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Body perception plays a fundamental role in social cognition. Yet, the neural mechanisms underlying this process in humans remain elusive given the spatiotemporal constraints of functional imaging. Here, we present intracortical recordings of single- and multiunit spiking activity in two epilepsy surgery patients in or near the extrastriate body area, a critical region for body perception. Our recordings revealed a strong preference for human bodies over a large range of control stimuli. Notably, body selectivity was driven by a distinct selectivity for body parts. The observed body selectivity generalized to nonphotographic depictions of bodies including silhouettes and stick figures. Overall, our study provides unique neural data that bridge the gap between human neuroimaging and macaque electrophysiology studies, laying a solid foundation for computational models of human body processing., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objectives: The objective of this study is to compare the vaginal uncomplicated delivery (VUD) rate, defined as all vaginal deliveries (including forceps and vacuum) without an adverse maternal or neonatal labour outcome, to the cesarean delivery (CD) rate, as a performance indicator., Methods: This is a retrospective cohort analysis from a provincial database of all term deliveries by an obstetrician in a single year, excluding diagnoses preventing active labour. Most obstetricians in this jurisdiction practice consultative obstetrics, focused on supporting primary maternity care. We investigated the association of adverse delivery (AD), measured by the adverse outcome index, with CD and VUD rates., Results: We report 16 620 deliveries by 210 obstetricians, with a vaginal delivery rate of 39.6%, of which 36.6% were operative vaginal delivery. The overall AD rate was 9.9%, and the overall VUD rate was 34%. While the CD and VUD both correlated with the mode of delivery, only the VUD rate was correlated to the AD rate., Conclusions: Quality assurance in obstetrics must balance the needs of 2 patients based on limited data. Our data shows the shortcomings of the prevailing performance indicator, CD rate, which does not correlate with birth outcomes for the pregnant patient or infant. The VUD rate provides an alternative that assesses both mode of delivery and labour outcomes. Shifting the quality lens to focus on the VUD rate will provide a better metric that measures optimal outcomes for pregnant people and their babies., (Copyright © 2024 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

One of the challenges in the plastic industry is the cost and time spent on the characterization of different grades of polymers. Compressed sensing is a data reconstruction method that combines linear algebra with optimization schemes to retrieve a signal from a limited set of measurements of that signal. Using a data set of signal examples, a tailored basis can be constructed, allowing for the optimization of the measurements that should be conducted to provide the highest and most robust signal reconstruction accuracy. In this work, compressed sensing was used to predict the values of numerous properties based on measurements for a small subset of those properties. A data set of 21 fully characterized acrylonitrile-butadiene-styrene samples was used to construct a tailored basis to determine the minimal subset of properties to measure to achieve high reconstruction accuracy for the remaining nonmeasured properties. The analysis showed that using only six measured properties, an average reconstruction error of less than 5% can be achieved. In addition, by increasing the number of measured properties to nine, an average error of less than 3% was achieved. Compressed sensing enables experts in academia and industry to substantially reduce the number of properties that must be measured to fully and accurately characterize plastics, ultimately saving both costs and time. In future work, the method should be expanded to optimize not only individual properties but also entire tests used to simultaneously measure multiple properties. Furthermore, this approach can also be applied to recycled materials, of which the properties are more difficult to predict.

