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Background: The emergence of new SARS-CoV-2 variants poses a new challenge for the treatment of immunocompromised patients against COVID-19. In this context, high titer COVID-19 Convalescent Plasma (CCP) is one of the few available therapeutics for these patients. We have revisited the selection of CCP samples and its efficacy against Omicron XBB.1.5 variant, dominant strain in 2023., Methods: We have reviewed a surrogate enzyme-linked immunoassay (ELISA) to select CCP samples that will guarantee a protective level of neutralizing antibodies as the main correlate of protection. We analyzed antibody titers in 500 serum samples from a population-based serosurvey at Mount Sinai Hospital collected in early 2023 and validated the results with a set of CCP samples (collected 2020-2023) and confirmed its protection in an immunosuppressed mouse model., Results: By using logistic regression modeling, we have redefined the definition of high titer CCP against the new variant in the post-pandemic era, where over 97% of the population have natural or vaccine-induced antibodies against the first SARS-CoV-2 strains. We next developed a new immunocompromised mouse model to validate the CCP in vivo against emerging variants. Equivalent to the two CCP units recommended for human use, the treatment of immunocompromised mice with two doses (100µL/dose) of CCP plasma via intraperitoneal injection showed a 46-fold reduction in lung viral titers 3-days-post-XBB.1.5-infection., Conclusions: We believe the present results will guide future efforts in the selection of high titer CCP against emerging SARS-CoV-2 variants., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Despite advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC), primary and secondary resistance to current therapies remains. Elevated circulating sphingolipids are associated with poor outcomes in patients with mCRPC, including therapeutic resistance and shorter overall survival. PCPro is a clinically accessible, regulatory compliant plasma lipid biomarker of poor prognosis in mCRPC, which incorporates prognostic sphingolipids. We hypothesize that reversal of the PCPro signature in men with mCRPC by sphingolipid-lowering agents will improve their clinical outcomes. However, the first step is to determine whether this poor prognostic lipid signature can be modulated. A potential sphingolipid-lowering agent is the PCSK9-inhibitor evolocumab, which is used in the management of hypercholesterolemia., Objectives: Our primary objective is to assess whether treatment with evolocumab during standard anticancer therapy can safely modify the PCPro signature in men with mCRPC., Design: This is a multicenter, open label phase II trial., Methods: Men with mCRPC commencing docetaxel, cabazitaxel, abiraterone, enzalutamide, olaparib, or lutetium-177 PSMA for disease progression will be screened for the presence of PCPro. Those who are PCPro positive will receive a 12-week course of evolocumab concurrent with their standard therapy. Dosage is as per cardiovascular guidelines (420 mg subcutaneously every 4 weeks). PCPro will be repeated after 12 weeks. The primary endpoint is reversal of PCPro. The secondary endpoint is the safety of combination therapy with exploratory endpoints characterizing changes in comprehensive lipid profiles pre- and post-treatment., Discussion: This study will evaluate whether evolocumab can safely modify the PCPro signature in men with mCRPC, providing essential data to the development of precision metabolic therapy in the management of prostate cancer., Trial Registration: This study is approved by the Human Research Ethics Committee (X22-0072 and 2022/ETH00427). It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622001003763)., (© The Author(s), 2024.)

Palliative care has evolved from its religious and historical roots to a specialized medical discipline, emphasizing quality of life for patients with serious illnesses. The foundational work of pioneers in palliative care has shaped modern practices in symptom management, emotional support, and holistic care. Despite challenges in integrating palliative care in critical care settings and overcoming barriers such as limited provider availability, enhancing training and broadening the application of palliative principles remain essential. Palliative care is crucial, not just for end-of-life scenarios, but for managing severe illness at any stage, ensuring compassionate, patient-centered care., Competing Interests: Disclosure The authors have no commercial or financial conflicts to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This article examines the pivotal role of critical care nurses in managing pediatric pain, emphasizing the multifaceted nature of care. It covers the challenges and opportunities nurses face, stressing the importance of education and training. The background section underscores the global issue of inadequately managed pediatric pain and the importance of addressing social determinants of health while recognizing perceptions, beliefs, stereotypes, and biases on pain management. A multimodal approach in treatment is detailed in pharmacologic and non-pharmacologic approaches. Barriers nurses encounter are discussed, with recommendations for a holistic and individualized approach to pediatric pain management in critical care settings., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This is the 12th in a series of salary surveys conducted at approximately 3-year intervals for toxicologists that began in 1988. Previous salary surveys were conducted in 1988, 1 1991, 2 1995, 3 1998, 4 2001, 5 2004, 6 2007 (which was posted electronically, but not published), 2012, 7 2016, 8 2020, 9 and 2022. 10 In addition to presenting the 2024 results, herein we are providing additional data and an analysis of the trends for employment and pay in toxicology over the last 37 years., 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.

