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Background: A growing literature documents how primary care practices adapted to the COVID-19 pandemic. We examine a topic that has received less attention-how participants in an advanced alternative payment model perceive the model influenced their ability to meet patients' care needs during the pandemic., Methods: Analysis of closed- and open-ended questions from a 2021 survey of 2496 practices participating in the Comprehensive Primary Care Plus (CPC+) model (92% response rate) and a 2021 survey of 993 randomly selected primary care physicians from these practices (55% response rate). Both surveys asked whether respondents agreed or disagreed that they or their practice was "better positioned to meet patients' care needs during the coronavirus pandemic" because of participation in CPC+. Both also included an open-ended question about CPC+'s effects., Results: Half of practices and one-third of physicians agreed or strongly agreed that participating in CPC+ better positioned them to meet patients' care needs during the pandemic. One in 10 practices and 2 in 10 physicians, disagreed or strongly disagreed, while 4 in 10 practices and slightly more than half of physicians neither agreed nor disagreed (or, for physicians, didn't know). The most commonly identified CPC+ activities that facilitated meeting patient care needs related to practices' work on care management (e.g., risk stratification), access (e.g., telehealth), payment outside of fee-for-service (FFS), and staffing (e.g., supporting care managers)., Conclusions: Most CPC+ practices and physicians were positive or neutral about participating in CPC+ in the context of COVID-19, indicating more benefit than risk to payment alternatives to FFS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Genna Cohen reports financial support was provided by U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services. Nancy Duda reports financial support was provided by U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services. Katie Morrison Lee reports financial support was provided by U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services. Kaylyn Swankoski reports financial support was provided by U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services. Gillian Giudice reports financial support was provided by U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services. Maya Palakal reports financial support was provided by U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services. Caroline Mack reports financial support was provided by U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services. Ann S. O'Malley reports financial support was provided by U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services., (Copyright © 2024. Published by Elsevier Inc.)

Objective: We aimed to determine the association of COVID-19 vaccination with flares of systemic rheumatic disease (SRD)., Methods: Adults with systemic rheumatic disease (SRD) in a single-center COVID-19 Rheumatology Registry were invited to enroll in a study of flares. COVID-19 vaccine information from March 5, 2021, to September 6, 2022, was obtained from chart review and self-report. Participants self-reported periods of SRD flare and periods without SRD flare. "Hazard periods" were defined as the time before a self-report of flare and "control periods" as the time before a self-report of no flare. The association between flare and COVID-19 vaccination was evaluated during hazard and control periods through univariate conditional logistic regression stratified by participant, using lookback windows of 2, 7, and 14 days., Results: A total of 434 participants (mean ± SD age 59 ± 13 years, 84.1% female, 81.8% White, 64.5% with inflammatory arthritis, and 27.0% with connective tissue diseases) contributed to both the hazard and control periods and were included in analysis. A total of 1,316 COVID-19 vaccinations were identified (58.5% Pfizer-BioNTech, 39.5% Moderna, and 1.4% Johnson & Johnson); 96.1% of participants received at least one dose and 93.1% at least two doses. There was no association between COVID-19 vaccination and flares in the subsequent 2, 7, or 14 days (odds ratio [OR] 1.46, 95% confidence interval [CI] 0.86-2.46; OR 1.09, 95% CI 0.76-1.55; and OR 0.85, 95% CI 0.64-1.13, respectively). Analyses stratified on sex, age, SRD subtype, and vaccine manufacturer similarly showed no association between vaccination and flare., Conclusion: COVID-19 vaccination was not associated with flares in this cohort of participants with SRD. These data are reassuring and can inform shared decision-making on COVID-19 immunization., (© 2024 American College of Rheumatology.)

Several psychosocial factors can impact surgical outcomes and overall patient wellbeing following surgery. Although advances in surgical interventions and pain management protocols can reduce surgical trauma and enhance recovery from surgery, additional intervention is warranted to optimize surgical outcomes and patient quality of life (QoL) in the short- and long-term. Research on mindfulness techniques suggests that mindfulness-based interventions (MBI) effectively promote health behaviors, reduce pain, and improve psychological wellbeing and QoL. Thus, there has been an increase in research evaluating the use of MBIs to improve postoperative outcomes and wellbeing in surgical patients. The authors provide a brief overview of psychosocial outcomes of surgery and MBIs and review the literature on the impact of MBIs on postoperative outcomes. The extant literature indicates that MBIs are feasible and acceptable for use in surgical patient populations and provides preliminary evidence of the benefits of mindfulness across a range of surgical patient populations. However, more research is needed to assess the long-term efficacy of MBIs delivered online and in-person across the perioperative continuum., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The number of young adults seeking help for emotional distress, subsyndromal-syndromal mood/anxiety symptoms, including those associated with neuroticism, is rising and can be an early manifestation of mood/anxiety disorders. Identification of gray matter (GM) thickness alterations and their relationship with neuroticism and mood/anxiety symptoms can aid in earlier diagnosis and prevention of risk for future mood and anxiety disorders. In a transdiagnostic sample of young adults (n = 252;177 females; age 21.7 ± 2), Hypothesis (H) 1:regularized regression followed by multiple regression examined relationships among GM cortical thickness and clinician-rated depression, anxiety, and mania/hypomania; H2:the neuroticism factor and its subfactors as measured by NEO Personality Inventory (NEO-PI-R) were tested as mediators. Analyses revealed positive relationships between left parsopercularis thickness and depression (B = 4.87, p = 0.002), anxiety (B = 4.68, p = 0.002), mania/hypomania (B = 6.08, p ≤ 0.001); negative relationships between left inferior temporal gyrus (ITG) thickness and depression (B = - 5.64, p ≤ 0.001), anxiety (B = - 6.77, p ≤ 0.001), mania/hypomania (B = - 6.47, p ≤ 0.001); and positive relationships between left isthmus cingulate thickness (B = 2.84, p = 0.011), and anxiety. NEO anger/hostility mediated the relationship between left ITG thickness and mania/hypomania; NEO vulnerability mediated the relationship between left ITG thickness and depression. Examining the interrelationships among cortical thickness, neuroticism and mood and anxiety symptoms enriches the potential for identifying markers conferring risk for mood and anxiety disorders and can provide targets for personalized intervention strategies for these disorders., (© 2024. The Author(s).)

Objective: To test the reliability of Medicare claims in measuring vertical integration. We assess the accuracy of a commonly used measure of integration, primary care physician (PCP) practices billing Medicare as a hospital outpatient department (HOPD) in claims., Data Sources and Study Setting: Medicare fee-for-service claims, IQVIA, and CPC+ practice surveys for this study., Study Design: We compare measures of integration from Medicare claims to self-reported indicators of integration from IQVIA and a survey of CPC+ participating practice sites., Data Collection/extraction Methods: We measure integration by using site-of-service billing in the 100% sample of Medicare Carrier claims from 2017-2020. In the IQVIA SK&A (2017-2018), OneKey (2019-2020), and practice survey data (2017-2019), we use self-reported responses to measure integration., Principal Findings: We find that currently most PCP practices sites that report themselves as being integrated with a health system do not bill as an HOPD. In 2017, 11% of CPC+ practices were identified as being vertically integrated in claims, while the equivalent numbers in SK&A and surveys were 52% and 54% integration, respectively. A t-test found that both datasets significantly differed from claims (Survey: 41.3%-45.1%; SK&A: 45.3%-51.1%); this gap persists in 2018-2019., Conclusion: Measuring physician-hospital vertical integration accurately is integral to determining consolidation. The overwhelming majority of PCP practice sites not billing as an HOPD may reflect Medicare regulatory changes that have reduced the financial incentives for doing so. These findings have implications for researchers that study the growth in PCP-hospital integration in health care markets., (© 2024 Health Research and Educational Trust.)