Background: Exercise therapy is recommended by international guidelines as a core treatment for patients with knee osteoarthritis. However, there is a significant gap between recommendations and practice in health care. Digital exercise apps are promising to help solve this undersupply., Objective: This study aims to evaluate the efficacy of a 12-week fully automated app-based exercise intervention with and without a supporting knee brace on health-related outcomes, performance measures, and adherence in patients with knee osteoarthritis., Methods: This closed user group trial included participants with moderate to severe unicondylar painful knee osteoarthritis. Randomization was 1:1:2 into an intervention group (IG) with 2 subgroups (app-based training [IG A] and app-based training and a supportive knee brace [IG AB]) and a control group (CG). The intervention included a 12-week home exercise program with 3 sessions per week. Instructions for the exercises were given via the app and monitored using 2 accelerometers placed below and above the affected knee joint. Participants in the CG did not receive any study intervention but were allowed to make use of usual care. Osteoarthritis-specific pain (Knee Injury and Osteoarthritis Outcome Score) was defined as the primary outcome, and secondary outcomes included all other Knee Injury and Osteoarthritis Outcome Score subscales, general health-related quality of life (Veterans RAND 12-item Health Survey), psychological measures (eg, exercise self-efficacy), performance measures (strength and postural control), and the monitoring of adherence and safety. Outcomes were assessed at baseline and after 12 weeks. Intervention effects were calculated using baseline-adjusted analysis of covariance for the joint comparison of IG A and IG AB versus the CG using a per-protocol approach. Subgroup analyses were conducted for each IG separately., Results: A total of 61 participants were included (IG: n=30, 49%; CG: n=31, 51%; male: n=31, 51%; female: n=30, 49%; mean age 62.9, SD 8.5 years; mean BMI 27.7, SD 4.5 kg/m 2 ). Analysis revealed statistically significant effects in favor of the IG for pain reduction (P<.001; effect size [ES]=0.76), improvements in physical function (P<.001; ES=0.64), improvements in symptoms (P=.01; ES=0.53), improvements in sport and recreation activities (P=.02; ES=0.47), improvements in knee-related quality of life (P<.001; ES=0.76), and improvements in the physical component of general health-related quality of life (P<.001; ES=0.74). Mean differences ranged from 6.0 to 13.2 points (scale range 0-100). ESs indicated small to medium effects. No effects were found for psychological and performance measures. Participants adhered to 92.5% (899/972) of all scheduled exercise sessions., Conclusions: Individuals with knee osteoarthritis undergoing a 12-week sensor-assisted app-based exercise intervention with or without an additional knee brace experienced clinically meaningful treatment effects regarding pain relief and improvements in physical function as well as other osteoarthritis-specific concerns compared to controls., Trial Registration: German Clinical Trials Register (DRKS) DRKS00023269; https://drks.de/search/de/trial/DRKS00023269., (©Valerie Dieter, Pia Janssen, Inga Krauss. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 09.09.2024.)

Background: It is well known that opiates slow gastrointestinal (GI) transit, via suppression of enteric cholinergic neurotransmission throughout the GI tract, particularly the large intestine where constipation is commonly induced. It is not clear whether there is uniform suppression of enteric neurotransmission and colonic motility across the full length of the colon. Here, we investigated whether regional changes in colonic motility occur using the peripherally-restricted mu opioid agonist, loperamide to inhibit colonic motor complexes (CMCs) in isolated mouse colon., Methods: High-resolution video imaging was performed to monitor colonic wall diameter on isolated whole mouse colon. Regional changes in the effects of loperamide on the pattern generator underlying cyclical CMCs and their propagation across the full length of large intestine were determined., Results: The sensitivity of CMCs to loperamide across the length of colon varied significantly. Although there was a dose-dependent inhibition of CMCs with increasing concentrations of loperamide (10 nM - 1 μM), a major observation was that in the mid and distal colon, CMCs were abolished at low doses of loperamide (100 nM), while in the proximal colon, CMCs persisted at the same low concentration, albeit at a significantly slower frequency. Propagation velocity of CMCs was significantly reduced by 46%. The inhibitory effects of loperamide on CMCs were reversed by naloxone (1 μM). Naloxone alone did not change ongoing CMC characteristics., Discussion: The results show pronounced differences in the inhibitory action of loperamide across the length of large intestine. The most potent effect of loperamide to retard colonic transit occurred between the proximal colon and mid/distal regions of colon. One of the possibilities as to why this occurs is because the greatest density of mu opioid receptors are located on interneurons responsible for neuro-neuronal transmission underlying CMCs propagation between the proximal and mid/distal colon. The absence of effect of naloxone alone on CMC characteristics suggest that the mu opioid receptor has little ongoing constitutive activity under our recording conditions., 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 Parkar, Spencer, Wiklendt, Olson, Young, Janssen, McNabb and Dalziel.)

