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Background: Services from specialized professionals in childcare settings contribute to support early childhood development. Little is known, however, about how services are delivered in this context. The aims of this scoping review were to propose a framework to describe services delivered by specialized professionals in childcare contexts and synthesize knowledge about those services., Methods: Documents published between 2000 and 2022 in APA PsychINFO, ERIC, CINAHL and MEDLINE were included. These documents described services delivered by a range of specialized professionals (e.g., speech-language pathologists, occupational therapists, physical therapists and early childhood special education teachers) in childcare contexts and whose aim was to support motor, cognitive, affective, language or social development of children. Deductive and inductive qualitative analyses and descriptive statistics were carried out., Results: The review included 47 documents. The Description of Services delivered by specialized Professionals in Early Childhood (D-SPEC) Framework emerged from qualitative analyses. The D-SPEC Framework included 11 dimensions: three actors and their context, specialized professionals involved, children served, purpose of service, type of service, service duration and intensity, mode of service delivery, mode of access to services and funding. Most services delivered by specialized professionals in childcare were provided by a single professional and targeted language. Two documents described multitiered service delivery models with a continuum of services ranging from general support for all children to individualized interventions for children with specific needs. In-context services were preferred to pull-out services in most documents reviewed., Conclusions: The D-SPEC Framework may be a useful tool to assist researchers in documenting and comparing services delivered by specialized professionals. More importantly, this framework will facilitate the development of intersectoral and interdisciplinary services essential for supporting early childhood development. Multitiered service delivery models appeared to be a promising way to develop those services addressing the various needs encountered in childcare., (© 2024 The Author(s). Child: Care, Health and Development published by John Wiley & Sons Ltd.)

This multi-methods study describes the development of a pediatric rehabilitation telehealth intervention fidelity checklist, estimates its inter-rater reliability, and documents raters' implementation experience. A literature scan and expert consultation identified eighteen key behaviors and categorized them into three subdomains, measured using a 5-point measurement system. To estimate the checklist's inter-rater reliability, three raters scored 33 video recordings. A Shrout and Fleiss Class 1,1 intraclass correlation (ICC)) and 95% confidence intervals (CI) calculated ICCs = 0.5 (CI: 0, 0.9) for both the Therapist and the Parent-Therapists subdomains, and the Parent subdomain an ICC = 0.3 (CI: 0, 0.8). In the implementation surveys, raters reported high levels of satisfaction (100%), ease of use (84% to 88%), and confidence in their video ratings (87% to 100%). Changes in procedures and scoring were recommended. Capturing raters' implementation experiences is crucial in the early evaluation of the fidelity checklists for telehealth., (Copyright © 2024 Karen Hurtubise, Michelle Phoenix, Chantal Camden, Raphaëlle Gauthier, Paul Stratford, Rosalie Dostie, Audrée Jeanne Beaudoin, Désirée Maltais, Jade Berbari, Isabelle Gaboury.)

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults., Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science., Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions., Clinical Trials.gov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Brett Anderson reported receiving direct support for work not related to RECOVER work/publications from Genentech and the National Institute of Allergy and Immunology. Walter Dehority reported receiving grant support from Merck and participating in research for the Moderna COVID-19 pediatric vaccine trial and the Pfizer Paxlovid trial. Alex Fiks reported receiving support from NJM insurance and personal consulting fees not related to this paper from Rutgers University and the American Academy of Pediatrics. Ashraf Harahsheh reported serving as a scientific advisory board member unrelated to this paper for OP2 DRUGS. Lawrence Kleinman reported serving as an unpaid member of the Board of Directors for the DARTNet Institute, as a principle investigator at Quality Matters, Inc., and as the Vice Chair for the Borough of Metuchen Board of Health. Dr. Kleinman also reported grant support for work not related to RECOVER work/publications from NIH, HRSA, and the Robert Wood Johnson Foundation. Dr. Kleinman also reported minority individual stock ownership in Apple Computer, Sanofi SA, Experion, GlaxoSmithKline, Magyar Bank, Regeneron Pharmaceuticals, JP Morgan Chase, and Amgen Inc. Torri Metz reported participating as a Principle Investigator in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She is also a principle investigator for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Joshua Milner reported serving as a member of the Scientific Advisory Board for Blueprint Medicines, in a capacity unrelated to RECOVER work/publications. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Gross et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The chromatin-associated protein WD Repeat Domain 5 (WDR5) is a promising target for cancer drug discovery, with most efforts blocking an arginine-binding cavity on the protein called the 'WIN' site that tethers WDR5 to chromatin. WIN site inhibitors (WINi) are active against multiple cancer cell types in vitro, the most notable of which are those derived from MLL-rearranged (MLLr) leukemias. Peptidomimetic WINi were originally proposed to inhibit MLLr cells via dysregulation of genes connected to hematopoietic stem cell expansion. Our discovery and interrogation of small-molecule WINi, however, revealed that they act in MLLr cell lines to suppress ribosome protein gene (RPG) transcription, induce nucleolar stress, and activate p53. Because there is no precedent for an anticancer strategy that specifically targets RPG expression, we took an integrated multi-omics approach to further interrogate the mechanism of action of WINi in human MLLr cancer cells. We show that WINi induce depletion of the stock of ribosomes, accompanied by a broad yet modest translational choke and changes in alternative mRNA splicing that inactivate the p53 antagonist MDM4. We also show that WINi are synergistic with agents including venetoclax and BET-bromodomain inhibitors. Together, these studies reinforce the concept that WINi are a novel type of ribosome-directed anticancer therapy and provide a resource to support their clinical implementation in MLLr leukemias and other malignancies., Competing Interests: GH, JW, KR, CJ, PP, TT, AF, LV, SL, BG, BS, MS, ER, SG, FM, QL No competing interests declared, MS Receives research funding from ALX Oncology, Astex, Incyte, Takeda and TG Therapeutics; has stock in Karyopharm and Ryvu; serves on advisory boards or consults for BMS, CTI, Forma, Geron, GSK, Karyopharm, Rigel, Ryvu, Taiho and Treadwell, TL, SF Patents: Lee T, Alvarado J, Tian J, Meyers KM, Han C, Mills JJ, Teuscher KB, Stauffer SR, Fesik SW. WDR5 inhibitors and modulators. WO 2020086857. 30 April 2020; Lee T, Han C, Mills JJ, Teuscher KB, Tian J, Meyers KM, Chowdhury S, Fesik SW. WDR5 inhibitors and modulators. WO 2020247679. 10 December 2020; Lee T, Teuscher KB, Tian J, Meyers KM, Chowdhury S, Fesik SW. WDR5 Inhibitors and modulators. WO 2021092525. 14 May 2021; Lee T, Teuscher KB, Chowdhury S, Tian J, Meyers KM, Fesik SW. WDR5 Inhibitors and modulators. WO2022236101. 10 November 2022, WT Patents: Fesik SW, Stauffer SR, Salovich JM, Tansey WP, Wang F, Phan J, Olejniczak ET, inventors. WDR5 inhibitors and modulators. United States Patent US 10,501,466. 10 December 2019; Fesik SW, Stauffer SR, Tansey WP, Olejniczak ET, Phan J, Wang F, Jeon K, Gogliotti RD, inventors. WDR5 inhibitors and modulators. United States Patent US 10,160,763. 25 December 2018, (© 2023, Howard et al.)