This study aimed to compare the bioaccessibility of docosahexaenoic acid (DHA) in naturally and artificially enriched milk and investigate the potential mechanisms involved. The results indicated that the DHA in naturally enriched milk (NEM) had a higher bioaccessibility (76.9 %) and a lower digestive loss rate (18.1 %) compared to artificially enriched milk (ArEM). Moreover, NEM contained a higher proportion of DHA-containing glycerophospholipids and sn-2 DHA, with fewer long-chain fatty acids and more saturated fatty acids adjacent to DHA in the same lipid molecule. During simulated intestinal digestion, NEM had a higher free fatty acid release and lipid digestion rate than ArEM. These findings suggested that the bioaccessibility of endogenous DHA in milk was superior to that of externally added DHA due to its more easily digestible and absorbable chemical binding form and lower digestive loss rate. The easy digestibility of milk lipids in NEM also contributed to its high DHA bioaccessibility., 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 Ltd. All rights reserved.)

Inherited defects in cytochrome c oxidase (COX) are associated with a substantial subset of diseases adversely affecting the structure and function of the mitochondrial respiratory chain. This multi-subunit enzyme consists of 14 subunits and numerous cofactors, and it requires the function of some 30 proteins to assemble. COX assembly was first shown to be the primary defect in the majority of COX deficiencies 36 years ago. Over the last three decades, most COX assembly genes have been identified in the yeast Saccharomyces cerevisiae , and studies in yeast have proven instrumental in testing the impact of mutations identified in patients with a specific COX deficiency. The advent of accessible genome-wide sequencing capabilities has led to more patient mutations being identified, with the subsequent identification of several new COX assembly factors. However, the lack of genotype-phenotype correlations and the large number of genes involved in generating a functional COX mean that functional studies must be undertaken to assign a genetic variant as being causal. In this review, we provide a brief overview of the use of yeast as a model system and briefly compare the COX assembly process in yeast and humans. We focus primarily on the studies in yeast that have allowed us to both identify new COX assembly factors and to demonstrate the pathogenicity of a subset of the mutations that have been identified in patients with inherited defects in COX. We conclude with an overview of the areas in which studies in yeast are likely to continue to contribute to progress in understanding disease arising from inherited COX deficiencies.

Purpose of Review: Despite effective available treatments, gout management is often unsuccessful in getting patients to target serum urate goal and in managing flares in the setting of comorbidities. Studies addressing future treatment options for short- and long-term management are reviewed., Recent Findings: URAT-1 blocking agents have been helpful but have had limitations related to effects on renal function, lack of efficacy with renal impairment, and potential to increase renal stones. Dotinurad may function in the setting of decreased renal function. Arhalofenate has anti-URAT-1 activity and may also blunt gout flares. A new xanthine oxidase inhibitor (XOI), tigulixostat, is under study. New uricase treatments manufactured in combination with agents that can reduce immunogenicity may make uricase treatment simpler. A unique strategy of inhibiting gut uricase may offer the benefits of avoiding systemic absorption. For gout flares, IL-1β inhibitor studies in progress include different dosing schedules. Dapansutrile, an oral agent under investigation, inhibits activation of the NLRP3 inflammasome and may be an effective anti-inflammatory. New treatments for gout that are under study may work in the setting of comorbidities, simplify management, utilize new mechanisms, or have reduced side effects., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Mania/hypomania is the pathognomonic feature of bipolar disorder (BD). Established, reliable neural markers denoting mania/hypomania risk to help with early risk detection and diagnosis and guide the targeting of pathophysiologically informed interventions are lacking., Objective: To identify patterns of neural responses associated with lifetime mania/hypomania risk, the specificity of such neural responses to mania/hypomania risk vs depression risk, and the extent of replication of findings in 2 independent test samples., Design, Setting, and Participants: This cross-sectional study included 3 independent samples of young adults aged 18 to 30 years without BD or active substance use disorder within the past 3 months who were recruited from the community through advertising. Of 603 approached, 299 were ultimately included and underwent functional magnetic resonance imaging at the University of Pittsburgh, Pittsburgh, Pennsylvania, from July 2014 to May 2023., Main Outcomes and Measures: Activity and functional connectivity to approach-related emotions were examined using a region-of-interest mask supporting emotion processing and emotional regulation. The Mood Spectrum Self-Report assessed lifetime mania/hypomania risk and depression risk. In the discovery sample, elastic net regression models identified neural variables associated with mania/hypomania and depression risk; multivariable regression models identified the extent to which selected variables were significantly associated with each risk measure. Multivariable regression models then determined whether associations in the discovery sample replicated in both test samples., Results: A total of 299 participants were included. The discovery sample included 114 individuals (mean [SD] age, 21.60 [1.91] years; 80 female and 34 male); test sample 1, 103 individuals (mean [SD] age, 21.57 [2.09] years; 30 male and 73 female); and test sample 2, 82 individuals (mean [SD] age, 23.43 [2.86] years; 48 female, 29 male, and 5 nonbinary). Associations between neuroimaging variables and Mood Spectrum Self-Report measures were consistent across all 3 samples. Bilateral amygdala-left amygdala functional connectivity and bilateral ventrolateral prefrontal cortex-right dorsolateral prefrontal cortex functional connectivity were positively associated with mania/hypomania risk: discovery omnibus χ2 = 1671.7 (P < .001); test sample 1 omnibus χ2 = 1790.6 (P < .001); test sample 2 omnibus χ2 = 632.7 (P < .001). Bilateral amygdala-left amygdala functional connectivity and right caudate activity were positively associated and negatively associated with depression risk, respectively: discovery omnibus χ2 = 2566.2 (P < .001); test sample 1 omnibus χ2 = 2935.9 (P < .001); test sample 2 omnibus χ2 = 1004.5 (P < .001)., Conclusions and Relevance: In this study of young adults, greater interamygdala functional connectivity was associated with greater risk of both mania/hypomania and depression. By contrast, greater functional connectivity between ventral attention or salience and central executive networks and greater caudate deactivation were reliably associated with greater risk of mania/hypomania and depression, respectively. These replicated findings indicate promising neural markers distinguishing mania/hypomania-specific risk from depression-specific risk and may provide neural targets to guide and monitor interventions for mania/hypomania and depression in at-risk individuals.