The lung is constantly exposed to airborne pathogens and particles that can cause alveolar damage. Hence, appropriate repair responses are essential for gas exchange and life. Here, we deciphered the spatiotemporal trajectory and function of an atypical population of macrophages after lung injury. Post-influenza A virus (IAV) infection, short-lived monocyte-derived Ly6G-expressing macrophages (Ly6G + Macs) were recruited to the alveoli of lung perilesional areas. Ly6G + Macs engulfed immune cells, exhibited a high metabolic potential, and clustered with alveolar type 2 epithelial cells (AT2s) in zones of active epithelial regeneration. Ly6G + Macs were partially dependent on granulocyte-macrophage colony-stimulating factor and interleukin-4 receptor signaling and were essential for AT2-dependent alveolar regeneration. Similar macrophages were recruited in other models of injury and in the airspaces of lungs from patients with suspected pneumonia. This study identifies perilesional alveolar Ly6G + Macs as a spatially restricted, short-lived macrophage subset promoting epithelial regeneration postinjury, thus representing an attractive therapeutic target for treating lung damage.

Meso-octaalkylcalix[4]pyrrolates are a class of redox-active porphyrinogen ligands. They have been well established in d- and f-block chemistry for over three decades but have only recently been introduced as ligands for p-block elements. Here, we present a study on the influence of meso-substituents on the redox chemistry of calix[4]pyrrolato stannate(II) dianions [2 R ] 2- (R=Me, Et). Expansion of the normal-mode structural decomposition (NSD) method, well known for porphyrin chemistry, provides insights into the ligand conformation of a calix[4]pyrrolato p-block complex. Combined with the results of spectroscopic donor scaling, electrochemical studies, and quantum mechanical bond analysis tools, subtle but significant substitution and conformational effects on the electronic structure are revealed. Exploiting this knowledge rationalizes the role of this class of tin(II) dianions to act as potent reducing agents, but can also be expanded for other central elements. Photoexcitation boosts this reactivity further, allowing for the reduction of even challenging chlorobenzene., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

High concentrations of low-density particles may cause effects in acute inhalation toxicity studies which can be easily underestimated or misinterpreted following strictly the OECD TG 436, i.e., limited parameters as mortality and gross lesions will be evaluated only. Seven particle types (synthetic amorphous silica (SAS) HMDZ-SAS, silica gel, pyrogenic SAS, and precipitated SAS, calcium carbonate, aluminum oxide pyrogenic alumina, organic red pigment) were chosen at the highest technically feasible concentration of approximately 500 mg/m 3 for acute inhalation studies with an expanded endpoint setup. Therefore additional parameters and a thorough histopathological evaluation of an extensive set of organs, including the respiratory tract emphasizing the nasal cavities were added. Six Crl:WI rats per study were exposed for four hours from which three animals were sacrificed after 24 hours and three animals after 14 days. HMDZ-SAS caused early death in all animals due to blockage of the nasal passages caused by its hydrophobicity. For all other Si-containing compounds, histology revealed minor inflammatory and reactive lesions in lungs after 24 hours that were still present after 14 days, except in silica gel-treated animals. After 14 days, for pyrogenic SAS, precipitated SAS, and pyrogenic alumina, granulomas formed in the BALT and lung-associated lymph nodes. In contrast, the calcium carbonate induced almost no findings, and the red pigment (also tested for the additional dose of 1000 mg/m 3 ) stuck partially to the nasal mucosa without causing pathological damage and partly entered the lungs without showing any adverse effects. The results of the present study highlight the advantage of improving the rather simple study design of acute inhalation studies by implementing an extended study design., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors reports financial support was provided by SASFORREACH, a consortium of the producers of synthetic amorphous silica. Each author certifies that their freedom to design, conduct, interpret, and publish research was not compromised by the sponsor. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Canine idiopathic pulmonary fibrosis (CIPF) is a progressive fibrotic interstitial lung disease of unknown etiology, afflicting aging West Highland white terriers (WHWTs) and leading to progressive respiratory failure. Fibroblast activation protein (FAP), a protease overexpressed in many cancers, is upregulated in idiopathic pulmonary fibrosis in humans. The aim of this study was to investigate FAP as a marker of active fibrosis in lung biopsies from WHWTs affected with CIPF, as well as the potential of plasmatic FAP as a biomarker. After establishing a scoring system to evaluate the severity and activity of fibrosis on histopathological lung sections, anti-FAP immunohistochemistry was performed on healthy and CIPF samples. FAP expression was characterized using both visual and digital quantitative pathology software analyses and then correlated to fibrosis severity and activity. Levels of plasmatic FAP in WHWTs affected with CIPF were measured by enzyme-linked immunosorbent assay and compared with healthy dogs. Lung samples from 22 WHWTs affected with CIPF were collected. According to the fibrosis scoring system, they were classified as cases of mild (5), moderate (9) and severe (8) fibrosis and were attributed scores of fibrosis activity. Fifteen healthy lung samples were classified as non-fibrotic. Healthy lung samples were FAP-negative, whereas fibroblasts were FAP-positive in 20 CIPF samples. FAP immunohistochemical expression correlated mildly with fibrosis severity ( p  < 0.05; R 2  = 0.22) but highly with fibrosis activity scores ( p  < 0.001; R 2  = 0.68). Digital image analysis detected a higher percentage of FAP-positive cells in areas of active fibrosis ( p  < 0.001) and FAP-positive cells were distributed outside mature fibrosis lesions, clustered in active fibrosis areas or scattered within alveolar septa. On the other hand, plasmatic FAP was significantly lower in dogs affected with CIPF compared with healthy dogs ( p  < 0.01). In conclusion, this study provides a valuable histological scoring system to assess the severity and activity of fibrosis in CIPF. It demonstrates that FAP is a good cellular marker of fibrotic activity in CIPF, and thus constitutes a promising target to be exploited for diagnostic and therapeutic applications. Additionally, it suggests that plasmatic FAP, although non-specific, could be altered in CIPF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rizzoli, de Meeûs d'Argenteuil, Fastrès, Roels, Janssen, Puré, Garigliany, Marichal and Clercx.)