Background: Percutaneous coronary intervention (PCI) is considered less safe in patients with reduced ejection fraction (EF), an impression based on older data. Whether the safety and durability of contemporary PCI are different in patients with reduced EF compared with normal EF patients is unknown., Methods: Patients from the BIOFLOW II, IV and V clinical trials were grouped as normal EF (≥50%) and reduced EF (30%-50%). Using multivariable logistic regression and cox proportional hazards regression, we determined relations of EF category with procedural safety (a composite of cardiac death, myocardial infarction, stroke and urgent coronary artery bypass grafting within 30 days of PCI) and target lesion failure (TLF; comprising cardiac death, target vessel myocardial infarction, target vessel revascularization within 1 year of PCI) respectively. In sensitivity analyses, we regrouped patients into EF < 45% and ≥55% and repeated the aforementioned analyses., Results: In 1685 patients with normal EF (mean age 65 years; 27% women; mean EF 61%) and 259 with low EF (mean age 64 years; 17% women; mean EF 41%), 101 safety and 148 TLF events occurred. Compared with patients in the normal EF group, those with reduced EF had neither a statistically significant higher proportion of safety events, nor a higher multivariable-adjusted risk for such events. Similarly, patients with reduced EF and normal EF did not differ in terms of TLF event proportions or multivariable-adjusted risk for TLF. The results were similar in sensitivity analyses with EF groups redefined to create a 10% between-group EF separation., Conclusion: PCI safety and durability outcomes are similar in patients with mild-moderately reduced EF and normal EF., (© 2024 Wiley Periodicals LLC.)

Background: Regionalization of surgical care shifts higher acuity patients to larger centers. Hospital-associated infections (HAIs) are important quality measures with financial implications. In our ongoing efforts to eliminate HAIs, we examined the potential role for inter-hospital transfer in our cases of HAI across a multihospital system. Hypothesis: Surgical patients transferred to a regional multihospital system have a higher risk of National Healthcare Safety Network (NHSN)-labeled HAIs. Patients and Methods: The analysis cohort of adult surgical inpatients was filtered from a five-hospital health system administration registry containing encounters from 2014 to 2021. The dataset contained demographics, health characteristics, and acuity variables, along with the NHSN defined HAIs of central line-associated blood stream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), and Clostridioides difficile infection (CDI). Univariable and multivariable statistics were performed. Results: The surgical cohort identified 92,832 patients of whom 3,232 (3.5%) were transfers. The overall HAI rate was 0.6% (528): 86 (0.09%) CLABSI, 133 (0.14%) CAUTI, and 325 (0.35%) CDI. Across the three HAIs, the rate was higher in transfer patients compared with non-transfer patients (CLABSI: n = 18 (1.3%); odds ratio [OR], 4.79; CAUTI: n = 25 (1.8%); OR, 4.20; CDI: n = 37 (1.1%); OR, 3.59); p < 0.001 for all. Multivariable analysis found transfer patients had an increased rate of HAIs (OR, 1.56; p < 0.001). Conclusions: There is an increased risk-adjusted rate of HAIs in transferred surgical patients as reflected in the NHSN metrics. This phenomenon places a burden on regional centers that accept high-risk surgical transfers, in part because of the downstream effects of healthcare reimbursement programs.

Objective: To demonstrate the added benefit of multiparametric (mp)MRI risk stratification during active surveillance., Methods: This prospective, single-arm, nonrandomized study included 82 men with low-risk prostate cancer (PCa). We compared two biopsy strategies in parallel. The first biopsy strategy was an in-bore and transrectal ultrasound (TRUS) biopsy in men with suspicious mpMRI findings. The second was a TRUS biopsy in all 82 men, blinded to the results of the previously performed mpMRI., Results: We identified 27/82 men with suspicious mpMRI. Of those 27 men, we detected 8/27 with csPCa on biopsy, and we identified two men with in-bore biopsy exclusively, three men with TRUS biopsy exclusively, and three men with both biopsy strategies. Of the 55/82 men with nonsuspicious mpMRI (who only received TRUS biopsies), two men had csPCa. TRUS biopsy of the entire cohort of 82 men would have led to the correct diagnosis of 80% men with csPCa, requiring all 82 men to receive biopsies (csPCa in 10% of the 82 biopsies). Conducting in-bore biopsies plus TRUS biopsies in men with suspicious mpMRI would have also led to the detection of 80% of men with csPCa, requiring only 27 men to receive biopsies (csPCa in 30% of the 27 biopsies)., Conclusion: The combination of TRUS and in-bore biopsies, limited to men with suspicious mpMRI, resulted in a similar detection rate of csPCa compared to TRUS biopsies of all men but required only one-third of men to undergo biopsy. Our results indicate that in-bore and TRUS biopsies continue to complement each other., Competing Interests: Declaration of Competing Interest No conflict., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Industrial hydrogen peroxide (H 2 O 2 ) is synthesized using carbon-intensive H 2 gas production and purification, anthraquinone hydrogenation, and anthrahydroquinone oxidation. Electrochemical hydrogenation (ECH) of anthraquinones offers a carbon-neutral alternative for generating H 2 O 2 using renewable electricity and water instead of H 2 gas. However, the H 2 O 2 formation rates associated with ECH are too low for commercialization. We report here that a membrane reactor enabled us to electrochemically hydrogenate anthraquinone (0.25 molar) with a current efficiency of 70% at current densities of 100 milliamperes per square centimeter. We also demonstrate continuous H 2 O 2 synthesis from the hydrogenated anthraquinones over the course of 48 h. This study presents a fast rate of electrochemically-driven anthraquinone hydrogenation (1.32 ± 0.14 millimoles per hour normalized per centimeter squared of geometric surface of electrode), and provides a pathway toward carbon-neutral H 2 O 2 synthesis., (© 2024. The Author(s).)

1-Methylxanthine is a high-value derivative of caffeine of limited natural availability with many potential pharmaceutical applications. Unfortunately, production of 1-methylxanthine through purely chemical methods of synthesis are unfavorable due to lengthy chemical processes and the requirement of hazardous chemicals, ultimately resulting in low yields. Here, we describe a novel biosynthetic process for the production of 1-methylxanthine from theophylline using engineered Escherichia coli whole-cell biocatalysts and reaction optimization. When scaled-up to 1590 mL, the simple biocatalytic reaction produced approximately 1188 mg 1-methylxanthine from 1444 mg theophylline, constituting gram-scale production of 1-methylxanthine in as little as 3 hours. Following HPLC purification and solvent evaporation, 1163 mg of dried 1-methylxanthine powder was collected, resulting in a 97.9 wt% product recovery at a purity of 97.8%. This is the first report of a biocatalytic process designed specifically for the production and purification of the high-value biochemical 1-methylxanthine from theophylline. This process is also the most robust methylxanthine N-demethylation process featuring engineered E. coli to date, capable of gram-scale production., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Meredith B Mock reports financial support was provided by US Department of Education. Ryan Summers has patent Bacterial N-Demethylases as Biocatalysts for the Production of Methylxanthines pending to United States Patent Office., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background Context: Postoperative physical therapy (PT) following lumbar spinal fusion is an effective form of postoperative rehabilitation. However, it is unknown when a postoperative PT protocol should be optimally initiated., Purpose: This study sought to compare lengths of stay between patients on a day zero PT protocol and those on a day one PT protocol., Study Design/setting: Retrospective chart review., Patient Sample: Patients who underwent lumbar spinal surgery at a large midwestern tertiary medical care center from January 1, 2018 through April 30, 2019 were eligible for their medical record's inclusion., Primary Outcome Measure: Length of hospital stay following surgery., Methods: Patients were stratified by having started postoperative PT on the same day as surgery (day zero) or having started postoperative PT on the day following surgery (day one)., Results: A total of 164 patients were included in the study, 69 in the day zero group and 95 patients in the day one group. Most patients were female (59%, n = 98), and patients' average age was 62 years (SD = 13). Average length of stay was 61 hours (SD = 20) for those on the day zero protocol and 75 hours (SD = 32) for those on the day one protocol., Conclusions: This study suggests that a postoperative physical therapy protocol initiated on day zero is associated with patients experiencing a shorter length of hospital stay compared to a similar PT protocol initiated on postoperative day one., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this report, the relative efficiency of cellulose nanocrystals (CNCs) and nanofibers (CNFs) to capture circulating tumor cells (CTCs) from the blood sample of head and neck cancer (HNC) patients was evaluated. Detection and enumeration of CTCs are critical for monitoring cancer progression. Both types of nanostructured cellulose were chemically modified with Epithelial Cell Adhesion Molecule (EpCAM) antibody and iron oxide nanoparticles. The EpCAM antibody facilitated the engagement of CTCs, promoting entrapment within the cellulose cage structure. Iron oxide nanoparticles, on the other hand, rendered the cages activatable via the use of a magnet for the capture and separation of entrapped CTCs. The efficiency of the network structures is shown in head and neck cancer (HNC) patients' blood samples. It was observed that the degree of chemical functionalization of hydroxyl groups located within the CNCs or CNFs with anti-EpCAM determined the efficiency of the system's interaction with CTCs. Further, our result indicated that inflexible scaffolds of nanocrystals interacted more efficiently with CTCs than that of the fibrous CNF scaffolds. Network structures derived from CNCs demonstrated comparable CTC capturing efficiency to commercial standard, OncoDiscover®. The output of the work will provide the chemical design principles of cellulosic materials intended for constructing affordable platforms for monitoring cancer progression in 'real time'., 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. Published by Elsevier Ltd.)