Background: Prior to undergoing bariatric surgery, many insurance companies require patients to attend medically supervised weight management visits for 3-6 months to be eligible for surgery. There have been few studies that have looked specifically at the relationship between medically supervised weight management visit attendance and postoperative outcomes, and the current literature reports discrepant findings., Objectives: This project aimed to better characterize the relationship between preoperative medically supervised weight management visit attendance and postoperative weight loss outcomes by examining weight loss up to 5 years postbariatric surgery, and by stratifying findings according to the type of surgery undergone., Setting: University Hospital., Methods: Participants were recruited during presurgical bariatric surgery clinic visits at a bariatric and metabolic weight loss center. As part of standard of care all participants were required to participate in monthly medically supervised weight management visits before surgery. Participants who completed bariatric surgical procedures participated in postsurgical follow-up at 3 weeks, 3 months, 6 months, and then annually for 5 years. Weight outcomes measured were percentage of total weight lost., Results: The results do not indicate a significant association between number of group visits attended and percent total weight loss at 1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, or 5 years postbariatric surgery., Conclusions: These data do not suggest a relationship between engagement in a medically supervised weight loss program prior to bariatric surgery and weight loss after surgery in either the short- or the long-term., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To understand the role of health information technology (IT) vendors and health IT functionality in supporting advanced primary care., Study Design: We synthesized multiple rounds of surveys and interviews (2017-2022) from a mixed-methods evaluation of Comprehensive Primary Care Plus (CPC+), a multipayer model developed by CMS. CPC+ was the first federal advanced primary care reform effort that formalized health IT vendors' roles in supporting health IT implementation and specified detailed health IT requirements for practices., Methods: We conducted content analysis to identify cross-cutting themes related to health IT for both practices and vendors, comparing similarities and differences across participants and (when possible) over time., Results: Vendors and practices reported advances in registries and dashboards for improved information management within the practice as well as strengthened relationships between vendors and practices that supported health IT implementation. However, CPC+ practices noted several gaps or challenges using existing functionalities, and both vendors and practices reported broader challenges for more transformative health IT change, particularly the lack of interoperable health information exchange needed to support care management and care coordination. Key factors constraining vendors' investment in further advances included long product development schedules, making it difficult to respond to rapidly evolving model requirements. Vendors also shared that CPC+ practices represented a small fraction of their client base, so investing in developing new functionality was not strategic unless it was more broadly relevant outside CPC+., Conclusions: Continued collaboration among health IT vendors, practices, policy makers, and payers could support continued technological improvements, particularly related to information exchange and communication. Aligning requirements more closely with other federal and private models could also help mitigate the risk for vendors.

Weight-related abuse is defined as verbal or physical maltreatment specific to one's weight. The Weight-Related Abuse Questionnaire (WRAQ) is an instrument specifically designed to measure weight-related abuse. The main goal of this research was to study the factor structure and measurement invariance of the Spanish version of the WRAQ in a non-clinical and a clinical sample. The clinical sample included 150 participants with obesity (60 % women) from the Hospital de Valme (Sevilla, Spain). The non-clinical sample included 301 students (79 % women) from the Spanish Open University (UNED). Scales to measure weight self-stigma and fear of gaining weight were used to analyze the convergent validity of the WRAQ. A confirmatory factor analysis showed that a two-factor model (verbal and physical abuse) was an acceptable fit for the data in both the clinical and non-clinical samples. Multigroup Confirmatory Factor Analysis revealed scalar measurement invariance by sample and gender. Cronbach's alpha coefficients and composite reliability for both samples were found to be good, with values ranging from 0.83 to 0.96. Fear of gaining weight was correlated to verbal (r = 0.36, p < .01) and physical (r = 0.12, p < .05) abuse, and weight self-stigma was also related to physical (r = 0.21, p < .01) and verbal (r = 0.41, p < .01) abuse. These results suggest that the WRAQ can be used in clinical and non-clinical samples to assess verbal and physical abuse in both men and women., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Heightened reward sensitivity/impulsivity, related neural activity, and sleep-circadian disruption are important risk factors for bipolar spectrum disorders, the defining feature of which is mania/hypomania. Our goal was to identify neurobehavioral profiles based on reward and sleep-circadian features and examine their specificity to mania/hypomania versus depression vulnerability., Methods: At baseline, a transdiagnostic sample of 324 adults (18-25 years) completed trait measures of reward sensitivity (Behavioral Activation Scale), impulsivity (UPPS-P-Negative Urgency), and a functional magnetic resonance imaging card-guessing reward task (left ventrolateral prefrontal activity to reward expectancy, a neural correlate of reward motivation and impulsivity, was extracted). At baseline, 6-month follow-up, and 12-month follow-up, the Mood Spectrum Self-Report Measure - Lifetime Version assessed lifetime predisposition to subthreshold-syndromal mania/hypomania, depression, and sleep-circadian disturbances (insomnia, sleepiness, reduced sleep need, rhythm disruption). Mixture models derived profiles from baseline reward, impulsivity, and sleep-circadian variables., Results: Three profiles were identified: 1) healthy (no reward or sleep-circadian disruption; n = 162); 2) moderate-risk (moderate reward and sleep-circadian disruption; n = 109); and 3) high-risk (high impulsivity and sleep-circadian disruption; n = 53). At baseline, the high-risk group had significantly higher mania/hypomania scores than the other groups but did not differ from the moderate-risk group in depression scores. Over the follow-up period, the high-risk and moderate-risk groups exhibited elevated mania/hypomania scores, whereas depression scores increased at a faster rate in the healthy group than in the other groups., Conclusions: Cross-sectional and next-year predisposition to mania/hypomania is associated with a combination of heightened reward sensitivity and impulsivity, related reward circuitry activity, and sleep-circadian disturbances. These measures can be used to detect mania/hypomania risk and provide targets to guide and monitor interventions., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Diffuse intrinsic pontine glioma (DIPG) is the most common and deadliest pediatric brainstem tumor and is difficult to treat with chemotherapy in part due to the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubbles (MBs) have been shown to cause BBB opening, allowing larger chemotherapeutics to enter the parenchyma. Panobinostat is an example of a promising in vitro agent in DIPG with poor clinical efficacy due to low BBB penetrance. In this study, we hypothesized that using FUS to disrupt the BBB allows higher concentrations of panobinostat to accumulate in the tumor, providing a therapeutic effect., Methods: Mice were orthotopically injected with a patient-derived diffuse midline glioma (DMG) cell line, BT245. MRI was used to guide FUS/MB (1.5 MHz, 0.615 MPa peak negative pressure, 1 Hz pulse repetition frequency, 10-ms pulse length, 3 min treatment time)/(25 µL/kg, i.v.) targeting to the tumor location., Results: In animals receiving panobinostat (10 mg/kg, i.p.) in combination with FUS/MB, a 3-fold increase in tumor panobinostat concentration was observed, without significant increase of the drug in the forebrain. In mice receiving 3 weekly treatments, the combination of panobinostat and FUS/MB led to a 71% reduction of tumor volumes ( P = .01). Furthermore, we showed the first survival benefit from FUS/MB improved delivery increasing the mean survival from 21 to 31 days ( P < .0001)., Conclusions: Our study demonstrates that FUS-mediated BBB disruption can increase the delivery of panobinostat to an orthotopic DMG tumor, providing a strong therapeutic effect and increased survival., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Individuals without stable housing experience high rates of mental illness and seek behavioral health care in emergency care settings. Little is known about the effect of homelessness on outpatient follow-up after utilizing emergency or urgent care for behavioral health care. Patient encounters with behavioral health diagnoses among 7 emergency department (ED) or urgent care (UC) locations over 4 years were used to determine the correlation between housing status and outpatient follow-up within 90 days. Of 1,160,386 visits by 269,615 unique patients, 55,738 (23%) encounters included a behavioral health diagnosis. Patients with stable housing were twice as likely to follow up with a primary care provider (PCP) and with an outpatient behavioral health provider than patients without housing (aOR 2.60; aOR 2.00, p < 0.0001). Homelessness is associated with difficulty in accessing follow-up behavioral health care. UCs and EDs may use specific interventions to improve outpatient follow-up., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the United States, science shapes federal health and safety protections, but political officials can and do politicize federal science and science-based safeguards. Many presidential administrations have politicized science, but under the administration of President Trump, these attacks on science-such as buried research, censored scientists, halted data collection-increased in number to unprecedented levels. Underserved communities bore the brunt of the harms. Such attacks disproportionately harm Black, Indigenous, low-income communities, and communities of color, all of whom have long been burdened by pollution exposure and other stressors. We analyze the effects on underserved communities of the Trump administration's anti-science environmental and public health policy actions and offer policy recommendations for current and future administrations. Our goal is to strengthen scientific integrity, prioritize health disparity research, and meaningfully engage affected communities in federal rulemaking., (© 2023. The Author(s).)

