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Introduction: Native bee communities of temperate forests are conventionally sampled from the understory, yet there is growing evidence that bee assemblages in forest canopies are distinct from those in the understory. Therefore, conventional approaches to quantify forest bee-habitat relationships may not comprehensively characterize forest bee communities. Methods: To examine this, we sampled bees 1--26 m from ground level at 5-m increments at 47 locations in forests located in western Massachusetts, USA. We evaluated bee abundance and species richness responses to a suite of environmental factors measured in the understory with linear and segmented regression comparing four bee sampling strategies: (1) understory sampling only, (2) understory and midstory, (3) understory and canopy, and (4) all strata combined. Results: We found that not sampling higher strata underestimated bee abundance and species richness, and linear models had less ability to explain the data when bees of higher strata were included. Among strategies, responses analyzed linearly differed in magnitude due to overall differences in abundance and species richness, but segmented regressions showed relationships with understory characteristics that also differed in slope, which would alter interpretation. Discussion: Collectively, our findings highlight the value of including vertically stratified sampling strategies throughout the flight season to fully characterize native bee and other pollinator communities of forests. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 46-year-old woman who presented with corneal nerve thickening (CNT), a characteristic feature of multiple endocrine neoplasia (MEN) type 2B. However, genetic testing revealed that she had a new lineage of MEN2A, which is typically associated with medullary thyroid carcinoma (MTC), phaeochromocytoma, and primary hyperparathyroidism. The article highlights that while CNT is commonly associated with MEN2B, it can also be present in MEN2A, emphasizing the importance of considering both syndromes when CNT is detected. The study also discusses the intrafamilial variation in the presence and degree of CNT in families with MEN2A. [Extracted from the article]

Purpose: Paediatric patients with heart failure requiring ventricular assist devices are at heightened risk of neurologic injury and psychosocial adjustment challenges, resulting in a need for neurodevelopmental and psychosocial support following device placement. Through a descriptive survey developed in collaboration by the Advanced Cardiac Therapies Improving Outcomes Network and the Cardiac Neurodevelopmental Outcome Collaborative, the present study aimed to characterise current neurodevelopmental and psychosocial care practices for paediatric patients with ventricular assist devices., Method: Members of both learning networks developed a 25-item electronic survey assessing neurodevelopmental and psychosocial care practices specific to paediatric ventricular assist device patients. The survey was sent to Advanced Cardiac Therapies Improving Outcomes Network site primary investigators and co-primary investigators via email., Results: Of the 63 eligible sites contacted, responses were received from 24 unique North and South American cardiology centres. Access to neurodevelopmental providers, referral practices, and family neurodevelopmental education varied across sites. Inpatient neurodevelopmental care consults were available at many centres, as were inpatient family support services. Over half of heart centres had outpatient neurodevelopmental testing and individual psychotherapy services available to patients with ventricular assist devices, though few centres had outpatient group psychotherapy (12.5%) or parent support groups (16.7%) available. Barriers to inpatient and outpatient neurodevelopmental care included limited access to neurodevelopmental providers and parent/provider focus on the child's medical status., Conclusions: Paediatric patients with ventricular assist devices often have access to neurodevelopmental providers in the inpatient setting, though supports vary by centre. Strengthening family neurodevelopmental education, referral processes, and family-centred psychosocial services may improve current neurodevelopmental/psychosocial care for paediatric ventricular assist device patients.

The U.S. Coast Guard led a clean-up response to the Deepwater Horizon (DWH) oil spill, the largest marine oil spill in history. Studies from the Deepwater Horizon Coast Guard Cohort (DWH-CG) have shown associations between crude oil exposure and various acute symptoms and longer-term health outcomes. Evidence has suggested genetic polymorphisms in metabolizing genes could modify the toxicity of crude oil and its components, which could impact health effects in responders exposed to crude oil. We applied log-binomial regression to calculate prevalence ratios (PRs) and 95 % confidence intervals (CIs) in the relationship between crude oil exposure (categorized to never, low, and high) and four acute symptoms (cough, shortness of breath/wheeze, skin rash/itching, headache) and to calculate risk ratios (RR) and 95 % CIs in the relationship between crude oil exposure and incidence of hypertension and asthma in the DWH-CG cohort. Effect modification by polymorphisms in 6 metabolizing genes [Cytochrome P450 family 2 subfamily E member 1 (CYP2E1), Glutathione S-Transferase Mu 1 (GSTM1), Glutathione S-Transferase Theta 1 (GSTT1), Epoxide Hydrolase 1 (EPHX1), NADPH quinone oxidoreductase-1 (NQO1), and Myeloperoxidase (MPO)] was evaluated. Results were stratified into wildtype and variant [i.e., those with at least one variant allele] for each gene. There was evidence of effect modification in the relationship between crude oil exposure and asthma by CYP2E1 [wildtype (RR High vs never/low , 95 % CI = 1.18, 0.99-1.42); variant (RR High vs never/low, 95 % CI = 2.27, 1.26-4.10); p interaction  = 0.04] and headache by NQO1 [wildtype (PR High vs never/low , 95 % CI = 2.1, 1.88-2.34); variant (PR High vs never/low , 95 % CI = 1.44, 1.07-1.94); p interaction  = 0.04]. Our study indicated the potential effect modification by metabolizing genotype in the relationship between crude oil exposure and headaches or asthma. These findings underscore the importance of considering potential genetic susceptibility among oil spill responders. Genotype variations, which are revealed only via specialized testing and thus not readily apparent, may contribute to differential vulnerability to the health effects associated with oil spill exposures., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jennifer A. Rusiecki reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Brain imaging performed in natural settings is known as mobile brain and body imaging (MoBI). One of the features which distinguishes MoBI and laboratory-based experiments is the body posture. Previous studies pointed to mechanical, autonomic, cortical and cognitive differences between upright stance and sitting or reclining. The purpose of this study was to analyse effects of posture on eye-movement related potentials (EMRP) recorded during free viewing of human faces. A 64-channel wireless EEG was recorded from 14 participants in either standing or reclining postures while they freely viewed pictures of emotional faces displaying fear, anger, sadness, and a neutral emotional state. Eye tracking data was used to insert triggers corresponding to the instant at which the gaze first landed on a face. Spatial filtering of the EEG data was performed using a group independent component analysis (ICA). Grand average EMRPs displayed the post-saccadic lambda component and the face-sensitive N170/vertex positive potential (VPP) complex. The lambda component but not the N170 component was stronger during reclining than upright posture. Emotional expression of faces showed no effects on EMRP components or subjective ratings. Results suggest that posture primarily affects early components of EMRPs recorded using wireless EEG recordings during free viewing of faces. Thus, findings from evoked potential data obtained in seated individuals, e.g., in laboratory experiments, should be interpreted with caution in MoBI experiments with posture affecting primarily the early latency component., 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 © 2024 Soto, Tyson-Carr, Kokmotou, Roberts, Byrne, Hewitt, Fallon, Giesbrecht and Stancak.)

