Investigating the association between discrimination, internalizing symptoms, and alcohol use among Latino/a immigrants in the United States.

Internalizing symptoms associated with anxiety and depression have been correlated with harmful alcohol use among Latino/as, but little attention has been paid to assessing the association between perceived discrimination and harmful alcohol use. The present study was designed to investigate the association between perceived discrimination, internalizing symptoms associated with anxiety and depression, and harmful alcohol use among Latino/a immigrants living in the United States (US). Our sample included 426 Latino/a immigrants. Their mean age was 40.05 years (SD = 6.50), 65.50% were women, 80.00% had a partner, 54.20% lived on less than $2,000 a month, and 41.50% reported having attained a college degree. Perceived discrimination was assessed using the Perceived Discrimination Scale, anxious symptoms were assessed using the GAD-7, depressive symptoms were assessed using the CES-D short form, and harmful alcohol use was assessed using AUDIT. We estimated a linear regression model using cross-sectional, self-reported data. The model was statistically significant, R 2 = 0.38, F (8, 425) = 32.09, p < 0.01. Discrimination was significantly associated with AUDIT scores, (ß = 0.21, p < 0.01) after accounting for covariates and for symptoms of anxiety and depression. Our results indicate that experiences of discrimination in the US are associated with increased harmful alcohol use even after controlling for other variables. These findings may be useful in designing coping interventions specifically for Latino/a immigrants to reduce the risk of alcohol use disorder. This study also has political and public health implications for acknowledging the detrimental health consequences of experiencing discrimination, providing support to the position that reducing racism and discrimination represent important public health priorities.

YDV Resistance in Barley: Phenotyping, Remote Imagery, and Virus-Vector Characterization.

Yellow Dwarf Viruses (YDV) spread by aphids are some of the most economically important barley (Hordeum vulgare L.) virus-vector complexes worldwide. Detection and control of these viruses are critical components in the production of barley, wheat, and numerous other grasses of agricultural importance. Genetic control of plant diseases is often preferable to chemical control to reduce the epidemiological, environmental, and economic cost of foliar insecticides. Accordingly, the objectives of this work were to I) screen a barley population for resistance to YDV under natural infection using phenotypic assessment of disease symptoms, II) implement drone imagery to further assess resistance and test its utility as a disease screening tool, III) identify the prevailing virus and vector types in the experimental environment, and IV) perform a genome-wide association study to identify genomic regions associated with measured traits. Significant genetic differences were found in a population of 192 barley inbred lines regarding their YDV symptom severity and symptoms were moderately to highly correlated with grain yield. The severity of YDV measured with aerial imaging was highly correlated with on-the-ground estimates (r=0.65). Three aphid species vectoring three YDV species were identified with no apparent genotypic influence on their distribution. A QTL impacting YDV resistance was detected on chromosome 2H, albeit undetected using aerial imaging. However, QTL for canopy cover and mean NDVI were successfully mapped using the drone. This work provides a framework for utilizing drone imagery in future resistance breeding efforts for YDV in cereals and grasses, and in other virus-vector disease complexes.

One size does not fit all: the personal nature of completed embryo donation.

PURPOSE: To assess factors associated with embryo donation among individuals interested in donation in the United States. METHODS: An invitation to complete the 123-item survey was emailed from June to September 2022 to patients at a private practice fertility clinic with interest in donation at the time of IVF. Survey questions included disposition decision, attitudes about embryo status and genetic relatedness, donation disclosure, ideal donation arrangement, and decision satisfaction. RESULTS: Three hundred thirty-seven completed the survey. Two hundred thirty donated to another person(s), 75 discarded embryos, 25 remained undecided, and disposition was unknown for 7 respondents. There were no demographic differences between groups based on final disposition or use of donor gametes. Few gamete recipients were interested in donation due to biological attachment to embryos. Final embryo disposition was associated with religious factors, not wanting to waste embryos, and storage fee concerns. Final disposition was also significantly associated with concern about donor-conceived children's (DCP) welfare, being denied the ability to complete donation, personal IVF outcomes, financial or legal issues, future contact with DCP, cognitive appraisal of disposition, beliefs about embryos, someone else raising their genetic child, anonymity, and beliefs about DCP not knowing genetic relationships (p < .001). Donation to others was associated with less regret and greater satisfaction with the emotional/medical aspects of donation and counseling compared to those who discarded embryos (p < .001). CONCLUSION: The decision to donate embryos to another person(s) is complex. Counseling that considers individual circumstances, values, and evolving dynamics may facilitate informed decision-making for those navigating infertility treatment, family building, and embryo disposition.