Objectives: To explore the association between the extent of CT abnormalities by quantitative imaging analysis (QIA) and clinical/physiological disease parameters in patients with antisynthetase syndrome associated interstitial lung disease (ARS-ILD)., Methods: We analysed 20 patients with antisynthetase antibodies and active ILD enrolled in the Abatacept in Myositis-Associated Interstitial Lung Disease study. High-resolution chest CT was obtained at weeks 0, 24 and 48 and QIA scored the extent of ground glass (quantitative score for ground glass), fibrosis (quantitative score for lung fibrosis, QLF) and total ILD (quantitative ILD, QILD). Mixed-effects models estimated longitudinal QIA scores over time. Associations between QIA scores with clinical/physiological parameters were analysed longitudinally using repeated-measures mixed-effects models., Results: Patients were median age 57 years, 55% males and 85% white. Higher (worse) baseline QIA scores correlated with lower baseline forced vital capacity (FVC) and diffusing capacity adjusted for haemoglobin (DLCO). Longitudinal QIA trajectories trended towards improving scores during the trial, and patients on O 2 at baseline had worsening QIA trajectories which were different from patients who were not on O 2 . Longitudinal QIA scores demonstrated strong associations with both FVC and DLCO over time. Higher QILD scores over time were also associated with worse dyspnoea scores, pulmonary visual analogue scale, physician and patient global disease activity, health status in 6/8 domains of the Short Form-36 and higher oxygen requirements. Patients with significant radiographic improvement at 48 weeks had higher baseline QLF, QILD and worse DLCO., Conclusions: Longitudinal QIA scores associate with lung physiology, patient perception of respiratory status, overall disease activity and quality of life over time in ARS-ILD. QIA may allow reproducible monitoring of disease progression and response to therapy over time., Trial Registration Number: NCT03215927., Competing Interests: Competing interests: GK and JG are on the UCLA patent for the quantitative imaging analysis. RA has received research grants from Boehringer Ingelheim, Bristol Myers Squibb, EMD Serono, Janssen, Mallinckrodt, Pfizer and Q32, and serves as a consultant for Actigraph, Alexion, ANI Pharmaceuticals, Argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta Bio, Capella Bioscience, Corbus, CSL Behring, EMD Serono, Galapagos, Horizon Therapeutics, I-Cell, Janssen, Kezar, Kyverna, Merck, Novartis, Nuvig Therapeutics, Octapharma, Pfizer, Regeneron, Roivant, Sanofi, Teva, Artsome, Capstanx and Manta. CC-S has received research grants from Priovant, CSL Behring, Janssen, Octapharma, Pfizer, AbbVie and Bristol Myers Squibb, and serves as a consultant for Boehringer Ingelheim, Recludix, Octapharma, Pfizer, AbbVie and Bristol Myers Squibb. PFD is editor of UpToDate and a member of the FDA Advisory Committee. TJD has received support from Bayer and has been part of a clinical trial funded by Genentech, all unrelated to this study. GMH receives grant support from the NIH including R01 HL111024, R01 HL135142 and R01130974. He has performed consulting work for Boehringer Ingelheim and the Gerson Lehrman Group., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: Familial hypercholesterolemia is a treatable genetic disorder of cholesterol metabolism. Genetic testing is the most specific method for diagnosing familial hypercholesterolemia, but it remains underutilized. Implementation science aims to bridge the gap between evidence and practice and, thereby, support improved familial hypercholesterolemia care. This review presents the current evidence on the use of implementation science to improve the use of genetic testing for familial hypercholesterolemia., Recent Findings: Recent research has focused on developing implementation strategies to improve the use of genetic testing, particularly cascade testing of at-risk blood relatives of known familial hypercholesterolemia cases. Stakeholder informed strategies aimed at improving communication between families and detection of familial hypercholesterolemia in primary care have been developed and implemented. Findings demonstrate implementation science methods can help remove barriers and improve the uptake of cascade genetic testing., Summary: Significant gaps in familial hypercholesterolemia care emphasize the importance of practical and realistic approaches to improve the detection of this preventable cause of premature heart disease, and recent efforts using implementation science have shown some promising results. More implementation science studies are needed that address the considerable gaps in familial hypercholesterolemia care, including the underutilization of genetic testing, so that all individuals receive the best clinical care., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While deep brain stimulation (DBS) targeting the ventral intermediate nucleus (VIM) of thalamus or posterior subthalamic area (PSA) can suppress forms of action tremor in people with Essential Tremor, previous studies have suggested postural tremor may respond more robustly than kinetic tremor to DBS., Objectives: In this study, we aimed to more precisely quantify the (1) onset/offset dynamics and (2) steady-state effects of VIM/PSA-DBS on postural and kinetic tremor., Methods: Tremor data from wireless inertial measurement units were collected from 11 participants with ET (20 unilaterally assessed DBS leads). Three postural hold tasks and one kinetic task were performed with stimulation turned off, in 2-min intervals after enabling unilateral DBS at the clinician-optimized DBS setting (15 min), and in 2-min intervals following cessation of DBS (5 min)., Results: At baseline, kinetic tremor had significantly higher amplitudes, standard deviation, and frequency than postural tremor (P < 0.001). DBS had a more robust acute effect on postural tremors (54% decrease, P < 0.001), with near immediate tremor suppression in amplitude and standard deviation, but had non-significant improvement of kinetic tremor on the population-level across the wash-in period (34% decrease). Tremor response was not equivalent between wash-in and wash-out timepoints and involved substantial individual variability including task-specific rebound or long wash-out effects., Conclusions: Programming strategies for VIM/PSA-DBS should consider the individual temporal and effect size variability in postural versus kinetic tremor improvement. Improved targeting and programming strategies around VIM and PSA may be necessary to equivalently suppress both postural and kinetic tremors., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective: To describe the management and outcomes of patients with Ta predominantly low-grade urothelial carcinoma with focal high-grade features (FHG) (<5%), compared to those with Ta low grade (LG) and Ta high grade (HG)., Methods: Retrospective review of all patients who underwent transurethral resection of bladder tumor between 2005 and 2023. Patients with Ta disease were identified and categorized into LG, FHG, and HG. Kaplan Meier method was used to depict high-grade recurrence, T-stage progression, and radical cystectomy-free survival., Results: Four hundred forty-nine patients with Ta disease were identified (LG 48%, FHG 12%, and HG 40%). Patients with FHG (32%) had a second-look transurethral resection of bladder tumor more frequently compared to LG (7%) and HG (29%) (P <.01). They received intravesical therapy more frequently compared to LG (36% vs 20%) but lower than HG (55%) (P <.01). They received radical cystectomy less frequently (7% compared to 20% for HG and 11% for LG, P = .01). HG recurrence-free survival at 1, 3, and 5years was HG (68%, 52%, and 43%), FHG (74%, 53%, and 49%), and LG (87%, 79%, and 73%) (log-rank P <.01). T progression-free survival at 1, 3, and 5years was HG (84%, 77%, and 70%), FHG (92%, 82%, and 82%), and LG (94%, 89%, and 85%) (log-rank P = .02). Cystectomy-free survival at 1, 3, and 5years was HG (92%, 84%, and 80%), FHG (96%, 94%, and 94%), and LG (99%, 95%, and 92%) (log-rank P <.01)., Conclusion: Patients with Ta FHG seem to behave more like Ta HG disease in terms of high-grade recurrences, but they are less likely to experience T-stage progression and convert to cystectomy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: A multi-laboratory validation study was performed on AOAC Official Method of Analysis (OMA) 2016.09, for final action. Eight different laboratories throughout the world participated in the study tested the same set of 6 different laboratory samples of raw materials (commercial) and formulated products (commercial), and all the laboratories successfully generated results within the acceptance criteria., Objective: The intention of the study was to evaluate specificity, precision (variation), linearity/range, system suitability, limit of detection (LOD), and limit of quantitation (LOQ) by multiple laboratories to satisfy the requirement of moving the OMA 2016.09 to the final action status. Accuracy and ruggedness were already validated in earlier work of single laboratory validation (1), and it was not necessary to include these validation parameters in the multi-laboratory validation study., Method: Laboratory samples containing Aloe were sent out to participating laboratories. Each lab followed AOAC 2016.09 (First Action status) to analyze contents of aloin A, aloin B, and aloe emodin using high performance liquid chromatography (HPLC) instrument. The results generated by each laboratory were collected and evaluated., Results: The specificity results show that blank and matrix chromatograms do not contain major interfering peaks on the retention time of aloin A, aloin B, and aloe-emodin. The precision (variation) results of duplicated preparations are not more than 0.05 parts per million (ppm) different. The linearity/range results from six standards (10 parts per billion (ppb), 20 ppb, 40 ppb, 80 ppb, 160 ppb, and 500 ppb) have correlation coefficient (R) value of ≥ 0.999. The system suitability results meet the acceptance criteria to show the instrument validity. The limit of detection (LOD) results show that the signal-to-noise (S/N) ratio of 10 ppb standards for all three components are about 3. The limit of quantitation (LOQ) results show that the S/N ratio of 20 ppb standards for all three components are about 10., Conclusions: The validation parameters (specificity, precision (variation), linearity/range, system suitability, LOD, and LOQ) have been successfully analyzed, and it shows that the test method is suitable for its intended use., Highlights: The test method has been successfully validated by the eight different laboratories around the world (US, UK, Germany, and Canada). Each of the laboratory is managed independently by the site lab management team. This multi-lab study validated the method of Determination of Aloin A, Aloin B, and Aloe-Emodin in Raw Materials and Finished Products Using high performance liquid chromatography (HPLC), and the method fits for its intended purpose., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To understand the neural basis of behavior, it is essential to measure spiking dynamics across many interacting brain regions. Although new technologies, such as Neuropixels probes, facilitate multi-regional recordings, significant surgical and procedural hurdles remain for these experiments to achieve their full potential. Here, we describe skull-shaped hemispheric implants enabling large-scale electrophysiology datasets (SHIELD). These 3D-printed skull-replacement implants feature customizable insertion holes, allowing dozens of cortical and subcortical structures to be recorded in a single mouse using repeated multi-probe insertions over many days. We demonstrate the procedure's high success rate, biocompatibility, lack of adverse effects on behavior, and compatibility with imaging and optogenetics. To showcase SHIELD's scientific utility, we use multi-probe recordings to reveal novel insights into how alpha rhythms organize spiking activity across visual and sensorimotor networks. Overall, this method enables powerful, large-scale electrophysiological experiments for the study of distributed neural computation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD)., Method: We analyzed data from the Abatacept in Myositis Associated Interstitial lung disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD. 6MWD, forced vital capacity (FVC), diffusing capacity (DLCO), high resolution CT, and various physician/patient reported outcome measures were obtained during the trial. Spearman's correlations and repeated-measures analysis with linear mixed-effects models were used to estimate the associations between 6MWD and various physiologic, clinical and radiographic parameters both cross-sectionally and longitudinally., Results: Twenty participants with a median age of 57, 55% male and 85% white were analyzed. Baseline 6MWD did not associate with baseline PFTs. Repeated-measures analysis showed 6MWD over time associated with FVC over time, but not with DLCO. 6MWD over time also correlated with UCSD dyspnea score, Borg scores, as well as global disease activity and muscle strength over time. Emotional role functioning, vitality, general health and physical functioning scores by short form 36 also correlated with 6MWD over time., Conclusions: : Exploratory work in a small cohort of MA-ILD demonstrated 6MWD over time associated with parallel changes in FVC and patient reported outcomes of dyspnea, but not with DLCO. Larger studies are needed to validate the reliability, responsiveness and utility of the 6MWT in MA-ILD., Clinical Trial Registration: ClinicalTrials.gov, NCT03215927., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Candida albicans causes millions of mucosal infections in humans annually. Hyphal overgrowth on mucosal surfaces is frequently associated with tissue damage caused by candidalysin, a secreted peptide toxin that destabilizes the plasma membrane of host cells thereby promoting disease and immunopathology. Candidalysin was first identified in C. albicans strain SC5314, but recent investigations have revealed candidalysin "variants" of differing amino acid sequence in isolates of C. albicans , and the related species C. dubliniensis , and C tropicalis , suggesting that sequence variation among candidalysins may be widespread in natural populations of these Candida species. Here, we analyzed ECE1 gene sequences from 182 C . albicans isolates, 10 C . dubliniensis isolates, and 78 C . tropicalis isolates and identified 10, 3, and 2 candidalysin variants in these species, respectively. Application of candidalysin variants to epithelial cells revealed differences in the ability to cause cellular damage, changes in metabolic activity, calcium influx, MAPK signalling, and cytokine secretion, while biophysical analyses indicated that variants exhibited differences in their ability to interact with and permeabilize a membrane. This study identifies candidalysin variants with differences in biological activity that are present in medically relevant Candida species., Importance: Fungal infections are a significant burden to health. Candidalysin is a toxin produced by Candida albicans that damages host tissues, facilitating infection. Previously, we demonstrated that candidalysins exist in the related species C. dubliniensis and C. tropicalis , thereby identifying these molecules as a toxin family. Recent genomic analyses have highlighted the presence of a small number of candidalysin "variant" toxins, which have different amino acid sequences to those originally identified. Here, we screened genome sequences of isolates of C. albicans , C. dubliniensis , and C. tropicalis and identified candidalysin variants in all three species. When applied to epithelial cells, candidalysin variants differed in their ability to cause damage, activate intracellular signaling pathways, and induce innate immune responses, while biophysical analysis revealed differences in the ability of candidalysin variants to interact with lipid bilayers. These findings suggest that intraspecies variation in candidalysin amino acid sequence may influence fungal pathogenicity., Competing Interests: The authors declare no conflict of interest.