Statement of Problem: The effect of 3-dimensional (3D) printed crown materials with lower flexural strength but higher ductility than lithium disilicate on enamel wear and fatigue resistance is unknown., Purpose: The purpose of this in vitro study was to compare the enamel wear and fatigue resistance of a 50% filled 3D printed crown material with lithium disilicate., Material and Methods: Disks of a 3D printed crown material (Ceramic Crown; SprintRay Inc) and lithium disilicate (IPS e.max CAD; Ivoclar AG) (n=8) were tested for wear in a custom Alabama wear testing device which applied a 20-N load and 2-mm horizontal slide. The test was run for 400 000 cycles at 1 Hz in a 33% glycerin solution. Cusps of extracted human molars were used as the antagonists. The volumetric wear of the restorative material and enamel antagonists were measured every 100 000 cycles using a profilometer. Worn specimens were examined with a scanning electron microscope. Human molars were prepared for occlusal onlay preparations, and 1.2-mm 3D printed (Ceramic Crown) or lithium disilicate (IPS e.max CAD) restorations (n=10) were bonded to the teeth with resin cement. Restorations were subjected to 2 million cycles of fatigue loading (50 N, 1 Hz) in water against a Ø7.8-mm steel ball. Restorations were monitored for cracks every 100 000 cycles with transillumination and every1 million cycles with microcomputed tomography (µCT). After fatigue, specimens were fractured in a load-to-failure test. Fractured specimens were examined with µCT. Statistical analyses were performed with 2-way mixed ANOVAs and a t test (α=.05)., Results: The wear and opposing enamel wear of lithium disilicate was greater than the 3D printed material at every interval of cycles tested (P<.001). None of the restorations showed signs of internal cracks up to 2 million cycles of fatigue. No statistical difference was found in the load-to-failure fracture load of the 3D printed (2574 ±303 N) or lithium disilicate (2396 ±277 N) restorations (P=.110)., Conclusions: For the conditions tested, the 3D printed crown material demonstrated less wear than lithium disilicate and created less opposing enamel wear. All the occlusal onlay restorations survived 2 million cycles of fatigue at a 50-N load without signs of cracks. These results provide some support for the use of these restorations at 1.2-mm occlusal thickness when bonded with a resin cement., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objective: Use of the Heart Team has been the standard of care for the treatment of aortic valve disease; however, its efficacy has not been evaluated. We sought to analyze its impact using the transcatheter aortic valve replacement (TAVR) use ratio (number of TAVR/total aortic valve replacement [AVR] volume) on TAVR, surgical aortic valve replacement (SAVR), and overall AVR outcomes., Methods: We analyzed all TAVRs and SAVRs sampled by the National Readmissions Database between 2016 and 2020. Hospitals were stratified into quartiles on the basis of their TAVR/AVR ratio. Centers with a ratio below the first quartile were considered "low ratio," centers in the second and the third quartile "balanced ratio," and centers above the third quartile "high ratio." Primary outcomes were 30-day mortality and complication rate, which included stroke, renal failure, heart block, pacemaker placement, and valve regurgitation., Results: For overall AVR outcomes, centers with a balanced ratio had lower mortality compared with centers with low ratio (1.9% vs 2.1%, P = .01) and lower complication rate compared with centers with high ratio (34.8% vs 36.8%, P < .001). Centers with a balanced ratio had lower TAVR complication rate compared with centers with low ratio (37.3% vs 39%, P < .001). For SAVR outcome, centers with an balanced ratio had lower post-SAVR mortality (2.1% vs 2.6%, P < .001) and complication rate (28.6% vs 30.3%, P < .001) than centers with high ratio., Conclusions: Centers with balanced TAVR ratios had superior outcomes compared with centers with low or high ratios. These data support the use of a balanced Heart Team to optimize AVR outcomes., Competing Interests: Conflict of Interest Statement T.K. is a speaker for Edwards Life Sciences and Medtronic and a consultant for Baylis Medical and 4C. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Research investigating gastrointestinal (GI) symptoms from oil spill-related exposures is sparse. We evaluated prevalent GI symptoms among U.S. Coast Guard responders deployed to the Deepwater Horizon oil spill cleanup., Methods: Crude oil (via skin contact, inhalation, or ingestion routes), combined crude oil/oil dispersant exposures, other deployment exposures, deployment characteristics, demographics, and acute GI symptoms during deployment (i.e., nausea/vomiting, diarrhea, stomach pain, and constipation) were ascertained cross-sectionally via a post-deployment survey (median time between deployment end and survey completion 185 days) (N = 4885). Log-binomial regression analyses were employed to calculate prevalence ratios (PRs) and 95 % confidence intervals (CI). Effect modification was evaluated., Results: In adjusted models, responders in the highest (versus lowest) tertile of self-reported degree of skin contact to crude oil were more than twice as likely to report nausea/vomiting (PR=2.45; 95 %CI, 1.85-3.23), diarrhea (PR=2.40; 95 %CI, 2.00-2.88), stomach pain (PR=2.51; 95 %CI, 2.01-3.12), and constipation (PR=2.21; 95 %CI, 1.70-2.89). Tests for trend were statistically significant (p < 0.05). Results were similar for crude oil exposure via inhalation and ingestion. Higher PRs for all symptoms were found with combined crude oil/dispersant exposure than with crude oil exposure alone., Conclusions: These results indicate positive associations between self-reported crude oil and combined crude oil/oil dispersant exposures and acute GI symptoms., 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., (Published by Elsevier Inc.)

In combination with cell-intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with neoadjuvant chemotherapy and radiotherapy. We developed spatially constrained optimal transport interaction analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an ex vivo tumoroid coculture system. We identified enrichment in interleukin-6 family signaling that functionally confers resistance to chemotherapy. Overall, this study demonstrates that characterization of the tumor microenvironment using single-cell spatial transcriptomics allows for the identification of molecular interactions that may play a role in the emergence of therapeutic resistance and offers a spatially based analysis framework that can be broadly applied to other contexts., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Alzheimer's disease (AD) disproportionately affects women, yet most preclinical research studies are male-centric. We performed lifespan analyses of male and female AD mouse models (APP/PS1 and APP NL-F/NL-F ) and their shared genetic background control (C57BL/6). Survival curves support significant sex differences between within genotypes. Minimal longevity revealed increased age in male APP/PS1, and decreased age in APP NL-F/NL-F mice. Maximal longevity revealed an increased average age in males. Furthermore, median lifespan differed between sex and genotype. This study supports sexual dimorphic survival in two mouse models of AD, emphasizing the need to examine mechanisms and treatments in both sexes., Competing Interests: CONFLICT OF INTEREST/ DISCLOSURE STATEMENT The authors have no conflict of interest to report.

In recent years, the number of Doctor of Osteopathic Medicine (DO) residents entering general surgery has increased. As DOs continue to solidify their role within the surgical domain, understanding their distribution, preferences, and the dynamics of their integration into residency programs becomes crucial for general surgery applicants. Publicly available data were gathered for each DO general surgery resident from residency programs across the nation, including details such as post-graduate year, degrees held, and residency program location. A comprehensive cross-sectional analysis was conducted to determine the geographical distribution and match trends of DO residents in these residency programs. Analysis revealed a significant rise in the number of DOs entering general surgery residencies, from 153 DO trainees beginning their residency training in 2019 to 274 DO trainees beginning their residency training in 2024. This upward trend indicates a growing presence of DOs in surgical practice. Examination of the geographical locations of programs for which DO applicants have matched showed variations nationwide. This analysis allows for a deeper understanding of the evolving match trends for DOs in surgery. It highlights the importance of addressing disparities in access to surgical training opportunities for osteopathic physicians nationwide., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ernst et al.)

