Implementation of a Secure Firearm Storage Program in Pediatric Primary Care: A Cluster Randomized Trial.

Importance: Increased secure firearm storage can reduce youth firearm injury and mortality, a leading cause of death for children and adolescents in the US. Despite the availability of evidence-based secure firearm storage programs and recommendations from the American Academy of Pediatrics, few pediatric clinicians report routinely implementing these programs. Objective: To compare the effectiveness of an electronic health record (EHR) documentation template (nudge) and the nudge plus facilitation (ie, clinic support to implement the program; nudge+) at promoting delivery of a brief evidence-based secure firearm storage program (SAFE Firearm) that includes counseling about secure firearm storage and free cable locks during all pediatric well visits. Design, Setting, and Participants: The Adolescent and Child Suicide Prevention in Routine Clinical Encounters (ASPIRE) unblinded parallel cluster randomized effectiveness-implementation trial was conducted from March 14, 2022, to March 20, 2023, to test the hypothesis that, relative to nudge, nudge+ would result in delivery of the firearm storage program to an additional 10% or more of the eligible population, and that this difference would be statistically significant. Thirty pediatric primary care clinics in 2 US health care systems (in Michigan and Colorado) were included, excluding clinics that were not the primary site for participating health care professionals and a subset selected at random due to resource limitations. All pediatric well visits at participating clinics for youth ages 5 to 17 years were analyzed. Interventions: Clinics were randomly assigned in a 1:1 ratio to receive either the nudge or nudge+. Main Outcomes and Measures: Patient-level outcomes were modeled to estimate the primary outcome, reach, which is a visit-level binary indicator of whether the parent received both components of the firearm storage program (counseling and lock), as documented by the clinician in the EHR. Secondary outcomes explored individual program component delivery. Results: A total of 47 307 well-child visits (median [IQR] age, 11.3 [8.1-14.4] years; 24 210 [51.2%] male and 23 091 [48.8%] female) among 46 597 children and 368 clinicians were eligible to receive the firearm storage program during the trial and were included in analyses. Using the intention-to-treat principle, a higher percentage of well-child visits received the firearm storage program in the nudge+ condition (49%; 95% CI, 37-61) compared to nudge (22%; 95% CI, 13-31). Conclusions and Relevance: In this study, the EHR strategy combined with facilitation (nudge+) was more effective at increasing delivery of an evidence-based secure firearm storage program compared to nudge alone. Trial Registration: ClinicalTrials.gov Identifier: NCT04844021.

Opportunities to Advance Equity Through Implementation Strategy Design.

Background: Implementation strategies are potential tools for advancing equity goals in healthcare. Implementation scientists have increased attention to the integration of equity considerations into implementation research, but limited concrete guidance is available for developing implementation strategies to improve equity. Main: In parallel to an active hybrid effectiveness-implementation trial in two large health systems, our research team explored potential inequities in implementation across four non-study clinics, developed equity focused audit and feedback procedures, examined the feasibility of our approach, and identified design insights that could be tested in future work to inform equitable program scale-up. Based on our experiences deploying these strategies in pilot format, our research team identified key complexities meriting further examination in future work. These considerations are vital given the dearth of guidance on delivering feedback to clinicians in efforts to improve equity. Key takeaways include the importance of understanding local data culture, engaging constituents in co-design for the full feedback cycle, leveraging feedback for shared discourse, and centering multi-level strategies as part of robust implementation approaches. Conclusion: Prioritizing health equity in implementation science requires that research teams probe, interrogate, and innovate - and in doing so, grapple with central conceptual and pragmatic considerations that arise in the design of implementation strategies. Our work emphasizes the value of bidirectional and continuous learning.

Integrating insights from implementation science and behavioral economics to strengthen suicide screening strategies for pediatric populations.

Suicide is a leading cause of death for young people globally. Professional organizations such as the American Academy of Pediatrics (AAP) recommend suicide screening for every young person at every healthcare contact and these guidelines are now being implemented across the US. To optimize deployment of these guidelines, we draw on insights from two parallel fields, implementation science - or the study of how to support clinicians in providing evidence-based care within organizational constraints - and behavioral economics, which centers human decision-making. In this brief review, we offer potential barriers to suicide screening and strategies to address barriers drawing on these two literatures, illustrating how best to integrate insights from these fields for maximal impact.

