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Abstract Background Tackling poor mental health in university students has been identified as a priority in higher education. However, there are few evidence-based prevention initiatives designed for students. Repetitive Negative Thought (RNT, e.g. worry, rumination) is elevated in university students and is a well-established vulnerability factor for anxiety and depression. Furthermore, there are now evidence-based cognitive-behavioural interventions to tackle RNT. A mobile self-help cognitive-behavioural app targeting RNT, adapted for students may therefore be an effective, scalable, and acceptable way to improve prevention in students. Methods An online single blind, two-arm parallel-group Randomised Controlled Trial (RCT) to examine the incidence of major depression and symptoms of anxiety and depression across 12 months in university students aged over 16 who screen into the study with self-reported high levels of worry and/or rumination and no current diagnosis of major depression. Eligible participants will be randomised to the active intervention arm (usual practice plus using a self-guided mobile app targeting RNT) or to the control arm (usual practice). In total, 648 participants aged over 16, with no current major depression, bipolar disorder or psychosis will be recruited from UK universities. Assessments will take place at baseline (pre-randomisation), 3 months and 12 months post- randomisation. Primary endpoint and outcome is incidence of major depression as determined by self-reported diagnostic criteria at 12-month follow-up. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and academic outcomes are secondary outcomes. Compliance, adverse events, and potentially mediating variables will be carefully monitored. Discussion The trial aims to provide a better understanding of the causal role of tackling RNT (worry, rumination) using a self-help mobile app with respect to preventing depression in university students. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective mobile-health public health strategies for preventing common mental health problems. Trial registration https://www.isrctn.com/ISRCTN86795807 Date of registration: 27 October 2022

Abstract Glioblastoma (GBM) is one of the deadliest brain cancers with a median survival of only 15 months. This poor prognosis has prompted exploration of novel therapeutic targets for GBM patients. Human cytomegalovirus (HCMV) has been implicated in GBM; however, its impact remains poorly defined, and there is conflicting data over the presence of HCMV in tumors. Nonetheless, clinical trials targeting HCMV have shown promising initial data, and evidence suggests that HCMV may negatively impact GBM patient survival by multiple mechanisms including changes in GBM cell behavior and the tumor microenvironment (TME) that potentiate tumor progression as well as therapy-induced virus reactivation. Moreover, HCMV has many effects on host immunity that could impact tumor behavior by altering the TME, which are largely unexplored. The goal of this review is to describe these potential interactions between HCMV and GBM. Better understanding of these processes may allow the development of new therapeutic modalities to improve GBM patient outcomes.

Abstract Background Despite research dedicated to understanding the health profiles and health-related outcomes of Hispanic individuals, the prevailing body of literature frequently homogenizes the Hispanic population, failing to address the role of race in Hispanic health discourse. Thus, the current study applies an intersectional lens to identify health differences and similarities among Hispanic subgroups. Methods Sociodemographic characteristics and health domain variables (i.e., health status, health services, and health behaviors) from participants (N = 11,192) were included in the analyses. Bivariate Chi-squared tests examined the relationship between sociodemographic and health domain variables Black Hispanic individuals, white Hispanic individuals, and non-Hispanic Black individuals. Results Findings suggest that Non-Hispanic Black American individuals reported the highest rates of hypertension (49.09%) and diabetes (19.62%) compared to Black-Hispanic individuals (22.45% and 12.98%) and white Hispanic individuals (22.22% and 8.02%). Black Hispanic individuals reported the greatest proportion of asthma diagnoses (35.10%) and those who saw a doctor in the previous year (95.52%) compared to white Hispanic individuals (26.84%, and 91.10%, respectively) and non-Hispanic Black individuals ( 21.74%, and 94.69%, respectively). Conclusion Specifically, we found that several health behaviors and health-related outcomes significantly varied across different racial/ethnic groups, demonstrating the advantage of an intersectional approach to identify health disparities among racially diverse ethnic groups. Public Health significance We encourage the development of health care services with an awareness of the complexities resulting from racial differences within the Hispanic diaspora.

