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To understand the acceptability for a model of chronic disease management, in which primary care patients see nurse practitioners for structured visits using an evidence-based encounter form, the authors sent a mailed survey to primary care physicians and nurse practitioners. A total of 212 subjects completed the survey, for a total response rate of 53% (physicians, 44%; nurse practitioners, 61%). Most physicians (79.5%) reported that nurse practitioners saw patients in their practice. Most physicians (80.0%) and nurse practitioners (95.7%) believed that the proposed model of care would improve the control of chronic illnesses. In addition, most physicians (73.8%) and nurse practitioners (87.6%) believed that the model of care would be of interest to similar providers. Overall, the high level of support for the model and the presence of nurse practitioners in most physician offices suggests that future studies are warranted to understand how best to implement this. [ABSTRACT FROM AUTHOR]

Using WISE data, we calibrated the W2-W3 colors in terms of star formation rates (SFRs) and applied this calibration to a sample of 1285 QSOs with the highest flux quality, covering a range in redshift from z ˜ 0.3 to z ˜ 3.8. According to our calibration, the SFR increases continuously, reaching a value at z ˜ 3.8 about 3 times higher on average than at lower redshift. This increase in SFR is accompanied by an increase of the BH mass by a factor 100 and a gradual increase of the mean Eddington ratio from 0.1 to 0.3 up to z ˜ 1.5 – 2.0, above which the ratio stays constant, despite a significant increase in BH mass. Therefore, QSOs at high redshifts have both more active BHs and higher levels of star formation activity. [ABSTRACT FROM AUTHOR]

Introduction: Insomnia has been identified as a risk factor for adolescent suicidal behavior, often via clinical and cross-sectional studies. Longitudinal associations between insomnia and suicidal behavior have not been well-established in adolescent community samples, and many studies fail to control for the effect of depressive symptoms and their overlapwith both insomnia and suicidal behavior. Objectives: We modeled longitudinal associations between insomnia and suicide attempts in a diverse community-based cohort of US adolescents interviewed at Wave 1 (n=4175; 11-17yo), W2 (+1yr; n=3134), and W3 (+5yrs; n=2503). Methods: We estimated the association of W1 insomnia with W2 and W3 12-month suicide attempts, controlling for W1 attempts. We then estimated the inverse association between W1 attempts and W2 and W3 insomnia, controlling for W1 insomnia. Analyses used weighted survey logistic regression models, controlling forW1 depressive symptoms (excluding insomnia/suicidality) and sociodemographics. Results: Weighted prevalence of any insomnia symptom ranged from 22.2%-26.8% across waves; insomnia with impairment ranged from 6.1%-8.1%. Any insomnia symptom at W1 was not associated with W2 attempts but significantly increased the odds of W3 attempts (OR=3.82). In contrast, insomnia with impairment at W1 was associated with W2 attempts (OR=3.14) but not W3. The inverse analysis showed no significant associations between W1 attempts and W2/W3 insomnia. Conclusions: Presence of any insomnia symptom in adolescence may represent a distal risk factor for later suicide attempts, while insomnia with impairment may be a short-term risk factor. Preventive interventions to improve adolescent sleep, combined with clinical interventions for sleep disorders, may be an important multilevel suicide prevention strategy. [ABSTRACT FROM AUTHOR]