Objective: The objectives of the study were (1) to assess whether resting energy expenditure (REE) equations have comparable validity for adolescents with overweight/obesity vs. adolescents with healthy weight and (2) to examine determinants of measured REE in adolescents with overweight/obesity vs. adolescents with healthy weight. Methods: Ten equations were used to predict REE for 109 adolescents (70% males; 36.7% with overweight/obesity); 95% equivalence testing was used to assess how well each equation agreed with the criterion measure of indirect calorimetry. Linear regression models were fitted to examine how much REE variance was accounted for by age, sex, race, fat-free mass (FFM), and fat mass. Results: For adolescents with healthy weight, all ten equations were significantly equivalent to the criterion measure within ±8.4% ( p < 0.05), whereas for participants with overweight/obesity, only three equations were equivalent within the same range ( p < 0.05). Controlling for age, sex, race, fat mass, and FFM accounted for 74% of REE variance. FFM explained the greatest amount (26%) of variance in REE, while weight status itself explained an additional 22%. Conclusions: Prediction equations tend to be more accurate for adolescents with healthy weight than adolescents with overweight/obesity unless the original sample specifically included participants with overweight/obesity. Determinants of REE are similar regardless of weight status.

Highly pathogenic avian influenza (HPAI) viruses have spread at an unprecedented scale, leading to mass mortalities in birds and mammals. In 2023, a transatlantic incursion of HPAI A(H5N5) viruses into North America was detected, followed shortly thereafter by a mammalian detection. As these A(H5N5) viruses were similar to contemporary viruses described in Eurasia, the transatlantic spread of A(H5N5) viruses was most likely facilitated by pelagic seabirds. Some of the Canadian A(H5N5) viruses from birds and mammals possessed the PB2-E627K substitution known to facilitate adaptation to mammals. Ferrets inoculated with A(H5N5) viruses showed rapid, severe disease onset, with some evidence of direct contact transmission. However, these viruses have maintained receptor binding traits of avian influenza viruses and were susceptible to oseltamivir and zanamivir. Understanding the factors influencing the virulence and transmission of A(H5N5) in migratory birds and mammals is critical to minimize impacts on wildlife and public health., Competing Interests: Declaration of interests The authors declare no competing interests., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Introduction: It is well established that personality traits impact cognition, as certain personality factors are associated with performance in specific cognitive domains. However, the findings on the relationships between the Big Five traits and cognition are mixed. Additionally, few studies have explored these relationships in older adults with a history of depression. The present study aimed to (a) evaluate the impact of the Big Five personality traits in older adults with and without a lifetime history of depression; and (b) test the hypotheses that higher trait neuroticism would correlate negatively with cognitive performance, while openness to experience would correlate positively with cognition., Methods: The sample consisted of 138 participants between the ages of 55 and 78 ( M = 65.56, SD = 6.36). Sixty-two participants met criteria for current or remitted Major Depressive Disorder, while 76 had no history of depression or other mental health disorders. Participants underwent comprehensive neuropsychological testing. Personality was assessed using the NEO Personality Inventory-Revised (NEO-PI-R), while depression status was determined using the Structured Clinical Interview for DSM-5 (SCID-5). Following a series of Pearson correlations of cognitive variables and the five personality factors, linear regression models were estimated for each significant correlation. Demographic variables (i.e., age, education and sex) were entered in block 1, depression status (never vs. ever) was entered in block 2, and the personality factor score, or sub-facet was entered in block 3., Results: Neuroticism was not associated with cognitive performance on any outcome measure. The facets Openness to Feelings and Openness to Values were positively related to phonemic fluency. Further Openness to Values was positively related to cognitive flexibility., Discussion: Our results suggest that older people who are (a) more capable of identifying and understanding their feelings and the feelings of others, and (b) who are more willing to re-examine social, political, and religious values perform stronger on tasks measuring verbal fluency and cognitive flexibility, which are aspects of executive functioning. Interventions that aim to enhance open mindedness in older adults may have a parallel impact on improving executive functioning, though this would need to be examined prospectively., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Armstrong, Kaufman, Maciarz, Sullivan, Kim, Koppelmans, Langenecker and Weisenbach.)

Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and β-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, β-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII., Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L.K. has participated in clinical trials sponsored by Amgen and Novartis; he has given lectures and received consulting fees from Seqiris (CSL), Amgen and Novartis. D.S. has participated in clinical trials sponsored by NHMRC Clinical Trials Centre; he has received support from Arrowhead Pharmaceuticals for previous publications; he has received grants/contracts sponsored by Regeneron Pharmaceuticals, Ionis Pharmaceuticals, Arrowhead Pharmaceuticals, Amgen and Novartis; he has given lectures and received consulting fees from Amgen and Novartis; he has received contributions from Sanofi., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: We aimed to investigate the differences in perioperative outcomes, especially ureteroenteric strictures, between patients who underwent a stented ureteroenteric anastomosis at the time of robot-assisted radical cystectomy (RARC) and ileal conduit vs those who did not., Methods: A retrospective review of our RARC database was performed (2009-2023). Patients were divided into those who received stented ureteroenteric anastomosis vs those who did not. Propensity score matching was performed in the ratio of 3 (stented ureteroenteric anastomosis) to 1 (stent-free) in terms of age, gender, BMI, race, American Society of Anesthesiologists score, neoadjuvant chemotherapy, Charlson Comorbidity Index, prior radiation therapy, previous abdominal surgery history, clinical T3/clinical T4 stage, preoperative metastasis, and preoperative hydronephrosis. A cumulative incidence curve was used to depict ureteroenteric strictures and a Cox regression model was used to identify variables associated with ureteroenteric strictures., Results: Four hundred eighty-eight patients underwent RARC, 366 individuals underwent a stented ureteroenteric anastomosis, and 122 patients underwent a stent-free approach. There was no significant difference in 90-day overall complications, high-grade complications, readmissions, UTIs, leakage, and ileus ( P > .05). Ureteroenteric strictures occurred at a rate of 13% and 18% at 1 and 2 years, respectively in the stented group, vs 7% and 10% in the stent-free group ( P = .05). Stent placement was significantly associated with ureteroenteric strictures., Conclusions: Stent-free ureteroenteric anastomosis was associated with fewer strictures following RARC and ileal conduit.

Introduction: Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disorder of lipid metabolism and a preventable cause of premature cardiovascular disease. Current detection rates for this highly treatable condition are low. Early detection and management of FH can significantly reduce cardiac morbidity and mortality. This study aims to implement a primary-tertiary shared care model to improve detection rates for FH. The primary objective is to evaluate the implementation of a shared care model and support package for genetic testing of FH. This protocol describes the design and methods used to evaluate the implementation of the shared care model and support package to improve the detection of FH., Methods and Analysis: This mixed methods pre-post implementation study design will be used to evaluate increased detection rates for FH in the tertiary and primary care setting. The primary-tertiary shared care model will be implemented at NSW Health Pathology and Sydney Local Health District in NSW, Australia, over a 12-month period. Implementation of the shared care model will be evaluated using a modification of the implementation outcome taxonomy and will focus on the acceptability, evidence of delivery, appropriateness, feasibility, fidelity, implementation cost and timely initiation of the intervention. Quantitative pre-post and qualitative semistructured interview data will be collected. It is anticipated that data relating to at least 62 index patients will be collected over this period and a similar number obtained for the historical group for the quantitative data. We anticipate conducting approximately 20 interviews for the qualitative data., Ethics and Dissemination: Ethical approval has been granted by the ethics review committee (Royal Prince Alfred Hospital Zone) of the Sydney Local Health District (Protocol ID: X23-0239). Findings will be disseminated through peer-reviewed publications, conference presentations and an end-of-study research report to stakeholders., Competing Interests: Competing interests: DS has received grants from Regeneron, Amgen, Arrowhead, Ionis and Novartis via Sydney Local Health District; consulting fees and speaker fees from Amgen and Novartis; and drug samples for a treatment adherence programme from Sanofi. CMH has received Amgen, Sanofi and MRFF grants looking at FH identification in the general practice setting, and assisted in the Amgen-funded independent education design for the GP. MNS is supported by an NHMRC Investigator Grant and received honoraria related to consulting, research and/or speaker activities from Amgen., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

We have recently determined dimethylguanidino valeric acid (DMGV) to be a novel biomarker of liver injury in non-alcoholic fatty liver disease (NAFLD) and an independent predictor of incident diabetes over a decade in advance. DMGV consists of two stereo-isomers, asymmetric dimethylguanidino valeric acid (ADGV) and symmetric dimethylguanidino valeric acid (SDGV). Here we report, for the first time, the upper limits of normal of both isomers in humans at the accepted 5.56% liver fat threshold for NAFLD, determined using in vivo magnetic resonance spectroscopy. We performed independent and blinded comparative analyses of ADGV and SDGV levels using two different liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods in (A) our laboratory, and (B) the New South Wales Chemical Pathology state laboratory, using unique columns, LC-MS/MS equipment, extraction protocols and normalisation approaches. Despite these differences, each laboratory reported consistent absolute concentrations across a range of liver fat percentages. We next determined the diagnostic performance of SDGV compared to ADGV in a cohort of 268 individuals with liver fat measurements. In derivation-validation analyses we determined rule-in/rule-out thresholds and the concentration of SDGV that provides optimal performance across sensitivity and specificity for the identification of NAFLD. In conclusion, we have herein determined for the first time the true human plasma reference range of both isoforms of an emerging novel biomarker of NAFLD, at the accepted upper normal threshold of liver fat. We have also identified that SDGV is the isoform with the best diagnostic performance and determined the optimal cut-point for its detection of NAFLD., (Copyright © 2023. Published by Elsevier B.V.)

Traumatic brain injury (TBI) is the leading cause of accident-related death and disability in the world and can lead to long-term neuropsychiatric symptoms, such as a decline in cognitive function and neurodegeneration. TBI includes primary and secondary injury, with head trauma and deformation of the brain caused by the physical force of the impact as primary injury, and cellular and molecular cascades that lead to cell death as secondary injury. Currently, there is no treatment for TBI-induced cell damage and neural circuit dysfunction in the brain, and thus, it is important to understand the underlying cellular mechanisms that lead to cell damage. In the current study, we use stretchable microelectrode arrays (sMEAs) to model the primary injury of TBI to study the electrophysiological effects of physically injuring cortical cells. We recorded electrophysiological activity before injury and then stretched the flexible membrane of the sMEAs to injure the cells to varying degrees. At 1, 24, and 72 h post-stretch, we recorded activity to analyze differences in spike rate, Fano factor, burstlet rate, burstlet width, synchrony of firing, local network efficiency, and Q statistic. Our results demonstrate that mechanical injury changes the firing properties of cortical neuron networks in culture in a time- and severity-dependent manner. Our results suggest that changes to electrophysiological properties after stretch are dependent on the strength of synchronization between neurons prior to injury., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Millions of individuals globally suffer from inadvertent, occupational or self-harm exposures from organophosphate (OP) insecticides, significantly impacting human health. Similar to nerve agents, insecticides are neurotoxins that target and inhibit acetylcholinesterase (AChE) in central and peripheral synapses in the cholinergic nervous system. Post-exposure therapeutic countermeasures generally include administration of atropine with an oxime to reactivate the OP-inhibited AChE. However, animal model studies and recent clinical trials using insecticide-poisoned individuals have shown minimal clinical benefits of the currently approved oximes and their efficacy as antidotes has been debated. Currently used oximes either reactivate poorly, do not readily cross the blood-brain barrier (BBB), or are rapidly cleared from the circulation and must be repeatedly administered. Zwitterionic oximes of unbranched and simplified structure, for example RS194B, have been developed that efficiently cross the BBB resulting in reactivation of OP-inhibited AChE and dramatic reversal of severe clinical symptoms in mice and macaques exposed to OP insecticides or nerve agents. Thus, a single IM injection of RS194B has been shown to rapidly restore blood AChE and butyrylcholinesterase (BChE) activity, reverse cholinergic symptoms, and prevent death in macaques following lethal inhaled sarin and paraoxon exposure. The present macaque studies extend these findings and assess the ability of post-exposure RS194B treatment to counteract oral poisoning by highly toxic diethylphosphorothioate insecticides such as parathion and chlorpyrifos. These OPs require conversion by P450 in the liver of the inactive thions to the active toxic oxon forms, and once again demonstrated RS194B efficacy to reactivate and alleviate clinical symptoms within 60 mins of a single IM administration. Furthermore, when delivered orally, the Tmax of RS194B at 1-2 h was in the same range as those administered IM but were maintained in the circulation for longer periods greatly facilitating the use of RS194B as a non-invasive treatment, especially in isolated rural settings., (© 2023 International Society for Neurochemistry.)