Differentiating multiple system atrophy (MSA) from related neurodegenerative movement disorders (NMD) is challenging. MRI is widely available and automated decision-tree analysis is simple, transparent, and resistant to overfitting. Using a retrospective cohort of heterogeneous clinical MRIs broadly sourced from a tertiary hospital system, we aimed to develop readily translatable and fully automated volumetric diagnostic decision-trees to facilitate early and accurate differential diagnosis of NMDs. 3DT1 MRI from 171 NMD patients (72 MSA, 49 PSP, 50 PD) and 171 matched healthy subjects were automatically segmented using Freesurfer6.0 with brainstem module. Decision trees employing substructure volumes and a novel volumetric pons-to-midbrain ratio (3D-PMR) were produced and tenfold cross-validation performed. The optimal tree separating NMD from healthy subjects selected cerebellar white matter, thalamus, putamen, striatum, and midbrain volumes as nodes. Its sensitivity was 84%, specificity 94%, accuracy 84%, and kappa 0.69 in cross-validation. The optimal tree restricted to NMD patients selected 3D-PMR, thalamus, superior cerebellar peduncle (SCP), midbrain, pons, and putamen as nodes. It yielded sensitivities/specificities of 94/84% for MSA, 72/96% for PSP, and 73/92% PD, with 79% accuracy and 0.62 kappa. There was correct classification of 16/17 MSA, 5/8 PSP, 6/8 PD autopsy-confirmed patients, and 6/8 MRIs that preceded motor symptom onset. Fully automated decision trees utilizing volumetric MRI data distinguished NMD patients from healthy subjects and MSA from other NMDs with promising accuracy, including autopsy-confirmed and pre-symptomatic subsets. Our open-source methodology is well-suited for widespread clinical translation. Assessment in even more heterogeneous retrospective and prospective cohorts is indicated., (© 2022. The Author(s).)

Background: HIV infection and abacavir-containing antiretroviral regimens are associated with vascular endothelial dysfunction and increased cardiovascular risk. Positron emission tomography (PET)-derived myocardial blood flow reserve (MBFR), the ratio of vasodilator stress to rest myocardial blood flow, is a well-validated measure of coronary microvascular health and marker of cardiovascular risk. Our objective was to compare MBFR among people with HIV (PWH) with matched non-HIV controls and to assess whether switching from dolutegravir/lamivudine/abacavir to the non-abacavir regimen bictegravir/emtricitabine/tenofovir alafenamide (TAF) would improve MBFR., Methods and Results: Thirty-seven PWH were 1:2 matched on cardiovascular risk factors to 75 people without HIV, and MBFR corrected for differences in resting hemodynamics was compared in a cross-sectional design. PWH were majority men (68%) with a mean age of 56 years. Mean stress myocardial blood flow (1.83 mL/min per g [95% CI, 1.68-1.98] versus 2.40 mL/min per g [95% CI, 2.25-2.54]; P <0.001) and MBFR (2.18 [95% CI, 1.96-2.40] versus 2.68 [95% CI, 2.47-2.89]; P =0.002) was significantly lower in PWH than in people without HIV. In a single-arm, multicenter trial, a subset of 25 PWH who were virologically suppressed on dolutegravir/lamivudine/abacavir underwent positron emission tomography myocardial perfusion imaging at baseline and after switching to bictegravir/emtricitabine/TAF. MBFR was unchanged after switching to bictegravir/emtricitabine/TAF for a mean of 27 weeks (MBFR, 2.34 to 2.29; P =0.61), except in PWH with impaired MBFR at baseline (<2.00; N=6) in whom MBFR increased from 1.58 to 2.02 ( P =0.02)., Conclusions: PWH had reduced coronary microvascular function compared with controls without HIV. Coronary microvascular function did not improve after switching from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/TAF., Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT03656783.

The Kaplan-Meier estimator is ubiquitously used to estimate survival probabilities for time-to-event data. It is nonparametric, and thus does not require specification of a survival distribution, but it does assume that the risk set at any time t consists of independent observations. This assumption does not hold for data from paired organ systems such as occur in ophthalmology (eyes) or otolaryngology (ears), or for other types of clustered data. In this article, we estimate marginal survival probabilities in the setting of clustered data, and provide confidence limits for these estimates with intra-cluster correlation accounted for by an interval-censored version of the Clayton-Oakes model. We develop a goodness-of-fit test for general bivariate interval-censored data and apply it to the proposed interval-censored version of the Clayton-Oakes model. We also propose a likelihood ratio test for the comparison of survival distributions between two groups in the setting of clustered data under the assumption of a constant between-group hazard ratio. This methodology can be used both for balanced and unbalanced cluster sizes, and also when the cluster size is informative. We compare our test to the ordinary log rank test and the Lin-Wei (LW) test based on the marginal Cox proportional Hazards model with robust standard errors obtained from the sandwich estimator. Simulation results indicate that the ordinary log rank test over-inflates type I error, while the proposed unconditional likelihood ratio test has appropriate type I error and higher power than the LW test. The method is demonstrated in real examples from the Sorbinil Retinopathy Trial, and the Age-Related Macular Degeneration Study. Raw data from these two trials are provided., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This clinical practice guide (CPG) aims to provide evidence-based recommendations for promoting and enhancing the participation and integration of children with developmental coordination disorder (DCD) into physical activities that take place in the home, school, community, or rehabilitation clinic contexts., Methods: A panel of key stakeholders relevant to these contexts (parents, instructors, rehabilitation professionals) developed evidence-based recommendations using a consensus methodology after reviewing results from a recent systematic review of relevant literature. The quality of the evidence on which the recommendations were based was evaluated (2011 Oxford Centre for Evidence-Based Medicine Levels of Evidence scale) as was the strength of the final CPG recommendations (American Society of Plastic Surgeons Grade Recommendation Scale)., Results: Recommendations (n = 50; 36% supported by robust, empirically derived evidence) for the different stakeholder groups fell into three categories: 1) Choose an appropriate activity for your child, 2) Harmonize the activity with the child's interests and abilities, and 3) Help the child learn new movements prior to the activity., Conclusions: This comprehensive CPG provides concrete recommendations, based on the currently available evidence, that can be used by stakeholders to address the physical activity participation and integration needs of children with DCD in a variety of contexts., Competing Interests: Competing Interests: None declared. Funding for the clinical practice guide (CPG) was obtained from Université Laval, Research Chair in Cerebral Palsy. Funders were not involved at any stage of the elaboration of the CPG. All participants declared no conflict of interest regarding their participation in this project. The first author is supported by scholarships from Université Laval and CIRRIS (Centre interdisciplinaire de recherche en réadaptation et intégration sociale). The literature review was financially supported by Fonds de recherche du Québec, Société et culture via CAPSEA (Communauté axée sur la participation sociale de l’enfant et de l’adolescent ayant des incapacités)., (© Canadian Physiotherapy Association, 2023.)

