda whole genome sequences characterized to date, covering eight continental states and a USA territory (Puerto Rico). The genomic resources presented provide foundational information to understand gene flow at the whole genome level among S. frugiperda populations. Based on the genomic similarities found between host strains and laboratory vs. field samples, our findings validate the experimental use of laboratory strains and the host strain differentiation based on mitochondria and sex-linked genetic markers extends to minor genome wide differences with some exceptions showing mixture between host strains is likely occurring in field populations.