Background: Using comprehensive plasma lipidomic profiling from men with metastatic castration-resistant prostate cancer (mCRPC), we have previously identified a poor-prognostic lipid profile associated with shorter overall survival (OS). In order to translate this biomarker into the clinic, these men must be identifiable via a clinically accessible, regulatory-compliant assay., Methods: A single regulatory-compliant liquid chromatography-mass spectrometry assay of candidate lipids was developed and tested on a mCRPC Discovery cohort of 105 men. Various risk-score Cox regression prognostic models of OS were built using the Discovery cohort. The model with the highest concordance index (PCPro) was chosen for validation and tested on an independent Validation cohort of 183 men., Results: PCPro, the lipid biomarker, contains Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1), triglycerides and total cholesterol. Within the Discovery and Validation cohorts, men who were PCPro positive had significantly shorter OS compared to those who were PCPro negative (Discovery: median OS 12.0 months vs 24.2 months, hazard ratio (HR) 3.75 [95% confidence interval (CI) 2.29-6.15], p < 0.001, Validation: median OS 13.0 months vs 25.7 months, HR = 2.13 [95% CI 1.46-3.12], p < 0.001)., Conclusions: We have developed PCPro, a lipid biomarker assay capable of prospectively identifying men with mCRPC with a poor prognosis. Prospective clinical trials are required to determine if men who are PCPro positive will benefit from therapeutic agents targeting lipid metabolism., (© 2023. The Author(s).)

The nursing workforce does not represent the diversity of patients in their care. Nursing students historically have been taught cultural competence, with a core value for diversity, equity, and inclusion, but health inequities remain a problem. Cultural humility goes beyond cultural competency, offering nurses a perpetual learning role from the individual patients in their care. The concept of cultural humility also offers bedside nurses a way to overcome implicit and explicit bias through self-awareness and active listening, but it may not be well understood., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The US government has established a national goal of hepatitis C virus (HCV) elimination by 2030. To date, most HCV elimination planning and activity have been at the state level. Fifteen states presently have publicly available HCV elimination plans. In 2019, Louisiana and Washington were the first states to initiate 5-year funded HCV elimination programs. These states differ on motivation for pursuing HCV elimination and ranking on several indicators. Simultaneously, however, they have emphasized several similar elimination components including HCV screening promotion through public awareness, screening expansion, surveillance enhancement (including electronic reporting and task force development), and harm reduction. The 13 other states with published elimination plans have proposed the majority of the elements identified by Louisiana and Washington, but several have notable gaps. Louisiana's and Washington's comprehensive plans, funding approaches, and programs provide a useful framework that can move states and the nation toward HCV elimination., Competing Interests: Financial Disclosures of Potential and Actual Conflicts of Interest: R.F. has received funds paid to his institution from Gilead Sciences, Inc, Abbvie, Merck & Co, Inc, and a consulting fee from Thera technologies. S.N.K. has received funds paid to his institution from Gilead Sciences, Inc, for research related to hepatitis C and COVID-19. G.L.T. is a member of the Speaker's Bureau for Gilead Sciences, Inc. A.H.T. has received honoraria and funds to his institution from Gilead Sciences. None of the other authors have any conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Spring dead spot (SDS) ( Ophiosphaerella spp.) is a soilborne disease of warm-season turfgrasses grown where winter dormancy occurs. The edaphic factors that influence where SDS epidemics occur are not well defined. A study was conducted during the spring of 2020 and repeated in the spring of 2021 on four 'TifSport' hybrid bermudagrass ( Cynodon dactylon × transvaalensis ) golf course fairways expressing SDS symptoms in Cape Charles, VA, U.S.A. SDS within each fairway was mapped from aerial imagery collected in the spring of 2019 with a 20 MP CMOS 4k true color sensor mounted on a DJI Phantom 4 Pro drone. Three disease intensity zones were designated from the maps (low, moderate, high) based on the density of SDS patches in an area. Disease incidence and severity, soil samples, surface firmness, thatch depth, and organic matter measurements were taken from 10 plots within each disease intensity zone from each of the four fairways ( n = 120). Multivariate pairwise correlation analyses ( P < 0.1) and best subset stepwise regression analyses were conducted to determine which edaphic factors most influenced the SDS epidemic within each fairway and each year. Edaphic factors that correlated with an increase in SDS or were selected for the best fitting model varied across holes and years. However, in certain cases, soil pH and thatch depth were predictors for an increase in SDS. No factors were consistently associated with SDS occurrence, but results from this foundational study of SDS epidemics can guide future research to relate edaphic factors to SDS disease development., Competing Interests: The author(s) declare no conflict of interest.

Bereavement increases in prevalence as people age and is associated with multiple psychological and health risks, including cardiovascular risk. Religious and existential variables may play an important role in the health impacts of bereavement. Theorized pathways linking religious and existential variables with health have suggested these associations are due to intermediary psychosocial variables, but have not been tested in bereavement. This research empirically tested these pathways in a bereaved population. In N = 73 adults within 1 year of bereavement (mean age = 64.36), this study examined associations between (1) religious and existential characteristics (religious and spiritual struggles, intrinsic religiosity, and existential quest) and intermediary psychosocial variables (depression, loneliness, and difficulties in emotion regulation), and between (2) intermediary psychosocial variables and bereavement-relevant health outcomes (self-reported health, change in health since last year, grief severity, and cardiovascular biomarkers). Cardiovascular biomarkers (heart rate, heart rate variability, and blood pressure) were collected before, during, and after a laboratory grief recall emotion elicitation. Anticipated associations between self-reported religious and existential characteristics and intermediary variables, and between intermediary variables and self-reported bereavement-relevant outcomes, were consistently observed. However, associations between intermediary variables and cardiovascular biomarkers were largely unobserved. This study examined the role of religious and existential variables in whole-person health after bereavement and is among the first to include biomarkers of cardiovascular risk. Results suggest that although religious and existential variables are associated with important bereavement-related outcomes, these associations may be "skin-deep," and extensions to cardiovascular functioning should be re-examined., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

This study aims to explore the potential psychological and cognitive advantages for older individuals engaged in hard martial arts (HMA), through a comprehensive scoping review of literature up to 2023. Specifically, it examines the extent of changes in cognition, mental state, and quality of life among elderly participants of HMA. Inclusion criteria were studies conducted on healthy persons who were over 50 years of age. Only papers published in the English language were included. The search was undertaken in electronic databases and sources of grey literature. Thirteen papers with a total of 514 participants met the inclusion criteria. Improved cognition and decreased levels of anxiety and depression were emerging themes. Together, these factors contributed to the quality of life of participants. HMA was found to benefit cognitive abilities and psychological well-being, increasing quality of life more than traditional exercise alone. Findings suggested duration of training influenced change more than frequency. The limited number of studies exploring the effects of HMA on mental wellness and cognitive ability in older adults underscores the need for further research. The findings of this review suggest cognitive and quality of life improvements and reduced depression and anxiety in individuals engaging in HMA. This review serves as a foundation for soundly designed future research.