Background: Gastrointestinal dysmotility is frequently suspected in patients with gastroparesis, functional dyspepsia, and ileus, and in the intensive care unit. Monitoring of gastric motility in clinical practice remains challenging. A novel technology was developed to meet the medical need for a widely available bedside tool to monitor gastric motility continuously. The VIPUN™ Gastric Monitoring System (GMS) comprises a nasogastric feeding tube with intragastric balloon to allow for measuring gastric contractions., Aims: To compare the performance of the VIPUN GMS versus a reference technique (manometry)., Methods: In this validation study in healthy subjects, the investigational catheter and a solid-state manometry catheter were placed in the stomach concomitantly. Motility was recorded for 2.5 h: 2 h in a fasting state, followed by a 400-kcal liquid meal, and monitoring of the fed state for the remaining half hour. The performance of both systems was compared by automated recognition and manual identification of the contractile activity. Data are presented as mean (standard deviation)., Key Results: The analysis set comprised 13 healthy subjects (6 women, age: 27.5 (8.1) years, BMI: 22.2 (2.46) kg/m 2 ). Automatically-recognized contractility was strongly correlated between the two techniques (endpoint: contraction duration; Spearman ρ = 0.96, p < 0.001). A correlation was also observed between the number of individual contractions identified by expert gastroenterologists on both technologies independently (ρ = 0.71, p = .007) and between the contractions identified by the experts and by the GMS software (ρ = 0.87, p = 0.001). No serious or unanticipated adverse events occurred., Conclusions & Inferences: The observed strong correlations with the gold standard, manometry, validate the performance of the VIPUN GMS as a gastric monitoring system., (© 2024 John Wiley & Sons Ltd.)

Object recognition and categorization are essential cognitive processes which engage considerable neural resources in the human ventral visual stream. However, the tuning properties of human ventral stream neurons for object shape and category are virtually unknown. We performed large-scale recordings of spiking activity in human Lateral Occipital Complex in response to stimuli in which the shape dimension was dissociated from the category dimension. Consistent with studies in nonhuman primates, the neuronal representations were primarily shape-based, although we also observed category-like encoding for images of animals. Surprisingly, linear decoders could reliably classify stimulus category even in data sets that were entirely shape-based. In addition, many recording sites showed an interaction between shape and category tuning. These results represent a detailed study on shape and category coding at the neuronal level in the human ventral visual stream, furnishing essential evidence that reconciles human imaging and macaque single-cell studies., (© 2024. The Author(s).)