Aim: Chronic stroke walking impairment is associated with high healthcare resource utilization (HCRU) costs. InTandem™ is a neurorehabilitation system that autonomously delivers a rhythmic auditory stimulation (RAS)-based intervention for the at-home rehabilitation of walking impairment in adults in the chronic phase of stroke recovery. This study was conducted to estimate the budget impact of InTandem in comparison with currently available intervention strategies for improvement of gait/ambulation in individuals with chronic stroke walking impairment. Methods & materials: A budget impact analysis (BIA) for InTandem was conducted based on a 1-million-member US third-party payer perspective over a 1-year time horizon. Key inputs for the budget impact model were: costs for each intervention strategy (InTandem, physical therapy, self-directed walking and no treatment), HCRU costs for persons with chronic stroke and anticipated HCRU cost offsets due to improvements in gait/ambulatory status as measured by self-selected comfortable walking speed (based on functional ability). In addition to the reference case analysis, a sensitivity analysis was conducted. Results: Based on the reference case, introduction of InTandem was projected to result in overall cost savings of $439,954 in one year. Reduction of HCRU costs (-$2,411,778) resulting from improved walking speeds with InTandem offset an increase in intervention costs (+$1,971,824). Demonstrations of cost savings associated with InTandem were robust and were consistently evident in nearly all scenarios evaluated in the sensitivity analysis (e.g., with increased/decreased patient shares, increased HCRU cost or increased InTandem rental duration). Conclusion: The InTandem system is demonstrated to improve walking and ambulation in adults in the chronic phase of stroke recovery after a five-week intervention period. The BIA predicts that introduction of InTandem will be associated with overall cost savings to the payer.

It is unknown if an online tool is wanted by therapists and parents of individuals with unilateral cerebral palsy (UCP) to support implementation of goal-directed home programs, and if wanted, the recommended features for the tool. The objective was to explore the experiences of therapists and parents who have implemented home programs, seek guidance on translating a paper-based home program toolbox into a mobile website, and develop the website. Qualitative descriptive methodology guided data collection using semi-structured interviews and thematic analysis, validated with field notes and member checking. A team science, iterative approach was used to integrate the themes into the development of the mobile website. Five primary themes including recommendations for the functionality, features, content, and naming of the mobile website were identified. Parents and therapists value home programs. Participants provided recommendations regarding content and features, and the GO Move mobile website was developed based on the recommendations., 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.

Rumination is a vulnerability for depression and potentially linked to inhibitory control weaknesses. We aimed to replicate the association observed in adults between inhibitory control and rumination in adolescents, and to examine putative moderating roles of childhood maltreatment and perceived family cohesion in an adolescent sample at risk for depression due to familial/personal history. Ninety adolescents aged 11-17 (M = 14.6, SD = 1.8) completed self-report scales of rumination, maltreatment, and family cohesion, and performed a task assessing inhibitory control. Hierarchical regression models showed no significant relation between inhibitory control and moderator variables on rumination. However, adolescents who reported higher levels of maltreatment and who perceived lower family cohesion tended to indicate higher levels of rumination (B Chilhood Maltreatment = 27.52, 95% CIs [5.63, 49.41], B Family Cohesion = -0.40, 95% CIs [-0.65, -0.15]). These findings demonstrate an alternative understanding of factors that increase depression onset risk and recurrence in adolescents., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Research has highlighted the psychosocial impact of living with food hypersensitivities (FHS) on children and young people (CYP). However, there is a paucity of qualitative data from CYP themselves in terms of the support they would like to receive to improve their psychological well-being., Objective: To further understand firsthand the experiences of CYP with FHS including the challenges they face and to inform structural changes in how their psychological well-being is supported., Methods: CYP aged 8 to 17 years were recruited with self-reported food allergy or celiac disease and asked about their experiences of living with and the psychological impact of FHS, through online, semistructured interviews. Interviews were transcribed verbatim, and data were analyzed using reflexive thematic analysis., Results: A total of 25 CYP participated in the interviews. Three themes were generated, which addressed an aspect of change that CYP felt would enable support and improve their well-being: desire to feel heard, need for control, and appreciation of the severity of their FHS., Conclusion: This is the first study to investigate what CYP with FHS would find beneficial for their psychological well-being with recommendations provided as to how these may be implemented across various systems. Recommendations include health professionals being more aware of the psychosocial impact from diagnosis, schools being more open and consistent with FHS management strategies, and friends being educated on the management of FHS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and rapidly progressive malignancy. A major challenge in patient management is the lack of a reliable imaging tool to monitor tumor response to treatment. Tumor-associated fibrosis characterized by high type I collagen is a hallmark of PDAC, and fibrosis further increases in response to neoadjuvant chemoradiotherapy (CRT). We hypothesized that molecular positron emission tomography (PET) using a type I collagen-specific imaging probe, 68 Ga-CBP8 can detect and measure changes in tumor fibrosis in response to standard treatment in mouse models and patients with PDAC. Methods: We evaluated the specificity of 68 Ga-CBP8 PET to tumor collagen and its ability to differentiate responders from non-responders based on the dynamic changes of fibrosis in nude mouse models of human PDAC including FOLFIRNOX-sensitive (PANC-1 and PDAC6) and FOLFIRINOX-resistant (SU.86.86). Next, we demonstrated the specificity and sensitivity of 68 Ga-CBP8 to the deposited collagen in resected human PDAC and pancreas tissues. Eight male participant (49-65 y) with newly diagnosed PDAC underwent dynamic 68 Ga-CBP8 PET/MRI, and five underwent follow up 68 Ga-CBP8 PET/MRI after completing standard CRT. PET parameters were correlated with tumor collagen content and markers of response on histology. Results: 68 Ga-CBP8 showed specific binding to PDAC compared to non-binding 68 Ga-CNBP probe in two mouse models of PDAC using PET imaging and to resected human PDAC using autoradiography (P < 0.05 for all comparisons). 68 Ga-CBP8 PET showed 2-fold higher tumor signal in mouse models following FOLFIRINOX treatment in PANC-1 and PDAC6 models (P < 0.01), but no significant increase after treatment in FOLFIRINOX resistant SU.86.86 model. 68 Ga-CBP8 binding to resected human PDAC was significantly higher (P < 0.0001) in treated versus untreated tissue. PET/MRI of PDAC patients prior to CRT showed significantly higher 68 Ga-CBP8 uptake in tumor compared to pancreas (SUV mean : 2.35 ± 0.36 vs. 1.99 ± 0.25, P = 0.036, n = 8). PET tumor values significantly increased following CRT compared to untreated tumors (SUV mean : 2.83 ± 0.30 vs. 2.25 ± 0.41, P = 0.01, n = 5). Collagen deposition significantly increased in response to CRT (59 ± 9% vs. 30 ± 9%, P=0.0005 in treated vs. untreated tumors). Tumor and pancreas collagen content showed a positive direct correlation with SUV mean (R 2 = 0.54, P = 0.0007). Conclusions: This study demonstrates the specificity of 68 Ga-CBP8 PET to tumor type I collagen and its ability to differentiate responders from non-responders based on the dynamic changes of fibrosis in PDAC. The results highlight the potential use of collagen PET as a non-invasive tool for monitoring response to treatment in patients with PDAC., Competing Interests: Competing Interests: PC has equity in and is a consultant to Collagen Medical LLC, has equity in Reveal Pharmaceuticals Inc., and has research support from Transcode Therapeutics and Pliant Therapeutics. PC is a co-inventor of US Patent 10,471,162 which covers 68Ga-CBP8 and is assigned to the General Hospital Corporation. SE has research support from Sofie Biosciences, Telix, and Novartis Pharmaceuticals. ARP has held Equity in C2i Genomics, XGenomes, Cadex, Vionix and Parithera. In the last 36 months, she has served as an advisor/consultant for Eli Lilly, Mirati, Pfizer, Inivata, Biofidelity, Checkmate Pharmaceuticals, FMI, Guardant, Abbvie, Bayer, Delcath, Taiho, CVS, Value Analytics Lab, Seagen, Saga, AZ, Scare Inc, Illumina, Taiho, Hookipa, Kahar Medical, Xilio Therapeutics, Sirtex, Takeda, and Science For America. She receives fees from Up to Date. She has received travel fees from Karkinos Healthcare. She has been on the DSMC for a Roche study and on the Steering Committee for Exilixis. She has received research funding to the Institution from PureTech, PMV Pharmaceuticals, Plexxicon, Takeda, BMS, Mirati, Novartis, Erasca, Genentech, Daiichi Sankyo, Syndax, Revolution Medicine and Parthenon. UM is a co-founder, shareholder, and consultant (Scientific Advisory Board) of CytoSite BioPharma. TSH is a consultant for Synthetic Biologics, Novocure, Boston Scientific, Neogenomics, Merck, GSK, NextCure, serves on the advisory board of PanTher Therapeutics (Equity), and Lustgarten Foundation, and has received research funding from Taiho, Astra-Zeneca, BMS, GSK, ItraOp and Ipsen. GMB has sponsored research agreements through her institution with: Olink Proteomics, Teiko Bio, InterVenn Biosciences, Palleon Pharmaceuticals. She served on advisory boards for Iovance, Merck, Nektar Therapeutics, Novartis, and Ankyra Therapeutics. She consults for Merck, InterVenn Biosciences, Iovance, and Ankyra Therapeutics. She holds equity in Ankyra Therapeutics. Other authors declare that they have no competing interests., (© The author(s).)