Abstract We used a probabilistic reversal learning task to examine prediction error-driven belief updating in three clinical groups with psychosis or psychosis-like symptoms. Study 1 compared people with at-risk mental state and first episode psychosis (FEP) to matched controls. Study 2 compared people diagnosed with treatment-resistant schizophrenia (TRS) to matched controls. The design replicated our previous work showing ketamine-related perturbations in how meta-level confidence maintained behavioural policy. We applied the same computational modelling analysis here, in order to compare the pharmacological model to three groups at different stages of psychosis. Accuracy was reduced in FEP, reflecting increased tendencies to shift strategy following probabilistic errors. The TRS group also showed a greater tendency to shift choice strategies though accuracy levels were not significantly reduced. Applying the previously-used computational modelling approach, we observed that only the TRS group showed altered confidence-based modulation of responding, previously observed under ketamine administration. Overall, our behavioural findings demonstrated resemblance between clinical groups (FEP and TRS) and ketamine in terms of a reduction in stabilisation of responding in a noisy environment. The computational analysis suggested that TRS, but not FEP, replicates ketamine effects but we consider the computational findings preliminary given limitations in performance of the model.

Abstract Background Breast cancer is the most common malignancy among women in the UK. Following mastectomy, reconstruction is now integral to the surgical management of breast cancer, of which implant-based reconstruction (IBBR) is the most common type. IBBR initially evolved from pre-pectoral to post-pectoral due to complications, but with developments in oncoplastic techniques and new implant technology, interest in pre-pectoral IBBR has increased. Many surgeons use acellular dermal matrices (ADM); however, there is little evidence in literature as to whether this improves surgical outcomes in terms of complications, failure and patient satisfaction. This review aims to assess the available evidence as to whether there is a difference in surgical outcomes for breast reconstructions using ADM versus non-use of ADM. Methods A database search will be performed using Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Clinicaltrials.org. The search timeframe will be 10 years. Studies will be screened using inclusion and exclusion criteria and data extracted into a standardised spreadsheet. Risk of bias will be assessed. Screening, extraction and risk-of-bias assessments will be performed independently by two reviewers and discrepancies discussed and rectified. Data analysis and meta-analysis will be performed using Microsoft Excel and R software. Forest plots will be used for two-arm studies to calculate heterogeneity and p-value for overall effect. Discussion With the renaissance of pre-pectoral IBBR, it is important that surgeons have adequate evidence available to assist operative decision-making. Assessing evidence in literature is important to help surgeons determine whether using ADM for IBBR is beneficial compared to non-use of ADM. This has potential impacts for patient complications, satisfaction and cost to healthcare trusts. Systematic review registration PROSPERO 2023 CRD42023389072.

Abstract Strengthening materials via conventional “top-down” processes generally involves restricting dislocation movement by precipitation or grain refinement, which invariably restricts the movement of dislocations away from, or towards, a crack tip, thereby severely compromising their fracture resistance. In the present study, a high-entropy alloy Al0.5CrCoFeNi is produced by the laser powder-bed fusion process, a “bottom-up” additive manufacturing process similar to how nature builds structures, with the microstructure resembling a nano-bridged honeycomb structure consisting of a face-centered cubic (fcc) matrix and an interwoven hexagonal net of an ordered body-centered cubic B2 phase. While the B2 phase, combined with high-dislocation density and solid-solution strengthening, provides strength to the material, the nano-bridges of dislocations connecting the fcc cells, i.e., the channels between the B2 phase on the cell boundaries, provide highways for dislocation movement away from the crack tip. Consequently, the nature-inspired microstructure imparts the material with an excellent combination of strength and toughness.