Neural markers of pathophysiological processes underlying the dimension of subsyndromal-syndromal-level depression severity can provide objective, biologically informed targets for novel interventions to help prevent the onset of depressive and other affective disorders in individuals with subsyndromal symptoms, and prevent worsening symptom severity in those with these disorders. Greater functional connectivity (FC) among the central executive network (CEN), supporting emotional regulation (ER) subcomponent processes such as working memory (WM), the default mode network (DMN), supporting self-related information processing, and the salience network (SN), is thought to interfere with cognitive functioning and predispose to depressive disorders. We examined in young adults (1) relationships among activity and FC in these networks and current depression severity, using a paradigm designed to examine WM and ER capacity in n = 90, age = 21.7 (2.0); (2) the extent to which these relationships were specific to depression versus mania/hypomania; (3) whether findings in a first, "discovery" sample could be replicated in a second, independent, "test" sample of young adults n = 96, age = 21.6 (2.1); and (4) whether such relationships also predicted depression at up to 12 months post scan and/or mania/hypomania severity in (n = 61, including participants from both samples, age = 21.6 (2.1)). We also examined the extent to which there were common depression- and anxiety-related findings, given that depression and anxiety are highly comorbid. In the discovery sample, current depression severity was robustly predicted by greater activity and greater positive functional connectivity among the CEN, DMN, and SN during working memory and emotional regulation tasks (all ps < 0.05 qFDR). These findings were specific to depression, replicated in the independent sample, and predicted future depression severity. Similar neural marker-anxiety relationships were shown, with robust DMN-SN FC relationships. These data help provide objective, neural marker targets to better guide and monitor early interventions in young adults at risk for, or those with established, depressive and other affective disorders., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Significance: The Lanthony D15 has been reported to have poorer repeatability than the Farnsworth D15. This study found that two trials of the test provide high short-term repeatability and can be administered this way for occupational testing., Purpose: This study aimed to determine the short-term repeatability of the Lanthony D15 in patients with color vision deficiency. Repeated trials were used to examine if learning effects occur and to determine how many trials would be necessary to ensure the highest short-term repeatability for occupational testing., Methods: Twenty male subjects (mean [standard deviation] age, 27.2 [4.3] years) with congenital color vision deficiency, ranging from mild to severe, participated in this single-visit study. Visual acuity, color vision book screening, Farnsworth D15, and anomaloscope testing were performed for classification purposes. Ten trials of the Lanthony D15 were performed. Color confusion index scores from each trial were determined, and a repeated-measures analysis of variance was used to compare the scores across trials. Orthogonal polynomial analysis was performed to detect any trends across trials through the third order. The intraclass correlation coefficient was calculated., Results: No differences in color confusion index (mean [standard error of the mean], 3.57 [0.04]) were found across the 10 trials ( P = .18). Legendre polynomials showed no statistical significance (all P > .39). The intraclass correlation coefficient was 0.81 (95% confidence interval, 0.70 to 0.90). Based on the method of Shrout and Fleiss, intraclass correlation coefficients of 0.7, 0.8, and 0.9 could be achieved with an average of one, two, and four trials of the test, respectively. However, empirically, 0.9 was not achievable., Conclusions: The Lanthony D15 test has fairly high short-term repeatability. Thus, although more trials would likely improve clinical certainty, the mean result of two trials appears sufficient for occupational testing., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2023 American Academy of Optometry.)

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas.

Yellowhorn tea (YT) is traditionally used as a lipid-lowering beverage in Mongolian minorities. However, the pharmacological effects of YT extract and its specific metabolic changes in hyperlipidemia models are not fully understood. The aim of this study was to identify biomarkers using untargeted metabolomics techniques and to investigate the mechanisms underlying the changes in metabolic pathways associated with lipid lowering, anti-inflammation and anti-oxidant in hyperlipidemic mice. A high-fat diet (HFD)-induced hyperlipidemic mouse model was established. YT extract was administered as oral gavage at 0.15, 0.3, and 0.6 g/kg doses for 10 weeks. HFD-induced hyperlipidemia and the therapeutic effect of YT extract were evaluated based on histopathology and by assessing blood lipid levels. Liver inflammatory factors and oxidative stress indices were determined using enzyme-linked immunosorbent assays. Liver metabolites were evaluated using untargeted metabolomics. Biochemical and histological examinations showed that YT extract significantly reduced body-weight gain ( p < 0.01) and fat deposition in tissues. YT extract significantly reduced the levels of serum and liver triglyceride and total cholesterol; inflammatory factors [interleukin (IL)-6, IL-1β, and tumor necrosis factor-α]; malondialdehyde; and leptin ( p < 0.05) in hyperlipidemic mice. YT extract also significantly increased the levels of oxidative stress indicators (superoxide dismutase, catalase, and glutathione peroxidase) and adiponectin. Metabolomics studies revealed several endogenous molecules were altered by the high-fat diet and recovery following intervention with YT extract. The metabolites that were significantly different in the liver after YT intake included citicoline, acetylcholine, pyridoxine, and NAD. Pathway analysis indicated that YT extract ameliorated HFD-induced hyperlipidemia in mice via three major metabolic pathways, namely, glycerophospholipid metabolism, vitamin B6 metabolism, and nicotinate and nicotinamide metabolism. This study demonstrates YT extract has profound effects on the alleviation of HFD-induced hyperlipidemia, inflammation and oxidative stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ta, A., E., Qi, Mu, Feng, Ba, Li, Zhang, Bai and Fu.)

Notwithstanding mass vaccination against specific SARS-CoV-2 variants, there is still a demand for complementary nutritional intervention strategies to fight COVID-19. The bovine milk protein lactoferrin (LF) has attracted interest of nutraceutical, food and dairy industries for its numerous properties-ranging from anti-viral and anti-microbial to immunological-making it a potential functional ingredient in a wide variety of food applications to maintain health. Importantly, bovine LF was found to exert anti-viral activities against several types of viruses, including certain SARS-CoV-2 variants. LF's potential effect on COVID-19 patients has seen a rapid increase of in vitro and in vivo studies published, resulting in a model on how LF might play a role during different phases of SARS-CoV-2 infection. Aim of this narrative review is two-fold: (1) to highlight the most relevant findings concerning LF's anti-viral, anti-microbial, iron-binding, immunomodulatory, microbiota-modulatory and intestinal barrier properties that support health of the two most affected organs in COVID-19 patients (lungs and gut), and (2) to explore the possible underlying mechanisms governing its mode of action. Thanks to its potential effects on health, bovine LF can be considered a good candidate for nutritional interventions counteracting SARS-CoV-2 infection and related COVID-19 pathogenesis.