Per- and polyfluoroalkyl substances (PFAS) are a class of manufactured chemicals that have been extensively utilized worldwide. We hypothesize that the presence, uptake, and accumulation of PFAS in aquatic vegetation (AV) is dependent upon several factors, such as the physiochemical properties of PFAS and proximity to potential sources. In this study, AV was collected from eight locations in Florida to investigate the PFAS presence, accumulation, and spatiotemporal distribution. PFAS were detected in AV at all sampling locations, with a range from 0.18 to 55 ng/g sum (∑)PFAS. Individual PFAS and their concentrations varied by sampling location, time, and AV species. A total of 12 PFAS were identified, with the greatest concentrations measured in macroalgae. The average bioconcentration factor (BCF) among all samples was 1225, indicating high PFAS accumulation in AV from surface water. The highest concentrations, across all AV types, were recorded in the Indian River Lagoon (IRL), a location with a history of elevated PFAS burdens. The present study represents the first investigation of PFAS in naturally existing estuarine AV, filling an important gap on PFAS partitioning within the environment, as well as providing insights into exposure pathways for aquatic herbivores. Examining the presence, fate, and transport of these persistent chemicals in Florida's waterways is critical for understanding their effect on environmental, wildlife, and human health.

Background: Deformational plagiocephaly can be prevented in many healthy infants if strategies are implemented early after birth. However, despite efforts to disseminate accurate information, parental adherence to evidence-based prevention strategies is a challenge. To date, factors - barriers and facilitators - influencing parental adherence to strategies have yet to be identified in a comprehensive manner., Objectives: This scoping review aims to identify and synthesize current evidence on barriers and facilitators impacting adherence of parents of newborns to deformational plagiocephaly prevention strategies., Methods: This review followed the Joanna Briggs Institute (JBI) process guidelines. Seven electronic (Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, SPORTDiscus, Academic Search Complete, AMED, PsychINFO and Scopus) and two grey literature (Health Systems Evidence and Grey Literature Report) databases were searched. Studies published between 2001 and 2022 were included. The deductive thematic data analysis used was guided by the Capability, Opportunity, Motivation Behavioral Model (COM-B) of health behaviour change., Results: From a total of 1172 articles, 15 met the eligibility criteria. All components of the COM-B framework were identified. Capability-psychological and opportunity-environmental factors dominated the literature, whereas capability-physical, motivation and, in particular, opportunity-social factors were understudied. The most often reported barriers were a lack of knowledge of deformational plagiocephaly and the associated prevention strategies, ambiguous or inconsistent messaging, intolerance of babies to prone positioning and a lack of time. The most frequently reported facilitators were an awareness of deformational plagiocephaly, postural asymmetry and prevention strategies, skill acquisition with practice, accurate convincing information, scheduled time and environmental organization to position the baby at home., Discussion: Recommendations focused on diffusing accurate and detailed information for parents. Our review also suggests a gap regarding the comprehensive identification of factors influencing parental adherence to deformational plagiocephaly prevention strategies. Further studies exploring comprehensive opportunity-social and motivation factors influencing parental adherence to deformational plagiocephaly prevention strategies are warranted to inform prevention programmes and foster better infant outcomes., (© 2023 The Authors. Child: Care, Health and Development published by John Wiley & Sons Ltd.)

Pain during sexual intercourse, also called dyspareunia, affects most women after treatment for gynecological cancer. Previous work adopted a biomedical approach to depict dyspareunia in this population, which provided a narrow perspective of this condition. Taking into account women's experiences of dyspareunia and the factors influencing their care-seeking behaviors would provide insight to improve care in the context of gynecological cancer. The aim of this study was to describe gynecological cancer survivors' experiences of dyspareunia and factors influencing care-seeking behavior. A qualitative study was performed with 28 gynecological cancer survivors with dyspareunia. Individual telephone interviews were conducted based on the Common-Sense Model of Self-Regulation. Interviews were recorded and transcribed for analysis using the interpretative description framework. Concerning their experience, participants reported the oncological treatments as the primary cause of dyspareunia. Loss of libido, lower vaginal lubrication, and smaller vaginal cavity were described as being linked with dyspareunia. Women explained how dyspareunia and these changes had led them to engage less in, and even interrupt, sexual activity. They expressed that they were distressed, felt less of a woman, and experienced low control and/or self-efficacy. Regarding the factors influencing women's care-seeking behaviors, participants emphasized that they were provided with insufficient information and support. Balancing priorities, denial or reluctance, misbeliefs, resignation and acceptance, and negative emotions were reported as barriers, whereas acknowledgement of sexual dysfunction, desire for improvement, awareness of treatment possibilities, willingness to undertake treatment and treatment acceptability were reported as facilitators to seeking care. Findings suggest that dyspareunia is a complex and impactful condition after gynecological cancer. While this study highlights the importance of alleviating the burden of sexual dysfunction in cancer survivors, it identified factors that should be considered in the provision of services to improve care., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Here, we determine how the hydrogen loading ( x ) of an electrochemical palladium membrane reactor (ePMR) varies with electrochemical conditions (e.g., applied current density, electrolyte concentration). We detail how x influences the thermodynamic driving force of an ePMR. These studies are accomplished by measuring the fugacity ( P ) of hydrogen desorbing from the palladium-hydrogen membrane and subsequently relating P to pressure-composition isotherms to determine x . We find that x increases with both applied current density and electrolyte concentration, but plateaus at a loading of x ≅ 0.92 in 1.0 M H 2 SO 4 at -200 mA·cm -2 . The validity of the fugacity measurements is supported experimentally and computationally by: (a) electrochemical hydrogen permeation studies; and (b) a palladium-hydrogen porous flow finite element analysis (FEA) model. Both (a) and (b) agree with the fugacity measurements on the following x -dependent properties of the palladium-hydrogen system during electrolysis: (i) the onset for spontaneous hydrogen desorption; (ii) the point of steady-state hydrogen loading; and (iii) the function describing hydrogen desorption between (i) and (ii). We proceed to detail how x defines the free energy of palladium-hydrogen alloy formation (Δ G ( x ) PdH ), which is a descriptor for the thermodynamic driving force of hydrogenation at the PdH x surface of an ePMR. A maximum value Δ G PdH of 11 kJ·mol -1 is observed, suggesting that an ePMR is capable of driving endergonic hydrogenation reactions. We empirically demonstrate this capability by reducing carbon dioxide to formate (Δ G CO 2 /HCO 2 H = 3.4 kJ·mol -1 ) at ambient conditions and neutral pH.

The first objective of this study was to establish clinically relevant techniques for cardiac echocardiography in nonanesthetized Galapagos ( Chelonoidis nigra complex) and Aldabra ( Aldabrachelys gigantea ) tortoises. A second objective was to establish guidelines for determining normal echocardiographic anatomy and function in both species. Select echocardiographic reference values were defined for 17 healthy Galapagos tortoises and 27 healthy Aldabra tortoises. Tortoises were either placed in ventral recumbency on an elevated surface or allowed to stand in a natural position by using food distraction. An ultrasound probe was applied in the left or right cervicobrachial window and was positioned in two long axis views to evaluate the three chambers of the heart and the associated great vessels, the presence of pericardial effusion, the atrioventricular inflow velocities, and pulmonic and aortic outflow velocities. The heart rate was 28 ± 12 (median ± SD) bpm, and the ejection fraction was 60.5 ± 10%. Thirty-four of 44 tortoises had identifiable physiologic pericardial effusion. All tortoises were successfully imaged using the techniques described, with consistent identification of cardiac structure and assessment of function. This study provides echocardiographic reference intervals for the clinical evaluation of suspected cardiac disease in captive-managed Galapagos and Aldabra tortoises.

Purpose: The purpose of this study is to explore the acceptability of a telerehabilitation intervention provided to parents of children with motor difficulties., Material and Methods: Sixteen parents of children were purposefully recruited to participate in semi-structured interviews aimed at assessing the acceptability of the telerehabilitation intervention. Interviews were analyzed thematically., Results: All participants described evolving acceptability associated with their interactions with the web platform. The opportunities generated, suitability in relation to families' values and perceived effects positively impacted acceptability. The understanding and consistency of intervention delivery, the child's level of involvement, the associated parental burden of the intervention and the therapeutic alliances created also affected acceptability., Conclusion: Our study findings support the acceptability of a telerehabilitation intervention for families of children with motor difficulties. Telerehabilitation seems to be more acceptable to families with children without suspected or confirmed diagnoses.

