Usability and Feasibility of the Antipsychotic Medication Decision Aid in a Community Program for First-Episode Psychosis.

OBJECTIVE: Although antipsychotic medications are considered first-line treatment for psychosis, rates of discontinuation and nonadherence are high, and debate persists about their use. This pilot study aimed to explore the usability, feasibility, and potential impact of a shared decision making (SDM) intervention, the Antipsychotic Medication Decision Aid (APM-DA), for decisions about use of antipsychotic medications. METHODS: A pilot randomized controlled trial was conducted with 17 participants in a first-episode psychosis program. Nine participants received the APM-DA, and eight received usual care. RESULTS: After their appointments, intervention group participants had less decisional conflict and greater satisfaction with decisions than control group participants had. Use of the APM-DA did not increase appointment length. Comparison of the intervention outcomes with the control outcomes was limited because of the small sample. CONCLUSIONS: The results support the feasibility and usability of an SDM process via the use of the APM-DA in routine community psychosis care.

The prevalence of ultrasound curricula in a sampling of U.S. physician assistant programs and recommendations for common ultrasound objectives: A national survey.

An increasing number of practicing physician assistants (PAs) are using ultrasound (US) in clinical settings. However, a lack of US learning objectives for PA students limits the optimal integration of this imaging modality in PA curricula. This study surveyed PA program directors across the United States to create a list of US learning objectives for PA students and to gauge their attitudes toward integrating US into anatomy curricula. Thirty-one of the 280 PA program directors responded to the survey. While 87% of participants reported that their institution includes ultrasound in its curriculum, 71% disagreed that the state of the use of ultrasound throughout their PA curriculum is fine and needs no modification. Based on the responses of the survey participants, this study categorized US learning objectives into high, medium, low, and no agreement for integration in PA curricula. As over half of the learning objectives (73%, 43/59) had high agreement for inclusion in curricula, this study demonstrates an opportunity for educators to include US in PA curricula.

Impaired robotic surgical visualization: archaic issues in a modern operating room.

While robotic-assisted surgery (RAS) has been revolutionizing surgical procedures, it has various areas needing improvement, specifically in the visualization sector. Suboptimal vision due to lens occlusions has been a topic of concern in laparoscopic surgery but has not received much attention in robotic surgery. This study is one of the first to explore and quantify the degree of disruption encountered due to poor robotic visualization at a major academic center. In case observations across 28 RAS procedures in various specialties, any lens occlusions or "debris" events that appeared on the monitor displays and clinicians' reactions, the cause, and the location across the monitor for these events were recorded. Data were then assessed for any trends using analysis as described below. From around 44.33 h of RAS observation time, 163 debris events were recorded. 52.53% of case observation time was spent under a compromised visual field. In a subset of 15 cases, about 2.24% of the average observation time was spent cleaning the lens. Additionally, cautery was found to be the primary cause of lens occlusions and little variation was found within the spread of the debris across the monitor display. This study illustrates that in 6 (21.43%) of the cases, 90% of the observation time was spent under compromised visualization while only 2 (7.14%) of the cases had no debris or cleaning events. Additionally, we observed that cleaning the lens can be troublesome during the procedure, interrupting the operating room flow.

Evaluating A Nonemergency Medical Transportation Benefit For Accountable Care Organization Members.

Nonemergency medical transportation benefits, often using smartphone application-based ridesharing services, are increasingly being offered as part of population health management programs. However, the impact of these programs on health care use and costs remains understudied. We conducted a mixed-methods evaluation of a nonemergency medical transportation benefit offered to members of a Medicare accountable care organization (ACO) within a large academic health system, the UNC Health Alliance ACO. Participation in the transportation program was associated with a greater number of per person per year outpatient visits (9.2) and higher outpatient spending ($4,420) than in a comparison group. However, there was no difference in inpatient admissions or emergency department visits, and the program was not cost saving. Qualitative analyses revealed that participants were highly satisfied with the program, reporting that it eased financial burdens and made them feel safer, more empowered, and better able to take control of their health. These findings suggest that although transportation programs are commonly introduced as ways to contain health care spending, it may be better to think of them as programs to improve health care access for people facing difficult circumstances.

Gender-Based Violence, Perspectives in Latin America and the Caribbean.

INTRODUCTION: To address the phenomenon of gender-based violence in Latin America and the Caribbean is an issue of epic proportion that reflects the unequal power dynamics created within the binary gender system and is often perpetrated by those with more physical, cultural, or social power and inflicted upon those without. METHOD: Each database was comprehensively searched for MeSH keyword combinations of gender violence (violence against women) or (gender-based violence) with the region of interest (Latin America and the Caribbean) in addition to a third word or phrase regarding health care (health care training, training, health care curricula, curricula, health care professionals). RESULTS: After completing this scope review, we have found a widespread call for more comprehensive preparation for health care professionals involved in identifying and addressing gender-based violence. CONCLUSIONS: Though some research has been conducted documenting the ways in which gender-based violence is managed or not managed by health care providers, Latin America and the Caribbean in particular represent a gap in research on health care tools and their effectiveness in these situations. There is a distinct need for the creation of context-specific protocols for vulnerable and underrepresented groups.