Introduction: Walking or gait impairment is a common consequence of stroke that persists into the chronic phase of recovery for many stroke survivors. The goals of this work were to obtain consensus from a multidisciplinary panel on current practice patterns and treatment options for walking impairment after stroke, to better understand the unmet needs for rehabilitation in the chronic phase of recovery and to explore opportunities to address them, and to discuss the potential role of rhythmic auditory stimulation (RAS) in gait rehabilitation., Methods: A panel of eight experts specializing in neurology, physical therapy, and physiatry participated in this three-part, modified Delphi study. Survey 1 focused on gathering information to develop statements that were discussed and polled during Survey 2 (interactive session), after which revised and new statements were polled in Survey 3. Consensus was defined as ≥75% (6/8 of panelists) agreement or disagreement with a statement., Results: Consensus agreement was ultimately reached on all 24 statements created and polled during this process. The panelists agreed that individuals with gait or walking impairment in the chronic phase of stroke recovery can achieve meaningful improvement in walking by utilizing various evidence-based interventions. Barriers to treatment included cost, access, participation in long-term treatment, and safety. Consensus was achieved for interventions that have the following features challenging, personalized, accessible, and engaging. Improvement of gait speed and quality, durability of effect, safety, affordability, and ability for home or community use also emerged as important treatment features. In addition to conventional treatments (e.g., physical therapy, including mobility-task training and walking/exercise therapy), RAS was recognized as a potentially valuable treatment modality.  Discussion: This panel highlighted limitations of current treatments and opportunities to improve access, participation, and outcomes through a consideration of newer treatment strategies and patient/healthcare provider education and engagement., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Kirsten E. Smayda declare(s) employment and stock/stock options from MedRhythms. KES is an employee of, and holds equity in, MedRhythms. Sabrina R. Taylor declare(s) employment and stock/stock options from MedRhythms. SRT is an employee of, and holds equity in, MedRhythms. David J. Lin declare(s) personal fees from MedRhythms. David Lin is a consultant for MedRhythms. Holly Roberts declare(s) personal fees from MedRhythms. HR is an independent consultant and has received professional fees from MedRhythms. Other relationships: DKR receives research funding (NIH R21AG076972: co-investigator, NIH R01AG081477-01: co-investigator, Florida Department of Health 20K08: principal investigator, VA RR&D RX003542: principal investigator) and is a consultant for Eversana and MedRhythms. CJW receives research funding (NIH R41 HD104296: principal investigator academic subcontract, NIH/NINDS R21 NS120264: co-investigator, and NIH/NICHD R01 HD059783: multiple principal investigator); is a contributing editor for and receives royalties from Human Kinetics, Motor Control and Learning, 6th edition and Demos Medical, Stroke Recovery and Rehabilitation, 2nd edition; serves as an external advisory board member/consultant for MicroTransponder, Inc., MedRhythms, Inc., and Axem Neurotechnology, Inc.; and serves on the data and safety monitoring boards for Enspire DBS Therapy, Inc., and Brain Q (Syntactx, LLC). MDL receives research funding (NIH R21-HD111833, NIH R01-HD110519, NIH R01-HD111074, NIDILRR REGE22000170, NSF 2306659) and is an editor of and receives royalties from FA Davis, Joint Structure and Function: A Comprehensive Analysis, 6th edition. DJL provides consultative input for the MGH Translational Research Center on a clinical research support agreement with MedRhythms. HR is an independent consultant and has received professional fees from MedRhythms. PR receives research funding (NIH R61AT012279, R61AT012286, American Heart Association, the Johns Hopkins Sheikh Khalifa Stroke Institute, and MedRhythms, Inc.); is an editor of and receives royalties from Elsevier, Stroke Rehabilitation, and Springer Nature, Spasticity and Muscle Stiffness: Restoring Form and Function; and is the co-founder of Mirrored Motion Works, Inc. and Movease, Inc. MWO serves as an advisory board member for Merz, Inc., (Copyright © 2024, Rose et al.)

Objective: To systematically review the literature describing children and young people (CYP) admissions to paediatric general wards because of primary mental health (MH) reasons, particularly in MH crisis., Design: PubMed, Embase, PsycINFO, Web of Science and Google Scholar were searched, with no restriction on country or language. We addressed five search questions to inform: trends and/or the number of admissions, the risk factors for adverse care, the experiences of CYP, families/carers and healthcare professionals (HCPs) and the evidence of interventions aimed at improving the care during admissions.Two reviewers independently assessed the relevance of abstracts identified, extracted data and undertook quality assessment. This review was registered with PROSPERO (CRD42022350655)., Results: Thirty-two studies met the inclusion criteria. Eighteen addressed trends and/or numbers/proportions of admissions, 12 provided data about the views/experiences of HCPs, two provided data about CYP's experiences and four explored improving care. We were unable to identify studies examining risk factors for harm during admissions, but studies did report the length of stay in general paediatric/adult settings while waiting for specialised care, which could be considered a risk factor while caring for this group., Conclusions: MH admissions to children's wards are a long-standing issue and are increasing. CYP will continue to need to be admitted in crisis, with paediatric wards a common location while waiting for assessment. For services to be delivered effectively and for CYP and their families/carers to feel supported and HCPs to feel confident, we need to facilitate more integrated physical and MH pathways of care., Prospero Registration Number: CRD42022350655., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: There is no agreed standard assessment of the minimum knowledge and skills that are required to provide healthcare to participants in individual or team sports. This study aims to develop a syllabus for the Faculty of Sport and Exercise Medicine (FSEM) Team Care Diploma examination. This will provide a recognised assessment of the minimum required skills and knowledge for healthcare professionals providing care in an individual and team sport environment., Methods: A modified Delphi approach was used. A syllabus was developed by a purposeful selection of members of the FSEM, all of whom have significant team care experience. This was then reviewed by the Delphi expert panel who were team care practitioners with at least 5 years of experience. A two-round Delphi approach was used to develop a consensus., Results: The expert panel consisted of 50 individuals, with 46 (92%) completing both rounds. Of the 447 learning objectives (LOs) proposed; 430 (96%) were accepted outright, 17 (4%) were rejected and four new LOs were introduced based on expert panel feedback. The final syllabus contained 434 LOs across 6 modules (clinical governance, safe and effective practice, interdisciplinary teamwork, specific athlete groups, specific health conditions and duties of the medical team)., Conclusion: This standardised syllabus will be used as the basis for the new FSEM Team Care Diploma examination which will aim to provide world-leading standardised assessment of the minimum skills and knowledge required for healthcare professionals across the multidisciplinary team providing care in individual and team sport., Competing Interests: None declared., (Copyright © 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.)