Population mental health science: Guiding principles and initial agenda.

A recent American Psychological Association Summit provided an urgent call to transform psychological science and practice away from a solely individual-level focus to become accountable for population-level impact on health and mental health. A population focus ensures the mental health of all children, adolescents, and adults and the elimination of inequities across groups. Science must guide three components of this transformation. First, effective individual-level interventions must be scaled up to the population level using principles from implementation science, investing in novel intervention delivery systems (e.g., online, mobile application, text, interactive voice response, and machine learning-based), harnessing the strength of diverse providers, and forging culturally informed adaptations. Second, policy-driven community-level interventions must be innovated and tested, such as public efforts to promote physical activity, public policies to support families in early life, and regulation of corporal punishment in schools. Third, transformation is needed to create a new system of universal primary care for mental health, based on models such as Family Connects, Triple P, PROmoting School-community-university Partnerships to Enhance Resilience, Communities That Care, and the Early Childhood Collaborative of the Pittsburgh Study. This new system must incorporate valid measurement, universal screening, and a community-based infrastructure for service delivery. Addressing tasks ahead, including scientific creativity and discovery, rigorous evaluation, and community accountability, will lead to a comprehensive strategic plan to shape the emergent field of public mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial.

BACKGROUND: Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science-including mixed-methods contextual inquiry with clinicians, patients, and health system constituents-to co-design two patient-facing implementation strategies to address this care gap: (a) an automated health system-mediated strategy and (b) a nonprofit foundation-mediated strategy with contact from a foundation-employed care navigator. This trial will test the comparative effectiveness of these strategies on completion of cascade screening for relatives of individuals with FH, centering equitable reach. METHODS: We will conduct a hybrid effectiveness-implementation type III randomized controlled trial testing the comparative effectiveness of two strategies for implementing cascade screening with 220 individuals with FH (i.e., probands) per arm identified from a large northeastern health system. The primary implementation outcome is reach, or the proportion of probands with at least one first-degree biological relative (parent, sibling, child) in the USA who is screened for FH through the study. Our secondary implementation outcomes include the number of relatives screened and the number of relatives meeting the American Heart Association criteria for FH. Our secondary clinical effectiveness outcome is post-trial proband cholesterol level. We will also use mixed methods to identify implementation strategy mechanisms for implementation strategy effectiveness while centering equity. DISCUSSION: We will test two patient-facing implementation strategies harnessing insights from behavioral economics that were developed collaboratively with constituents. This trial will improve our understanding of how to implement evidence-based cascade screening for FH, which implementation strategies work, for whom, and why. Learnings from this trial can be used to equitably scale cascade screening programs for FH nationally and inform cascade screening implementation efforts for other genetic disorders. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05750667. Registered 15 February 2023-retrospectively registered, https://clinicaltrials.gov/study/NCT05750667 .

Transcriptome analysis of polyploid giant cancer cells and their progeny reveals a functional role for p21 in polyploidization and depolyploidization.

Polyploid giant cancer cells (PGCC) are frequently detected in tumors and are increasingly recognized for their roles in chromosomal instability and associated genome evolution that leads to cancer recurrence. We previously reported that therapy stress promotes polyploidy, and that acid ceramidase plays a role in depolyploidization. In this study, we used an RNA-seq approach to gain a better understanding of the underlying transcriptomic changes that occur as cancer cells progress through polyploidization and depolyploidization. Our results revealed gene signatures that are associated with disease-free and/or overall survival in several cancers and identified the cell cycle inhibitor CDKN1A/p21 as the major hub in PGCC and early progeny. Increased expression of p21 in PGCC was limited to the cytoplasm. We previously demonstrated that the sphingolipid enzyme acid ceramidase is dispensable for polyploidization upon therapy stress but plays a crucial role in depolyploidization. The current study demonstrates that treatment of cells with ceramide is not sufficient for p53-independent induction of p21 and that knockdown of acid ceramidase, which hydrolyzes ceramide, does not interfere with upregulation of p21. In contrast, blocking the expression of p21 with UC2288 prevented the induction of acid ceramidase and inhibited both the formation of PGCC from parental cells as well as the generation of progeny from PGCC. Taken together, our data suggest that p21 functions upstream of acid ceramidase and plays an important role in polyploidization and depolyploidization.