NRG-CC004 ancillary data study-exploring the effect of bupropion on sexual desire in female cancer survivors with and without vulvovaginal symptoms.

BACKGROUND: Female cancer survivors often experience estrogen-deprivation symptoms, which may lead to decreases in sexual desire, vulvovaginal health (lubrication, dryness, discomfort), and sexual satisfaction. Interventions are needed to address these concerns. AIM: The objective of this secondary analysis was to determine if women with higher (better) scores on the Female Sexual Function Index (FSFI) lubrication and pain subscales reported higher desire scores based on treatment with bupropion vs placebo. METHODS: Participants were part of NRG Oncology's NRG-CC004 (NCT03180294), a randomized placebo-controlled clinical trial evaluating bupropion (150 vs 300 mg) to improve sexual desire in survivors of breast or gynecologic cancer. All participants with baseline data from the FSFI lubrication, pain, and desire subscales with 5- and/or 9-week data were analyzed. The FSFI subscale scores were correlated using Spearman correlation coefficients. Logistic regression was used to determine associations between FSFI desire and other FSFI subscales while accounting for treatment arm and other covariates. OUTCOMES: The primary outcome of NRG Oncology's NRG-CC004 (NCT03180294) randomized phase II dose-finding trial was change from baseline to 9 weeks on the FSFI desire subscale score. Similar to the parent study, the primary outcome for this ancillary data study was the FSFI desire subscale score at 5 and 9 weeks. RESULTS: Overall, 230 participants completed the FSFI at baseline and 189 at 9 weeks. The strongest correlations were between lubrication and pain at baseline (all participants, rho = 0.77; bupropion arms, rho = 0.82), week 5 (all participants, rho = 0.71; bupropion arms, rho = 0.68), and week 9 (all participants, rho = 0.75; bupropion arms, rho = 0.78), and the weakest correlations were between desire and pain. In patients in the treatment arms there were no interactions between lubrication or pain.The impact of various covariates on the FSFI score for desire at 9 weeks demonstrated that participants of non-White race (odds ratio [OR], 0.42; 95% CI, 0.21-0.81; P = .010), with a high lubrication score (OR, 0.36; 95% CI, 0.21-0.61; P = .0002), with a high pain score (less pain) (OR, 0.50; 95% CI, 0.29-0.87; P = .014), or with prior pelvic surgery (OR, 0.38; 95% CI, 0.23-0.63; P = .0002) had lower odds of having low desire. CLINICAL IMPLICATIONS: Acute estrogen-deprivation symptoms should be addressed prior to sexual desire intervention. STRENGTHS AND LIMITATIONS: This secondary analysis was not powered to examine all variables. CONCLUSION: Lubrication and pain were predictors of low desire. Therefore, vulvovaginal atrophy and associated genitourinary symptoms of menopause such as vaginal dryness and dyspareunia should be addressed prior to or in parallel with interventions for sexual desire.

Effects of the March 2021 Allocation Policy Change on Key Deceased-donor Kidney Transplant Metrics.