Objectives: Open tibia fractures are associated with substantial morbidity and impact on quality of life. Despite increasing incidence in low-resource settings, most open tibia fracture research comes from high-resource settings. This study aimed to assess the impact of socioeconomic status on treatment modality and evaluate predictors of health-related quality of life following open tibia fractures in Ghana., Design: A single-center prospective observational study was conducted in Kumasi, Ghana, from May 2020 to April 2022. Adults with open tibial shaft fractures presenting within 2 weeks of injury were eligible. Demographics, comorbidities, socioeconomic factors, and hospital course were collected at enrollment. Follow-up was scheduled at 8, 12, 26, and 52 weeks. A telephone survey assessing reasons for loss to follow-up was initiated on enrollment completion., Results: A total of 180 patients were enrolled. Most patients were employed before injury (79.9%), had government insurance (67.2%), and were from rural areas (59.4%). Fracture classification was primarily Gustilo-Anderson type 3A (49.1%). No relationship between socioeconomic predictors and treatment modality was identified. The largest barriers to follow-up were preference for bonesetter treatment (63.1%), treatment cost (48.8%), and travel cost (29.8%). Of the lost to follow-up patients contacted, 67 (79.8%) reported receiving traditional bonesetter care. Reasons for seeking traditional bonesetter care included ease of access (83.6%), lower cost (77.6%), and familial influence (50.7%)., Conclusion: No association was identified between socioeconomic predictors and choice of treatment. Bonesetter treatment plays a substantial role in the care of open tibia fractures in Ghana, largely because of ease of access and lower cost., Competing Interests: The authors have no conflict of interest to report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Competing Interests: The authors declare no conflicts of interest.

Objective: The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in most bothersome symptom, distress, bother or interference of genitourinary symptoms, satisfaction with treatment, and side effects., Methods: We conducted a systematic review to identify possible definitions and PROMs, including their measurement properties. Identified definitions and relevant PROMs with acceptable measurement properties were entered into an international consensus process involving 28 participants from 10 countries to achieve final recommendations for each core outcome., Results: A total of 87 publications reporting on 34 PROMs were identified from 21,207 publications screened. Of these 34 PROMs, 29 were not considered to sufficiently map onto the core outcomes, and 26 of these also had insufficient measurement properties. Therefore, only five PROMs corresponding to two core outcomes were considered for recommendation. We recommend the PROMIS Scale v2.0 - Sexual Function and Satisfaction: Vaginal Discomfort with Sexual Activity to measure the outcome of "pain with sexual activity" and the Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire to measure "distress, bother or interference" from genitourinary symptoms. Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events in study participants, which is a requirement of Good Clinical Practice., Conclusions: Suitable PROMs and definitions were identified to measure three of eight core outcomes. Because of the lack of existing measures, which align with the core outcomes and have evidence of high-quality measurement properties, future work will focus on developing or validating PROMs for the remaining five core outcomes., Competing Interests: Financial disclosure/conflicts of interest: M.G. received past funding from Effik SA. M.P. received institutional funding from University of Melbourne (Internal Grant Schemes), Royal Women's Hospital (Internal grant scheme), and Cancer Council NSW Project Grant RG 21-06, Centre for Research Excellence in Women's Health in Reproductive Life (CREWHiRL) Seed Funding and Project Support Grant, NHMRC (APP1163202), and Royal Children's Hospital Foundation. She received past funding from FertilityIQ webinar honorarium. She has received fee registration fees as an invited speaker by the Pacific Society of Reproductive Medicine 2023 Conference and had subsidized flights and accommodations as an invited speaker for the European Society of Human Reproduction and Embryology 2022 Conference. She was also given free registration as an invited speaker for the Annual Scientific Meeting of Breast Cancer Trials 2021. D.A. has consulted for Evestra, Exeltis, Lupin, Mithra, ObsEva, and TherapeuticsMD, received industry support for research from AbbVie, Mithra, Myovant, and ObsEva, and has stock holdings in Agile Therapeutics and InnovaGyn, Inc. R.B. was named CI on two grants to Monash University, one from the National Health and Medical Research Council of Australia and one from the Medical Research Future Fund for work not related to the current publication. M.C. has been paid for developing and delivering educational presentations for AllianceChicago, wrote a White Paper on GSM for Materna (no financial reimbursement), and is a member of The Menopause Society Board of Trustees, FDA BRUDAC Committee, and Grand Rounds Presenter University of Indians. S.R.D. reports honoraria from BesinsHealthcare, Mayne Pharma, Health Ed, BioSyent, Lawley Pharmaceuticals, Abbott Laboratories, and Que Oncology. She has served on advisory boards for Mayne Pharm, Astellas Pharmaceuticals, Theramex, Abbott Laboratories, and Gedeon Richterand and has been an institutional investigator for QueOncology and Ovoca Bio. L.K. has lectured and/or acted in an advisory capacity for Gedeon Richter, Dr. KADE Besins and Mithra. C.M.M. has served as a consultant for Scynexis and Ferring Pharmaceuticals, receives research funding from Scynexis, and receives Royalties from UpToDate. R.E.N. has ongoing relationships with Abbott, Astellas, Bayer HealthCare AG, Besins Healthcare, Exeltis, Fidia, Gedeon Richter, HRA Pharma, Merck Healthcare, Novo Nordisk, Shionogi Limited, Theramex, and Viatris. N.P. has lectured and/or acted in an advisory capacity for Abbott, Bayer, Besins, Gedeon Richter, Kora, Lawley, Mithra, Mylan, Novo Nordisk, Roche Diagnostics, SeCur, Shionogi, Theramex, and Viatris. S.R. has lectured and/or acted in an advisory capacity or conducted studies for Abbott, Bayer, Gedeon Richter, Mylan, Amgen, UCB, Theramex, and Viatris. J.S. receives grant/research support from AbbVie, Inc., Bayer Healthcare LLC., Dare´ Bioscience, Ipsen, Mylan/Viatris Inc., Myovant Sciences, and Sebela Pharmaceuticals Inc. He acts as a consultant is on advisory boards for Bayer HealthCare Pharmaceuticals Inc., Besins Healthcare, California Institute of Integral Studies (CIIS), Dare´ Bioscience, Femasys Inc., Khyria, Madorra Pty Ltd., Mayne Pharma, Inc., and Vella Bioscience Inc. He serves on speaker's bureaus for Astellas Pharma, Inc., Mayne Pharma, Inc., Myovant Sciences, Inc., Pfizer Inc., Pharmavite LLC., and Scynexis Inc. He is a stockholder (direct purchase) of Sermonix Pharmaceuticals. P.S. has received fees for giving educational presentations, and participating in advisory boards and conducting research by Besins Healthcare, Astellas, Mylan, Labatec, Exeltis, Effik, Theramex, and Gedeon-Richter. A.J.V. has received fees for presentations and participation in an advisory board from Besins and Theramex. W.W. has received institutional support with an unrestricted grant from Pfizer and sits on the advisory boards of Pfizer, Lupin, and Biosyent. She has received fees for educational presentations for Lupin, Astellas, Bayer and Pfizer, and Biosyent. She is currently president of the Canadian Menopause Society and a Board Member of the International Menopause Society. M.H. has received funding from Madorra for a study of a device to manage GU symptoms. All other authors report no conflicts of interest., (Copyright © 2024 by The Menopause Society.)