Introduction: With new effective treatments for SARS-CoV-2, patient outcomes have greatly improved. However, new medications bring a risk of drug interactions with other medications. People living with HIV (PLWH) are at particular risk for these interactions due to heightened risk of immunosuppression, polypharmacy, and overlap in affected organs. It is critical to identify drug interactions are a significant barrier to care for PLWH. Establishing a better understanding of the pharmacologic relationships between COVID-19 therapies and antiretrovirals will improve patient-centered care in COVID-19., Areas Covered: Potential drug-drug interactions between Human Immunodeficiency Virus (HIV) and COVID-19 treatments are detailed and reviewed here. The mechanisms seen in these interactions include alterations in metabolic enzymes, drug transporters, pharmacoenhancement, and organ toxicities. We also review the limitations and solutions that can be used to combat drug-drug interactions between these two disease states., Expert Opinion: While current drug interactions are relatively mild between HIV and COVID-19 therapies, improvements in identifying these beforehand must take place as new therapies are approved. Antiretroviral therapy (ART) is essential in PLWH and must be maintained when treating COVID-19. As advancements in care occur, there is the possibility that newly approved drugs may have additional unknown interactions.

Purpose: The Response Assessment in Neuro-Oncology (RANO) criteria are widely used in high-grade glioma clinical trials. We compared the RANO criteria with updated modifications (modified RANO [mRANO] and immunotherapy RANO [iRANO] criteria) in patients with newly diagnosed glioblastoma (nGBM) and recurrent GBM (rGBM) to evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update., Materials and Methods: Evaluation of tumor measurements and fluid-attenuated inversion recovery (FLAIR) sequences were performed by blinded readers to determine disease progression using RANO, mRANO, iRANO, and other response assessment criteria. Spearman's correlations between progression-free survival (PFS) and overall survival (OS) were calculated., Results: Five hundred twenty-six nGBM and 580 rGBM cases were included. Spearman's correlations were similar between RANO and mRANO (0.69 [95% CI, 0.62 to 0.75] v 0.67 [95% CI, 0.60 to 0.73]) in nGBM and rGBM (0.48 [95% CI, 0.40 to 0.55] v 0.50 [95% CI, 0.42 to 0.57]). In nGBM, requirement of a confirmation scan within 12 weeks of completion of radiotherapy to determine progression was associated with improved correlations. Use of the postradiation magnetic resonance imaging (MRI) as baseline scan was associated with improved correlation compared with use of the pre-radiation MRI (0.67 [95% CI, 0.60 to 0.73] v 0.53 [95% CI, 0.42 to 0.62]). Evaluation of FLAIR sequences did not improve the correlation. Among patients who received immunotherapy, Spearman's correlations were similar among RANO, mRANO, and iRANO., Conclusion: RANO and mRANO demonstrated similar correlations between PFS and OS. Confirmation scans were only beneficial in nGBM within 12 weeks of completion of radiotherapy, and there was a trend in favor of the use of postradiation MRI as the baseline scan in nGBM. Evaluation of FLAIR can be omitted. The iRANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors.

Purpose: This review aimed to synthesize knowledge about multi-criteria decision analysis methods for supporting rehabilitation service design and delivery decisions, including: (1) describing the use of these methods within rehabilitation, (2) identifying decision types that can be supported by these methods, (3) describing client and family involvement, and (4) identifying implementation considerations., Methods: We conducted a rapid review in collaboration with a knowledge partner, searching four databases for peer-reviewed articles reporting primary research. We extracted relevant data from included studies and synthesized it descriptively and with conventional content analysis., Results: We identified 717 records, of which 54 met inclusion criteria. Multi-criteria decision analysis methods were primarily used to understand the strength of clients' and clinicians' preferences ( n  = 44), and five focused on supporting decision making. Shared decision making with stakeholders was evident in only two studies. Clients and families were mostly engaged in data collection and sometimes in selecting the relevant criteria. Good practices for supporting external validity were inconsistently reported. Implementation considerations included managing cognitive complexity and offering authentic choices., Conclusions: Multi-criteria decision analysis methods are promising for better understanding client and family preferences and priorities across rehabilitation professions, contexts, and caseloads. Further work is required to use these methods in shared decision making, for which increased use of qualitative methods and stakeholder engagement is recommended. IMPLICATIONS FOR REHABILITATIONMulti-criteria decision analysis methods are promising for evidence-based, shared decision making for rehabilitation.However, most studies to date have focused on estimating stakeholder preferences, not supporting shared decision making.Cognitive complexity and modelling authentic and realistic decision choices are major barriers to implementation.Stakeholder-engagement and qualitative methods are recommended to address these barriers.

The area under the true ROC curve (AUC) is routinely used to determine how strongly a given model discriminates between the levels of a binary outcome. Standard inference with the AUC requires that outcomes be independent of each other. To overcome this limitation, a method was developed for the estimation of the variance of the AUC in the setting of two-level hierarchical data using probit-transformed prediction scores generated from generalized estimating equation models, thereby allowing for the application of inferential methods. This manuscript presents an extension of this approach so that inference for the AUC may be performed in a three-level hierarchical data setting (e.g., eyes nested within persons and persons nested within families). A method that accounts for the effect of tied prediction scores on inference is also described. The performance of 95% confidence intervals around the AUC was assessed through the simulation of three-level clustered data in multiple settings, including ones with tied data and variable cluster sizes. Across all settings, the actual 95% confidence interval coverage varied from 0.943 to 0.958, and the ratio of the theoretical variance to the empirical variance of the AUC varied from 0.920 to 1.013. The results are better than those from existing methods. Two examples of applying the proposed methodology are presented., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest.

Mycobacterium tuberculosis (Mtb) WhiB3 is an iron-sulfur cluster-containing transcription factor belonging to a subclass of the WhiB-Like (Wbl) family that is widely distributed in the phylum Actinobacteria. WhiB3 plays a crucial role in the survival and pathogenesis of Mtb. It binds to the conserved region 4 of the principal sigma factor (σ A 4 ) in the RNA polymerase holoenzyme to regulate gene expression like other known Wbl proteins in Mtb. However, the structural basis of how WhiB3 coordinates with σ A 4 to bind DNA and regulate transcription is unclear. Here we determined crystal structures of the WhiB3:σ A 4 complex without and with DNA at 1.5 Å and 2.45 Å, respectively, to elucidate how WhiB3 interacts with DNA to regulate gene expression. These structures reveal that the WhiB3:σ A 4 complex shares a molecular interface similar to other structurally characterized Wbl proteins and also possesses a subclass-specific Arg-rich DNA-binding motif. We demonstrate that this newly defined Arg-rich motif is required for WhiB3 binding to DNA in vitro and transcriptional regulation in Mycobacterium smegmatis. Together, our study provides empirical evidence of how WhiB3 regulates gene expression in Mtb by partnering with σ A 4 and engaging with DNA via the subclass-specific structural motif, distinct from the modes of DNA interaction by WhiB1 and WhiB7., Competing Interests: Conflict of interest The authors declare no conflict of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Decades of ongoing research has established that oral microbial communities play a role in oral diseases such as periodontitis and caries. Yet the detection of oral bacteria and the profiling of oral polymicrobial communities currently rely on methods that are costly, slow, and technically complex, such as qPCR or next-generation sequencing. For the widescale screening of oral microorganisms suitable for point-of-care settings, there exists the need for a low-cost, rapid detection technique. Here, we tailored the novel CRISPR-Cas-based assay SHERLOCK for the species-specific detection of oral bacteria. We developed a computational pipeline capable of generating constructs suitable for SHERLOCK and experimentally validated the detection of seven oral bacteria. We achieved detection within the single-molecule range that remained specific in the presence of off-target DNA found within saliva. Further, we adapted the assay for detecting target sequences directly from unprocessed saliva samples. The results of our detection, when tested on 30 healthy human saliva samples, fully aligned with 16S rRNA sequencing. Looking forward, this method of detecting oral bacteria is highly scalable and can be easily optimized for implementation at point-of-care settings., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Children and adolescents are a population at particular risk of experiencing adverse mental health repercussions related to pandemics. To understand vulnerability factors and repercussions of pandemics and related sanitary measures on children and adolescents' mental health, we performed a scoping review to examine and synthesize literature. In total, 66 articles were included. Results present: (1) factors that increase vulnerability to adverse mental health repercussions (e.g., having a pre-existing mental health condition, social isolation, low socio-economic status, parental distress, and overexposure to media content) and (2) specific mental health repercussions (e.g., anxiety, fear, depression, and externalizing behaviors). Addressing concerns underlined in this review could contribute to preventing further negative mental health repercussions of pandemics for children and adolescents and better prepare governments and professionals to address these highly challenging situations. Recommendations for practice include enhancing healthcare professionals' awareness about possible detrimental repercussions pandemics and sanitary measures have on children and adolescents' mental health, assessing changes for those with pre-existing mental health conditions, allocating funding for telehealth research, and providing greater support to healthcare providers.