BACKGROUND: A major change to deceased-donor kidney allocation in the United States, Kidney Allocation System 250 (KAS250), was implemented on March 15, 2021. Evaluating the consequences of this policy on critical system performance metrics is critical to determining its success. METHODS: We performed a retrospective analysis of critical performance measures of the kidney transplant system by reviewing all organs procured during a 4-y period in the United States. To mitigate against possible effects of the COVID-19 pandemic, Scientific Registry of Transplant Recipients records were stratified into 2 pre- and 2 post-KAS250 eras: (1) 2019; (2) January 1, 2020-March14, 2021; (3) March 15, 2021-December 31, 2021; and (4) 2022. Between-era differences in rates of key metrics were analyzed using chi-square tests with pairwise z-tests. Multivariable logistic regression and analysis of variations methods were used to evaluate the effects of the policy on rural and urban centers. RESULTS: Over the period examined, among kidneys recovered for transplant, nonuse increased from 19.7% to 26.4% (all between-era P < 0.05) and among all Kidney Donor Profile Index strata. Cold ischemia times increased (P < 0.001); however, the distance between donor and recipient hospitals decreased (P < 0.05). Kidneys from small-metropolitan or nonmetropolitan hospitals were more likely to not be used over all times (P < 0.05). CONCLUSIONS: Implementation of KAS250 was associated with increased nonuse rates across all Kidney Donor Profile Index strata, increased cold ischemic times, and shorter distance traveled.

Comprehensive Analyses of the Effects of the Small-Molecule Inhibitor of the UHM Domain in the Splicing Factor U2AF1 in Leukemia Cells.

Mutations in RNA splicing factor genes including SF3B1, U2AF1, SRSF2, and ZRSR2 have been reported to contribute to development of myeloid neoplasms including myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML). Chemical tools targeting cells carrying these mutant genes remain limited and underdeveloped. Among the four proteins, mutant U2AF1 (U2AF1mut) acquires an altered 3' splice site selection preference and co-operates with the wild-type U2AF1 (U2AF1wt) to change various gene isoform patterns to support MDS cells survival and proliferation. U2AF1 mutations in MDS cells are always heterozygous and the cell viability is reduced when exposed to additional insult affecting U2AF1wt function. To investigate if the pharmacological inhibition of U2AF1wt function can provoke drug-induced vulnerability of cells harboring U2AF1 mut , we conducted a fragment-based library screening campaign to discover compounds targeting the U2AF homology domain (UHM) in U2AF1 that is required for the formation of the U2AF1/U2AF2 complex to define the 3' splice site. The most promising hit (SF1-8) selectively inhibited growth of leukemia cell lines overexpressingU2AF1 mut and human primary MDS cells carrying U2AF1 mut . RNA-seq analysis of K562-U2AF1mut following treatment with SF1-8 further revealed alteration of isoform patterns for a set of proteins that impair or rescue pathways associated with endocytosis, intracellular vesicle transport, and secretion. Our data suggested that further optimization of SF1-8 is warranted to obtain chemical probes that can be used to evaluate the therapeutic concept of inducing lethality to U2AF1 mut cells by inhibiting the U2AF1wt protein.

Disparities in access to hematopoietic cell transplant persist at a transplant center.

Disparities in access to hematopoietic cell transplant (HCT) are well established. Prior studies have identified barriers, such as referral and travel to an HCT center, that occur before consultation. Whether differences in access persist after evaluation at an HCT center remains unknown. The psychosocial assessment for transplant eligibility may impede access to transplant after evaluation. We performed a single-center retrospective review of 1102 patients who underwent HCT consultation. We examined the association between race/ethnicity (defined as Hispanic, non-Hispanic Black, non-Hispanic White, and Other) and socioeconomic status (defined by zip code median household income quartiles and insurance type) with receipt of HCT and Psychosocial Assessment of Candidates for Transplantation (PACT) scores. Race/ethnicity was associated with receipt of HCT (p = 0.02) with non-Hispanic Whites comprising a higher percentage of HCT recipients than non-recipients. Those living in higher income quartiles and non-publicly insured were more likely to receive HCT (p = 0.02 and p < 0.001, respectively). PACT scores were strongly associated with income quartiles (p < 0.001) but not race/ethnicity or insurance type. Race/ethnicity and socioeconomic status impact receipt of HCT among patients evaluated at an HCT center. Further investigation as to whether the psychosocial eligibility evaluation limits access to HCT in vulnerable populations is warranted.