Objective: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects., Methods: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome., Results: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice., Conclusions: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes., Competing Interests: Financial disclosure/conflicts of interest: V.P. received past funding from Sigvaris AG. M.P. received institutional funding from University of Melbourne (Internal Grant Schemes), Royal Women's Hospital (Internal grant scheme), and Cancer Council NSW Project Grant RG 21-06, Centre for Research Excellence in Women's Health in Reproductive Life (CREWHiRL) Seed Funding and Project Support Grant, NHMRC (APP1163202), and Royal Children's Hospital Foundation. She received past funding from FertilityIQ webinar honorarium. She has received fee registration fees as an invited speaker by the Pacific Society of Reproductive Medicine 2023 Conference and had subsidized flights and accommodations as an invited speaker for the European Society of Human Reproduction and Embryology 2022 Conference. She was also given free registration as an invited speaker for the Annual Scientific Meeting of Breast Cancer Trials 2021. D.A. has consulted for Evestra, Exeltis, Lupin, Mithra, ObsEva, and TherapeuticsMD, received industry support for research from AbbVie, Mithra, Myovant, and ObsEva, and has stock holdings in Agile Therapeutics, InnovaGyn, Inc. N.A. receives ongoing institutional funding from the National Cancer Institute. J.C. is owner of JSCarpenter, LLC which received scale licensing fees from Mapi Research Trust (2022), consulting fees from the University of Wisconsin (spring 2022), and consulting fees from Simumetrix SMX Health (spring 2022). M.C. has been paid for developing and delivering educational presentations for Alliance Chicago, received fees for an educational video and speaking engagements with Fertility IQ, wrote a White Paper on GSM for Materna (no financial reimbursement), and is a member of The Menopause Society Board of Trustees. M.D. receives current institutional funding from National Institute of Health Research. She serves as a chief investigator on POISE study (research relevant to HRT) and a chief investigator for BLUSH study (research on treatment of menopause). She received past institutional funding from Best Practice & Research Clinical Obstetrics & Gynaecology as editor of volume on menopause management published 2022. She is an elected member of the Medical Advisory Council of the British Menopause Society, is a member of the ESHRE guideline update group on Premature Ovarian Insufficiency, is a member of the British Endocrine Society working group producing clinical guidelines on estrogen treatment, and is a member of the British Gynaecological Cancer Society working group producing clinical guidelines on HRT. T.H. received past funding from Besins and Astellas. M.H. receives ongoing funding from Rightsteps and current funding from Hello Therapeutics. L.K. has lectured and/or acted in an advisory capacity for Gedeon Richter, Dr. KADE Besins and Mithra. P.M. has received compensation as a member of the scientific advisory board of Astellas, Bayer, and Johnson & Johnson; compensation from AbbVie and Pfizer for consulting; and serves as a member of the scientific advisory board and has/had equity in Alloy, Estrigenix, and MidiHealth. She has received speaking fees and travel support from Mithra. R.E.N. has ongoing relationships with Abbott, Astellas, Bayer HealthCare AG, Besins Healthcare, Exeltis, Fidia, Gedeon Richter, HRA Pharma, Merck Healthcare, Novo Nordisk, Shionogi Limited, Theramex, and Viatris. N.P. has lectured and/or acted in an advisory capacity for Abbott, Lawley, Mithra, Novo, SeCur, and Viatris. S.R. has lectured and/or acted in an advisory capacity or conducted studies for Abbott, Bayer, Gedeon Richter, Mylan, Amgen, UCB, Theramex, and Viatris. J.S. receives grant/research support from AbbVie, Inc., Bayer Healthcare LLC., Dare´ Bioscience; Ipsen, Mylan/Viatris Inc., Myovant Sciences, Sebela Pharmaceuticals Inc. He acts as a consultant is on advisory boards for Bayer HealthCare Pharmaceuticals Inc., Besins Healthcare, California Institute of Integral Studies (CIIS), Dare´ Bioscience, Femasys Inc., Khyria, Madorra Pty Ltd., Mayne Pharma, Inc., and Vella Bioscience Inc. He serves on speaker's bureaus for Astellas Pharma, Inc., Mayne Pharma, Inc., Myovant Sciences, Inc., Pfizer Inc., Pharmavite LLC., Scynexis Inc. He is a stockholder (direct purchase) of Sermonix Pharmaceuticals. P.S. has received fees for giving educational presentations, participating in advisory boards and conducting research by Besins Healthcare, Astellas, Mylan, Labatec, Exeltis, Effik, Theramex, and Gedeon-Richter. A.J.V. has received fees for presentations and participation in an advisory board from Besins and Theramex. W.W. has received institutional support with an unrestricted grant from Pfizer and sits on the advisory boards of Pfizer, Lupin, and Biosyent. She has received fees for educational presentations for Lupin, Astellas, Bayer and Pfizer, and Biosyent. She is a board member of the International Menopause Society and the President of the Canadian Menopause Society. M.H. has received funding from Madorra for a study of a device to manage GU symptoms and is a clinical expert for the NICE Menopause Guidelines. J.T.G. is a speaker for NurtureMed Pharma, Bayer Phils, Corbridge Phils, and Zuellig Pharma. P.S. has a research consultancy relationship with Chugai Pharmaceuticals. H.J. receives grant funding from the National Institutes of Health, Merck, and Pfizer and is a consultant to Bayer, Merck, and Hello Therapeutics. She receives in kind support from Sage to her institution (drug provided to support NIH-funded trial), funds from Bayer support a pilot grant program she lead within an NIH-funded Center grant. Her spouse is employed by Arsenal Biosciences and receives equity from Merck Research Labs. N.J. is on the advisory board of Vira Health, UK. All other authors report no conflicts of interest., (Copyright © 2024 by The North American Menopause Society.)

Objective: Screening and diagnostic follow-up to prevent cervical cancer are influenced by socioeconomic and systemic factors. This study sought to characterize intervals from abnormal cervical cancer screening to colposcopy between practices differing by insurance status at a large, urban academic center., Materials and Methods: This retrospective cohort study included patients aged 21-65 who presented for colposcopy between January 1, 2021, and January 1, 2022, at the resident and faculty gynecology practices of a single large urban academic medical center. Patient characteristics were compared using t tests or Wilcoxon rank sum tests for continuous measures and χ 2 or Fisher exact tests for categorical measures. Intervals from abnormal cervical cancer screening to colposcopy were compared using the Wilcoxon rank sum test and linear regression analysis with multivariable models adjusted for age, cervical cytology result, human papillomavirus result, and HIV status., Results: Resident practice patients were publicly insured and more likely to be Black or Hispanic ( p < .0001); rates of high-risk human papillomavirus and smoking were similar. Resident practice patients had longer intervals from abnormal cervical cancer screening to colposcopy compared with faculty practice patients (median 79.5 vs 34 d, p < .0001). On adjusted analysis, resident practice patients faced a 95% longer interval ( p < .0001)., Conclusions: Publicly insured patients of a resident-based practice faced significantly longer intervals from abnormal cervical cancer screening to colposcopy than faculty practice patients at a single urban academic center. Effort to address these differences may be an area of focus in improving health disparities., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2024, ASCCP.)

Adenylyl cyclases (ACs) are a group of enzymes that convert adenosine-5'-triphosphate (ATP) to cyclic adenosine 3',5' monophosphate (cAMP), a vital and ubiquitous signalling molecule in cellular responses to hormones and neurotransmitters. There are nine transmembrane (tmAC) forms, which have been widely studied; however, the tenth, soluble AC (sAC) is less extensively characterised. The eye is one of the most metabolically active sites in the body, where sAC has been found in abundance, making it a target for novel therapeutics and biomarking. In the cornea, AC plays a role in endothelial cell function, which is vital in maintaining stromal dehydration, and therefore, clarity. In the retina, AC has been implicated in axon cell growth and survival. As these cells are irreversibly damaged in glaucoma and injury, this molecule may provide focus for future therapies. Another potential area for glaucoma management is the source of aqueous humour production, the ciliary body, where AC has also been identified. Furthering the understanding of lacrimal gland function is vital in managing dry eye disease, a common and debilitating condition. sAC has been linked to tear production and could serve as a therapeutic target. Overall, ACs are an exciting area of study in ocular health, offering multiple avenues for future medical therapies and diagnostics. This review paper explores the diverse roles of ACs in the eye and their potential as targets for innovative treatments.