With the arrival of biologics and the shift toward treat-to-target therapy, the possibility of a sustained clinical response has become an achievable goal for many patients with rheumatoid arthritis (RA). Although biologics have revolutionized the treatment of RA, they are costly, potentially inconvenient, and carry risks of side effects. Whether they can or should be tapered in patients with tight disease control is a matter of clinical uncertainty. The major international rheumatology professional societies have all issued guidelines on this question, but across recommendations, consensus is lacking on how and when to consider therapy de-escalation. Recent evidence suggests that sustained remission or low disease activity is more attainable with dose reduction as opposed to outright discontinuation of biologic therapy, and certain predictors of successful taper have begun to be described. This article will (1) summarize the current evidence base for biologic tapering in RA, (2) outline real-world outcomes findings, (3) review important contextual factors relevant to therapy de-escalation, such as cost-effectiveness considerations and patient perspectives, and (4) conclude by summarizing current guidelines., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Understanding neurobiological characteristics of cognitive dysfunction in distinct psychiatric disorders remains challenging. In this secondary data analysis, we examined neurobiological differences in brain response during working memory updating among individuals with bipolar disorder (BD), those with unipolar depression (UD), and healthy controls (HC). Individuals between 18-45 years of age with BD (n = 100), UD (n = 109), and HC (n = 172) were scanned using fMRI while performing 0-back (easy) and 2-back (difficult) tasks with letters as the stimuli and happy, fearful, or neutral faces as distractors. The 2(n-back) × 3(groups) × 3(distractors) ANCOVA examined reaction time (RT), accuracy, and brain activation during the task. HC showed more accurate and faster responses than individuals with BD and UD. Difficulty-related activation in the prefrontal, posterior parietal, paracingulate cortices, striatal, lateral occipital, precuneus, and thalamic regions differed among groups. Individuals with BD showed significantly lower difficulty-related activation differences in the left lateral occipital and the right paracingulate cortices than those with UD. In individuals with BD, greater difficulty-related worsening in accuracy was associated with smaller activity changes in the right precuneus, while greater difficulty-related slowing in RT was associated with smaller activity changes in the prefrontal, frontal opercular, paracingulate, posterior parietal, and lateral occipital cortices. Measures of current depression and mania did not correlate with the difficulty-related brain activation differences in either group. Our findings suggest that the alterations in the working memory circuitry may be a trait characteristic of reduced working memory capacity in mood disorders. Aberrant patterns of activation in the left lateral occipital and paracingulate cortices may be specific to BD., (© 2022. The Author(s).)

Introduction: Unihemispheric head gunshot wound (HGSW) are associated with improved survival; however, specific clinical and radiographic characteristics associated with survival have not been clearly defined. To further guide prognosis estimates and care discussions, this study aims to identify unihemispheric HGSWs injury patterns; comparing them to bihemispheric HGSWs characterizing factors associated with improved clinical outcomes and survival., Methods: Patients presenting to our Level 1 trauma center from January 2013 through May 2019 with HGSW injury were reviewed. Patients were grouped into those with unihemispheric versus bihemispheric HGSWs and survivors versus non-survivors. Clinical variables and head computed tomography (CT) features were compared using comparative statistics., Results: 62 HGSW patients met study criteria (unihemispheric = 33, bihemispheric = 29). Regardless of injury type, avoidance of injury to multiple lobes, temporal, parietal and basal ganglia brain regions and intracranial vascular injury were also associated with survival (p < 0.05). Lower admission GCS score and lower motor GCS score was associated with reduced survival in unihemispheric HGSW injury (p < 0.05). Unihemispheric HGSW survivors demonstrated improved clinical outcomes, with reduced hospital length of stay (5 days vs. 47 days, p = 0.014) and intensive care unit length of stay (3 days vs. 20 days, p = 0.021) and more favorable disposition location., Conclusion: We found presenting clinical features and CT imaging patterns previously associated with improved survival in HGSW patients is similar in unihemispheric specific injuries. Importantly, a more favorable admission GCS score may portend survivability in unihemsipheric HGSW. Furthermore, unihemispheric HGSW survivors may have improved clinical outcomes, length of stay and disposition location., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: The goal of this review is to outline the main considerations when treating transgender patients with epilepsy. Points to be addressed include the gender affirming hormone therapy regimens and how they interact with anti-seizure medications and seizure control, as well as common co-morbidities in the transgender epilepsy population., Recent Findings: Gender affirming hormone therapy (GAHT) may affect seizure control directly, due to proconvulsant or anticonvulsant properties. GAHT may interact with anti-seizure medications; most notably, estrogen will decrease serum concentration of lamotrigine. Enzyme-inducing anti-seizure medications may decrease hormone levels, potentially interfering with goals of GAHT. Transgender epilepsy patients are at risk for co-morbidities such as decreased bone mineral density and depression. There are minimal direct studies on treatment or outcomes in the transgender epilepsy population. Providers must be knowledgeable about the bi-directional interactions between gender affirming hormone therapy and anti-seizure medications, as well as direct hormonal influences on seizure control. Future research should directly evaluate outcomes in transgender epilepsy patients with regard to seizure control, success of hormone therapy, and management of co-morbidities, to further educate providers and patients how to best manage their healthcare., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Corydalis bungeana (CB) is a well-used medicinal herb in Mongolian folk medicine and has been traditionally applied as an antiobesity agent. However, the evidence-based pharmacological effects of CB and its specific metabolic alterations in the obese model are not entirely understood. This study aimed to utilize untargeted metabolomic techniques to identify biomarkers and gain mechanistic insight into the serum metabolite alterations associated with weight loss and lipid metabolism in obese rats., Methods: A high-fat high-sugar (HFHS) diet was used to induce obese models in rats. CB extract was orally gavaged at 0.18, 0.9 and 1.8 g/kg doses for six weeks, and feed intake, body weight, fat pad weight, and blood indexes were measured. Blood serum metabolites were evaluated by gas chromatography/quadrupole time-of-flight tandem mass spectrometry (GC-TOF/MS)., Results: The results showed that compared with the obese group, the administration of CB extract caused significant decreases in body weight ( P  < 0.05), feed intake, Lee's index, and perirenal, mesenteric, epididymal fat weight. CB extract also reduced blood triglyceride and total cholesterol levels ( P  < 0.05) of obese rats. Metabolomic findings showed that nine differential metabolites, including pyruvic acid, D -glucuronic acid, malic acid, dimethylglycine, oxoglutaric acid, pantothenic acid, sorbitol acid, fumaric acid and glucose 6-phosphate were identified under CB treatment and altered metabolic pathways such as TCA cycle, pantothenate and CoA biosynthesis, and glycolysis/gluconeogenesis., Conclusion: This study demonstrated weight loss and lipid lowering effects of CB on HFHS diet-induced obese rats and identified nine metabolites as potential biomarkers for evaluating the favorable therapeutic mechanism of CB via regulation of lipid and glucose metabolism., Competing Interests: 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., (© 2022 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Diffusion Magnetic Resonance Imaging (dMRI) studies have reported abnormalities in emotion regulation circuits in BD; however, no study has examined the contribution of previous illness on these mechanisms. Using global probabilistic tractography, we aimed to identify neural correlates of previous BD illness and the extent to which these can help predict one-year recurrence of depressive episodes. dMRI data were collected in 70 adults with early-onset BD who were clinically followed for up to 18 years and 39 healthy controls. Higher number of depressive episodes during childhood/adolescence and higher percentage of time with syndromic depression during longitudinal follow-up was associated with lower fractional anisotropy (FA) in focal regions of the forceps minor (left, F = 4.4, p = 0.003; right, F = 3.1, p = 0.021) and anterior cingulum bundle (left, F = 4.7, p = 0.002; right, F = 7.0, p < 0.001). Lower FA in these regions was also associated with higher depressive and anxiety symptoms at scan. Remarkably, those having higher FA in the right cluster of the forceps minor (AOR = 0.43, p = 0.017) and in a cluster of the posterior cingulum bundle (right, AOR = 0.50, p = 0.032) were protected against the recurrence of depressive episodes. Previous depressive symptomatology may cause neurodegenerative effects in the forceps minor that are associated with worsening of BD symptomatology in subsequent years. Abnormalities in the posterior cingulum may also play a role.