Topic: Public health measures implemented in response to the COVID-19 pandemic severely disrupted children and adolescents' (C&A) lives, affecting their sense of structure, predictability, and security., Purpose: To examine C&A' experiences during the COVID-19 pandemic to better understand how this context and its associated public health measures affected them and their mental health, and to identify helpful coping strategies., Sources Used: The study was guided by a participatory hermeneutic framework. Semistructured interviews were conducted with 25 C&A aged 6-17 years during the first and second pandemic waves. Participants' interviews were analyzed following a narrative synthesis approach, through which C&A' experiences were contrasted and contextualized to highlight relevant themes., Conclusions: Participants described a distinct pattern related to their mental health as the pandemic unfolded, which followed the severity of the pandemic in the province. Negative repercussions on their mental health were linked to the loss of social activities, imposed public health measures, transition to online learning, and challenges with family relationships. Certain youth shared positive societal and moral reflections triggered by the pandemic context. Coping strategies reported include: having a variety of hobbies; expressing their emotions; and accessing financial and material resources. This study highlights the importance of supporting C&A' mental health during crisis situations such as a pandemic. Their perspectives are vital for clinical practice and policy improvement, particularly to find means for social engagement while maintaining safety., (© 2022 Wiley Periodicals LLC.)

Introduction and Hypothesis: Multimodal pelvic floor physical therapy (PFPT) is recommended after gynecological malignancies to treat dyspareunia. However, data to strongly support its implementation in the cancer care continuum are lacking. The aim of this study was to explore the views and experiences of gynecological cancer survivors with dyspareunia regarding the acceptability of multimodal PFPT., Methods: This qualitative study was conducted with the participants (n = 28) of a study investigating a 12-week multimodal PFPT treatment. Individual semi-structured telephone interviews served to collect qualitative data pertaining to women's views and experiences of the treatment they received. Interviews were recorded and transcribed for analysis using the interpretative description framework., Results: Our cohort described the appropriateness of the treatment in terms of modalities, physical therapist, care delivery, and intensity (Theme 1). While the intensity was reported as demanding by a few, all participants stressed that it was relevant to see significant improvements (Theme 2). In addition to the treatment characteristics and women's beliefs and attitudes, noticing the treatment effects motivated their participation (Theme 2). Women expressed being highly satisfied with the treatment based on their positive experiences and the balance between their efforts and the results they obtained (Theme 3). As a result, they all recommended this treatment (Theme 3)., Conclusions: This is the first study to examine the acceptability of multimodal PFPT in the context of gynecological malignancies. This treatment was found acceptable and can be offered to gynecological cancer survivors., (© 2022. The Author(s).)

The climate crisis not only has significant impacts on biodiversity and the physical health of humans, but its ramifications are also affecting people's mental health. Eco-anxiety, or the emotions that emerge with the awareness of climate change and the apprehension of its detrimental effects, has been investigated in adults and adolescents, but much less attention has been given to the impacts on children's mental health and well-being. Initial evidence confirms that youth are significantly concerned about climate change, but few studies have investigated the resulting emotional responses of children and the role of their parents in tempering these, especially using qualitative methodologies. The present study used a descriptive qualitative design with a convenience sample of parents and child dyads, assessed separately. Children's (n = 15, ages 8-12 years) experiences were explored using semi-structured interviews and their parents' (n = 12) perceptions were captured using a survey with closed and open-ended questions. A reflexive thematic analysis was used to analyze the interview data, and content analysis was used to investigate parent-child experiences. Three themes emerged from the thematic analysis: 1. children's understanding of climate change, 2. their emotional reaction to climate change, and 3. their coping mechanisms to deal with these emotions. The comparative content analysis revealed that parents who were aware that their children had concerns about climate change, had children who used more adaptive coping mechanisms. The results of this qualitative study contribute to a better understanding of children's emotional experience of the awareness of climate change in Canada and how they cope with these emotions. Furthermore, the results provide insight into the role parents might play in helping their children cope with their feelings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Léger-Goodes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC., (© 2023. The Author(s) under exclusive license to Springer Nature America, Inc.)

Enzyme catalysis is used to generate approximately 50,000 tons of value-added chemical products per year. Nearly a quarter of this production requires a stoichiometric cofactor such as NAD + /NADH. Given that NADH is expensive, it would be beneficial to regenerate it in a way that does not interfere with the enzymatic reaction. Water electrolysis could provide the proton and electron equivalent necessary to electrocatalytically convert NAD + to NADH. However, this form of electrocatalytic NADH regeneration is challenged by the formation of inactive NAD 2 dimers, the use of high overpotentials or mediators, and the long-term electrochemical instability of the enzyme during electrolysis. Here, we show a means of overcoming these challenges by using a bioelectrocatalytic palladium membrane reactor for electrochemical NADH regeneration from NAD + . This achievement is possible because the membrane reactor regenerates NADH through reaction of hydride with NAD + in a compartment separated from the electrolysis compartment by a hydrogen-permselective Pd membrane. This separation of the enzymatic and electrolytic processes bypasses radical-induced NAD + degradation and enables the operator to optimize conditions for the enzymatic reaction independent of the water electrolysis. This architecture, which mechanistic studies reveal utilizes hydride sourced from water, provides an opportunity for enzyme catalysis to be driven by clean electricity where the major waste product is oxygen gas., (© 2023. The Author(s).)

Here, we detail how the catalytic behavior of immobilized molecular electrocatalysts for the CO 2 reduction reaction (CO 2 RR) can be impacted by catalyst aggregation. Operando Raman spectroscopy was used to study the CO 2 RR mediated by a layer of cobalt phthalocyanine (CoPc) immobilized on the cathode of an electrochemical flow reactor. We demonstrate that during electrolysis, the oxidation state of CoPc in the catalyst layer is dependent upon the degree of catalyst aggregation. Our data indicate that immobilized molecular catalysts must be dispersed on conductive supports to mitigate the formation of aggregates and produce meaningful performance data. We leveraged insights from this mechanistic study to engineer an improved CO-forming immobilized molecular catalyst─cobalt octaethoxyphthalocyanine (EtO 8 -CoPc)─that exhibited high selectivity (FE CO ≥ 95%), high partial current density ( J CO ≥ 300 mA/cm 2 ), and high durability (ΔFE CO < 0.1%/h at 150 mA/cm 2 ) in a flow cell. This work demonstrates how to accurately identify CO 2 RR active species of molecular catalysts using operando Raman spectroscopy and how to use this information to implement improved molecular electrocatalysts into flow cells. This work also shows that the active site of CoPc during CO 2 RR catalysis in a flow cell is the metal center.