Cultural stressors, acculturation processes, and mental health among adolescents in Korean multicultural families.

OBJECTIVES: To ascertain, among a sample of Korean multicultural adolescents, the longitudinal predictive effects of acculturative stress and parent-adolescent conflict on depressive symptoms and life satisfaction, both (a) directly and (b) indirectly through Korean and heritage cultural practices and identifications. METHOD: We analyzed longitudinal data from the nationally representative Korean Multicultural Adolescents Panel Study (MAPS; 2011-2016). The sample consisted of 1,433 households at Wave 3 (the first timepoint used in the present analyses), and 92.7% of families were retained until the end of the study. Adolescents completed measures of acculturative stress and parent-adolescent conflict at Timepoint 1, heritage and Korean cultural practices and identifications at Timepoints 2 and 3, and depressive symptoms and life satisfaction at Timepoint 4. RESULTS: Acculturative stress at Timepoint 1 predicted both depressive symptoms and life satisfaction at Timepoint 4 indirectly through Korean cultural practices and identifications. Parent-adolescent conflict at Timepoint 1 directly predicted depressive symptoms at Timepoint 4 and predicted life satisfaction indirectly through heritage-cultural practices and identifications. These links were invariant across adolescent sex. CONCLUSIONS: Among Korean multicultural adolescents, acculturative stressors inhibit engagement in Korean cultural practices and identification as Korean, whereas conflict with parents inhibits engagement in heritage cultural practices and identification with the foreign-born parent's cultural heritage. Decreased Korean and heritage cultural practices and cultural identifications predict increased depressive symptoms and lowered life satisfaction. These findings suggest that culturally stressful experiences can impair psychological functioning among Korean multicultural adolescents by undermining acculturation to both Korean and heritage cultural systems. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines.

Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination1,2. The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike protein minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2-infected and uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses.

Interplay of premigration crisis exposure and postmigration cultural stress on depressive symptoms among Venezuelan crisis migrants in Colombia.

OBJECTIVES: A growing body of research points to a relationship between exposure to migration-related cultural stress and mental health problems. However, such research is often conducted with the tacit assumption that postmigration experiences are the primary-if not singular-driver of psychological distress. In the present study, we aim to extend the cultural-stress paradigm by examining the influences of both premigration crisis exposure and postmigration cultural stress on depression in a sample of Venezuelan crisis migrants in Colombia. METHOD: Survey data for the present study were collected from Venezuelan youth (N = 429, ages 12-17, Mage = 14.0 years, 49% female) and adults (N = 566, ages 18+, Mage = 35.1 years, 82% female) in Bogota and Medellin, Colombia between April and June 2023. RESULTS: Both crisis exposure and discrimination were independently related to depressive symptoms. However, when examined in a multivariate model along with discrimination, crisis exposure was not a significant predictor of depressive symptoms among youth, and its influence weakened considerably among adults. Among both youth and adults, a Crisis Exposure × Discrimination interaction term significantly predicted depressive symptoms, indicating that discrimination was a more robust predictor of depressive symptoms among those endorsing lower levels of crisis exposure than among those reporting high levels of crisis exposure. CONCLUSION: Our research provides new insights into the experiences of Venezuelan migrant youth and adults in Colombia. It provides further support for the importance of drawing from a crisis-informed cultural-stress framework when working with crisis migrant populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Computationally restoring the potency of a clinical antibody against Omicron.