Background Carotid intima‐media thickness (cIMT) and carotid plaque are reliable indicators of cardiovascular disease risk, and research highlights that racial and ethnic minority individuals generally exhibit higher cIMT and carotid plaque than White individuals. At present, the mechanisms driving these disparities among different racial and ethnic and biological sex groups are poorly understood. Methods and Results Data came from the baseline examination of MESA (Multi‐Ethnic Study of Atherosclerosis). A total of 6814 participants aged 45 to 84 years free of clinical cardiovascular disease completed assessments on health behavior and perceived discrimination. Four sex‐stratified moderated mediation models examined associations between discrimination, cigarette smoking, and mean cIMT and plaque. We hypothesized that cigarette use would mediate the association between discrimination and carotid artery disease features, and that these would differ by race and ethnicity. Indirect effects of discrimination on plaque were observed among Hispanic women such that discrimination was associated with cigarette use and, in turn, higher plaque (β=0.04 [95% CI, 0.01–0.08]). Indirect effects of discrimination on mean cIMT were found among Hispanic (β=0.003 [95% CI, 0.0001–0.007]) and White men (β=0.04 [95% CI, 0.01–0.08]) such that discrimination was associated with cigarette use and, in turn, higher cIMT. Finally, a positive indirect effect of discrimination on plaque was observed among Hispanic men (β=0.03 [95% CI, 0.004–0.07]). No other racial and ethnic differences were observed. Conclusions To understand and address social determinants of cardiovascular disease, researchers must incorporate an intersectional framework that will allow us to understand the complex nature of discrimination and cardiovascular disease risk for individuals of varying intersecting identities and social positions.

BackgroundYoung sexual minority men (YSMM) engage in cardiometabolic risk behaviors (eg, substance use) at higher rates than their heterosexual counterparts. Theory and previous research suggest that these risk behaviors may stem, in part, from exposure to minority stress (ie, discrimination based on sexual identity and other identities such as race). ObjectiveThis pilot study examined the feasibility and acceptability of a virtual 2-day daily diary study that examined daily experiences with discrimination, cardiometabolic risk behaviors (ie, sleep, physical activity, and substance use behaviors), and patterns of physiological stress and inflammation among YSMM aged 18 to 35 years. MethodsParticipants (n=20) were recruited from the greater New York metropolitan area and engaged in a 2-day daily diary protocol wherein they provided web-based consent, took a web-based baseline survey, and then, starting the next day, provided 3 saliva samples a day for 2 consecutive days to measure salivary cortisol, engaged in 3 daily diaries per day, and provided 1 blood spot sample via the finger prick method to measure high-sensitivity C-reactive protein. At follow-up, participants were interviewed via videoconferencing to ascertain their experiences and feelings related to the study protocol. Qualitative analyses explored the feasibility and acceptability of the study protocol, and exploratory quantitative analyses explored the descriptive statistics and Pearson correlations among the main study variables of interest. ResultsThe retention rate was high (19/20, 95%) in our study sample. Qualitative analyses demonstrated that participants were willing to engage in similar, longer-term studies (eg, studies that include both week and weekend days) in the future and suggested the feasibility and acceptability of our study protocol among YSMM. However, participants noted several areas for improvement (eg, redundancy of survey items and difficulty pricking one’s finger) that should be considered in future research. Preliminary quantitative analyses revealed a moderate negative correlation between everyday discrimination and mean cortisol levels (r=−0.51; P=.03). Furthermore, descriptive analyses suggest that that daily cortisol curves differ across races or ethnicities among YSMM. White and other-identified YSMM experienced the highest cortisol awakening response (mean 0.39, SD 0.21 µg/dL for White participants; mean 0.34, SD 0.34 µg/dL for others) with the steepest decline around bedtime (mean 0.05, SD 0.04 µg/dL for White participants; mean 0.09, SD 0.13 µg/dL for others) followed by a lower cortisol awakening response (mean 0.31, SD 0.11 µg/dL for Hispanic participants; mean 0.23, SD 0.15 µg/dL for Black participants) and a slower decline around bedtime (mean 0.10, SD 0.09 µg/dL for Hispanic participants; mean 0.03, SD 0.02 µg/dL for Black participants) among Hispanic and Black YSMM. ConclusionsOverall, the results suggest that similar study protocols are feasible and acceptable among YSMM. Future research should highlight the pathways through which cardiovascular disease risk may arise among YSMM using longer-term study designs and more diverse study samples.