Introduction: Variant Creutzfeld Jacob Disease (vCJD) may be a new threat to the blood supply, mainly in Western Europe. Brazil is the largest South American country and there have been no cases of the disease reported neither in human beings nor in cattle. Prion diseases transmission by blood transfusion is uncertain. FDA's recommendation to defer blood donors who have lived six or more months,continuously or not, in the UK between 1980 and 1996, may be one of the few practical approaches in countries with no or very few cases reported. Objectives: Evaluate the feasibility of applying FDA's rule in Brazil, and the relationship of the deferred donors and their socio-economic classification (SEC). Material and Methods: FDA's recommendation was included in the blood donor selection criteria for two months. Between March and April 2001, every candidate for blood donation was asked about living in the UK (1951 individuals). Also, a socio-economic evaluation was applied to 241 random candidates and to every candidate deferred because of living in the UK, in order to evaluate how this variable might influence the outcome. SEC ranged from A (higher) to E (lower). Results: 14 candidates (0,72%; 95% Cl 0,34%-1,09%) were rejected because of living in the UK. Among the 241 random candidates,32% were classified as class A, 39% as B, 18% as C, 9% as D and none as E. Among the 14 deferred, 8 (57%) were classified as class A, 4 (29%) as B, 2 (14%) as C and none as D or E. Conclusions: In Brazil, socio-economic differences are quite marked. FDA's rule is feasible, took to an acceptable percentage of deferrals and, presumably, preserved the reliability of the blood supply. When segregated by SEC, 86% of the deferred donors belonged to classes A and B (95% Cl 67%-100%). The higher the level, the higher the probability of being deferred for this reason. Therefore, SEC can be used to predict the percentage of donors that would be lost by that rule. In blood banks where the percentage of A and B class individuals is lower, the impact on the blood supply would be even less representative. [ABSTRACT FROM AUTHOR]

Congenital isolated unilateral hypertrophy of upper extremity secondary to muscular hyperplasia is a rare phenomenon of unknown etiology. There are only few reports variably defining it as an aberrant muscle syndrome or congenital monomelic muscular hypertrophy. We report the case of a 6-year old girl with a congenital enlargement of the whole left arm, and hand deformity. MRI showed a generalized enlargement given by homogenous increase in muscle bulk with no fat replacement together with aberrant muscles in the hand. No dysfunctions of the shoulder, elbow or wrist were detected. The patient presented normal development, with no cutaneous stigma nor additional features usually seen in Proteus syndrome. The left hand was wider with ulnar drift of the index finger, increased muscle bulk of the first dorsal interosseous and widening of the 2nd and 3rd metacarpal space. A muscle biopsy of the prominent tissue in the dorsal face of the hand revealed dystrophic features with abnormally increased variability of fibres together with many hypertrophic fibres associated with increased perimysial and endomysial fibrosis. Type 1 fiber predominance, and disorganization of the intermyofibrilar network was evident at histochemistry for NADH, COX and SDH. Mosaic activating mutation in the PI3K–AKT cell signaling pathway have been described in overgrowth syndromes such as Proteus syndrome, CLOVES syndrome, megalencephaly–capillary malformation, fibroadipose hyperplasia and macrodactyly. Given the relationship of mosaic activating mutations in the PI3K–AKT cell signaling pathway with other overgrowth syndromes, Sanger sequencing for AKT, PIK3CA, and PTEN was performed. A mutation c.3140A>G, p.H1047R in PIK3CA was detected in DNA from the affected muscle but not from blood leucocytes. Isolated congenital upper limb hypertrophy with aberrant hand muscles is another condition related genetically to overgrowth syndromes. [Copyright &y& Elsevier]

The effects of the intergenerational continuity of adverse childhood experiences (ACEs) on youth outcomes have been documented, particularly among mother-child dyads. Most literature has focused on the continuity of family-level ACEs (Traditional ACEs [T-ACEs]) and not community-level ACEs (Expanded ACEs [E-ACEs]) that disproportionately impact minoritized individuals. We aimed to (a) examine the effect of mothers' and fathers' T-ACEs and E-ACEs on youth's T-ACEs and E-ACEs, respectively, and on youth's depressive and anxiety symptoms; (b) examine whether youth's own ACE exposure explains the link between parental ACEs and youth depressive and anxiety symptoms; and (c) explore differential risks by mothers versus fathers. We collected cross-sectional data from a community sample of Mexican-origin youth (M age , 13.5 years; 51.7% males; 93.0% US-born), mothers (M age , 41.4 years; 7.2% US-born), and fathers (M age , 44.0 years; 5.1% US-born) from the Seguimos Avanzando project (167 youth-mother-father triads, 177 youth-mother/father dyads). Results showed that (a) fathers', but not mothers', T-ACEs and E-ACEs were associated with youth's T-ACES and E-ACEs, respectively, (b) youth's T-ACEs explained the association between fathers' T-ACEs and youth's depressive symptoms, and (c) only youth's E-ACEs were associated with anxiety symptoms. These findings highlight the greater need to understand how fathers' childhood experiences may impact outcomes across generations and that targeting youth's ACEs can reduce the pervasive effects of intergenerational continuity of ACEs., (© 2024 Family Process Institute.)