BACKGROUND: Apolipoprotein C-III (APOC3) inhibits triglyceride clearance by reducing lipoprotein lipase–mediated hydrolysis and hepatocyte uptake of triglyceride-rich lipoproteins. ARO-APOC3, a hepatocyte-targeting RNA interference therapeutic, inhibits APOC3 messenger ribonucleic acid expression, lowering triglyceride levels. The objective of this trial was to assess the safety, pharmacodynamic variables, and pharmacokinetic variables of ARO-APOC3 treatment. METHODS: Healthy participants and adults with hypertriglyceridemia were randomly assigned to receive escalating single (day 1) or repeat (days 1 and 29) doses, respectively, of subcutaneous injections of ARO-APOC3 10, 25, 50, or 100 mg or placebo; they were followed up until day 113. Additional cohorts of healthy participants and adults with chylomicronemia received repeat doses of open-label ARO-APOC3. The primary objective was to evaluate the safety and side effect profile of ARO-APOC3. Key secondary and exploratory objectives included pharmacokinetic variables and changes in serum APOC3, triglyceride, and cholesterol levels. RESULTS: Eighty-eight participants received ARO-APOC3 and 24 participants received placebo across double-blind and open-label cohorts. Treatment-emergent adverse events (AEs) of transient, mild to moderate liver transaminase changes occurred in 10 participants: 1 patient receiving ARO-APOC3 25 mg, 5 patients receiving ARO-APOC3 50 mg, and 4 participants receiving ARO-APOC3 100 mg (1 healthy participant and 3 patients with hypertriglyceridemia). These events were asymptomatic, and transaminase levels returned to near baseline by the end of the trial. No AEs related to thrombocytopenia or platelet declines were reported. In the hypertriglyceridemia cohorts, the day 113 mean changes from baseline in APOC3 at the 10-, 25-, 50-, and 100-mg doses were −62.0%, −81.7%, −90.1%, and −94.4%, respectively, compared with −1.6% with placebo. This corresponded to median changes in triglyceride levels of −65.6%, −69.9%, −81.2%, and −81.0% compared with −2.8% with placebo. CONCLUSIONS: In this small trial of short duration, ARO-APOC3 was associated with few AEs and reduced serum levels of APOC3 and triglycerides in healthy participants and patients with hypertriglyceridemia. (Funded by Arrowhead Pharmaceuticals, Inc.; ClinicalTrials.gov number, NCT03783377.)

Purpose: The aim of our article is to describe our learning based on challenges encountered implementing two related pediatric to adult primary care transition pilots for medically complex adolescents and young adults as part of the Children with Medical Complexity Collaborative for Improvement and Innovation Network., Design: We undertook two sequential pilot projects. The first focused on supporting the transfer stage for an older group of medically complex young adults to facilitate their establishment with an adult primary care provider. Based on our learning from barriers encountered, and setting constraints due to COVID-19, we developed and implemented a second project to engage pediatric primary care providers in initiating and documenting transition preparation discussions for a younger group of medically complex youth. A multi-disciplinary Implementation Team guided each phase's implementation., Results: We did not achieve our objective in the first pilot, partly due to provider reluctance. Providers perceived the patient was not ready, reported that the patient was experiencing active health problems, or wanted to keep the patient on their panel. We partially achieved the second pilot's objective; three-quarters of identified patients completed their appointments, and electronic health record documentation suggests that providers initiated transition discussions with more than half of those patients., Conclusions: Pediatric primary care has an important role in supporting health care transition for medically complex youth. Our findings suggest that pediatric primary care providers require time, connection to adult PCPs, and educational support to realize this role., Practice Implications: To provide comprehensive transition services for medically complex patients, pediatric primary care will need to develop relationships with adult primary care providers, make available training about transition preparation for its providers, and support patients and families in locating adult primary care providers who are accepting new patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alison Martin reports financial support was provided by Health Services and Resources Administration Maternal and Child Health Bureau., (© 2023 The Authors.)

Background: Familial hypercholesterolaemia (FH) is a genetic condition that is a preventable cause of premature cardiovascular morbidity and mortality. High-level evidence and clinical practice guidelines support preventative care for people with FH. However, it is estimated that less than 10% of people at risk of FH have been detected using any approach across Australian health settings. The aim of this study was to identify the implementation barriers to and facilitators of the detection of FH in Australia., Methods: Four, 2-hour virtual focus groups were facilitated by implementation scientists and a clinicians as part of the 2021 Australasian FH Summit. Template analysis was used to identify themes., Results: There were 28 workshop attendees across four groups (n=6-8 each), yielding 13 barriers and 10 facilitators across three themes: (1) patient related, (2) provider related, and (3) system related. A "lack of care pathways" and "upskilling clinicians in identifying and diagnosing FH" were the most interconnected barriers and facilitators for the detection of FH., Conclusions: The relationships between barriers and facilitators across the patient, provider, and system themes indicates that a comprehensive implementation strategy is needed to address these different levels. Future research is underway to develop a model for implementing the Australian FH guidelines into practice., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Adolescents with intellectual and developmental disabilities (IDD) experience overweight and obesity (OW/OB) up to 1.8 times the rate of their typically developing peers. Parents may influence adolescent weight management behaviors in this population, but the association between parent factors and adolescent weight management behaviors is unclear., Objective: To examine the associations between parent BMI and sociodemographic characteristics with adolescents' BMI, diet quality, daily energy intake, moderate to vigorous physical activity (MVPA), and sedentary behavior., Methods: This study analyzed baseline data from an 18-month randomized controlled weight loss trial for adolescents with IDD. We assessed parent BMI (kg/m 2 ) and sociodemographic factors, and adolescent BMI z-score, MVPA, sedentary time, daily energy intake, and diet quality. Associations between parent and adolescent factors were assessed with Pearson, Spearman or Kendall Tau-b correlations; mean differences for categorical outcomes were assessed with independent samples t-tests/Mann-Whitney U tests or ANOVA/Kruskall-Wallis tests., Results: Ninety-five adolescent and parent dyads were included. Parent BMI was positively correlated with adolescent BMI z-score (n = 94: r s  = 0.37, p < 0.01). Household income was inversely correlated with adolescent BMI z-score (n = 95: T b  = -0.18, p = 0.02). Parents with less than a bachelor's degree had adolescents with higher BMI z-scores than those with bachelor's or higher (2.1 ± 0.5 vs. 1.8 ± 0.5, p = 0.02) as well as higher sedentary behavior (n = 28, 515.2 ± 102.6 min/day vs. n = 40, 463.9 ± 148.1 min/day, p = 0.02)., Conclusion: We found parent BMI, income, and education associated with adolescent BMI z-score. These findings contribute to the sparse literature on parental factors associated with OW/OB in this population., Clinical Trials Number: NCT02561754., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The aerial crop dusting and spraying of fields with the phosphorothioate insecticide parathion in the late 1900s, significantly improved crop yields but resulted in high levels of occupational toxicity in handlers and agricultural workers, as well as cases of intentional self-harm poisoning, culminating in its banning in many western countries by early 2000s. However because of the low solubility and volatility of parathion, most available products were formulated using organic solvents e.g. xylene, to increase the efficacy of the aerosols and dusts. In the present study, the toxicity of parathion was assessed when formulated in an aqueous solvents (ethanol/PBS (1:9)), and delivered to macaques as an aerosol. Doses of 780 μg/kg and 1.56 mg/kg were delivered one day apart, using a modified nebulizer calculated to result in lung deposition of ∼480 μg/kg with a similar or larger amount being swallowed; these doses being similar to the estimated lethal oral dose 286ug/kg - 1.43 mg/kg of formulated parathion in humans. Surprisingly, this dose (a combined amount of ∼14 mg) caused only low AChE inhibition and moderate BChE inhibition with no clinical symptoms, indicating that the use of organic solvents may have previously played a critical role in the severity of parathion toxicity following inhalation exposure. In addition, unlike constitutively toxic OPs, which are highly toxic when inhaled, these results are consistent with the idea that phosphorothioate insecticides appear to be more intoxicating following oral than inhalation exposure. However, this still remains uncertain because the presence of organic solvents in the ingested parathion studies was not always known., 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 B.V. All rights reserved.)