ABSTRACT Pathogenic Rickettsia species proliferate within the cytoplasm of permissive host cells in vivo. The cytoplasm of these host cells is adequate to support the complex metabolic and physiological needs for Rickettsia growth. However, a dramatic host/pathogen interplay occurs when Rickettsia encounter innate immune cells, whereby the bacteria can proliferate as normal or the host can restrict bacterial growth. This interplay is most divergent within myeloid host cells, where intra- and extracellular factors can produce either successful Rickettsia parasitism or innate immune control of bacterial proliferation. With the prior knowledge that the mammalian complement system is activated during mammalian infection, we sought to determine if extracellular complement activation and anaphylatoxin signaling can modify the fate of Rickettsia within mononuclear host cells. Results indicate that supplementation of growth media with either C3a or C5a anaphylatoxin peptides is sufficient for many myeloid cells to control the proliferation of multiple different Rickettsia species. Chemical or genetic disruption of anaphylatoxin signaling or anaphylatoxin receptors eliminates complement-induced restriction of bacterial proliferation. Finally, anaphylatoxin signaling modifies macrophage physiology by inducing inflammatory phenotypes that ultimately control the intracellular proliferation of these pathogens. IMPORTANCE Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can “win” by taking over the host, or the bacteria can “lose” if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that “activate” innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.

ObjectiveTo examine the impact of resilience on the association between discrimination and trajectories of depressive symptoms during the COVID-19 pandemic across racial and ethnic groups.MethodsData were drawn from 5 waves of the All of Us Research Program’s survey on the impact of COVID-19 on the lives of American adults. Linear mixed-effects models were fitted to assess the association between discrimination exposure throughout the pandemic and depressive symptoms over time. An interaction term was introduced between resilience and discrimination exposure to assess if resilience buffered the association between discrimination and depressive symptoms over time. Race-stratified linear mixed-effects models examined racial/ethnic differences in the association between resilience, discrimination, and depressive symptoms over time.ResultsFifty-one thousand nine hundred fifty-eight participants completed surveys between May and December of 2020. Results indicated that exposure to more discrimination was associated with increasing trajectories of depressive symptoms over time (b = 0.48, p

U.S. military veterans have been heavily impacted by the opioid overdose crisis, with drug overdose mortality rates increasing by 53% from 2010–2019. Risk for overdose among veterans is complex and influenced by ongoing interaction among physiological/biological, psychological, and socio-structural factors. A thorough understanding of opioid-related overdose among veterans, one that goes beyond simple pharmacological determinism, must examine the interplay of pain, pain treatment, and stress, as well as psychological and social experiences—before, during, and after military service. Comprehensive efforts to tackle the overdose crisis among veterans require interventions that address each of these dimensions. Promising interventions include widespread naloxone distribution and increased provision of low-threshold wrap-around services, including medications for opioid use disorder (MOUD) and holistic/complementary approaches. Interventions that are delivered by peers – individuals who share key experiential or sociodemographic characteristics with the population being served – may be ideally suited to address many of the barriers to opioid-related risk mitigation common among veterans. Community care models could be beneficial for the large proportion of veterans who are not connected to the Veterans Health Administration and for veterans who, for various reasons including mental health problems and the avoidance of stigma, are socially isolated or reluctant to use traditional substance use services. Interventions need to be tailored in such a way that they reach those more socially isolated veterans who may not have access to naloxone or the social support to help them in overdose situations. It is important to incorporate the perspectives and voices of veterans with lived experience of substance use into the design and implementation of new overdose prevention resources and strategies to meet the needs of this population. Key messagesU.S. military veterans have been heavily impacted by the opioid overdose crisis, with drug overdose mortality rates increasing by 53% from 2010–2019.The risks for overdose that veterans face need to be understood as resulting from an ongoing interaction among biological/physiological, psychological, and social/structural factors.Addressing drug overdose in the veteran population requires accessible and non-judgemental, low threshold, wraparound, and holistic solutions that recognise the complex aetiology of overdose risk for veterans.