Per-and polyfluorinated substances (PFAS) are synthetic chemicals that are used to make fluoropolymer coatings found in many products, such as non-stick pans, clothing, cosmetics, and food packaging. These highly persistent molecules are known as "forever chemicals" since they neither degrade environmentally nor break down enzymatically within biological systems. PFAS compounds readily contaminate water sources, and as a result, certain PFAS molecules have bioaccumulated in exposed species including humans. The purpose of this study was to define the effect of two PFAS molecules, the ostensibly more toxic perfluorooctanoic acid (PFOA) and the more recent, reportedly safer chemical hexafluoropropylene oxide dimer acid (Gen X), on the development of Lytechinus variegatus sea urchin embryos. We examined the effects of PFOA and Gen X on development and patterning using morphological analysis, immunostaining, HCR-FISH, and Particle Image Velocimetry (PIV). The results show that both PFAS compounds are teratogenic to sea urchin embryos. PFOA and Gen X each function at different intervals during development and provoke distinct phenotypic and gene expression outcomes. Despite beliefs that Gen X would be a safer alternative, our findings indicate that Gen X has earlier and more severe effects on endomesoderm and dorsal-ventral axis specification, neural development and function, and pattern formation compared to PFOA. These results illustrate the dangerous teratogenic potential of environmentally accumulating PFAS like Gen X, underscoring the negative ecological implications that accompany continuing commercial and industrial use of PFAS in the absence of remediation strategies., Highlights: Gen X is more teratogenic in sea urchins than PFOAGen X acts earlier than PFOA and perturbs axial and germ layer specificationEach PFAS reduces neural numbers and perturbs ciliary behavior and swimming.

Objective: Research is needed to examine discrimination-related stressors and their social and psychological shaping of mental health and sleep outcomes of Latinx youth. The background, design, and methodology of a longitudinal study of Mexican families in Indiana and the initial findings of associations between discrimination-related stressors and youth mental health and sleep outcomes are presented., Method: Initiating wave 1 of a 3-wave (yearly) longitudinal study, investigators surveyed an ethnically homogeneous sample of 344 Mexican-origin adolescents (ages 12-15) and their primary caregivers, assessing risks and protective factors for mental health and sleep outcomes. Youth also completed a one-time 21-day daily diary after wave 1. Self-reported measures of youth mental health, sleep, and discrimination across wave 1 and the daily diary were evaluated to compare the cross-sectional (wave 1) and daily associations between discrimination and youth mental health and sleep outcomes., Results: Of youth, 88.1% reported at least one incident of lifetime discrimination. Almost one-third had elevated depressive symptoms, 44.5% had probable generalized anxiety disorder, and 50.9% had poor sleep quality. Between-youth correlations at wave 1 and in the daily diary were consistent in that perceived racial discrimination was positively correlated with worse mental health and poorer sleep quality. Smaller within-youth correlations were observed in the daily diary, but there was striking variability in the effect of discrimination across youth., Conclusion: The present results illustrate the powerful methods of combining yearly and daily time data to investigate how and for whom discrimination-related stressors lead to adverse outcomes., Plain Language Summary: Latinx youth are the largest and fastest growing minoritized youth group in the United States. This study surveyed 344 Mexican-origin adolescents and their primary caregivers to assess risk and protective factors for mental health and sleep outcomes. The authors found that 88.1% of youth reported at least one incident of lifetime discrimination, 29.7% reported elevated depressive symptoms, 44.5% reported elevated anxiety symptoms, and 50.9% reported poor sleep quality. Youth who experienced racial discrimination were more likely to have worse mental health and lower sleep quality than those who did not experience racial discrimination., Diversity & Inclusion Statement: We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list., Clinical Trial Registration Information: Seguimos Avanzando - Latino Youth Coping With Discrimination; https://clinicaltrials.gov/; NCT04875208., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