Introduction and Methods: In this study, we evaluated self-reported respiratory symptoms during agricultural work, respiratory protection use and experience, and perceived value of receiving respirators using Gear Up for Ag Health and Safety Program™ pre- and post-surveys from 703 to 212 young adult hog producers in the United States. To our knowledge, this is one of the most extensive survey data sets on self-reported respiratory symptoms and respiratory protection behaviors of collegiate-aged young adults working in US livestock production., Results: About one-third (37%) of young adult hog producers stated that they have experienced cough, shortness of breath, fever, and chills after working in dusty areas on the farm. Most (76.2%) stated that they were already "always" or "sometimes" wearing filtering facepiece (N95-style) respirators, even before participating in an outreach program. About one-third (30%) reported experience wearing a cartridge-style respirator but only 5% reported having been fit-tested for a respirator. Young adult male producers were significantly more likely to report use of both respirator types when compared to females, both before and after the program. Male producers were also more likely than females to engage in high-risk farm tasks where respirators are recommended, such as cleaning out grain bins and mixing or grinding feed. Following an educational program, males and females reported using the respirators that they received at similar rates, and 20% of overall participants purchased additional respiratory protection., Discussion: The study found that young adult hog producers in postsecondary education are already wearing respirators with some frequency and at rates higher than previously reported by agricultural workers. More research is needed to make effective task-based respirator-use recommendations and investigate some significant gender differences among young adult hog producers observed in this study., (© 2023 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals LLC.)

Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This first-in-human, phase 1, randomized, placebo-controlled, open-label trial investigated single and repeat ARO-ANG3 doses in four cohorts of fifty-two healthy participants and one cohort of nine participants with hepatic steatosis, part of a basket trial. Safety (primary objective) and pharmacokinetics (in healthy participants) and pharmacodynamics (secondary objectives) of ARO-ANG3 were evaluated. ARO-ANG3 was generally well tolerated, with similar frequencies of treatment-emergent adverse events in active and placebo groups. Systemic absorption of ARO-ANG3 in healthy participants was rapid and sustained, with a mean T max of 6.0-10.5 h and clearance from plasma within 24-48 h after dosing with a mean t ½ of 3.9-6.6 h. In healthy participants, ARO-ANG3 treatment reduced ANGPTL3 (mean -45% to -78%) 85 days after dose. Reductions in triglyceride (median -34% to -54%) and non-HDL-C (mean -18% to -29%) (exploratory endpoints) concentrations occurred with the three highest doses. These early-phase data support ANGPTL3 as a potential therapeutic target for ASCVD treatment. ClinicalTrials.gov identifier: NCT03747224., (© 2023. Crown.)

In December 2022 and January 2023, we isolated clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) viruses from six American crows ( Corvus brachyrhynchos ) from Prince Edward Island and a red fox ( Vulpes vulpes ) from Newfoundland, Canada. Using full-genome sequencing and phylogenetic analysis, these viruses were found to fall into two distinct phylogenetic clusters: one group containing H5N1 viruses that had been circulating in North and South America since late 2021, and the other one containing European H5N1 viruses reported in late 2022. The transatlantic re-introduction for the second time by pelagic/Icelandic bird migration via the same route used during the 2021 incursion of Eurasian origin H5N1 viruses into North America demonstrates that migratory birds continue to be the driving force for transcontinental dissemination of the virus. This new detection further demonstrates the continual long-term threat of H5N1 viruses for poultry and mammals and the subsequent impact on various wild bird populations wherever these viruses emerge. The continual emergence of clade 2.3.4.4b H5Nx viruses requires vigilant surveillance in wild birds, particularly in areas of the Americas, which lie within the migratory corridors for long-distance migratory birds originating from Europe and Asia. Although H5Nx viruses have been detected at higher rates in North America since 2021, a bidirectional flow of H5Nx genes of American origin viruses to Europe has never been reported. In the future, coordinated and systematic surveillance programs for HPAI viruses need to be launched between European and North American agencies.

The 1.6-megabase deletion at chromosome 3q29 (3q29Del) is the strongest identified genetic risk factor for schizophrenia, but the effects of this variant on neurodevelopment are not well understood. We interrogated the developing neural transcriptome in two experimental model systems with complementary advantages: isogenic human cortical organoids and isocortex from the 3q29Del mouse model. We profiled transcriptomes from isogenic cortical organoids that were aged for 2 and 12 months, as well as perinatal mouse isocortex, all at single-cell resolution. Systematic pathway analysis implicated dysregulation of mitochondrial function and energy metabolism. These molecular signatures were supported by analysis of oxidative phosphorylation protein complex expression in mouse brain and assays of mitochondrial function in engineered cell lines, which revealed a lack of metabolic flexibility and a contribution of the 3q29 gene PAK2. Together, these data indicate that metabolic disruption is associated with 3q29Del and is conserved across species.

Purpose: Incidental radiologic findings are commonplace, but the episodic nature of emergency department (ED) care makes it challenging to ensure that patients obtain appropriate follow-up. Rates of follow-up range from 30% to 77%, with some studies demonstrating that more than 30% have no follow-up at all. The aim of this study is to describe and analyze the outcomes of a collaborative emergency medicine and radiology initiative to establish a formal workflow for the follow-up of pulmonary nodules identified during ED care., Methods: A retrospective analysis was performed of patients referred to the pulmonary nodule program (PNP). Patients were divided into two categories: those with follow-up and those who do not have post-ED follow-up. The primary outcome was determining follow-up rates and outcomes, including patients referred for biopsy. The characteristics of patients who completed follow-up compared with those lost to follow-up were also examined., Results: A total of 574 patients were referred to the PNP. Initial follow-up was established in 390 (69.1%); 30.8% were considered lost to follow-up, and more than half of these patients did not respond to initial contact. There were minimal differences in characteristics between patients in these two categories. Of the 259 patients who completed PNP follow-up, 26 were referred for biopsy (13%)., Conclusions: The PNP provided effective transitions of care and potentially improved patient health care. Strategies to further enhance follow-up adherence will provide iterative improvement of the program. The PNP provides an implementation framework for post-ED pulmonary nodule follow-up in other health care systems and can be modified for use with other incidental diagnostic findings., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Visuospatial perspective taking (VPT) refers to the process of mentally representing a viewpoint different from one's own. It is related to mental rotation and theory of mind and helps to support some complex spatial activities such as wayfinding. Despite research advances in spatial cognition, little is known about VPT in people with Down syndrome (DS). Here, we examined VPT in people with DS. A total of 38 individuals with DS (aged 12-25 years old) and nonverbal ability-matched typically developing (TD) children (aged 4-9 years old) participated. They completed two VPT tasks: the classic Piagetian Three Mountains Task and a modified version of the "Dog Task" (Newcombe & Huttenlocher, 1992). For both groups, the Three Mountains Task was more difficult than the Dog Task, implying the impact of task complexity on assessing VPT. However, the overall performance did not differ between the TD and DS groups in either VPT task. Implications of the results were discussed., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To examine if there is a relationship between introducing a Homeless Health Outreach Team (HHOT) and reduced acute Mental Health service usage., Methods: Electronic Medical Record (EMR) data were collected on a group of clients of the Tweed Byron HHOT 6 months before and after establishing the service. The data were evaluated for demographics, and differences in Emergency Department (ED) presentations, mental health admissions, length of stay and community mental health engagement., Results: The introduction of the team coincided with a significant reduction in ED presentations and an increase in community mental health engagement. There was an overall reduction in bed days but an increase in mean length of stay for those admitted post-intervention., Conclusions: The establishment of the HHOT coincided with reduced acute mental health service usage via ED and inpatient Mental Health Units (MHU). There is scope for expansion of such a service as well as exploration of costings analysis. A long-term focus on 'housing first' and outreach approaches to homeless service provision could improve individual and service provision outcomes.