Theology and psychiatry have a common concern with the human mind or soul, but very different histories of how they have understood and investigated their respective interests. Christian theology, which we might refer to here as the ‘science of God’, has developed over a period of two thousand years or more and draws on resources found in scripture, tradition, and philosophy. Psychiatry, both as a science and body of clinical practice, is little more than two hundred years old and is concerned with the aetiology, phenomenology, and treatment of mental disorders. It draws on the medical and social sciences as its primary resources, although it has also been influenced by philosophy. Whilst mental illness has been recognized in some form or another since ancient times, the last two centuries have seen increasing medicalization of conditions that would previously have been described in primarily theological terms. Thus, for example, ‘chronic inebriety’ has come to be seen primarily as addiction or alcohol misuse. Antagonisms between theology and psychiatry, as representing different worldviews and ways of thinking about the human condition, date back at least to the late nineteenth century and were particularly heightened as a result of the negative views of both Freud and behavioural psychology towards religion. Serious interdisciplinary engagement between theology and psychiatry has thus been limited until recently. Whilst this engagement might be seen as a part of the broader field of science and theology, it has received much less attention than issues such as cosmology, quantum physics, or evolution. In contrast, the place of spirituality within clinical care has been hotly debated, driven particularly by the concerns of patients who have found that their spiritual and religious concerns have been treated in a prejudicial fashion as a part of their illness, rather than as a resource to aid in their recovery.

BackgroundFirefighters are often exposed to occupational stressors that can result in psychological distress (ie, anxiety and depression) and burnout. These occupational stressors have only intensified with the onset of the COVID-19 pandemic and will likely persist in the postpandemic world. ObjectiveTo address occupational stressors confronting firefighters, we pilot tested a novel, cost-effective, smartphone app–based meditation intervention created by Healthy Minds Innovations that focused on mindfulness (awareness) training along with practices designed to cultivate positive relationships (connection), insight into the nature of the self (insight), and a sense of purpose in the context of challenge (purpose) with a sample of professional firefighters from a large metropolitan area in southwestern United States. MethodsA total of 35 participants were recruited from a closed online group listserv and completed the self-guided 10-unit meditation app over the course of 10 days, at 1 unit per day. We assessed anxiety symptoms, depression symptoms, burnout, and negative affect as well as saliva diurnal cortisol rhythm, an objective indicator of stress-related biology, before and after use of the meditation app. ResultsThis study demonstrated the meditation app was both feasible and acceptable for use by the majority of firefighters. We also found significant reductions in firefighters’ anxiety (P=.01), burnout (P=.05), and negative affect (P=.04), as well as changes in cortisol diurnal rhythm, such as waking cortisol (P=.02), from before to after use of the meditation app. ConclusionsOur study findings call for future research to demonstrate the efficacy of this meditation app to reduce psychological distress and burnout in firefighters.

The KRAS gene is often mutated at several hotspot codons in cancer, resulting in similar, yet distinct, functional impacts on the KRAS protein. Here, the authors examine the genetic interactions of the different KRAS mutations across multiple cancer types and discover that KRAS mutations have allele- and tissue-specific mutagenic origins, comutation patterns, and dependency interactions.

Uric acid levels during pregnancy have been examined as a potential indicator of risk for gestational diabetes mellites, hypertension, and related adverse birth outcomes. However, evidence supporting the utility of serum uric acid levels in predicting poor maternal and fetal health has been mixed. The lack of consistent findings may be due to limitations inherent in serum-based biomeasure evaluations, such as minimal repeated assessments and variability in the timing of these assessments. To address these gaps, we examined repeated measurements of diurnal salivary uric acid (sUA) levels in a sample of 44 healthy women across early-mid and late pregnancy. We assessed potential covariates and confounds of sUA levels and diurnal trajectories, as well as associations between maternal weight gain and blood pressure during pregnancy and sUA concentrations. Using multilevel linear models, we found sUA increased across pregnancy and displayed a robust diurnal pattern with the highest concentrations at waking, a steep decline in the early morning, and decreasing levels across the day. Maternal pre-pregnancy BMI, age, prior-night sleep duration, and fetal sex were associated with sUA levels and/or diurnal slopes. Maternal blood pressure and gestational weight gain also showed significant associations with sUA levels across pregnancy. Our results expand upon those found with serum UA measurements. Further, they demonstrate the feasibility of using at-home, minimally-invasive saliva sampling procedures to track UA levels across pregnancy with potential applications for the long-term monitoring of maternal cardiometabolic risk.