MUTYH-Associated Polyposis (MAP) is caused by biallelic pathogenic germline variants in the MUTYH gene. However, individuals harboring monoallelic MUTYH pathogenic variants in the presence of a positive family history have been reported to have a twofold increased risk of colorectal cancer (CRC) and extra colonic cancers. Our aim was to characterize the spectrum of monoallelic and biallelic germline MUTYH pathogenic variants in Latin American patients and to describe their clinical and genetic characteristics. Patients were identified from eight high-risk genetic cancer centers of five Latin American countries. Statistical analysis was performed using the two-sided P test using the Vassarstats statistical tools. Statistical significance was set at a p value ≤ 0.05. Of the 105 unrelated patients with cancer or colorectal polyposis, 84.8% and 15.2% carried pathogenic monoallelic and biallelic MUTYH variants, respectively. The most common pathogenic variants were p.Gly396Asp and p.Tyr179Cys (55% and 23%, respectively). The mean age at first diagnosis was 48.29 years (range 31-71) and 49.90 years (range 27-87) in biallelic and monoallelic MUTYH patients, respectively. CRC was the only cancer diagnosed in patients with biallelic MUTYH pathogenic variants (75%), while breast cancer (46.1%) was more common than CRC (24.7%) in individuals with monoallelic MUTYH pathogenic variants. We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Early identification of children at risk for PTSD is critical for improving mental health outcomes after traumatic injury. Currently, there is no standard PTSD screen for pediatric trauma patients and limited data on long-term quality of life for those who screen positive., Methods: In 2022, we piloted a comprehensive routine screening program for ASD and PTSD at our Level I PTC. All admitted trauma patients ≥8 years old were eligible for screening. Inpatients were administered the ASC3. Those who screened positive were referred for follow-up and repeat mental health evaluation. PTSD screening (CTSQ, CPSS) and quality-of-life screening (PedsQL™) surveys were administered to eligible discharged trauma patients at 1-month post-injury. Children who screened positive on the CTSQ or CPSS were referred for behavioral health services., Results: 205 children were screened for ASD using the ASC3. 49/205 children (23.9 %) had a positive screen (score ≥3). 56 children completed PTSD screening at 1-month post-discharge. 14/54 children (25.9 %) screened positive on CTSQ, and 8/50 children (16 %) screened positive on CPSS. There was a significant positive correlation between CTSQ and CPSS scores (r 0.76, ∗P<0.0001). When stratified by screening results, patients who screened positive on CTSQ and CPSS were found to have the most significant correlations with poor School and Emotional Functioning on their quality-of-life inventory., Conclusion: Early screening for ASD may be predictive of later development of PTSD in children. Screening using previously validated tools (ASC3, CTSQ, CPSS) were effective in identifying children with negative emotional functioning lasting beyond the acute phase of physical recovery following injury. CTSQ and CPSS both performed well for screening at one-month post-discharge. Early identification can facilitate timely referral to mental health services to potentially minimize long-term socioemotional impact of PTSD., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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).

The present 21-day daily diary study (conducted 2021-2022) tested anger and racism-related vigilance as potential transdiagnostic mediators linking exposure to racial and ethnic discrimination (RED) to distress (negative affect and stress, respectively). The data analytic sample included N = 317 Mexican-origin adolescents (M age  = 13.5 years; 50.8% male, 46.7% female; 2.5% non-binary) from the Midwestern United States. Results from longitudinal mediation models revealed significant mediation effects through anger and racism-related vigilance, respectively, in the association between daily RED and daily distress, both within and across adolescents. Implications for theory, research, and practice are discussed so that future work can leverage these novel findings toward promoting the well-being of Mexican-origin adolescents, especially those who live in contexts of ethnoracial adversity., (© 2024 The Authors. Child Development © 2024 Society for Research in Child Development.)