Neurons responding during action execution and action observation were discovered in the ventral premotor cortex 3 decades ago. However, the visual features that drive the responses of action observation/execution neurons (AOENs) have not been revealed at present. We investigated the neural responses of AOENs in ventral premotor area F5c of 4 macaques during the observation of action videos and crucial control stimuli. The large majority of AOENs showed highly phasic responses during the action videos, with a preference for the moment that the hand made contact with the object. They also responded to an abstract shape moving towards but not interacting with an object, even when the shape moved on a scrambled background, implying that most AOENs in F5c do not require the perception of causality or a meaningful action. Additionally, the majority of AOENs responded to static frames of the videos. Our findings show that very elementary stimuli, even without a grasping context, are sufficient to drive responses in F5c AOENs., Competing Interests: The authors have declared no competing interests exist., (Copyright: © 2024 De Schrijver 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.)

xCT (Slc7a11), the specific subunit of the cystine/glutamate antiporter system x c - , is present in the brain and on immune cells, where it is known to modulate behavior and inflammatory responses. In a variety of cancers -including pancreatic ductal adenocarcinoma (PDAC)-, xCT is upregulated by tumor cells to support their growth and spread. Therefore, we studied the impact of xCT deletion in pancreatic tumor cells (Panc02) and/or the host (xCT -/- mice) on tumor burden, inflammation, cachexia and mood disturbances. Deletion of xCT in the tumor strongly reduced tumor growth. Targeting xCT in the host and not the tumor resulted only in a partial reduction of tumor burden, while it did attenuate tumor-related systemic inflammation and prevented an increase in immunosuppressive regulatory T cells. The latter effect could be replicated by specific xCT deletion in immune cells. xCT deletion in the host or the tumor differentially modulated neuroinflammation. When mice were grafted with xCT-deleted tumor cells, hypothalamic inflammation was reduced and, accordingly, food intake improved. Tumor bearing xCT -/- mice showed a trend of reduced hippocampal neuroinflammation with less anxiety- and depressive-like behavior. Taken together, targeting xCT may have beneficial effects on pancreatic cancer-related comorbidities, beyond reducing tumor burden. The search for novel and specific xCT inhibitors is warranted as they may represent a holistic therapy in pancreatic cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Phenomenon : Entrustable professional activities (EPAs) delineate major professional activities that an individual in a given specialty must be "entrusted" to perform, ultimately without supervision, to provide quality patient care. Until now, most EPA frameworks have been developed by professionals within the same specialty. As safe, effective, and sustainable health care ultimately depends on interprofessional collaboration, we hypothesized that members of interprofessional teams might have clear and possibly additional insight into which activities are essential to the professional work of a medical specialist. Approach : We recently employed a national modified Delphi study to develop and validate a set of EPAs for Dutch pediatric intensive care fellows. In this proof-of-concept study, we explored what pediatric intensive care physicians' non-physician team members (physician assistants, nurse practitioners, and nurses) constitute as essential professional activities for PICU physicians and how they regarded the newly developed set of nine EPAs. We compared their judgments with the PICU physicians' opinions. Findings : This study shows that non-physician team members share a mental model with physicians about which EPAs are indispensable for pediatric intensive care physicians. Despite this agreement however, descriptions of EPAs are not always clear for non-physician team members who have to work with them on a daily basis. Insights : Ambiguity as to what an EPA entails when qualifying a trainee can have implications for patient safety and trainees themselves. Input from non-physician team members may add to the clarity of EPA descriptions. This finding supports the involvement of non-physician team members in the developmental process of EPAs for (sub)specialty training programs.