During hybrid speciation, homoeologues combine in a single genome. Homoeologue expression bias (HEB) occurs when one homoeologue has higher gene expression than another. HEB has been well characterized in plants but rarely investigated in animals, especially invertebrates. Consequently, we have little idea as to the role that HEB plays in allopolyploid invertebrate genomes. If HEB is constrained by features of the parental genomes, then we predict repeated evolution of similar HEB patterns among hybrid genomes formed from the same parental lineages. To address this, we reconstructed the history of hybridization between the New Zealand stick insect genera Acanthoxyla and Clitarchus using a high-quality genome assembly from Clitarchus hookeri to call variants and phase alleles. These analyses revealed the formation of three independent diploid and triploid hybrid lineages between these genera. RNA sequencing revealed a similar magnitude and direction of HEB among these hybrid lineages, and we observed that many enriched functions and pathways were also shared among lineages, consistent with repeated evolution due to parental genome constraints. In most hybrid lineages, a slight majority of the genes involved in mitochondrial function showed HEB towards the maternal homoeologues, consistent with only weak effects of mitonuclear incompatibility. We also observed a proteasome functional enrichment in most lineages and hypothesize this may result from the need to maintain proteostasis in hybrid genomes. Reference bias was a pervasive problem, and we caution against relying on HEB estimates from a single parental reference genome., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

Introduction: SARS COVID-19 pandemic resulted in major changes to how daily life was conducted. Health officials instituted policies to decelerate the spread of the virus, resulting in changes in physical activity patterns of school-aged children. The aim of this study was to utilize a wearable activity monitor to assess ambulatory activity in elementary-school aged children in their home environment during a COVID-19 Stay-at-Home mandate., Methods: This institutional review board approved research study was performed between April 3rd - May 1st of 2020 during which health officials issued several stay-at-home (shelter-in-place) orders. Participant recruitment was conducted using a convenience sample of 38 typically developing children. Participants wore a StepWatch Activity Monitor for one week and data were downloaded and analyzed to assess global ambulatory activity measures along with ambulatory bout intensity/duration. For comparison purposes, SAM data collected before the pandemic, of a group of 27 age-matched children from the same region of the United States, was included. Statistical analyses were performed comparing SAM variables between children abiding by a stay-at-home mandate (Stay-at-Home) versus the Historical cohort (alpha=0.05)., Results: Stay-at-Home cohort took on average 3737 fewer daily total steps compared to the Historical cohort (p<0.001). Daily Total Ambulatory Time (TAT), across all days was significantly lower in the Stay-at-Home cohort compared to the Historical cohort (mean difference: 81.9 minutes, p=0.001). The Stay-at-Home cohort spent a significantly higher percentage of TAT in Easy intensity ambulatory activity (mean difference: 2%, p<0.001) and therefore a significantly lower percentage of TAT in Moderate+ intensity (mean difference: 2%, p<0.001)., Conclusions: The stay-at-home mandates resulted in lower PA levels in elementary school-aged children, beyond global measures to also bout intensity/duration. It appears that in-person school is a major contributor to achieving higher levels of PA and our study provides additional data for policymakers to consider for future decisions., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Previous research investigated cross-modal influence of olfactory stimuli on perception and evaluation of faces. However, little is known about the neural dynamics underpinning this multisensory perception, and no research examined perception for images of oneself, and others, in presence of fragrances. This study investigated the neural mechanisms of olfactory-visual processing using electroencephalography (EEG) and subjective evaluations of self- and other-images. 22 female participants evaluated images of female actors and themselves while being exposed to the fragrance of a commercially available body wash or clean air delivered via olfactometer. Participants rated faces for attractiveness, femininity, confidence and glamorousness on visual analogue scales. EEG data was recorded and event-related potentials (ERPs) associated with onset of face stimuli were analysed to consider effects of fragrance presence on face processing, and interactions between fragrance and self-other image-type. Subjective ratings of confidence, attractiveness and femininity were increased for both image-types in pleasant fragrance relative to clean air condition. ERP components covering early-to-late stages of face processing were modulated by the presence of fragrance. Findings also revealed a cross-modal fragrance-face interaction, with pleasant fragrance particularly affecting ERPs to self-images in mid-latency ERP components. Results showed that the pleasant fragrance of the commercially available body wash impacted how participants perceived faces of self and others. Self- and other-image faces were subjectively rated as more attractive, confident and feminine in the presence of the pleasant fragrance compared to an un-fragranced control. The pleasant fragrance also modulated underlying electrophysiological activity. For the first time, an effect of pleasant fragrance on face perception was observed in the N1 component, suggesting impact within 100 ms. Pleasant fragrance also demonstrated greater impact on subsequent neural processing for self, relative to other-faces. The findings have implications for understanding multisensory integration during evaluations of oneself and others., Competing Interests: Conflict of interest The work was funded by Unilever U.K. Central Resources Limited. Unilever provided the commercial products used in the study. TG, AT, MS, SSo and SSe work for Unilever. Unilever was not involved in the collection and analysis of the data., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: This study's purpose was to evaluate the effect of simulated in vitro hydrostatic pulpal pressure (HPP) on microleakage., Methods and Materials: Extracted third molars (n=12) were sectioned 5 mm below the cementoenamel junction, pulp tissue removed, and the sectioned crowns mounted on a Plexiglas plate penetrated by an 18-gauge stainless steel tube. The mounted specimen mesial surface received a 2×4×6 mm Class V preparation followed by restoration with a strongly acidic, one-step dental adhesive and a flowable microfilled resin, following all manufacturers' instructions. Restorations were finished to contour, and tubing was attached to a 20-cm elevated, 0.2% rhodamine G reservoir to the specimen steel tube for 48 hours. Specimens then received a nail polish coating to within 1 mm of the restoration margins and were placed in 2% methylene blue (MB) dye for 24 hours, followed by rinsing, embedding in epoxy resin, and sectioning into 1 mm slices using a diamond saw. Controls were intact molars (n=12) processed as above but without HPP. Specimen slices were evaluated using laser confocal microscopy with images exported to ImageJ software with microleakage assessed as the MB linear penetration as a percentage of the total interfacial wall length. Mean values were evaluated with the Kruskal Wallis/Dunn test at a 95% confidence level., Results: The control specimens demonstrated significantly greater (p<0.0001) MB penetration than experimental specimens with simulated HPP. Under this study's conditions, simulated HPP significantly decreased MB dye penetration., Conclusion: Studies accomplished without simulated HPP may overestimate microleakage results., (©Operative Dentistry, 2024.)