Background: Identifying neural predictors of worsening subthreshold hypomania severity can help identify risk of progression to BD. While diffusion Magnetic Resonance Imaging (dMRI) studies reported white matter microstructural abnormalities in tracts supporting emotional regulation in individuals with BD, it remains unknown whether similar patterns of white matter microstructure predict worsening of subthreshold hypomania severity in non-BD individuals., Methods: dMRI data were collected in: 81 non-BD individuals recruited across a range of subthreshold depression and hypomania, and followed for six months; and independent samples of 75 BD and 58 healthy individuals. All individuals were assessed using standardized diagnostic assessments, mood and anxiety symptom rating scales. Global probabilistic tractography and a tract-profile approach examined fractional anisotropy (FA), a measure of fiber collinearity, in tracts supporting emotional regulation shown to have abnormalities in BD: forceps minor (FMIN), anterior thalamic radiation (ATR), cingulum bundle (CB), and uncinate fasciculus (UF)., Results: Lower FA in left CB (middle, β = -0.22, P = 0.022; posterior, β = -0.32, P < 0.001), right CB (anterior, β = -0.30, P = 0.003; posterior, β = -0.27, P = 0.005), and right UF (frontal, β = -0.29, P = 0.002; temporal, β = -0.40, P < 0.001) predicted worsening of subthreshold hypomania severity in non-BD individuals. BD versus healthy individuals showed lower FA in several of these segments: middle left CB (F = 8.7, P = 0.004), anterior right CB (F = 9.8, P = 0.002), and frontal right UF (F = 7.0, P = 0.009). Non-BD individuals with worsening 6-month hypomania had lower FA in these three segments versus HC and non-BD individuals without worsening hypomania, but similar FA to BD individuals., Limitations: Relatively short follow-up., Conclusions: White matter predictors of worsening subthreshold hypomania in non-BD individuals parallel abnormalities in BD individuals, and can guide early risk identification and interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ixeris chinensis (Thunb.) Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1β, IL-6, and TNF-α. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites.

Soil lead (Pb) contamination is a recognized environmental and global health problem. Phytoextraction of Pb using switchgrass ( Panicum virgatum L.), a second-generation biofuel crop, is typically enhanced by soil chelation. The effectiveness of four different chelating agents, phytic acid (inositol hexaphosphate), citric acid, NTA (nitrilotriacetic acid), and EDTA (ethylenediaminetetraacetic acid) was examined in pot culture. Plants treated with EDTA (1 mM) showed significantly higher shoot Pb concentrations compared to control plants and plants treated with other chelates. Lead-solubility following phytoextraction was examined by soil washing using 0.01 and 0.05 M acetic acid as an extractant solution revealed no significant differences in Pb concentrations in soil among different chelate treatments and control. Furthermore, the effects of different concentrations (1, 2, 5 and 10 mM) of NTA on Pb phytoextraction of switchgrass were examined. Plants receiving 5 mM and 10 mM NTA had significantly higher foliage concentrations of Pb compared to plants treated with lower levels (1 and 2 mM) of NTA. Moreover, the effect of NTA application alone was significantly improved by a combined application of Triton X-100, an alkyl polyglucoside (APG); the Pb concentration in the foliage of switchgrass was more than doubled when treated with NTA combined with APG. The use of NTA combined with APG has great potential in improving phytoextraction efficiencies of switchgrass on Pb-contaminated soils.

Biological soil crusts (BSC) are important contributors to nutrient cycling in arid environments such as the Sonoran Desert. BSC at an urban (University Indian Ruins) and at a non-urban site (Santa Rita Experimental Range) were compared to determine if their structure or function was influenced by proximity to an urban environment. The Step Point method was used in the field to determine ground cover; which was found to be similar between sites. However, the spatial distribution of the BSCs was significantly different, such that more BSCs were found under plants at the non-urban site (P < 0.05). Relative gross photosynthesis was measured in the lab by addition of a watering event. Gross photosynthesis was found to be higher in the non-urban BSCs (P < 0.001), indicating lowered productivity in urban BSCs due to effects caused by proximity to urban environments. This study provides evidence that BSCs at urbanized sites are affected functionally, and therefore may be contributing differently to carbon and nitrogen cycling in these ecosystems., (© 2022. The Author(s).)

Competing Interests: Competing interests: None declared.

Background: Guidelines for penetrating occult pneumothoraces (OPTXs) are based on blunt injury. Further understanding of penetrating OPTX pathophysiology is needed. In observational management of penetrating OPTX, we hypothesized that specific clinical and radiographic features may be associated with interval tube thoracostomy (TT) placement. Our aims were to (1) describe OPTX occurrence in penetrating chest injury, (2) determine the rate of interval TT placement in observational management and clinical outcomes compared with immediate TT placement, and (3) describe risk factors associated with failure of observational management., Methods: Penetrating OPTX patients presenting to our level 1 trauma center from 2004 to 2019 were reviewed. Occult pneumothorax was defined as a pneumothorax on chest computed tomography but not on chest radiograph. Patient groups included immediate TT placement versus observation. Clinical outcomes compared were TT duration and complications, need for additional thoracic procedures, length of stay (LOS), and disposition. Clinical and radiographic factors associated with interval TT placement were determined by multivariable regression., Results: Of 629 penetrating pneumothorax patients, 103 (16%) presented with OPTX. Thirty-eight patients underwent immediate TT placement, and 65 were observed. Twelve observed patients (18%) needed interval TT placement. Regardless of initial management strategy, TT placement was associated with longer LOS and more chest radiographs. Chest injury complications and outcomes were similar. Factors associated with increased odds of interval TT placement included Chest Abbreviated Injury Scale score of ≥4 (adjusted odds ratio [aOR], 7.38 [95% confidence interval, 1.43-37.95), positive pressure ventilation (aOR, 7.74 [1.07-56.06]), concurrent hemothorax (aOR, 6.17 [1.08-35.24]), and retained bullet fragment (aOR, 11.62 [1.40-96.62]) (all p < 0.05)., Conclusion: The majority of patients with penetrating OPTX can be successfully observed with improved clinical outcomes (LOS, avoidance of TT complications, reduced radiation). Interval TT intervention was not associated with risk for adverse outcomes. In patients undergoing observation, specific clinical factors (chest injury severity, ventilation) and imaging features (hemothorax, retained bullet) are associated with increased odds for interval TT placement, suggesting need for heightened awareness in these patients., Level of Evidence: Prognostic, level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

For decades, corporate undermining of scientific consensus has eroded the scientific process worldwide. Guardrails for protecting science-informed processes, from peer review to regulatory decision making, have suffered sustained attacks, damaging public trust in the scientific enterprise and its aim to serve the public good. Government efforts to address corporate attacks have been inadequate. Researchers have cataloged corporate malfeasance that harms people's health across diverse industries. Well-known cases, like the tobacco industry's efforts to downplay the dangers of smoking, are representative of transnational industries, rather than unique. This contribution schematizes industry tactics to distort, delay, or distract the public from instituting measures that improve health-tactics that comprise the "disinformation playbook." Using a United States policy lens, we outline steps the scientific community should take to shield science from corporate interference, through individual actions (by scientists, peer reviewers, and editors) and collective initiatives (by research institutions, grant organizations, professional associations, and regulatory agencies)., (© 2021. The Author(s).)