Cross-species comparisons studying primate pluripotent stem cells and their derivatives are crucial to better understand the molecular and cellular mechanisms behind human disease and development. Within this context, Baboons (Papio anubis) have emerged as a prominent primate model for such investigations. Herein, we reprogrammed skin fibroblasts of one male individual and generated two induced pluripotent stem cell (iPSC) lines, which exhibit the characteristic ESC-like morphology, demonstrated robust expression of key pluripotency factors and displayed multilineage differentiation potential. Notably, both iPSC lines can be cultured under feeder-free conditions in commercially available medium, enhancing their value for cross-species comparisons., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wolfgang Enard reports financial support, article publishing charges, and travel were provided by German Research Foundation., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cross-species comparisons using pluripotent stem cells from primates are crucial to better understand human biology, disease, and evolution. The Vervet monkey (Chlorocebus aethiops sabaeus) serves as an important primate model for such studies, and therefore we reprogrammed skin fibroblasts derived from a male and a female individual, resulting in two induced pluripotent stem cell lines (iPSCs). These iPSCs display the characteristic ESC-like colony morphology, express key pluripotency markers, and possess the ability to differentiate into cells representing all three germ layers. Importantly, both generated cell lines can be maintained in feeder-free culture conditions using commercially available medium., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wolfgang Enard reports financial support, article publishing charges, and travel were provided by German Research Foundation., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Group B streptococcus (GBS), or Streptococcus agalactiae , remains a leading cause of neonatal morbidity and mortality. Canadian guidelines advise universal maternal screening for GBS colonisation in pregnancy in conjunction with selective antibiotic therapy. This results in over 1000 pregnant individuals receiving antibiotic therapy to prevent one case of early-onset neonatal GBS disease, and over 20 000 pregnant individuals receiving antibiotic therapy to prevent one neonatal death. Given the growing concern regarding the risk of negative sequela from antibiotic exposure, it is vital that alternative approaches to reduce maternal GBS colonisation are explored.Preliminary studies suggest some probiotic strains could confer protection in pregnancy against GBS colonisation., Methods and Analysis: This double-blind parallel group randomised trial aims to recruit 450 pregnant participants in Vancouver, BC, Canada and will compare GBS colonisation rates in those who have received a daily oral dose of three strains of probiotics with those who have received a placebo. The primary outcome will be GBS colonisation status, measured using a vaginal/rectal swab obtained between 35 weeks' gestation and delivery. Secondary outcomes will include maternal antibiotic exposure and urogenital infections. Analysis will be on an intention-to-treat basis., Patient or Public Involvement: There was no patient or public involvement in the design of the study protocol., Ethics and Dissemination: This study protocol received ethics approval from the University of British Columbia's Clinical Research Ethics Board, Dublin City University and Health Canada. Findings will be presented at research rounds, conferences and in peer-reviewed publications., Trial Registration Number: NCT03407157., Competing Interests: Competing interests: None declared., (© 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.)