Background and Aims: Transoral incisionless fundoplication (TIF) using the EsophyX device (EndoGastric Solutions, Inc, Redmond, Wash, USA) is a minimally invasive endoscopic fundoplication technique. Our study aimed to assess the efficacy of TIF for atypical GERD symptoms in patients with chronic or refractory GERD., Methods: A systematic search of 4 major databases was performed. All original studies assessing atypical GERD using a validated symptom questionnaire (the reflux symptom index [RSI]) were included. The RSI score was assessed before and after TIF at a 6- and 12-month follow-up. Data on technical success rate, adverse events, proton pump inhibitor (PPI) use, and patient satisfaction were also collected. Only TIF procedures currently in practice using the EsophyX device (ie, TIF 2.0) and TIF with concomitant hiatal hernia repair were included in the review., Results: Ten studies (564 patients) were included. At the 6- and 12- month follow-up, there was a mean reduction of 15.72 (95% confidence interval, 12.15-19.29) and 14.73 (95% confidence interval, 11.74-17.72) points, respectively, in the RSI score post-TIF, with a technical success rate of 99.5% and a pooled adverse event rate of 1%. At both time intervals, more than two-thirds of the patients were satisfied with their health condition and roughly three-fourths of the patients were off daily PPIs., Conclusions: Our study shows that TIF using the EsophyX device is safe and effective in reducing atypical GERD symptoms at 6 and 12 months of follow-up. It improves patient-centered outcomes and can be a minimally invasive therapeutic option for patients suffering from atypical GERD symptoms on chronic medical therapy., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background. Occupational therapy interventions that promote and prevent children's health and well-being aim to reduce health inequalities and foster protective factors. The purpose of this study is to describe a pilot community-based occupational therapy project for preschoolers in partnership with community organizations and childcare services. Method. A participatory action research approach was implemented with support from an advisory committee. An occupational therapist provided community-based occupational therapy services in a tiered organization model over one year. Findings. Services were offered in three tiers: 7 awareness workshops for parents and caregivers (Tier 1), 57 visits and 27 consultations in 8 community agencies (Tier 2), and 23 individual follow-ups (Tier 3). Implications. There is an opportunity to implement with community agencies and daycare settings an occupational therapy service based on community-based rehabilitation for children under 5 years of age.

Importance: Chronic obstructive pulmonary disease (COPD) is underdiagnosed in primary care., Objective: To evaluate the operating characteristics of the CAPTURE (COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk) screening tool for identifying US primary care patients with undiagnosed, clinically significant COPD., Design, Setting, and Participants: In this cross-sectional study, 4679 primary care patients aged 45 years to 80 years without a prior COPD diagnosis were enrolled by 7 primary care practice-based research networks across the US between October 12, 2018, and April 1, 2022. The CAPTURE questionnaire responses, peak expiratory flow rate, COPD Assessment Test scores, history of acute respiratory illnesses, demographics, and spirometry results were collected., Exposure: Undiagnosed COPD., Main Outcomes and Measures: The primary outcome was the CAPTURE tool's sensitivity and specificity for identifying patients with undiagnosed, clinically significant COPD. The secondary outcomes included the analyses of varying thresholds for defining a positive screening result for clinically significant COPD. A positive screening result was defined as (1) a CAPTURE questionnaire score of 5 or 6 or (2) a questionnaire score of 2, 3, or 4 together with a peak expiratory flow rate of less than 250 L/min for females or less than 350 L/min for males. Clinically significant COPD was defined as spirometry-defined COPD (postbronchodilator ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity [FEV1:FVC] <0.70 or prebronchodilator FEV1:FVC <0.65 if postbronchodilator spirometry was not completed) combined with either an FEV1 less than 60% of the predicted value or a self-reported history of an acute respiratory illness within the past 12 months., Results: Of the 4325 patients who had adequate data for analysis (63.0% were women; the mean age was 61.6 years [SD, 9.1 years]), 44.6% had ever smoked cigarettes, 18.3% reported a prior asthma diagnosis or use of inhaled respiratory medications, 13.2% currently smoked cigarettes, and 10.0% reported at least 1 cardiovascular comorbidity. Among the 110 patients (2.5% of 4325) with undiagnosed, clinically significant COPD, 53 had a positive screening result with a sensitivity of 48.2% (95% CI, 38.6%-57.9%) and a specificity of 88.6% (95% CI, 87.6%-89.6%). The area under the receiver operating curve for varying positive screening thresholds was 0.81 (95% CI, 0.77-0.85)., Conclusions and Relevance: Within this US primary care population, the CAPTURE screening tool had a low sensitivity but a high specificity for identifying clinically significant COPD defined by presence of airflow obstruction that is of moderate severity or accompanied by a history of acute respiratory illness. Further research is needed to optimize performance of the screening tool and to understand whether its use affects clinical outcomes.

Objectives: Specialized pain rehabilitation is recognized as the treatment of choice for youth with pain-related disability. Appropriate outcomes for program evaluation are critical. This study aimed to summarize the effect domains and methods used to evaluate pediatric-specialized outpatient pain rehabilition programs, map them to the PedIMMPACT statement, and highlight future directions., Methods: An integrated review framework, incorporating stakeholders, was used. Academic Search Complete, CINAHL, ERIC, MEDLINE, PsycINFO, and Google Scholar were searched for studies published in 1999-2021 featuring the treatment effects of specialized outpatient pain rehabilitation on youth with pain-related disability and their parents. Selected studies were critically appraised using the Quality Assessment Tool for Studies of Diverse Design, organized by study characteristics, and analyzed using constant comparison., Results: From the 1951 potentially relevant titles, 37 studies were selected. Twenty-five effects targeted youth and 24 focused on parents, with a maximum of 15 youth and 11 parent effect domains (median = 5 domains per study). Although most studies measured a combination of effect domains and were inclusive of some recommended in the PedIMMPACT statement, no effect was measured consistently across studies. Youth physical functioning and parent emotional functioning were measured most often. Eighty-five instruments were used to assess youth outcomes and 59 for parents, with self-report questionnaires dominating., Discussion: A lack of standardization exists associated with the domains and methods used to evaluate the effects of pediatric-specialized outpatient pain rehabilitation programs, hindering comparisons. Future program evaluations should be founded on their theory, aim, and anticipated outcomes., (© 2022 World Institute of Pain.)

Prenatal fine particulate matter (PM 2.5 ) exposure is an understudied risk factor for neurodevelopmental outcomes, including intellectual disability (ID). Associations among prenatal exposures and neurodevelopmental outcomes may vary depending on the timing of exposure. Limited numbers of studies examining PM 2.5 and neurodevelopmental outcomes have considered exposures occurring during the preconception period. To address these gaps, we conducted a case-control study of children born in Utah between 2002 and 2008 (n = 1032). Cases were identified using methods developed by the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network and matched with controls on birth year, sex, and birth county. We estimated the daily average PM 2.5 concentration during a period spanning 12 weeks before the estimated conception date, as well as during each of the three trimesters at the maternal residential address listed on the child's birth certificate. In a multivariable model, the third (OR: 2.119, CI: 1.123-3.998, p = .021) and fourth (OR: 2.631, CI: 1.750-3.956, p < .001) quartiles for preconception average PM 2.5 demonstrated significantly increased risk of ID relative to the first quartile. Second quartile preconception exposure was also associated with increased risk, though it did not reach significance (OR: 1.385, CI: 0.979-1.959, p = .07). The fourth quartile of first trimester average PM 2.5 was positive and significant (OR: 2.278, CI: 1.522-3.411, p < .001); the third quartile was positive, but not significant (OR: 1.159, CI: 0.870-1.544, p = .312). Quartiles of second and third trimester were not associated with higher risk of ID. These findings from Utah, which were robust to a variety of sensitivity analyses, provide initial evidence that preconception and prenatal PM 2.5 exposure may be associated with ID. Future studies are needed across other geographic locations and populations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sara Grineski reports financial support was provided by National Institutes of Health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Synthetic DNA barcodes are double-stranded DNA molecules designed to carry recoverable information, information that can be used to represent and track objects and organisms. DNA barcodes offer robust, sensitive detection using standard amplification and sequencing techniques. While numerous research groups have promoted DNA as an information storage medium, less attention has been devoted to the design of economical, scalable DNA barcode libraries. Here, we present an alternative modular approach to sequence design. Barcode sequences were constructed from smaller, interchangeable blocks, allowing for the combinatorial assembly of numerous distinct tags. We demonstrated the design and construction of first-generation (N = 256) and second-generation (N = 512) modular barcode libraries, from fewer than 50 total single-stranded oligonucleotides for each library. To avoid contamination during experimental validation, a liquid-handling robot was employed for oligonucleotide mixing. Generating barcode sequences in-house reduces dependency upon external entities for unique tag generation, increasing flexibility in barcode generation and deployment. Next generation sequencing (NGS) detection of 256 different samples in parallel highlights the multiplexing afforded by the modular barcode design coupled with high-throughput sequencing. Deletion variant analysis of the first-generation library informed sequence design for enhancing barcode assembly specificity in the second-generation library.