Bemnifosbuvir (AT-527) and AT-752 are guanosine analogues currently in clinical trials against several RNA viruses. Here, we show that these drugs require a minimal set of 5 cellular enzymes for activation to their common 5'-triphosphate AT-9010, with an obligate order of reactions. AT-9010 selectively inhibits essential viral enzymes, accounting for antiviral potency. Functional and structural data at atomic resolution decipher N6-purine deamination compatible with its metabolic activation. Crystal structures of human histidine triad nucleotide binding protein 1, adenosine deaminase-like protein 1, guanylate kinase 1, and nucleoside diphosphate kinase at 2.09, 2.44, 1.76, and 1.9 Å resolution, respectively, with cognate precursors of AT-9010 illuminate the activation pathway from the orally available bemnifosbuvir to AT-9010, pointing to key drug-protein contacts along the activation pathway. Our work provides a framework to integrate the design of antiviral nucleotide analogues, confronting requirements and constraints associated with activation enzymes along the 5'-triphosphate assembly line., Competing Interests: S.G., A.M. and J.P.S. are employees of ATEA Pharmaceuticals, Inc., (Copyright: © 2024 Chazot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study., Main Methods: PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or 10 Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid., Key Findings: PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stage-dependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth., Significance: PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Parental psychopathology is associated with their children's posttraumatic stress symptoms (PTSS). However, the mechanisms through which this occurs remain unclear. We hypothesized that exposure to childhood adversities is the mechanism linking parental psychopathology to child PTSS and that parenting practices moderated these associations., Methods: Participants (N = 1,402) with an average age of 24.03 years old (SD = 2.20), were all Puerto Ricans (50% Male and 50% Female) from the Boricua Youth Study, which is a four-wave longitudinal study spanning almost 20 years, following individuals from childhood (ages 5-13 at Wave 1) to young adulthood. Measured variables include parental psychopathology at Wave 1, childhood adversities and parenting practices at Waves 2-3, and PTSS at Wave 4. A traditional mediation model estimated the association between parental psychopathology and child PTSS via childhood adversities. A moderated mediation model was used to examine whether parenting practices moderated this mediation model., Results: Results showed that the total effect of parental psychopathology at Wave 1 on PTSS at Wave 4 was fully mediated by childhood adversities at Waves 2-3 (direct effect b = 1.72, 95% CI = [-0.09, 3.83]; indirect effect b = 0.40, 95% CI = [0.15, 0.81]). In addition, the magnitude of this pathway varied by levels of parenting practices (i.e. parental monitoring and parent-child relationship quality). Specifically, the indirect effect of additional adversities in the psychopathology-PTSS link was stronger with higher levels of parental monitoring but weaker with higher parent-child relationship quality scores., Conclusions: Intergenerational continuity of psychopathology may be mitigated through the prevention of additional childhood adversities via upstream interventions, emphasizing providing parents with mental health needs with parenting tools. Family-based interventions focused on providing families with the tools to improve parent-child relationships may reduce the negative impact of childhood adversities on mental health across the life course., (© 2023 Association for Child and Adolescent Mental Health.)

The large Bunyavirales order includes several families of viruses with a segmented ambisense (-) RNA genome and a cytoplasmic life cycle that starts by synthesizing viral mRNA. The initiation of transcription, which is common to all members, relies on an endonuclease activity that is responsible for cap-snatching. In La Crosse virus, an orthobunyavirus, it has previously been shown that the cap-snatching endonuclease resides in the N-terminal domain of the L protein. Orthobunyaviruses are transmitted by arthropods and cause diseases in cattle. However, California encephalitis virus, La Crosse virus and Jamestown Canyon virus are North American species that can cause encephalitis in humans. No vaccines or antiviral drugs are available. In this study, three known Influenza virus endonuclease inhibitors (DPBA, L-742,001 and baloxavir) were repurposed on the La Crosse virus endonuclease. Their inhibition was evaluated by fluorescence resonance energy transfer and their mode of binding was then assessed by differential scanning fluorimetry and microscale thermophoresis. Finally, two crystallographic structures were obtained in complex with L-742,001 and baloxavir, providing access to the structural determinants of inhibition and offering key information for the further development of Bunyavirales endonuclease inhibitors., (open access.)