Cross-species comparisons using pluripotent stem cells from primates are crucial to better understand human biology, disease, and evolution. An important primate model is the Rhesus macaque (Macaca mulatta), and we reprogrammed skin fibroblasts from a male individual to generate three induced pluripotent stem cell (iPSC) lines. These cells exhibit the typical ESC-like colony morphology, express common pluripotency markers, and can differentiate into cells of the three germ layers. All generated iPSC lines can be cultured under feeder-free conditions in commercially available medium and are therefore valuable resources for cross-species comparisons., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wolfgang Enard reports financial support, article publishing charges, and travel were provided by German Research Foundation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The purpose of this systematic literature review was to systematically compile the state of knowledge on correlates of physical activity enjoyment in children and adolescents to influence the perspective of future physical activity promotion approaches especially for children and adolescents affected by overweight or obesity. The electronic database search was executed in the five databases PubMed, PsychINFO, SPORTDiscus, Web of Science, and BISp-SURF, from inception to December 6, 2021. A semi-quantitative method was used for summarizing the resulted correlates. For final analysis, 85 studies comprising 48,144 children and adolescents were included. Fifty-seven variables could be coded for their relationship with physical activity enjoyment. Of these, 12 psychological variables, for example, the basic psychological needs, task orientation, or self-efficacy; six interpersonal variables, for example, peer/group acceptance, parental support, and autonomy support; and one behavioral variable, the higher self-reported physical activity, are consistent positively associated to physical activity enjoyment. A scientifically based overview could be extracted for the promotion of physical activity enjoyment in children and adolescents. There is a gap in literature focusing the perception of physical activity enjoyment in the subgroup of children and adolescents affected by overweight or obesity. Therefore, recommendations were made to enable the development of further innovative research approaches in this population., (© 2023 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Introduction: Prenatal education is associated with positive health behaviours, including optimal weight gain, attendance at prenatal care, acceptance of routine screening tests, smoking cessation, decreased alcohol consumption and breast feeding. Adoption of these behaviours has been associated with reduced rates of caesarean birth, preterm birth and low birth weight. Barriers to prenatal class attendance faced by parents in Canada include geography, socioeconomic status, age, education, and, among Indigenous peoples and other equity-deserving groups, stigma. To address the need for easily accessible and reliable information, we created 'SmartMom', Canada's first prenatal education programme delivered by short message service text messaging. SmartMom provides evidence-based information timed to be relevant to each week of pregnancy. The overall goal of SmartMom is to motivate the adoption of positive prenatal health behaviours with the ultimate goal of improving health outcomes among women and their newborns., Methods and Analysis: We will conduct a two-arm single-blinded randomised controlled trial. Blinding of participants to trial intervention will not be possible as they will be aware of receiving the intervention, but data analysts will be blinded. Our primary research questions are to determine if women experiencing uncomplicated pregnancies randomly assigned to receive SmartMom messages versus messages addressing general topics related to pregnancy but without direction for behaviour change, have higher rates of: (1) weight gain within ranges recommended for prepregnancy body mass index and (2) adherence to Canadian guidelines regarding attendance at prenatal care appointments., Ethics and Dissemination: The study has been granted a Certificate of Approval, number H22-00603, by the University of British Columbia Research Ethics Board. To disseminate our findings, we are undertaking both integrated and end-of-grant knowledge translation, which will proactively involve potential end-users and stakeholders at every phase of our project., Trial Registration Number: NCT05793944., Competing Interests: Competing interests: None declared., (© 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.)

Background: Preserved cycling capabilities in patients with Parkinson's disease, especially in those with freezing of gait are still poorly understood. Previous research with invasive local field potential recordings in the subthalamic nucleus has shown that cycling causes a stronger suppression of β oscillations compared to walking, which facilitates motor continuation., Methods: We recorded local field potentials from 12 patients with Parkinson's disease (six without freezing of gait, six with freezing of gait) who were bilaterally implanted with deep brain stimulation electrodes in the subthalamic nucleus. We investigated β (13-30 Hz) and high γ (60-100 Hz) power during both active and passive cycling with different cadences and compared patients with and without freezing of gait. The passive cycling experiment, where a motor provided a fixed cadence, allowed us to study the effect of isolated sensory inputs without physical exercise., Results: We found similarly strong suppression of pathological β activity for both active and passive cycling. In contrast, there was stronger high γ band activity for active cycling. Notably, the effects of active and passive cycling were all independent of cadence. Finally, β suppression was stronger for patients with freezing of gait, especially during passive cycling., Conclusions: Our results provide evidence for a link between proprioceptive input during cycling and β suppression. These findings support the role of continuous external sensory input and proprioceptive feedback during rhythmic passive cycling movements and suggest that systematic passive mobilization might hold therapeutic potential. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Purpose: Total body irradiation (TBI) followed by bone marrow transplantation (BMT) is used in pre-clinical research to generate mouse chimeras that allow to study the function of a protein specifically on immune cells. Adverse consequences of irradiation on the juvenile body and brain are well described and include general fatigue, neuroinflammation, neurodegeneration and cognitive impairment. Yet, the long-term consequences of TBI/BMT performed on healthy adult mice have been poorly investigated., Material and Methods: We developed a robust protocol to achieve near complete bone marrow replacement in mice using 2x550cGy TBI and evaluated the impact of the procedure on their general health, mood disturbances, memory, brain atrophy, neurogenesis, neuroinflammation and blood-brain barrier (BBB) permeability 2 and/or 16 months post-BMT., Results: We found a persistent decrease in weight along with long-term impact on locomotion after TBI and BMT. Although the TBI/BMT procedure did not lead to anxiety- or depressive-like behavior 2- or 16-months post-BMT, long-term spatial memory of the irradiated mice was impaired. We also observed radiation-induced impaired neurogenesis and cortical microglia activation 2 months post-BMT. Moreover, higher levels of hippocampal IgG in aged BMT mice suggest an enhanced age-related increase in BBB permeability that could potentially contribute to the observed memory deficit., Conclusions: Overall health of the mice did not seem to be majorly impacted by TBI followed by BMT during adulthood. Yet, TBI-induced alterations in the brain and behavior could lead to erroneous conclusions on the function of a protein on immune cells when comparing mouse chimeras with different genetic backgrounds that might display altered susceptibility to radiation-induced damage. Ultimately, the BMT model we here present could also be used to study the related long-term consequences of TBI and BMT seen in patients.