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs1-3 and revealed how quickly viral escape can curtail effective options4,5. When the SARS-CoV-2 Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab4-6. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination4 and is challenging to replace with existing approaches. Rapidly modifying such high-value antibodies to restore efficacy against emerging variants is a compelling mitigation strategy. We sought to redesign and renew the efficacy of COV2-2130 against Omicron BA.1 and BA.1.1 strains while maintaining efficacy against the dominant Delta variant. Here we show that our computationally redesigned antibody, 2130-1-0114-112, achieves this objective, simultaneously increases neutralization potency against Delta and subsequent variants of concern, and provides protection in vivo against the strains tested: WA1/2020, BA.1.1 and BA.5. Deep mutational scanning of tens of thousands of pseudovirus variants reveals that 2130-1-0114-112 improves broad potency without increasing escape liabilities. Our results suggest that computational approaches can optimize an antibody to target multiple escape variants, while simultaneously enriching potency. Our computational approach does not require experimental iterations or pre-existing binding data, thus enabling rapid response strategies to address escape variants or lessen escape vulnerabilities.

Papule Protruding Into the Nasal Cavity.

An 18-year-old male with no significant medical history presented for evaluation of a nasal papule that was asymptomatic without any associated pain, pruritus, or bleeding with no changes for a year. What is your diagnosis?

Protocol for a nationwide case-control study of firearm violence prevention tactics and policies in K-12 schools.

BACKGROUND: Most U.S. K-12 schools have adopted safety tactics and policies like arming teachers and installing metal detectors, to address intentional school gun violence. However, there is minimal research on their effectiveness. Furthermore, sociodemographic factors may influence their implementation. Controlled studies are necessary to investigate their impact on gun violence and related disciplinary outcomes. OBJECTIVE: The paper outlines the protocol for a case-control study examining gun violence prevention policies in U.S. K-12 schools. The study aims to investigate if there is an association between the total number and type of specific safety tactics and policies and the occurrence of intentional shootings in K-12 public schools, student disciplinary outcomes, and if urbanicity, economic, and racial factors modify these associations. METHODS: We will create a nationally representative dataset for this study and ascertain a full census of case schools (schools that experienced intentional gunfire on the campus during school hours since 2015) through national school shooting databases. Matched control schools will be randomly selected from U.S. Department of Education's national database of all public schools. We will analyze 27 school safety strategies organized into seven key exposure groupings. RESULTS: Supported by the National Institutes for Child Health and Development (R01HD108027-01) and having received Institutional Review Board approval, our study is currently in the data collection phase. Our analytical plan will determine the association between the number and type of school safety tactics and policies with the occurrence of intentional shootings and suspensions and expulsions in a national sample of approximately 650 K-12 public schools. Additional analyses will investigate the effect modification of specific covariates. CONCLUSION: As the first national, controlled study, its results will provide novel and needed data on the effectiveness of school safety tactics and policies in preventing intentional shootings at K-12 public schools.

Liver Transplant Costs and Activity After United Network for Organ Sharing Allocation Policy Changes.