The current study evaluated cultural values and family processes that may moderate associations between daily racial-ethnic discrimination and distress among Mexican-origin youth. Integrating micro-time (daily diary) and macro-time (longitudinal survey) research design features, we examined familism, family cohesion, and ethnic-racial socialization from youth-, mother-, and father- reports as potential buffers of daily associations between youth racial-ethnic discrimination and youth distress (negative affect and anger). The analytic sample, drawn from the Seguimos Avanzando study, included 317 Mexican-origin adolescents (M age = 13.5 years) and their parents, recruited from the Midwestern United States. Results indicated that youth-reported familism and family cohesion significantly buffered daily associations between youth racial-ethnic discrimination and youth distress. In contrast, parent-reported familism and family cohesion and some aspects of ethnic-racial socialization exacerbated the discrimination to distress link. The implications of these results are discussed to inform efforts supporting the healthy development of Mexican-origin youth and their families.

Introduction: Latinx immigrant-origin youth (IOY) have unique risks for suicidal thoughts and behaviors. It has been suggested that these risks should be addressed from an ecological perspective, addressing cultural and family context as well as structural and systemic barriers to prevention. This study sought to explore perspectives of immigrant-origin Latinx adolescents and their caregivers on suicide and its prevention, including the potential impact of stressors specific to immigrant status., Method: Focus groups were conducted in 2018-2019 with Latinx immigrant-origin caregivers ( N = 41, 97.5% female) and adolescents (ages = 14-19, N = 56, 50% female). Participants were recruited from community-based organizations in two different cities. A codebook approach to thematic analysis was used to identify themes, which were subsequently mapped onto levels of the Center for Disease Control's Social-Ecological Framework for Violence Prevention., Results: Participants identified both contributors to suicidal behavior and potential components of prevention programming across ecological levels. Specific recommendations for suicide prevention included engaging in recreation, parenting education and support, enhancing academic supports for adolescents, and enhancing school-family communication. Structural barriers (e.g., caregiver work schedules) to implementing recommendations were described., Discussion: Our results highlight the potential role of access to school and community-based supports as public health-oriented suicide prevention strategies and suggest a need to address barriers faced by immigrant families in accessing these supports alongside addressing barriers to mental health treatment. Policies impacting immigrant families' financial stability and increasing the availability of recreational and academic opportunities may promote mental health and prevent suicidal thoughts and behavior among IOY. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Nucleotide analogues (NA) are currently employed for treatment of several viral diseases, including COVID-19. NA prodrugs are intracellularly activated to the 5'-triphosphate form. They are incorporated into the viral RNA by the viral polymerase (SARS-CoV-2 nsp12), terminating or corrupting RNA synthesis. For Coronaviruses, natural resistance to NAs is provided by a viral 3'-to-5' exonuclease heterodimer nsp14/nsp10, which can remove terminal analogues. Here, we show that the replacement of the α-phosphate of Bemnifosbuvir 5'-triphosphate form (AT-9010) by an α-thiophosphate renders it resistant to excision. The resulting α-thiotriphosphate, AT-9052, exists as two epimers (RP/SP). Through co-crystallization and activity assays, we show that the Sp isomer is preferentially used as a substrate by nucleotide diphosphate kinase (NDPK), and by SARS-CoV-2 nsp12, where its incorporation causes immediate chain-termination. The same -Sp isomer, once incorporated by nsp12, is also totally resistant to the excision by nsp10/nsp14 complex. However, unlike AT-9010, AT-9052-RP/SP no longer inhibits the N-terminal nucleotidylation domain of nsp12. We conclude that AT-9052-Sp exhibits a unique mechanism of action against SARS-CoV-2. Moreover, the thio modification provides a general approach to rescue existing NAs whose activity is hampered by coronavirus proofreading capacity., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Body mass index (BMI) is moderately correlated with %Fat and often used to assess obesity in athletes. Limited research assesses BMI as a surrogate for %Fat in female collegiate athletes. Body Adiposity Index (BAI) is an anthropometric measurement suggested to be superior to BMI at predicting adiposity but has not been well assessed within female athletic populations. This study aimed to determine if BAI is superior to other anthropometric indices to predict %Fat in female collegiate athletes and college-aged female non-athletes. Collegiate female athletes and female non-athletes were invited into the laboratory for anthropometrics and %Fat measurements via BOD POD. BAI was calculated as Hip Circumference/Height 1.5 - 18. Eighty-eight female non-athletes and 72 female athletes from soccer ( n = 27), softball ( n = 28), and basketball ( n = 17) completed the study. Using BMI, 19% of non-athletes had a false positive (FP). Sensitivity of BMI in non-athletes was 85.5%, while specificity was 73%. 16% of athletes had a FP. Sensitivity of BMI within athletes was 100%, specificity was 81%. BMI outperformed BAI in athletic (BMI: r = .725, p < .001; BAI: r = .556, p < .001) and nonathletic (BMI: r = .650, p < .001; BAI: r = .499, p < .001) groups. The strongest anthropometric predictor of %Fat within the non-athlete population was BMI ( r 2 = .42, p < .001). Waist circumference was the strongest predictor in the athletic population ( r 2 = .62, p < .001). BMI outperformed BAI in its ability to predict %Fat.