Abstract Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism, intellectual disability, hypotonia, and epilepsy. The 15q region harbors genes critical for brain development, particularly UBE3A and a cluster of gamma-aminobutyric acid type A receptor (GABAAR) genes. We recently described an electrophysiological biomarker of the syndrome, characterized by excessive beta oscillations (12–30 Hz), resembling electroencephalogram (EEG) changes induced by allosteric modulation of GABAARs. In this follow-up study, we tested a larger cohort of children with Dup15q syndrome to comprehensively examine properties of this EEG biomarker that would inform its use in future clinical trials, specifically, its (1) relation to basic clinical features, such as age, duplication type, and epilepsy; (2) relation to behavioral characteristics, such as cognition and adaptive function; (3) stability over time; and (4) reproducibility of the signal in clinical EEG recordings. Methods We computed EEG power and beta peak frequency (BPF) in a cohort of children with Dup15q syndrome (N = 41, age range 9–189 months). To relate EEG parameters to clinical (study 1) and behavioral features (study 2), we examined age, duplication type, epilepsy, cognition, and daily living skills (DLS) as predictors of beta power and BPF. To evaluate stability over time (study 3), we derived the intraclass correlation coefficients (ICC) from beta power and BPF computed from children with multiple EEG recordings (N = 10, age range 18–161 months). To evaluate reproducibility in a clinical setting (study 4), we derived ICCs from beta power computed from children (N = 8, age range 19–96 months), who had undergone both research EEG and clinical EEG. Results The most promising relationships between EEG and clinical traits were found using BPF. BPF was predicted both by epilepsy status (R 2 = 0.11, p = 0.038) and the DLS component of the Vineland Adaptive Behavior Scale (R 2 = 0.17, p = 0.01). Beta power and peak frequency showed high stability across repeated visits (beta power ICC = 0.93, BPF ICC = 0.92). A reproducibility analysis revealed that beta power estimates are comparable between research and clinical EEG (ICC = 0.94). Conclusions In this era of precision health, with pharmacological and neuromodulatory therapies being developed and tested for specific genetic etiologies of neurodevelopmental disorders, quantification and examination of mechanistic biomarkers can greatly improve clinical trials. To this end, the robust beta oscillations evident in Dup15q syndrome are clinically reproducible and stable over time. With future preclinical and computational studies that will help disentangle the underlying mechanism, it is possible that this biomarker could serve as a robust measure of drug target engagement or a proximal outcome measure in future disease modifying intervention trials.

BackgroundYoung sexual and gender minorities (SGMs) of color may face unique experiences of discrimination based on their intersectional positions (eg, discrimination based on both racial or ethnic identity and sexual identity). Emerging evidence suggests that mindfulness practices may reduce stress from discrimination and improve overall well-being among young SGM. Moreover, the omnipresence of smartphone access among racial or ethnic and sexual minority communities provides a method through which to administer mindfulness-based interventions among young SGMs of color. ObjectiveThis paper outlines the protocol of the Optimizing a Daily Mindfulness Intervention to Reduce Stress from Discrimination among Young Sexual and Gender Minorities of Color (REDUCE) study, a pilot optimization trial of a smartphone-based mindfulness intervention that was developed in conjunction with the Healthy Minds Program (HMP) with the aim of reducing stress from discrimination among young SGMs. MethodsIn total, 80 young (ages 18-29 years) SGMs of color will be enrolled in the study. The HMP is a self-guided meditation practice, and participants will be randomized to either a control condition or an intervention that uses a neuroscience-based approach to mindfulness. We will use the multiphase optimization strategy to assess which combination of mindfulness interventions is the most effective at reducing stress from discrimination among young SGMs of color. A combination of mindfulness-based meditation intervention components will be examined, comprising mindfulness-based practices of awareness, connection, and purpose. Awareness refers to the practice of self-awareness, which reduces the mind’s ability to be distracted and instead be present in the moment. Connection refers to the practice of connection with oneself and others and emphasizes on empathy and compassion with oneself and others. Purpose encourages goal-making in accordance with one’s values and management of behavior in accordance with these goals. In addition, we will assess the feasibility and acceptability of the HMP application among young SGMs of color. ResultsThe REDUCE study was approved by the Institutional Review Board of New York University, and recruitment and enrollment began in the winter of 2021. We expect to complete enrollment by the summer of 2022. The results will be disseminated via social media, journal articles, abstracts, or presentations, as well as to participants, who will be given the opportunity to provide feedback to the researchers. ConclusionsThis optimization trial is designed to test the efficacy, feasibility, and acceptability of implementing an application-based, mindfulness-based intervention to reduce stress from discrimination and improve well-being among young SGMs of color. Evidence from this study will assist in the creation of a sustainable, culturally relevant mobile app–based mindfulness intervention to reduce stress from discrimination among young SGMs of color. Trial RegistrationClinicaltrials.gov NCT05131360; https://clinicaltrials.gov/ct2/show/NCT05131360 International Registered Report Identifier (IRRID)DERR1-10.2196/35593