Functional heterogeneity of alveolar macrophage population based on expression of CXCL2.

Alveolar macrophages (AMs) are the major lung-resident macrophages and have contradictory functions. AMs maintain tolerance and tissue homeostasis, but they also initiate strong inflammatory responses. However, such opposing roles within the AM population were not known to be simultaneously generated and coexist. Here, we uncovered heterogeneous AM subpopulations generated in response to two distinct pulmonary fungal infections, Cryptococcus neoformans and Aspergillus fumigatus Some AMs are bona fide sentinel cells that produce chemoattractant CXCL2, which also serves as a marker for AM heterogeneity, in the context of pulmonary fungal infections. However, other AMs do not produce CXCL2 and other pro-inflammatory molecules. Instead, they highly produce anti-inflammatory molecules, including interleukin-10 (IL-10) and complement component 1q (C1q). These two AM subpopulations have distinct metabolic profiles and phagocytic capacities. We report that polarization of pro-inflammatory and anti-inflammatory AM subpopulations is regulated at both epigenetic and transcriptional levels and that these AM subpopulations are generally highly plastic. Our studies have uncovered the role of C1q expression in programming and sustaining anti-inflammatory AMs. Our finding of the AM heterogeneity upon fungal infections suggests a possible pharmacological intervention target to treat fungal infections by tipping the balance of AM subpopulations.

Regulation of γδ T Cell Effector Diversification in the Thymus.

γδ T cells are the first T cell lineage to develop in the thymus and take up residence in a wide variety of tissues where they can provide fast, innate-like sources of effector cytokines for barrier defense. In contrast to conventional αß T cells that egress the thymus as naïve cells, γδ T cells can be programmed for effector function during development in the thymus. Understanding the molecular mechanisms that determine γδ T cell effector fate is of great interest due to the wide-spread tissue distribution of γδ T cells and their roles in pathogen clearance, immunosurveillance, cancer, and autoimmune diseases. In this review, we will integrate the current understanding of the role of the T cell receptor, environmental signals, and transcription factor networks in controlling mouse innate-like γδ T cell effector commitment.

c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program.

CCR6- group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function that possess the capacity to acquire type 1 effector features and fully convert into ILC1s. The molecular mechanisms governing such plasticity are undefined. Here, we identified c-Maf as an essential regulator of ILC3 homeostasis and plasticity that limits physiological ILC1 conversion. Phenotypic analysis of effector status in Maf-deficient CCR6- ILC3s, coupled with evaluation of global changes in transcriptome, chromatin accessibility, and transcription factor motif enrichment, revealed that c-Maf enforces ILC3 identity. c-Maf promoted ILC3 accessibility and supported RORγt activity and expression of type 3 effector genes. Conversely, c-Maf antagonized type 1 programming, largely through restraint of T-bet expression and function. Mapping of the dynamic changes in chromatin landscape accompanying CCR6- ILC3 development and ILC1 conversion solidified c-Maf as a gatekeeper of type 1 regulatory transformation and a controller of ILC3 fate.

The benefits and implementation challenges of the first state-wide comprehensive medication for addictions program in a unified jail and prison setting.

The prevalence of opioid use disorders among people who are incarcerated is high. People who are released from incarceration are at increased risk for overdose. The current study details the first year of implementation of a state-wide medications for addiction treatment (MAT) program in a unified jail and prison setting at the Rhode Island Department of Corrections in Cranston, Rhode Island. We conducted 40 semi-structured, qualitative interviews with people who were incarcerated and concurrently enrolled in the MAT program. Analysis employed a general, inductive approach in NVivo 12. We found that a majority of participants discussed program benefits such as reduced withdrawal symptoms, decreased prevalence of illicit drug use in the facility, improved general environment at the RIDOC, and increased post-release intentions to continue MAT. Suggested areas of improvement include reducing delays to first dose, increasing access to other recovery services in combination with MAT, improving staff training on stigma, and earlier access to medical discharge planning information prior to release. Our findings suggest that correctional MAT programs are acceptable to targeted populations and are a feasible intervention that may be transferable to other states.

Publisher Correction: The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.

In the version of this article initially published, the top right plot in Figure 4a was aligned incorrectly. The error has been corrected in the HTML and PDF versions of the article. The original and corrected figures are provided in the accompanying Publisher Correction.

The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.

γδ T cells that produce the cytokine IL-17 (Tγδ17 cells) are innate-like mediators of immunity that undergo effector programming in the thymus. While regulators of Tγδ17 specialization restricted to various Vγ subsets are known, a commitment factor essential to all Tγδ17 cells has remained undefined. In this study, we identified the transcription factor c-Maf as a universal regulator of Tγδ17 cell differentiation and maintenance. Maf deficiency caused an absolute lineage block at the immature CD24+CD45RBlo γδ thymocyte stage, which revealed a critical checkpoint in the acquisition of effector functions. Here, c-Maf enforced Tγδ17 cell identity by promoting chromatin accessibility and expression of key type 17 program genes, notably Rorc and Blk, while antagonizing the transcription factor TCF1, which promotes interferon-γ-producing γδ T cells (Tγδ1 cells). Furthermore, γδ T cell antigen receptor (γδTCR) signal strength tuned c-Maf expression, which indicates that c-Maf is a core node that connects γδTCR signals to Tγδ17 cell transcriptional programming.

Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.C gp120 prime-combined intramuscular-intranasal gp120 boost administered during pregnancy and postpartum to confer passive protection on infant rhesus macaques against weekly oral exposure to subtype C simian-human immunodeficiency virus 1157ipd3N4 (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting a robust systemic envelope (Env)-specific IgG response, as well as durable milk IgA responses, the maternal vaccine did not have a discernible impact on infant oral SHIV acquisition. This study revealed considerable variation in vaccine-elicited IgG placental transfer and a swift decline of both Env-specific antibodies (Abs) and functional Ab responses in the infants prior to the first challenge, illustrating the importance of pregnancy immunization timing to elicit optimal systemic Ab levels at birth. Interestingly, the strongest correlation to the number of challenges required to infect the infants was the percentage of activated CD4+ T cells in the infant peripheral blood at the time of the first challenge. These findings suggest that, in addition to maternal immunization, interventions that limit the activation of target cells that contribute to susceptibility to oral HIV-1 acquisition independently of vaccination may be required to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus acquisition. It revealed highly variable placental transfer of potentially protective antibodies and emphasized the importance of pregnancy immunization timing to reach peak antibody levels prior to delivery. While there was no discernible impact of maternal immunization on late infant oral virus acquisition, we observed a strong correlation between the percentage of activated CD4+ T cells in infant peripheral blood and a reduced number of challenges to infection. This finding highlights an important consideration for future studies evaluating alternative strategies to further reduce the vertical HIV-1 transmission risk.

The blasticidin S biosynthesis gene cluster from Streptomyces griseochromogenes: sequence analysis, organization, and initial characterization.

Blasticidin S is a potent antifungal and cytotoxic peptidyl nucleoside antibiotic from Streptomyces griseochromogenes. The mixed biosynthesis of the compound is evident from the three distinct structural components: a cytosine base, an amino deoxyglucuronic acid, and N-methyl beta-arginine. The blasticidin S biosynthesis gene cluster was cloned from S. griseochromogenes and the pathway heterologously expressed in S. lividans from a cosmid harboring a 36.7-kb fragment of S. griseochromogenes DNA. The complete DNA sequence of this insert has now been determined and evidence suggests a contiguous 20-kb section defines the blasticidin S biosynthesis cluster. The predicted functions of several open reading frames are consistent with the expected biochemistry and include an arginine 2,3-aminomutase, a cytosylglucuronic acid synthase, and a guanidino N-methyltransferase. Insight into other steps in the assembly of blasticidin S was evident from sequence homology with proteins of known function and heterologous expression of fragments of the cluster. Additionally, the gene that directs the production of free cytosine, blsM, was subcloned and expressed in Escherichia coli. Characterization of BlsM revealed that cytidine monophosphate serves as the precursor to cytosine.

Specificity and sensitivity of automated external defibrillator rhythm analysis in infants and children.

STUDY OBJECTIVES: The rhythm detection algorithms of automated external defibrillators have been derived from adult rhythms, and their ability to discriminate between shockable and nonshockable rhythms in children is largely unknown. This study evaluates the performance of 1 automated external defibrillator algorithm in infants and children and evaluates algorithm performance with anterior-posterior versus sternal-apex lead placement. METHODS: We enrolled pediatric patients in a critical care unit, an electrophysiology laboratory, and a cardiac operating room. A monitor-defibrillator recorded ECGs by means of standard defibrillation-monitor pads. Selected 15-second rhythm samples were played into a LIFEPAK 500 automated external defibrillator, and the automated external defibrillator "shock/no shock" decision was documented. To determine sensitivity and specificity, the automated external defibrillator decision was compared with the "shockable" versus "nonshockable" rhythm classification provided by 3 expert clinicians who were blinded to the automated external defibrillator decision. RESULTS: We recorded 1,561 rhythm samples from 203 pediatric patients (median age 11 months; range, day of birth to 7 years). The automated external defibrillator recommended a shock for 72 of 73 rhythm samples classified as coarse ventricular fibrillation by expert review (sensitivity 99%; 95% confidence interval [CI] 93% to 100%); and correctly reached a "no shock advised" decision for 1,465 of 1,472 rhythm samples classified as nonshockable by experts (specificity 99.5%). Specificity was 99.1% (95% CI 97.8% to 99.8%) with the sternal-apex lead and 99.4% (95% CI 98.1% to 99.9%) with the anterior-posterior lead. CONCLUSION: This automated external defibrillator algorithm has high specificity and sensitivity when used in infants and children with either sternal-apex or anterior-posterior lead placement.