Implementing trauma-focused cognitive behavioral therapy in Philadelphia: A 10-year evaluation.

Background: In 2012, Philadelphia's Department of Behavioral Health and Intellectual disAbility Services (DBHIDS) developed an initiative to implement an evidence-based treatment for posttraumatic stress disorder (PTSD), trauma-focused cognitive behavioral therapy (TF-CBT), across the city's behavioral health system. This report evaluates the initiative's 10-year implementation and effectiveness outcomes. Method: The Exploration, Preparation, Implementation, and Sustainment framework guided our implementation evaluation. The implementation outcomes include adoption, reach, and sustainment; these were obtained during regular evaluation data collection from publicly funded behavioral health agencies participating in the TF-CBT initiative. We analyze effectiveness outcomes (i.e., changes in PTSD symptoms) from a subset of patients receiving TF-CBT, which were collected in 6-month intervals by our research team between 2013 and 2021. Results: From 2012 to 2021, DBHIDS trained 478 clinicians in TF-CBT across 20 behavioral health agencies. During this time, 23,401 youths were screened for potentially traumatic events and PTSD symptoms, and 7,550 youths received TF-CBT. Through the TF-CBT initiative, the city expanded the network of TF-CBT providers from 3 to 20 agencies. DBHIDS sustained this network by maintaining the participation of 16 behavioral health agencies over the course of a decade. The subset of 202 youths who were evaluated to assess TF-CBT effectiveness was drawn from 94 therapists and 20 agencies across Philadelphia. All participating youths completed a baseline assessment, and 151 (75%) completed at least one follow-up assessment. Linear mixed-effects models accounting for observations nested within participants and nested within clinicians found that treatment significantly reduced PTSD symptoms. Conclusion: Between 2012 and 2021, DBHIDS successfully implemented and sustained TF-CBT across the city's behavioral health system. Adoption, reach, and sustainment of TF-CBT were high. Despite the considerable adverse experiences faced by youths seeking treatment in Philadelphia's behavioral health system, TF-CBT was effective. Future directions to improve TF-CBT implementation in the next iteration of the initiative are described.

This practical implementation report describes a 10-year effort by the city of Philadelphia to develop a trauma-informed behavioral health system, making this report one of the longest evaluations of an implementation initiative in a large metropolitan area in the United States. In particular, the report describes the implementation and effectiveness outcomes of Philadelphia's Department of Behavioral Health and Intellectual disAbility Services (DBHIDS)'s implementation of the evidence-based treatment for posttraumatic stress disorder (PTSD), trauma-focused cognitive behavioral therapy (TF-CBT), across the city's behavioral health agencies. From 2012 to 2021, DBHIDS trained 478 clinicians in TF-CBT across 20 behavioral health agencies. During this time, 23,401 youths were screened for posttraumatic stress symptoms, and 7,550 youths received TF-CBT. A subset of 202 youths receiving TF-CBT from 94 therapists across 20 Philadelphia agencies were evaluated to assess the initiative's effectiveness. Linear mixed-effects models revealed that youths receiving TF-CBT from DBHIDS-trained clinicians saw their PTSD symptoms significantly reduce. The initiative's success in adoption, reach, sustainment, and effectiveness reveals the promise of sustained, multipronged, community-partnered implementation initiatives. In the future, researchers and policymakers must account for and address the structural and financial barriers that hinder these community-partnered implementation efforts from realizing their full potential in improving population health.

The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics.

Polyploid cells contain more than two copies of each chromosome. Polyploidy has important roles in development, evolution, and tissue regeneration/repair, and can arise as a programmed polyploidization event or be triggered by stress. Cancer cells are often polyploid. C. elegans nematodes are typically diploid, but stressors such as heat shock and starvation can trigger the production of tetraploid offspring. In this study, we utilized a recently published protocol to generate stable tetraploid strains of C. elegans and compared their physiological traits and sensitivity to two DNA-damaging chemotherapeutic drugs, cisplatin and doxorubicin. As prior studies have shown, tetraploid worms are approximately 30% longer, shorter-lived, and have a smaller brood size than diploids. We investigated the reproductive defect further, determining that tetraploid worms have a shorter overall germline length, a higher rate of germ cell apoptosis, more aneuploidy in oocytes and offspring, and larger oocytes and embryos. We also found that tetraploid worms are modestly protected from growth delay from the chemotherapeutics but are similarly or more sensitive to reproductive toxicity. Transcriptomic analysis revealed differentially expressed pathways that may contribute to sensitivity to stress. This study reveals phenotypic consequences of whole-animal tetraploidy that make C. elegans an excellent model for ploidy differences.