Importance: A new liver allocation policy was implemented by United Network for Organ Sharing (UNOS) in February 2020 with the stated intent of improving access to liver transplant (LT). There are growing concerns nationally regarding the implications this new system may have on LT costs, as well as access to a chance for LT, which have not been captured at a multicenter level. Objective: To characterize LT volume and cost changes across the US and within specific center groups and demographics after the policy implementation. Design, Setting, and Participants: This cross-sectional study collected and reviewed LT volume from multiple centers across the US and cost data with attention to 8 specific center demographics. Two separate 12-month eras were compared, before and after the new UNOS allocation policy: March 4, 2019, to March 4, 2020, and March 5, 2020, to March 5, 2021. Data analysis was performed from May to December 2022. Main Outcomes and Measures: Center volume, changes in cost. Results: A total of 22 of 68 centers responded comparing 1948 LTs before the policy change and 1837 LTs postpolicy, resulting in a 6% volume decrease. Transplants using local donations after brain death decreased 54% (P < .001) while imported donations after brain death increased 133% (P = .003). Imported fly-outs and dry runs increased 163% (median, 19; range, 1-75, vs 50, range, 2-91; P = .009) and 33% (median, 3; range, 0-16, vs 7, range, 0-24; P = .02). Overall hospital costs increased 10.9% to a total of $46 360 176 (P = .94) for participating centers. There was a 77% fly-out cost increase postpolicy ($10 600 234; P = .03). On subanalysis, centers with decreased LT volume postpolicy observed higher overall hospital costs ($41 720 365; P = .048), and specifically, a 122% cost increase for liver imports ($6 508 480; P = .002). Transplant centers from low-income states showed a significant increase in hospital (12%) and import (94%) costs. Centers serving populations with larger proportions of racial and ethnic minority candidates and specifically Black candidates significantly increased costs by more than 90% for imported livers, fly-outs, and dry runs despite lower LT volume. Similarly, costs increased significantly (>100%) for fly-outs and dry runs in centers from worse-performing health systems. Conclusions and Relevance: Based on this large multicenter effort and contrary to current assumptions, the new liver distribution system appears to place a disproportionate burden on populations of the current LT community who already experience disparities in health care. The continuous allocation policies being promoted by UNOS could make the situation even worse.

Assessing LSAM's ability to account for changes in organ donation and transplant center behavior.

The Liver Simulated Allocation Model (LSAM) is used to evaluate proposed organ allocation policies. Although LSAM has been shown to predict the directionality of changes in transplants and nonused organs, the magnitude is often overestimated. One reason is that policymakers and researchers using LSAM assume static levels of organ donation and center behavior because of challenges with predicting future behavior. We sought to assess the ability of LSAM to account for changes in organ donation and organ acceptance behavior using LSAM 2019. We ran 1-year simulations with the default model and then ran simulations changing donor arrival rates (ie, organ donation) and center acceptance behavior. Changing the donor arrival rate was associated with a progressive simulated increase in transplants, with corresponding simulated decreases in waitlist deaths. Changing parameters related to organ acceptance was associated with important changes in transplants, nonused organs, and waitlist deaths in the expected direction in data simulations, although to a much lesser degree than changing the donor arrival rate. Increasing the donor arrival rate was associated with a marked decrease in the travel distance of donor livers in simulations. In conclusion, we demonstrate that LSAM can account for changes in organ donation and organ acceptance in a manner aligned with historical precedent that can inform future policy analyses. As Scientific Registry of Transplant Recipients develops new simulation programs, the importance of considering changes in donation and center practice is critical to accurately estimate the impact of new allocation policies.

Buccal Fat Advancement-Transposition Flap for Reconstruction of Midface Volume Defects.

Background: The buccal fat pad (BFP) has previously been utilized for repair of various defects of the head and neck. Objectives: We explore the utility of a pedicled buccal fat advancement-transposition (BFAT) flap in various forms of midface reconstruction through a variety of surgical approaches and characterize its volume and axial reach in human anatomic specimens. Methods: Ten adult full-head human anatomic specimens were dissected, and a single surgical case demonstrating the use of a BFAT flap is described. Results: Nasolabial, subciliary, and deep plane facelift incisions all provided access to the BFP for use as a BFAT flap. The mean volume of mobilizable fat contained within a BFAT flap accessible through external incision was 7.1 cm3. Once fully mobilized, the externalized BFAT flap had a mean axial reach of 6.9 cm without tension. We also present a case illustrating the successful use of a BFAT flap for volumization of a large midface defect secondary to Mohs micrographic surgical resection of a cutaneous malignancy. Discussion: The BFAT flap, which exhibited substantial volume and reach in this study, can be harvested through multiple dissection windows or pre-existing defects and be used to reconstruct a variety of midface defects.