Background: Direct oral anticoagulant (DOAC) use in cancer-associated venous thromboembolism (CA-VTE) has increased due to updates in recent guidelines and literature. However, select guidelines caution against DOAC use in patients with gastrointestinal (GI) malignancies due to reported increased bleeding events. The objective of this study was to compare the safety and effectiveness of DOACs versus low-molecular-weight heparins (LMWHs) for CA-VTE treatment in patients with GI malignancies., Patients and Methods: This multicenter, retrospective cohort study included patients with primary GI malignancies who received therapeutic anticoagulation with a DOAC or LMWH for CA-VTE between January 1, 2018, and December 31, 2019. The primary outcome was the incidence rate of bleeding events (major, clinically relevant non-major, or minor bleeding events) within a 12-month period following the initiation of therapeutic anticoagulation. The secondary endpoint was the incidence rate of recurrent VTE events within a 12-month period following the start of therapeutic anticoagulation., Results: After screening, 141 patients met inclusion criteria. The incidence rate of all bleeding events significantly differed between DOAC (4.98 events/100 person-months) and LWMH (10.2 events/100 person-months) recipients. The corresponding incidence rate ratio (IRR) with the DOAC group serving as the reference was 2.05 (p = 0.01), with the majority of bleeds in both groups presenting as minor bleeds. No difference was found between the incidence rate of recurrent VTE within a 12-month period of starting therapeutic anticoagulation between groups (IRR 3.08, p = 0.06)., Conclusion: Our results suggest that DOACs do not pose an additional bleeding risk compared to LMWH in patients with certain GI malignancies. Careful selection of DOAC therapy with respect to bleeding risk is still warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To assess mental health-related stigma in an emerging Latino immigrant community and explore demographic characteristics associated with stigma. We surveyed 367 Spanish-speaking Latino adults recruited at community-based venues in Baltimore, Maryland. The survey included sociodemographic questions, the Depression Knowledge Measure, Personal Stigma Scale, and the Stigma Concerns about Mental Health Care (SCMHC) assessment. Multiple regression models examining associations between personal stigma and stigma concerns about mental health care, respectively, were constructed using variables that were statistically significant in bivariate analyses. Being male, having less than high school education, reporting high importance of religion, and having lower depression knowledge contributed to higher personal stigma. When controlling for other variables, only depression knowledge contributed unique variance to the prediction of higher SCMHC. Efforts to improve access to and quality of mental health care must be paralleled by ongoing efforts to reduce depression stigma within emergent immigrant Latino communities., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The significance of youth suicide as a public health concern is underscored by the fact that it is the second-leading cause of death for youth globally. While suicide rates for White groups have declined, there has been a precipitous rise in suicide deaths and suicide-related phenomena in Black youth; rates remain high among Native American/Indigenous youth. Despite these alarming trends, there are very few culturally tailored suicide risk assessment measures or procedures for youth from communities of color. This article attempts to address this gap in the literature by examining the cultural relevancy of currently widely used suicide risk assessment instruments, research on suicide risk factors, and approaches to risk assessment for youth from communities of color. It also notes that researchers and clinicians should consider other, nontraditional but important factors in suicide risk assessment, including stigma, acculturation, and racial socialization, as well as environmental factors like health care infrastructure and exposure to racism and community violence. The article concludes with recommendations for factors that should be considered in suicide risk assessment for youth from communities of color. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