The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics.

Polyploid cells contain more than two copies of each chromosome. Polyploidy has important roles in development, evolution, and tissue regeneration/repair, and can arise as a programmed polyploidization event or be triggered by stress. Cancer cells are often polyploid. C. elegans nematodes are typically diploid, but stressors such as heat shock and starvation can trigger the production of tetraploid offspring. In this study, we utilized a recently published protocol to generate stable tetraploid strains of C. elegans and compared their physiological traits and sensitivity to two DNA-damaging chemotherapeutic drugs, cisplatin and doxorubicin. As prior studies have shown, tetraploid worms are approximately 30% longer, shorter-lived, and have a smaller brood size than diploids. We investigated the reproductive defect further, determining that tetraploid worms have a shorter overall germline length, a higher rate of germ cell apoptosis, more aneuploidy in oocytes and offspring, and larger oocytes and embryos. We also found that tetraploid worms are modestly protected from growth delay from the chemotherapeutics but are similarly or more sensitive to reproductive toxicity. Transcriptomic analysis revealed differentially expressed pathways that may contribute to sensitivity to stress. Overall, this study reveals the phenotypic consequences of whole-animal tetraploidy in C. elegans.

A Randomized Trial of Quadruple-Fortified Salt for Anemia and Birth Defects Prevention in Southern India: Protocol Design and Methods.

Background: Women of reproductive age are at an increased risk of anemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of neural tube defects (NTDs) and other pregnancy complications. Vitamin B12 deficiency is a risk factor for NTDs and may modify folate biomarkers that predict NTD risk at the population level. There is an interest in mandatory fortification with vitamin B12 and folic acid for anemia and birth defect prevention. However, there are limited population-representative data needed to inform policy and guidelines. Objectives: This randomized trial will be conducted to evaluate the efficacy of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B12) in 1,000 households in Southern India. Methods: Women 18 to 49 y who are not pregnant or lactating and reside within the catchment area of our community-based research site in Southern India will be screened and invited to participate in the trial. After informed consent, women and their households will be randomized to receive one of the following 4 interventions: 1) double-fortified salt (DFS; iron, iodine), 2) DFS + folic acid (iron, iodine, folic acid), 3) DFS + vitamin B12 (iron, iodine, vitamin B12), or 4) DFS + folic acid and vitamin B12 (QFS; iron, iodine, folic acid, vitamin B12) for 12 mo. Structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, anthropometric, dietary, health, and reproductive history data. Biological samples will be collected at baseline, midpoint, and endpoint. Whole blood will be analyzed for hemoglobin using Coulter Counter. Total vitamin B12 will be measured by chemiluminescence; red blood cell folate and serum folate will be evaluated using the World Health Organization-recommended microbiologic assay. Conclusions: The results of this randomized trial will help to evaluate the efficacy of QFS to prevent anemia and micronutrient deficiencies. Clinical trial registration numbers: NCT03853304 and Clinical Trial Registry of India REF/2019/03/024479. Registration number: NCT03853304 and REF/2019/03/024479.

Estimating the serum folate concentration that corresponds to the red blood cell folate concentration threshold associated with optimal neural tube defects prevention: A population-based biomarker survey in Southern India.