Young adults are at high risk for suicide, yet there is limited ability to predict suicidal thoughts and behaviors. Machine learning approaches are better able to examine a large number of variables simultaneously to identify combinations of factors associated with suicidal thoughts and behaviors. The current study used LASSO regression to investigate extent to which a number of demographic, psychiatric, behavioral, and functional neuroimaging variables are associated with suicidal thoughts and behaviors during young adulthood. 78 treatment seeking young adults (ages 18-25) completed demographic, psychiatric, behavioral, and suicidality measures. Participants also completed an implicit emotion regulation functional neuroimaging paradigm. Report of recent suicidal thoughts and behaviors served as the dependent variable. Five variables were identified by the LASSO regression: Two were demographic variables (age and level of education), two were psychiatric variables (depression and general psychiatric distress), and one was a neuroimaging variable (left amygdala activity during sad faces). Amygdala function was significantly associated with suicidal thoughts and behaviors above and beyond the other factors. Findings inform the study of suicidal thoughts and behaviors among treatment seeking young adults, and also highlight the importance of investigating neurobiological markers., (Copyright © 2021. Published by Elsevier B.V.)

Background and Objectives: Transversus abdominis plane (TAP) blocks are associated with an improvement in postoperative analgesia following kidney transplant surgery. However, these blocks carry inherent risk and require a degree of expertise to perform successfully. Continuous intravenous lidocaine may be an effective alternative. In this randomized, non-inferiority study, we hypothesized that a continuous lidocaine infusion provides similar postoperative analgesia to a TAP block., Methods: Subjects presenting for kidney transplant surgery were randomized in a 1:1 ratio to either an ultrasound-guided unilateral, single-injection TAP block (TAP group) or a continuous infusion of lidocaine (Lido group). The primary outcome of this non-inferiority study was opioid consumption within the first 24 hours following surgery. Secondary outcomes included pain scores, patient satisfaction, opioid-related adverse events, time to regular diet, and persistent opioid use., Results: One hundred and twenty subjects, 59 from the TAP group and 61 from the Lido group, completed the study per protocol. Analysis of the primary outcome showed a cumulative geometric mean intravenous morphine equivalent difference between the TAP (14.6±3.2 mg) and Lido (15.9±2.4 mg) groups of 1.27 mg (95% CI -4.25 to 6.79; p<0.001), demonstrating non-inferiority of the continuous lidocaine infusion. No secondary outcomes showed clinically meaningful differences between groups., Conclusions: This study demonstrates that a continuous infusion of lidocaine offers non-inferior postoperative analgesia compared with an ultrasound-guided unilateral, single-injection TAP block in the first 24 hours following kidney transplant surgery., Trial Registration Number: NCT03843879., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In trauma, direct pulmonary injury and innate immune response activation primes the lungs for acute respiratory distress syndrome (ARDS). The inflammasome-dependent release of interleukin-18 (IL-18) was recently identified as a key mediator in ARDS pathogenesis, leading us to hypothesize that plasma IL-18 is a diagnostic predictor of ARDS in severe blunt trauma. Patients and Methods: Secondary analysis of the Inflammation and Host Response to Injury database was performed on plasma cytokines collected within 12 hours of severe blunt trauma. Trauma-related cytokines, including IL-18, were compared between patients with and without ARDS and were evaluated for association with ARDS using regression analysis. Threshold cytokine concentrations predictive of ARDS were determined using receiver-operating curve (ROC) analysis. Results: Cytokine analysis of patients without ARDS patients (n = 61) compared with patients with ARDS (n = 19) demonstrated elevated plasma IL-18 concentration in ARDS and IL-18 remained correlated with ARDS on logistic regression after confounder adjustment (p = 0.008). Additionally, ROC analysis revealed IL-18 as a strong ARDS predictor (area under the curve [AUC] = 0.83), with a threshold IL-18 value of 170 pg/mL (Youden index, 0.3). Unlike in patients without ARDS, elevated IL-18 persisted in patients with ARDS during the acute injury phase (p ≤ 0.02). Other trauma-related cytokines did not correlate with ARDS. Conclusions: In severe blunt trauma, IL-18 is a robust predictor of ARDS and remains elevated throughout the acute injury phase. These findings support the use of IL-18 as a key ARDS biomarker, promoting early identification of trauma patients at greater risk of developing ARDS. Timely recognition of ARDS and implementation of advantageous supportive care practices may reduce trauma-related ARDS morbidity and costs.

Bipolar disorder (BD) is highly heritable. Identifying objective biomarkers reflecting pathophysiological processes predisposing to, versus protecting against BD, can help identify BD risk in offspring of BD parents. We recruited 21 BD participants with a first-degree relative with BD, 25 offspring of BD parents, 27 offspring of comparison parents with non-BD psychiatric disorders, and 32 healthy offspring of healthy parents. In at-risk groups, 23 had non-BD diagnoses and 29, no Axis-I diagnoses(healthy). Five at-risk offspring who developed BD post scan(Converters) were included. Diffusion imaging(dMRI) analysis with tract segmentation identified between-group differences in the microstructure of prefrontal tracts supporting emotional regulation relevant to BD: forceps minor, anterior thalamic radiation(ATR), cingulum bundle(CB), and uncinate fasciculus(UF). BD participants showed lower fractional anisotropy (FA) in the right CB (anterior portion) than other groups (q < 0.05); and in bilateral ATR (posterior portion) versus at-risk groups (q < 0.001). Healthy, but not non-BD, at-risk participants showed significantly higher FA in bilateral ATR clusters than healthy controls (qs < 0.05). At-risk groups showed higher FA in these clusters than BD participants (qs < 0.05). Non-BD versus healthy at-risk participants, and Converters versus offspring of BD parents, showed lower FA in the right ATR cluster (qs < 0.05). Low anterior right CB FA in BD participants versus other groups might result from having BD. High bilateral ATR FA in at-risk groups, and in healthy at-risk participants, versus healthy controls might protect against BD/other psychiatric disorders. Absence of elevated right ATR FA in non-BD versus healthy at-risk participants, and in Converters versus non-converter offspring of BD parents, might lower protection against BD in at-risk groups., (© 2021. The Author(s).)

Background: Patients 65 years old or older with early endocrine-responsive breast cancer have many treatment options, including no radiation. This study aimed to evaluate treatment preference when intraoperative radiation therapy (IORT) is offered in this population., Methods: The study reviewed patients 65 years old or older with a diagnosis of early-stage endocrine-responsive breast cancer in 2016-2019 at a single hospital in a large integrated health care system. Electronic medical records of multidisciplinary breast tumor board discussion, treatment options documented by the treatment team, and final treatment offered were reviewed. Variables including age at biopsy, language, endocrine treatment, and comorbidities were collected. Regression analysis was used to evaluate for variables associated with patients' choice regarding radiation treatment., Results: The institutional IORT guidelines were met by 63 patients in the described age group who had a documented offer of all radiation treatment options. The median age of the patients was 70 years (interquartile range 63-77 years). Overall, 74.6% of the patients chose IORT, and 14.3% opted for whole-breast irradiation. Only 4.8% chose to omit radiation after breast-conserving surgery, and 6.3% chose mastectomy. The patients who chose IORT were more likely to receive endocrine treatment (odds ratio 3.70; p = 0.03). Age, race, language, and comorbidities were not associated with preference for IORT (p < 0.05)., Conclusions: Patients 65 years old or older with early-stage endocrine-responsive breast cancer preferred to have IORT despite counsel about the lack of survival benefit. This study suggests that local cancer control with the convenient radiation delivery method is important to the described patient population., (© 2021. Society of Surgical Oncology.)