Cardiac outcomes of 131 children with multisystem inflammatory syndrome (MIS-C) were examined. The majority of the cohort was male (66.4%) and half were Black (49.6%). Cardiac involvement was evident in 25% of the cohort at diagnosis. Favorable short- and mid-term outcomes were documented on follow-up, irrespective of the severe acute respiratory syndrome coronavirus 2 variants causing the infection., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Data are limited regarding adverse reactions after COVID-19 vaccination in patients with a history of multisystem inflammatory syndrome in children (MIS-C). The lack of vaccine safety data in this unique population may cause hesitancy and concern for many families and health care professionals., Objective: To describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C., Design, Setting, and Participants: In this multicenter cross-sectional study including 22 North American centers participating in a National Heart, Lung, and Blood Institute, National Institutes of Health-sponsored study, Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC), patients with a prior diagnosis of MIS-C who were eligible for COVID-19 vaccination (age ≥5 years; ≥90 days after MIS-C diagnosis) were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions., Exposures: COVID-19 vaccination after MIS-C diagnosis., Main Outcomes and Measures: The main outcome was adverse reactions following COVID-19 vaccination. Comparisons were made using the Wilcoxon rank sum test for continuous variables and the χ2 or Fisher exact test for categorical variables., Results: Of 385 vaccine-eligible patients who were surveyed, 185 (48.1%) received at least 1 vaccine dose; 136 of the vaccinated patients (73.5%) were male, and the median age was 12.2 years (IQR, 9.5-14.7 years). Among vaccinated patients, 1 (0.5%) identified as American Indian/Alaska Native, non-Hispanic; 9 (4.9%) as Asian, non-Hispanic; 45 (24.3%) as Black, non-Hispanic; 59 (31.9%) as Hispanic or Latino; 53 (28.6%) as White, non-Hispanic; 2 (1.1%) as multiracial, non-Hispanic; and 2 (1.1%) as other, non-Hispanic; 14 (7.6%) had unknown or undeclared race and ethnicity. The median time from MIS-C diagnosis to first vaccine dose was 9.0 months (IQR, 5.1-11.9 months); 31 patients (16.8%) received 1 dose, 142 (76.8%) received 2 doses, and 12 (6.5%) received 3 doses. Almost all patients received the BNT162b2 vaccine (347 of 351 vaccine doses [98.9%]). Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness (62 patients [33.5%]) and/or fatigue (32 [17.3%]). In 32 patients (17.3%), adverse reactions were treated with medications, most commonly acetaminophen (21 patients [11.4%]) or ibuprofen (11 [5.9%]). Four patients (2.2%) sought medical evaluation, but none required testing or hospitalization. There were no patients with any serious adverse events, including myocarditis or recurrence of MIS-C., Conclusions and Relevance: In this cross-sectional study of patients with a history of MIS-C, no serious adverse events were reported after COVID-19 vaccination. These findings suggest that the safety profile of COVID-19 vaccination administered at least 90 days following MIS-C diagnosis appears to be similar to that in the general population.

Oral temperature is a sensory cue relevant to food preference and nutrition. To understand how orally sourced thermal inputs are represented in the gustatory cortex (GC), we recorded neural responses from the GC of male and female mice presented with deionized water at different innocuous temperatures (14 °C, 25 °C, and 36 °C) and taste stimuli (room temperature). Our results demonstrate that GC neurons encode orally sourced thermal information in the absence of classical taste qualities at the single neuron and population levels, as confirmed through additional experiments comparing GC neuron responses to water and artificial saliva. Analysis of thermal-evoked responses showed broadly tuned neurons that responded to temperature in a mostly monotonic manner. Spatial location may play a minor role regarding thermosensory activity; aside from the most ventral GC, neurons reliably responded to and encoded thermal information across the dorso-ventral and antero-postero cortical axes. Additional analysis revealed that more than half of the GC neurons that encoded chemosensory taste stimuli also accurately discriminated thermal information, providing additional evidence of the GC's involvement in processing thermosensory information important for ingestive behaviors. In terms of convergence, we found that GC neurons encoding information about both taste and temperature were broadly tuned and carried more information than taste-selective-only neurons; both groups encoded similar information about the palatability of stimuli. Altogether, our data reveal new details of the cortical code for the mammalian oral thermosensory system in behaving mice and pave the way for future investigations on GC functions and operational principles with respect to thermogustation., (© The Author(s) 2023. Published by Oxford University Press.)

The addition of supplemental food sources for natural enemies is a growing component of conservation and augmentative biological control. Supplemental foods can be used to retain natural enemies when prey are scarce and to promote survival, fecundity, longevity, and development of natural enemy populations, especially generalist natural enemies. Amblydromella caudiglans (Schuster) (Acari: Phytoseiidae) is one of the most abundant predatory mites found in commercial apple orchards in Washington, USA, and contributes to spider mite control. However, because its widespread presence in commercial apple orchards was only recently discovered, how supplementary food sources affect its performance is unknown. In laboratory studies, we evaluated the performance (fecundity, retention, prey consumption) of the generalist phytoseiid A. caudiglans on commercially available supplemental food sources, including factitious prey (Ephestia eggs and Artemia brine shrimp cysts), and pollens of apple, pear, and cattail. We determined that A. caudiglans will not consume Ephestia eggs and performs best on cattail and pear pollens. Combinations of food sources did not enhance the performance of this predator compared to the best performing single-sources. The presence of alternative food sources did not decrease A. caudiglans predation of twospotted spider mite nymphs, except for Artemia brine shrimp cysts, which had a substantial handling time. These results lay the groundwork for identifying a way to promote and retain this natural enemy in tree fruit cropping systems through the use of food resource applications or floral plantings., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Purpose: Ensuring access to high quality services in paediatric physiotherapy (PT) is important to respond to the diverse needs of children. The accessibility and quality of paediatric PT services has however never been explored internationally. The purpose of this study is to explore the perceived strengths, weaknesses, opportunities, and threats (SWOT) of paediatric PT services offered around the world., Method: A cross-sectional survey design method was used with a subsample of physiotherapists (PTs) who had previously participated in an online survey. The survey used for this study included close- and open-ended questions about access to services and the SWOT of PT services within participants' country. Descriptive statistics were used to summarize quantitative data and a content analysis was performed on open-ended questions., Results: Overall, 47 PTs from 47 countries completed the survey; 36% of participants reported that free access was available to all children in their country while 34% stated that a referral was always required when accessing services. Lack of direct access, insufficient specialized PT, financial and geographical issues were the main perceived barriers to access services. Access also emerged as one of the nine themes following the SWOT analysis. Other themes included education, quality of PT approaches, PT practices, communication and cooperation, teamwork, government, resources, and attitudes of PTs., Discussion: Despite variations in accessing services and how services are delivered across countries, some similar themes influencing PTs practices were found. Future opportunities for PTs working with children should aim at optimizing the initial training and professional development of PTs in paediatrics, increasing access to services for all children and advocating for sustainable and well-coordinated models of care building on best practices., (© 2022 John Wiley & Sons Ltd.)