Background: Malaria during pregnancy can cause serious consequences including maternal anemia and low birthweight (LBW). Routine antenatal care (ANC) in Rwanda includes malaria symptom screening at each ANC visit. This cluster randomized controlled trial investigated whether adding intermittent screening with a malaria rapid diagnostic test at each routine ANC visit and treatment of positives during pregnancy (ISTp) is more effective than routine ANC for reducing malaria prevalence at delivery., Methods: Between September 2016 and June 2018, pregnant women initiating ANC at 14 health centers in Rwanda were enrolled into ISTp or control arms. All women received an insecticide-treated bed net at enrollment. Hemoglobin concentration, placental and peripheral parasitemia, newborn outcome, birthweight, and prematurity were assessed at delivery., Results: Nine hundred seventy-five women were enrolled in ISTp and 811 in the control group. Routine ANC plus ISTp did not significantly reduce polymerase chain reaction-confirmed placental malaria compared to control (adjusted relative risk [aRR], 0.94 [95% confidence interval {CI}, .59-1.50]; P = .799). ISTp had no impact on anemia (aRR, 1.08 [95% CI, .57-2.04]; P = .821). The mean birthweight of singleton newborns was not significantly different between arms (3054 g vs 3096 g, P = .395); however, women in the ISTp arm had a higher proportion of LBW (aRR, 1.59 [95% CI, 1.02-2.49]; P = .042)., Conclusions: This is the only study to compare ISTp to symptomatic screening at ANC in a setting where intermittent preventive treatment is not routinely provided. ISTp did not reduce the prevalence of malaria or anemia at delivery and was associated with an increased risk of LBW., Clinical Trials Registration: NCT03508349., Competing Interests: Potential conflicts of interest. D. S. reports serving as founder and board member with stock options from AliquantumRx; data and safety monitoring board (DSMB) for the National Institute of Allergy and Infectious Diseases (NIAID) safety monitoring committee/Independent Safety Monitor (SMC/ISM); royalties for malaria test from Binax Inc/D/B/A Inverness Medical; the following grants or contracts: Department of Defense (DoD) W911QY2090012 (payment to Johns Hopkins University [JHU]), NIAID 3R01AI152078-01S1 (payment to JHU), NIAID R01 AI150763-01A1, DoD TB210115 (payment to JHU), NIH/NIAID R01 AI111962-01 (payment to JHU), and NCATS R21 TR001737-01 (payment to JHU); royalties or licenses for plasmids for horseradish peroxidase aldolase for malaria diagnostic test; and patents (US patent [USP] 9 642 865, 9 May 2017, New angiogenesis inhibitors; issued USP 9 568 471, 14 February 2017, Malaria diagnosis in urine; issued USP 7 270 948, 18 September 2007, Detection of malaria parasites by laser desorption mass spectrometry; patent application #20210163522 (Salts and polymorphs of cethromycin for the treatment of disease). J. R. G. reports participation on DSMBs for the Pyrapreg study for the treatment of falciparum malaria in African pregnant women (PACTR202011812241529) and the ASPIRE trial (ClinicalTrials.gov identifier NCT04189744), and a leadership role as Co-Chair for the Roll Back Malaria, Malaria in pregnancy working group (unpaid). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Objective: Bereavement is among the most impactful psychosocial stressors for cardiovascular health, and hypertensive episodes accompanying bereavement-related distress are one putative mechanism for this effect. The present study examined hemodynamic responses to the Grief Recall (GR), a promising method for studying the effects of acute grief on cardiovascular function, and the relationship of grief severity to blood pressure (BP) response., Methods: N = 59 participants within 1 year of the loss of a close loved one completed the GR, a semistructured interview protocol for eliciting bereavement-related distress (a "grief pang") and cardiovascular response. Systolic (SBP) and diastolic BP (DBP) were measured at two time points: a) an attention-control baseline and (2) after a 10-minute GR interview. Baseline versus post-GR SBP and DBP differences (i.e., BP response) were measured. Grief severity was examined as a predictor of SBP and DBP response, as well as BP recovery., Results: SBP and DBP increased significantly after GR (SBP, +21.10 mm Hg; DBP, +8.10 mm Hg). Adjusting for variables relevant to cardiovascular function and bereavement (antihypertensive medication use, days since death, gender, age), grief severity predicted the magnitude of increase after GR in SBP but not DBP. No relationship of grief severity and recovery was observed., Conclusions: The observed association between hemodynamic response and grief severity suggests a mechanistic contribution from hemodynamic effects of acute grief episodes to the cardiovascular impact of grief. This is the first study to show that increased symptoms of prolonged grief disorder are associated with an elevated SBP response. The GR may have further utility for research examining physiological responses to bereavement-related emotions., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

This study aimed to examine the experiences of graduates of online interdisciplinary postgraduate mental health programmes in Australia. The program was delivered in 6-week terms. Seven graduates from diverse backgrounds were interviewed about their experiences with the course and its impact on their practice, confidence, professional identity, views on mental health service users, and their motivation for additional learning. The interviews were recorded and transcribed and underwent thematic content analysis. The graduates reported an increase in confidence and knowledge after completing the course, which led to a change in their views and attitudes towards service users. They appreciated the examination of psychotherapies and motivational interviewing, and applied their newly acquired skills and knowledge in their practice. The course was found to have improved their clinical practice. This study highlights a departure from traditional pedagogical approaches in mental health skill acquisition, as the entire program was delivered online. There is a need for further research to determine who might benefit most from this mode of delivery and to verify the competencies acquired by graduates in real-world situations. Online mental health courses are a feasible option and have been positively received by graduates. To enable graduates to participate in transforming mental health services, systemic change and recognition of their capabilities, particularly those from non-traditional backgrounds, is required. The results of this study suggest the potential for online postgraduate programs to play a significant role in transforming mental health services.

Measurement of antibody content and function after a viral illness is important for diagnosis and selection of the best convalescent plasma (CP) units for passive immunization. Zhang et al. (mBio 14:e03523-22, 2013, https://doi.org/10.1128/mbio.03523-22) analyzed over 19,000 coronavirus disease 2019 (COVID-19) CP (CCP) samples from the early days of the COVID-19 pandemic and reported a moderately strong correlation between antibody amount and neutralizing titer. Strikingly, about one-third of the samples had little or no neutralizing activity. The results provide a detailed glimpse of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunologically naive humans and reveal major differences in the quality of CP units collected for passive therapy before antibody screening. Heterogeneity in CCP quality undoubtedly contributed to the variable therapeutic efficacy. Analysis of the COVID-19 serology data suggest that, for the next infectious disease emergency, the best approach after quick establishment of methods for robust antibody-level stratification would be to use CP units in the top quintile of antibody content and neutralizing capacity., Competing Interests: The authors declare no conflict of interest.