SARS-CoV-2 is a large, enveloped and positive sense single stranded RNA virus. Its genome codes for 16 non-structural proteins. The largest protein of this complex is nsp3, that contains a well conserved Macro1 domain. Viral Macro domains were shown to bind to mono-ADP-ribose (MAR) and poly-ADP-ribose (PAR) in their free form or conjugated to protein substrates. They carry ADP-ribose hydrolase activities implicated in the regulation of innate immunity. SARS-CoV-2 and SARS-CoV show widely different induction and handling of the host interferon response. Herein, we have conducted a mutational study on the key amino-acid residue F156 in SARS-CoV-2, pinpointed by bioinformatic and structural studies, and its cognate residue N157 in SARS-CoV. Our data suggest that the exchange of these residues slightly modifies ADP-ribose binding, but drastically impacts de-MARylation activity. Alanine substitutions at this position hampers PAR binding, abolishes MAR hydrolysis of SARS-CoV-2, and reduces by 70% this activity in the case of SARS-CoV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Group A streptococcus (GAS) is a global pathogen associated with significant morbidity and mortality for which there is currently no licensed vaccine. Vaccine development has been slow, mostly due to safety concerns regarding streptococcal antigens associated with autoimmunity and related complications. For a GAS vaccine to be safe, it must be ensured that the antigens used in the vaccine do not elicit an antibody response that can cross-react with host tissues. In this study, we evaluated the safety of our GAS vaccine candidate called VaxiStrep in New Zealand White rabbits. VaxiStrep is a recombinant fusion protein comprised of streptococcal pyrogenic exotoxin A (SpeA) and exotoxin B (SpeB), also known as erythrogenic toxins, adsorbed to an aluminum adjuvant. The vaccine elicited a robust immune response against the two toxins in the rabbits without any adverse events or toxicity. No signs of autoimmune pathology were detected in the rabbits' brains, hearts, and kidneys via immunohistochemistry, and serum antibodies did not cross-react with cardiac or neuronal tissue proteins associated with rheumatic heart disease or Sydenham chorea (SC). This study further confirms that VaxiStrep does not elicit autoantibodies and is safe to be tested in a first-in-human trial.

Objective: To determine whether youth, family, and neighborhood factors and minoritized status are associated with youth-reported sexual victimization from childhood through young adulthood., Methods: We analyzed longitudinal data from 2 population-based samples of Puerto Rican youth living in the South Bronx (as a minoritized group) and Puerto Rico (as a nonminoritized group). Waves 1 to 3 were collected annually beginning in 2000 (youth age 5-13). Wave 4 was collected 2013 to 2017 (youth age 15-29). We estimated multivariable associations between youth, family, and neighborhood factors and minoritized status at Wave 1 (independent variables); and youth-reported sexual victimization at Waves 1 to 4 (dependent variables)., Results: None of the factors was associated with youth-reported sexual victimization at Wave 1 (N = 1911). Among youth reporting no previous history of sexual victimization at Wave 1 (n = 1823), youth in the South Bronx vs Puerto Rico were more likely to report sexual victimization at Waves 2 or 3 (odds ratio (OR) [95% confidence interval (CI)] = 3.62 [1.46-8.97]). Older youth were less likely to report sexual victimization (OR [95% CI] = 0.77 [0.65-0.91]) (all P < .01). Among youth reporting no history of sexual victimization at Waves 1 to 3 (n = 1782), youth in the South Bronx (OR [95% CI] = 2.53 [1.52-4.22]), female youth (OR [95% CI] = 2.81 [1.83-4.30]), and youth whose parents had more than a high school degree (OR [95% CI] = 2.25 [1.38-3.67]) were more likely to report sexual victimization at Wave 4 than their counterparts (all P ≤ .001)., Conclusions: Future research should investigate how living as a minoritized youth may contribute to an increased risk of sexual victimization., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)