Single-pollutant methods to evaluate associations between endocrine disrupting chemicals (EDCs) and thyroid cancer risk may not reflect realistic human exposures. Therefore, we evaluated associations between exposure to a mixture of 18 EDCs, including polychlorinated biphenyls (PCBs), brominated flame retardants, and organochlorine pesticides, and risk of papillary thyroid cancer (PTC), the most common thyroid cancer histological subtype. We conducted a nested case-control study among U.S. military servicemembers of 652 histologically-confirmed PTC cases diagnosed between 2000 and 2013 and 652 controls, matched on birth year, sex, race/ethnicity, military component (active duty/reserve), and serum sample timing. We estimated mixture odds ratios (OR), 95% confidence intervals (95% CI), and standard errors (SE) for associations between pre-diagnostic serum EDC mixture concentrations, overall PTC risk, and risk of histological subtypes of PTC (classical, follicular), adjusted for body mass index and military branch, using quantile g-computation. Additionally, we identified relative contributions of individual mixture components to PTC risk, represented by positive and negative weights (w). A one-quartile increase in the serum mixture concentration was associated with a non-statistically significant increase in overall PTC risk (OR = 1.19; 95% CI = 0.91, 1.56; SE = 0.14). Stratified by histological subtype and race (White, Black), a one-quartile increase in the mixture was associated with increased classical PTC risk among those of White race (OR = 1.59; 95% CI = 1.06, 2.40; SE = 0.21), but not of Black race (OR = 0.95; 95% CI = 0.34, 2.68; SE = 0.53). PCBs 180, 199, and 118 had the greatest positive weights driving this association among those of White race (w = 0.312, 0.255, and 0.119, respectively). Findings suggest that exposure to an EDC mixture may be associated with increased classical PTC risk. These findings warrant further investigation in other study populations to better understand PTC risk by histological subtype and race., Competing Interests: Declaration of competing interest The authors report no competing interests. Disclosures The authors have no disclosures to report., (Published by Elsevier B.V.)

Background: Trait rumination is a habitual response to negative experiences that can emerge during adolescence, increasing risk of depression. Trait rumination is correlated with poor inhibitory control (IC) and altered default mode network (DMN) and cognitive control network (CCN) engagement. Provoking state rumination in high ruminating youth permits investigation of rumination and IC at the neural level, highlighting potential treatment targets., Methods: Fifty-three high-ruminating youth were cued with an unresolved goal that provoked state rumination, then completed a modified Sustained Attention to Response Task (SART) that measures IC (commissions on no-go trials) in a functional MRI study. Thought probes measured state rumination about that unresolved goal and task-focused thoughts during the SART., Results: Greater state rumination during the SART was correlated with more IC failures. CCN engagement increased during rumination (relative to task-focus), including left dorsolateral prefrontal cortex and dorsalmedial prefrontal cortex. Relative to successful response suppression, DMN engagement increased during IC failures amongst individuals with higher state and trait rumination. Exploratory analyzes suggested more bothersome unresolved goals predicted higher left DLPFC activation during rumination., Limitations: The correlational research design did not permit a direct contrast of causal accounts of the relationship between rumination and IC., Conclusions: State rumination was associated with impaired IC and disrupted modulation of DMN and CCN. Increased CCN engagement during rumination suggested effortful suppression of negative thoughts, and this was greater for more bothersome unresolved goals. Relative task disengagement was observed during rumination-related errors. DMN-CCN dysregulation in high-ruminating youth may be an important treatment target., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ERW receives royalties from the treatment manual for rumination-focused cognitive-behavioral therapy published by Guilford Press and licensing of rumination-focused cognitive-behavioral therapy for internet treatment packages. SEC is a co-owner of the Utah Center for Evidence Based Treatment, an outpatient psychotherapy practice, unrelated to this work. SAL receives consultant payments from Stony Brook University, Johns Hopkins University (unrelated to this work), payments from the Center for Scientific Review (unrelated to this work), and reports part ownership of Secondary Triad Inc. (unrelated to this work).

Background: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk., Methods: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined., Results: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

Dysphagia commonly affects older adults, making them nutritionally vulnerable. There is significant variation in the reported prevalence of dysphagia in aged care. The aim of this systematic review and meta-analysis was to determine the prevalence of dysphagia in individuals living in residential aged care facilities using appropriate assessment methods, and in four subgroups at higher risk: individuals with nervous system diseases, dementia, malnutrition, and poor dentition. Scopus, Web of Science, Medline, and CINAHL Plus were searched, and study selection was conducted in Covidence. Meta-analysis using a random effects model was used to obtain the pooled prevalence of dysphagia. Seven studies were eligible for inclusion. Dysphagia prevalence ranged from 16 to 69.6%. The pooled prevalence of dysphagia was 56.11% (95% CI 39.363-72.172, p < 0.0001, I 2 = 98.61%). Sensitivity analysis examining the prevalence of dysphagia using only the CSE indicated a pooled prevalence of 60.90% (95% CI 57.557-64.211, p = 0.9994, I 2 = 0%). Only one study each reported on dysphagia prevalence in individuals with nervous system diseases (31%), poor dentition (92%), and dementia (68.4%), meaning that meta-analysis could not be completed. No studies reported on the prevalence of dysphagia in individuals with malnutrition. The prevalence of dysphagia is high amongst residents of aged care facilities. This evidence should be used to guide improvements in the health outcomes and quality of life of aged care residents. Future research should explore the prevalence in the subgroups at higher risk.

The corneal epithelium, comprising three layers of cells, represents the outermost portion of the eye and functions as a vital protective barrier while concurrently serving as a critical refractive structure. Maintaining its homeostasis involves a complex regenerative process facilitated by the functions of the lacrimal gland, tear film, and corneal nerves. Crucially, limbal epithelial stem cells located in the limbus (transitional zone between the cornea and the conjunctiva) are instrumental for the corneal epithelium integrity by replenishing and renewing cells. Re-epithelialization failure results in persistent defects, often associated with various ocular conditions including diabetic keratopathy. The insulin-like growth factor (IGF) system is a sophisticated network of insulin and other proteins essential for numerous physiological processes. This review examines its role in maintaining the corneal epithelium homeostasis, with a special focus on the interplay with corneal limbal stem cells and the potential therapeutic applications of the system components.

Introduction: Children and young people (CYP) presenting with a mental health (MH) crisis are frequently admitted to general acute paediatric wards as a place of safety. Prior to the pandemic, a survey in England showed that CYP occupied 6% of general paediatric inpatient beds due to an MH crisis, and there have been longstanding concerns about the quality of care to support these patients in this setting. Mental Health Admissions to Paediatric Wards Study aims to generate a theory of change (ToC) model to improve the quality of care for CYP admitted to acute paediatric services after presenting in a MH crisis., Methods and Analysis: We will undertake a national (England), sequential, mixed methods study to inform a ToC framework alongside a stakeholder group consisting of patients, families/carers and healthcare professionals (HCPs). Our study consists of four work packages (WP) undertaken over 30 months. WP1 is limited to using national routine administrative data to identify and characterise trends in MH admissions in acute paediatric wards in England between 2015- 2022., Ethics and Dissemination: WP1 received ethical approval (Ref 23/NW/0192). We will publish the overall synthesis of data and the final ToC to improve care of CYP with MH crisis admitted to general acute paediatric settings. As coproducers of the ToC, we will work with our stakeholder group to ensure wide dissemination of findings. Potential impacts will be on service development, new models of care, training and workforce planning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Stimulating the innate immune system has been explored as a therapeutic option for the treatment of gliomas. Inactivating mutations in ATRX, defining molecular alterations in IDH-mutant astrocytomas, have been implicated in dysfunctional immune signaling. However, little is known about the interplay between ATRX loss and IDH mutation on innate immunity. To explore this, we generated ATRX-deficient glioma models in the presence and absence of the IDH1 R132H mutation. ATRX-deficient glioma cells are sensitive to dsRNA-based innate immune agonism and exhibit impaired lethality and increased T-cell infiltration in vivo. However, the presence of IDH1 R132H dampens baseline expression of key innate immune genes and cytokines in a manner restored by genetic and pharmacological IDH1 R132H inhibition. IDH1 R132H co-expression does not interfere with the ATRX deficiency-mediated sensitivity to dsRNA. Thus, ATRX loss primes cells for recognition of dsRNA, while IDH1 R132H reversibly masks this priming. This work reveals innate immunity as a therapeutic vulnerability of astrocytomas., (© 2024. The Author(s).)