Abstract Background Diminished cognitive control, including reduced behavioral flexibility and behavioral response inhibition, has been repeatedly documented in autism spectrum disorder (ASD). We evaluated behavioral flexibility and response inhibition in probands and their parents using a family trio design to determine the extent to which these cognitive control impairments represent familial traits associated with ASD. Methods We examined 66 individuals with ASD (probands), 135 unaffected biological parents, and 76 typically developing controls. Participants completed a probabilistic reversal learning task (PRL) and a stop-signal task (SST) to assess behavioral flexibility and response inhibition respectively. Rates of PRL and SST errors were examined across groups, within families, and in relation to clinical and subclinical traits of ASD. Based on prior findings that subclinical broader autism phenotypic (BAP) traits may co-segregate within families and reflect heritable risk factors, we also examined whether cognitive control deficits were more prominent in families in which parents showed BAP features (BAP+). Results Probands and parents each showed increased rates of PRL and SST errors relative to controls. Error rates across tasks were not related. SST error rates inter-correlated among probands and their parents. PRL errors were more severe in BAP+ parents and their children relative to BAP− parents and their children. For probands of BAP+ parents, PRL and SST error rates were associated with more severe social-communication abnormalities and repetitive behaviors, respectively. Conclusion Reduced behavioral flexibility and response inhibition are present among probands and their unaffected parents, but represent unique familial deficits associated with ASD that track with separate clinical issues. Specifically, behavioral response inhibition impairments are familial in ASD and manifest independently from parental subclinical features. In contrast, behavioral flexibility deficits are selectively present in families with BAP characteristics, suggesting they co-segregate in families with parental subclinical social, communication, and rigid personality traits. Together, these findings provide evidence that behavioral flexibility and response inhibition impairments track differentially with ASD risk mechanisms and related behavioral traits.

Purpose: To evaluate the agreement of selected higher order aberration measurements between aberrometers based on three different wavefront technologies. Methods: Twenty-three eyes of 23 participants were compared between Zywave, OPD-Scan III, and iDesign aberrometers, for total ocular aberrations. Participants were between 19 and 69 years of age, and exclusion criteria were previous ocular surgery or trauma, contact lens wear within the preceding 2 weeks, and ocular or systemic disease. Corneal aberrations were compared between the OPD-Scan III and GALILEI™ G2 aberrometers. Zernike coefficients of vertical and oblique trefoil, vertical and horizontal coma, and spherical aberration were analyzed in R software. Results: In all, 276 scans were captured in total, with a male-to-female ratio of 11:12. Total ocular vertical coma [mean difference (MD) = 0.026 μm, P < 0.005], vertical trefoil (MD = 0.033 μm, P < 0.05), and spherical aberration (MD = 0.022 μm, P < 0.05) differed significantly between the iDesign and OPD-Scan III. Differences in total vertical (MD = 0.072 μm, P < 0.05) and oblique trefoil (MD = 0.058 μm, P < 0.05) were demonstrated between the Zywave and OPD-Scan III, and spherical aberration (MD = 0.030 μm, P < 0.005) between iDesign and Zywave. iDesign corneal horizontal coma (MD = 0.025 μm, P < 0.05) and spherical aberration (MD = 0.043 μm, P < 0.005) measurements were significantly different between the GALILEI™ G2 and the OPD-Scan III. Conclusion: Zywave, iDesign, and OPD-Scan III, and GALILEITM G2 and OPD-Scan III may be used interchangeably for their total ocular and corneal wavefront functions, respectively; however, care must be taken if using these devices for guiding ablation or monitoring corneal disease.