Background: Sensation Seeking, the proclivity toward novel and stimulating experiences, is associated with greater left ventrolateral prefrontal cortex (vlPFC) activity during uncertain reward expectancy. Here, we examined relationships between sensation seeking and vlPFC oscillatory dynamics using electroencephalography (EEG)., Methods: In 26 adolescents/young adults (16 female; 22.3 ± 1.7yrs), EEG was measured during uncertain reward expectancy. Event-related spectral perturbations (ERSP) from 15-80 Hz (beta/gamma bands) were compared as a function of uncertain reward expected value and assessed for relationships with feedback-related negativity (FRN) response to outcome feedback and response tendency measures of risk for BD., Results: Event-related synchronization (ERS) between 15-25 Hz (beta) over left vlPFC was sensitive to the expected value of uncertain reward (rho=0.46; p = 0.048), and correlated with sensation seeking (r = 0.49, p < 0.01) and feedback-related negativity (FRN), where greater beta ERS was related to larger FRN (r = -0.39, p = 0.047). FRN was also related to behavioral inhibition (r = 0.49, p < 0.01)., Limitations: It is unknown whether results may extrapolate to clinical populations, given the healthy sample used here. Further, although we have confidence that the beta-band signal we measure in this study arises from left prefrontal cortex, we largely infer a left vlPFC source., Conclusions: These findings highlight the role of left vlPFC in evaluation of immediate rewards. We now provide a link between reward expectancy-related left vlPFC activity and the well-characterized FRN, with a known role in attentive processing. These findings can guide treatment development for mania/hypomania at-risk individuals, including transcranial alternating current stimulation., (Copyright © 2021. Published by Elsevier B.V.)

Background: Dysregulation of the inflammatory and immune response to injury may increase susceptibility to secondary infections after trauma. It is unknown whether cytokines involved in this response could function as plasma biomarkers for surgical site infection (SSI). We hypothesized that the early cytokine response differs between patients who develop SSI and those who do not and that critical cytokine threshold values could be used to predict risk of SSI. Patients and Methods: Using the Glue Grant database, we performed an analysis of severely injured blunt trauma patients who underwent a major procedure and had available cytokine data. Patients were divided into SSI and no SSI groups. Receiver operating curve analysis was used to determine acceptable early cytokine predictors of SSI and critical threshold values. Multivariable regression analysis was then performed to determine the odds of developing SSI using threshold values, adjusting for key patient or injury factors. Cytokine levels were compared between SSI and no SSI groups at three time points. Results: The study cohort consisted of 70 patients and 11 patients developed SSI. Monocyte chemoattractant protein-1 (MCP-1) was the only acceptable early predictor of SSI with an area under the curve (AUC) of 0.71 (p = 0.03) and a critical threshold value of 490 pg/mL. Monocyte chemoattractant protein-1 levels above this threshold within 24 hours of injury were associated with SSI (adjusted odds ratio [AOR] 8.1; p = 0.01). Monocyte chemoattractant protein-1 levels within 24 hours of injury were higher in those who developed SSI (994 vs. 259 pg/mL; p < 0.01) and remained higher in the SSI group at 33 hours from injury (338 vs. 144 pg/mL; p = 0.01), but were similar by 106 hours (155 vs. 97 pg/mL; p = 0.19). Conclusion: Among cytokines involved in the early response to trauma, only early elevation of MCP-1 predicted SSI after blunt trauma. Monocyte chemoattractant protein-1 may act as a specific and early marker for SSI after blunt trauma, allowing for preventative measures to mitigate risks.

Impulsivity (rash action with deleterious outcomes) is common to many psychiatric disorders. While some studies indicate altered amygdala and prefrontal cortical (PFC) activity associated with impulsivity, it remains unclear whether these patterns of neural activity are specific to impulsivity or common to a range of affective and anxiety symptoms. To elucidate neural markers specific to impulsivity, we aimed to differentiate patterns of amygdala-PFC activity and functional connectivity associated with impulsivity from those associated with affective and anxiety symptoms, and identify measures of this circuitry predicting future worsening of impulsivity. Using a face emotion processing task that reliably activates amygdala-PFC circuitry, neural activity and connectivity were assessed in a transdiagnostically-recruited sample of young adults, including healthy (N = 47) and treatment-seeking individuals (N = 67). Relationships were examined between neural measures and impulsivity, anhedonia, and affective and anxiety symptoms at baseline (N = 114), and at 6 months post scan (N = 30). Impulsivity, particularly negative urgency and lack of perseverance, was related to greater amygdala activity (beta = 0.82, p = 0.003; beta = 0.68, p = 0.004; respectively) and lower amygdala-medial PFC functional connectivity (voxels = 60, t peak  = 4.45, p FWE  = 0.017; voxels = 335, t peak  = 5.26, p FWE  = 0.001; respectively) to facial fear. Left vlPFC, but not amygdala, activity to facial anger was inversely associated with mania/hypomania (beta = -2.08, p = 0.018). Impulsivity 6 months later was predicted by amygdala activity to facial sadness (beta = 0.50, p = 0.017). There were no other significant relationships between neural activity and 6-month anhedonia, affective, and anxiety symptoms. Our findings are the first to associate amygdala-PFC activity and functional connectivity with impulsivity in a large, transdiagnostic sample, providing neural targets for future interventions to reduce predisposition to impulsivity and related future mental health problems in young adults., (© 2021. The Author(s).)

In October 2019, public health surveillance systems in Scotland identified an increase in the number of reported infections of Shiga toxin-producing Escherichia coli (STEC) O26:H11 involving bloody diarrhoea. Ultimately, across the United Kingdom (UK) 32 cases of STEC O26:H11 stx1a were identified, with the median age of 27 years and 64% were male; six cases were hospitalised. Among food exposures there was an association with consuming pre-packed sandwiches purchased at outlets belonging to a national food chain franchise (food outlet A) [odds ratio (OR) = 183.89, P < 0.001]. The common ingredient identified as a component of the majority of the sandwiches sold at food outlet A was a mixed salad of Apollo and Iceberg lettuce and spinach leaves. Microbiological testing of food and environmental samples were negative for STEC O26:H11, although STEC O36:H19 was isolated from a mixed salad sample taken from premises owned by food outlet A. Contamination of fresh produce is often due to a transient event and detection of the aetiological agent in food that has a short-shelf life is challenging. Robust, statistically significant epidemiological analysis should be sufficient evidence to direct timely and targeted on-farm investigations. A shift in focus from testing the microbiological quality of the produce to investigating the processes and practices through the supply chain and sampling the farm environment is recommended.

Purpose: To determine the positive predictive value (PPV) of magnetic resonance imaging (MRI)-guided breast biopsy stratified by body mass index (BMI). Secondary endpoints include evaluation of indications for breast MRI and identification of factors associated with malignant biopsy., Methods: We retrospectively analyzed results of MRI-guided breast biopsies in a consecutive cohort of women at a single institution between 2014 and 2019. The PPV was compared between BMI subgroups and the overall group by the one-sample z-test. Factors associated with malignant biopsy were analyzed using multivariate regression analysis., Results: Among 427 MRI-guided breast biopsies, the PPV was significantly higher in patients with a BMI ≥ 35 compared to BMI < 35 (38.6% versus 24.5%, p = 0.043). This remained true in the 180 biopsies from high-risk screening studies, but there was no difference in PPV by BMI in the 205 biopsies performed to evaluate extent of known disease. Among this cohort who underwent MRI-guided breast biopsy, the underlying indication for MRI was less likely to be high-risk screening in those with a higher BMI or Black or Hispanic race (p = 0.015 and p < 0.001, respectively). For high-risk screening studies, only BMI ≥ 35 was associated with malignant biopsies (OR 37.5, p = 0.003). For evaluation of extent of disease studies, only increased lesion size was a significant predictor of malignant result (OR 1.01, p = 0.04)., Conclusions: Among women who underwent MRI-guided breast biopsy, elevated BMI was associated with increased PPV and malignant biopsies. Patients with a higher BMI or Black or Hispanic race who had MRI-guided biopsy were less likely to be undergoing high-risk screening and more likely to have breast MRI to evaluate extent of known disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)