BACKGROUND: RBC folate concentrations are monitored at the population level, with a recommended threshold for optimal neural tube defect (NTD) prevention. A corresponding threshold for serum folate has not been established. OBJECTIVES: This study aimed to estimate the serum folate insufficiency threshold corresponding to the RBC folate threshold for NTD prevention and examine how this threshold is modified by vitamin B12 status. METHODS: Participants were women (15-40 y; not pregnant or lactating; n = 977) from a population-based biomarker survey in Southern India. RBC folate and serum folate were measured via microbiologic assay. RBC folate deficiency (<305 nmol/L) and insufficiency (<748 nmol/L), serum vitamin B12 deficiency (<148 pmol/L) and vitamin B12 insufficiency (<221 pmol/L), elevated plasma MMA (>0.26 µmol/L), elevated plasma homocysteine (>10.0 µmol/L), and elevated HbA1c (≥6.5%) were evaluated. Bayesian linear models were used to estimate unadjusted and adjusted thresholds. RESULTS: Compared with adequate vitamin B12 status, the estimated serum folate threshold was higher in participants with serum vitamin B12 deficiency (72.5 vs. 28.1 nmol/L) or vitamin B12 insufficiency (48.7 vs. 24.3 nmol/L) and elevated MMA (55.6 vs. 25.9 nmol/L). The threshold was lower in participants with elevated HbA1c (HbA1c ≥6.5% vs. <6.5%; 21.0 vs. 40.5 nmol/L). CONCLUSIONS: The estimated serum folate threshold for optimal NTD prevention was similar to previous reports (24.3 vs. 25.6 nmol/L) among participants with sufficient vitamin B12 status. However, this threshold was more than 2-fold higher in participants with vitamin B12 deficiency and substantially higher across all indicators of insufficient vitamin B12 status (<221 pmol/L, elevated MMA, combined B12, impaired vitamin B12 status), and lower in participants with elevated HbA1c. Findings suggest a serum folate threshold for NTD prevention may be possible in some settings; however, it may not be appropriate in populations with high prevalence of vitamin B12 insufficiency. Am J Clin Nutr 2023;xx:xx-xx. This trial was registered at https://clinicaltrials.gov as NCT04048330.

Outcomes of the "BRCA Quality Improvement Dissemination Program": An initiative to improve patient receipt of cancer genetics services at five health systems.

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC). METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, chi-squared/Fisher's exact test, and logistic regression. RESULTS: For patients with OC, improvement was observed in the rate of referral (from 70% to 79%), GC (from 44% to 61%), GT (from 54% to 62%) and decreased time from diagnosis to GC and GT. For patients with TNBC, increased rates of referral (from 90% to 92%), GC (from 68% to 72%) and GT (81% to 86%) were observed. Effective interventions streamlined GC scheduling and standardized referral processes. CONCLUSION: A multi-year QII increased patient referral and uptake of recommended genetics services across five unique community-based oncology care settings.

Meta-analysis of the space flight and microgravity response of the Arabidopsis plant transcriptome.

Spaceflight presents a multifaceted environment for plants, combining the effects on growth of many stressors and factors including altered gravity, the influence of experiment hardware, and increased radiation exposure. To help understand the plant response to this complex suite of factors this study compared transcriptomic analysis of 15 Arabidopsis thaliana spaceflight experiments deposited in the National Aeronautics and Space Administration's GeneLab data repository. These data were reanalyzed for genes showing significant differential expression in spaceflight versus ground controls using a single common computational pipeline for either the microarray or the RNA-seq datasets. Such a standardized approach to analysis should greatly increase the robustness of comparisons made between datasets. This analysis was coupled with extensive cross-referencing to a curated matrix of metadata associated with these experiments. Our study reveals that factors such as analysis type (i.e., microarray versus RNA-seq) or environmental and hardware conditions have important confounding effects on comparisons seeking to define plant reactions to spaceflight. The metadata matrix allows selection of studies with high similarity scores, i.e., that share multiple elements of experimental design, such as plant age or flight hardware. Comparisons between these studies then helps reduce the complexity in drawing conclusions arising from comparisons made between experiments with very different designs.

Evaluating Diabetes Group Medical Visits in a Family Medicine Residency Program.