Different glial cell types are found throughout the central (CNS) and peripheral nervous system (PNS), where they have important functions. These cell types are also involved in nervous system pathology, playing roles in neurodegenerative disease and following trauma in the brain and spinal cord (astrocytes, microglia, oligodendrocytes), nerve degeneration and development of pain in peripheral nerves (Schwann cells, satellite cells), retinal diseases (Müller glia) and gut dysbiosis (enteric glia). These cell type have all been proposed as potential targets for treating these conditions. One approach to target these cell types is the use of gene therapy to modify gene expression. Adeno-associated virus (AAV) vectors have been shown to be safe and effective in targeting cells in the nervous system and have been used in a number of clinical trials. To date, a number of studies have tested the use of different AAV serotypes and cell-specific promoters to increase glial cell tropism and expression. However, true glial-cell specific targeting for a particular glial cell type remains elusive. This review provides an overview of research into developing glial specific gene therapy and discusses some of the issues that still need to be addressed to make glial cell gene therapy a clinical reality.

This study assessed the modifying role of primary source of COVID-19 information in the association between knowledge and protective behaviors related to COVID-19 among adults living in the United States (US). Data was collected from 6,518 US adults through an online cross-sectional self-administered survey via social media platforms in April 2020. Linear regression was performed on COVID-19 knowledge and behavior scores, adjusted for sociodemographic factors. An interaction term between knowledge score and primary information source was included to observe effect modification by primary information source. Higher levels of knowledge were associated with increased self-reported engagement with protective behaviors against COVID-19. The primary information source significantly moderated the association between knowledge and behavior, and analyses of simple slopes revealed significant differences by primary information source. This study shows the important role of COVID-19 information sources in affecting people's engagement in recommended protective behaviors. Governments and health agencies should monitor the use of various information sources to effectively engage the public and translate knowledge into behavior change during an evolving public health crisis like COVID-19.

Imagine trying to reconstruct someone’s pulmonary vein in an austere Syrian operating theatre. Now imagine six men dressed in black and wielding AK-47s crashing in and interrogating you as to why you have your hand in their comrade’s chest. This was just one of David Nott’s brushes with the Islamic State of Iraq and Syria (ISIS), amongst the many other dangerous encounters that nearly cost him his head.

Abstract Background Giant vertebral and vertebrobasilar aneurysms have proven to be extremely challenging vascular entities to treat despite many advances in microsurgical and endovascular techniques. In recent years, there has been more attention paid to combined approaches, including combinations of endovascular and surgical procedures in hopes of decreasing the associated morbidity and mortality of these lesions. Clinical Presentation We present a case of a giant fusiform vertebral artery aneurysm that was initially treated with flow-diverting stents. After the failure of flow diversion to occlude the aneurysm, the lesion was definitively treated with an occipital artery to the posterior inferior cerebellar artery (PICA) bypass and coil embolization of residual aneurysm. Conclusion After bypass and parent vessel deconstruction, angiography confirmed the aneurysm has remained occluded and the PICA patent. This case highlights the use of an extracranial-to-intracranial bypass to salvage a complex residual aneurysm after failed flow diversion.

Context: We noted a bimodal relationship between mortality and shock index (SI), the ratio of heart rate to systolic blood pressure. Aims: To determine if extremes of SI can predict mortality in trauma patients. Settings and Designs: Retrospective evaluation of adult trauma patients at a tertiary care center from 2000 to 2012 in the United States. Materials and Methods: We examined the SI in trauma patients and determined the adjusted mortality for patients with and without head injuries. Statistical Analysis Used: Descriptive statistics and multivariable logistic regression. Results: SI values demonstrated a U-shaped relationship with mortality. Compared with patients with a SI between 0.5 and 0.7, patients with a SI of 1.3 had an odds ratio of death of 3.1. (95% CI 1.6–5.9). Elevated SI is associated with increased mortality in patients with isolated torso injuries, and is associated with death at both low and high values in patients with head injury. Conclusion: Our data indicate a bimodal relationship between SI and mortality in head injured patients that persists after correction for various co-factors. The distribution of mortality is different between head injured patients and patients without head injuries. Elevated SI predicts death in all trauma patients, but low SI values only predict death in head injured patients.