Background: Group medical visits (GMV) have been shown to improve metrics in patients with type 2 diabetes mellitus (DM). Overlook Family Medicine, a teaching residency program, anticipated that medical residents trained in the GMV model of care by interdisciplinary team members may improve cholesterol, HbA1C, BMI, and blood pressure in patients. The objective of this study was to compare metrics between group 1: GMV patients with DM whose primary care provider (PCP) was an attending physician/nurse practitioner (NP) and group 2: GMV patients with DM whose PCP was a family medicine (FM) medical resident receiving GMV training. We seek to provide guidance on implementation of GMV in residency teaching practices. Methods: We performed a retrospective analysis to evaluate total cholesterol, LDL, HDL, TG, BMI, HbA1C, and BP in GMV patients between 2015-2018. We used a t test to compare outcomes between the two groups. Diabetes training was provided to family medicine residents by an interdisciplinary team. Results: There were 113 patients enrolled in the study: 53 in group 1 and 60 in group 2. There was a statistically significant decrease in LDL and triglycerides, and an increase in HDL in group 2 (P<.05). There was a clinically significant decrease in HbA1C in group 2 (-0.56, P=.0622). Conclusion: Sustainability of GMV can be achieved with a champion diabetes education specialist. Interdisciplinary team members are integral in training residents and addressing patients' barriers. GMV training should be incorporated into family medicine residency programs to improve metrics for patients with diabetes. FM residents who received interdisciplinary training had improved metrics in GMV patients compared to patients whose providers did not. Therefore, GMV training should be incorporated into family medicine residency programs to improve metrics for patients with diabetes.

Comparison of Anemia Screening Methods Using Paired Venous Samples in Women of Reproductive Age in Southern India.

BACKGROUND: Anemia is an important public health problem, and accurate estimates may inform policy and programs. Although hemoglobin (Hb) assessment of venous blood via automated hematology analyzers (AHAs) is recommended, most population-based surveys estimate anemia prevalence based on analysis of capillary blood via portable hemoglobinometers. OBJECTIVES: We aimed to evaluate screening methods for hemoglobin and anemia assessment using paired venous samples. METHODS: Participants were women 15-40 y who were not pregnant or lactating. Paired venous whole blood samples (n = 896) were analyzed for hemoglobin (Hb) via portable hemoglobinometer (HemoCue 301) and Coulter Counter AHA. Anemia and severe anemia were defined as Hb <12.0g/dL and <8.0 g/dL, respectively. Bland-Altman methods were used to assess the level of agreement for Hb results (mean difference, SD of differences, limits of agreement). Diagnostic accuracy parameters (sensitivity, specificity, positive predictive value, negative predictive value, accuracy) were calculated to evaluate HemoCue performance compared to the AHA reference, overall and by sociodemographic, nutritional, and metabolic characteristics. RESULTS: The estimated anemia prevalence was significantly lower via HemoCue vs. AHA (36.3% compared with 41.6%; P value < 0.0001). The HemoCue had 84.4% accuracy for anemia screening and 98.8% for severe anemia, compared to the AHA reference. The HemoCue had 74.8% sensitivity and 91.2% specificity, compared to AHA. HemoCue sensitivity was higher in women with iron deficiency [serum ferritin (SF) <15.0 µg/L: 81.6% compared with SF ≥15.0 µg/L: 41.3%], and lower in women with metabolic risk factors, including overweight [BMI ≥25.0 kg/m2: 63.9% vs. BMI <25.0 kg/m2: 78.8%], or elevated CRP (>1.0 mg/L: 67.2% vs. ≤1.0 mg/L: 82.9%), trunk fat (>35%: 62.7% vs. ≤35%: 80.1%), or whole-body fat (>35%: 63.9% vs. ≤35%: 80.3%). CONCLUSIONS: Findings suggest that women with anemia may be incorrectly identified as not anemic via portable hemoglobinometer, and anemia prevalence may be underestimated at the population level.This study was registered at clinicaltrials.gov as NCT04048330.

Microgreens for Home, Commercial, and Space Farming: A Comprehensive Update of the Most Recent Developments.

Microgreens are edible young plants that have recently attracted interest because of their color and flavor diversity, phytonutrient abundance, short growth cycle, and minimal space and nutrient requirements. They can be cultivated in a variety of systems from simple home gardens to sophisticated vertical farms with automated irrigation, fertilizer delivery, and lighting controls. Microgreens have also attracted attention from space agencies hoping that their sensory qualities can contribute to the diet of astronauts in microgravity and their cultivation might help maintain crew physical and psychological health on long-duration spaceflight missions. However, many technical challenges and data gaps for growing microgreensboth on and off Earth remain unaddressed. This review summarizes recent studies on multiple aspects of microgreens, including nutritional and socioeconomic benefits, cultivation systems, operative conditions, innovative treatments, autonomous facilities, and potential space applications. It also provides the authors' perspectives on the challenges to stimulating more extensive interdisciplinary research.

Say My Name: Understanding the Power of Names, Correct Pronunciation, and Personal Narratives.

Introduction: Names are a reflection of identity and often have personal meaning. The chronic mispronunciation of names can undermine one's identity and be experienced as a microaggression. This workshop aims to provide historical context for names as well as resources for correct name pronunciation. Methods: We developed a 60-minute interactive virtual workshop with didactics, small-group sharing of personal experiences, and case discussions. We used an anonymous postworkshop survey to evaluate workshop effectiveness. Results: We presented the workshop at one local academic conference and two local educational conferences to learners of all levels from medical students to faculty. We collected postworkshop survey results from 78 participants of diverse racial and ethnic backgrounds. Participants reported learning historical context, ways to ask about correct name pronunciation, correcting name mispronunciation, documenting pronunciation, and sources for applications to practice. The main barriers to implementing workshop lessons included personal and structural factors. Discussion: This workshop effectively fills an educational gap by addressing the importance of correct name pronunciation in order to provide a more inclusive environment for clinicians and patients alike.

Crosstalk between pro-survival sphingolipid metabolism and complement signaling induces inflammasome-mediated tumor metastasis.

Crosstalk between metabolic and signaling events that induce tumor metastasis remains elusive. Here, we determine how oncogenic sphingosine 1-phosphate (S1P) metabolism induces intracellular C3 complement activation to enhance migration/metastasis. We demonstrate that increased S1P metabolism activates C3 complement processing through S1P receptor 1 (S1PR1). S1P/S1PR1-activated intracellular C3b-α'2 is associated with PPIL1 through glutamic acid 156 (E156) and aspartic acid 111 (D111) residues, resulting in NLRP3/inflammasome induction. Inactivation mutations of S1PR1 to prevent S1P signaling or mutations of C3b-α'2 to prevent its association with PPIL1 attenuate inflammasome activation and reduce lung colonization/metastasis in mice. Also, activation of the S1PR1/C3/PPIL1/NLRP3 axis is highly associated with human metastatic melanoma tissues and patient-derived xenografts. Moreover, targeting S1PR1/C3/PPIL1/NLRP3 signaling using molecular, genetic, and pharmacologic tools prevents lung colonization/metastasis of various murine cancer cell lines using WT and C3a-receptor1 knockout (C3aR1-/-) mice. These data provide strategies for treating high-grade/metastatic tumors by targeting the S1PR1/C3/inflammasome axis.

Computational reinforcement learning, reward (and punishment), and dopamine in psychiatric disorders.

In the DSM-5, psychiatric diagnoses are made based on self-reported symptoms and clinician-identified signs. Though helpful in choosing potential interventions based on the available regimens, this conceptualization of psychiatric diseases can limit basic science investigation into their underlying causes. The reward prediction error (RPE) hypothesis of dopamine neuron function posits that phasic dopamine signals encode the difference between the rewards a person expects and experiences. The computational framework from which this hypothesis was derived, temporal difference reinforcement learning (TDRL), is largely focused on reward processing rather than punishment learning. Many psychiatric disorders are characterized by aberrant behaviors, expectations, reward processing, and hypothesized dopaminergic signaling, but also characterized by suffering and the inability to change one's behavior despite negative consequences. In this review, we provide an overview of the RPE theory of phasic dopamine neuron activity and review the gains that have been made through the use of computational reinforcement learning theory as a framework for understanding changes in reward processing. The relative dearth of explicit accounts of punishment learning in computational reinforcement learning theory and its application in neuroscience is highlighted as a significant gap in current computational psychiatric research. Four disorders comprise the main focus of this review: two disorders of traditionally hypothesized hyperdopaminergic function, addiction and schizophrenia, followed by two disorders of traditionally hypothesized hypodopaminergic function, depression and post-traumatic stress disorder (PTSD). Insights gained from a reward processing based reinforcement learning framework about underlying dopaminergic mechanisms and the role of punishment learning (when available) are explored in each disorder. Concluding remarks focus on the future directions required to characterize neuropsychiatric disorders with a hypothesized cause of underlying dopaminergic transmission.