In this study, an in-depth comparison was made between batch and continuous direct compression using similar compression set-ups. The overall material processability and final tablet quality were compared and evaluated. Correlations between material properties, process parameters and final tablet properties were made via multivariate data analyses. In total, 10 low-dosed (1% w /w) and 10 high-dosed (40% w/w) formulations were processed, using a total of 10 different fillers/filler combinations. The trials indicated that the impact of filler type, drug load or process settings was similar for batch and continuous direct compression. The main differentiator between batch and continuous was the flow dynamics in the operating system, where properties related to flow, compressibility and permeability played a crucial role. The less consistent flow throughout a batch process resulted in a significantly higher variability within the tablet press (σ CF ) and for the tablet quality responses (σ Mass , σ TS ). However, the better controlled blending procedure prior to batch processing was reflected in a more consistent API concentration variability. Overall, the comparison showed the benefits of selecting appropriate excipients and process settings to achieve a specific outcome, keeping in mind some key differentiators between both processes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: Nephrotoxicity can occur as a side effect after treatment for kidney tumor in childhood. The use of radiotherapy (RT) has a potential additional effect., Methods: A systematic electronic literature search that combined childhood kidney cancer with different treatments and nephrotoxicity terms was performed in EMBASE. Studies were included based on the reporting of nephrotoxicity occurrence after treatment for kidney tumor during pediatric age, with 75% of participants being under the age of 25 years at the time of diagnosis, and having been treated with any type of kidney surgery, chemotherapy, and/or RT., Results: A pooled analysis did not show significant difference in estimated glomerular filtration rate between the group of patients who received RT compared with the group treated without RT (SMD -0.11 [95% CI -1.07-0.84] p = .733)., Conclusion: The current literature suggests that the use of RT does not have a significant impact on the decline of kidney function as independent factor., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Acinar cell dedifferentiation is one of the most notable features of acute and chronic pancreatitis. It can also be the initial step that facilitates pancreatic cancer development. In the present study, we further decipher the precise mechanisms and regulation using primary human cells and murine experimental models. Our RNAseq analysis indicates that, in both species, early acinar cell dedifferentiation is accompanied by multiple pathways related to cell survival that are highly enriched, and where SLC7A11 (xCT) is transiently upregulated. xCT is the specific subunit of the cystine/glutamate antiporter system x C - . To decipher its role, gene silencing, pharmacological inhibition and a knock-out mouse model were used. Acinar cells with depleted or reduced xCT function show an increase in ferroptosis relating to lipid peroxidation. Lower glutathione levels and more lipid ROS accumulation could be rescued by the antioxidant N-acetylcysteine or the ferroptosis inhibitor ferrostatin-1. In caerulein-induced acute pancreatitis in mice, xCT also prevents lipid peroxidation in acinar cells. In conclusion, during stress, acinar cell fate seems to be poised for avoiding several forms of cell death. xCT specifically prevents acinar cell ferroptosis by fueling the glutathione pool and maintaining ROS balance. The data suggest that xCT offers a druggable tipping point to steer the acinar cell fate in stress conditions., (© 2023. The Author(s).)

Anti-van't Hoff-Le Bel configured p-block element species possess intrinsically high reactivity and are thus challenging to isolate. Consequently, numerous elements in this configuration, including square-planar germanium(IV), remain unexplored. Herein, we follow a concept to reach anti-van't Hoff-Le Bel reactivity by ligand dissociation from a rigid calix[4]pyrrole germane in its bis(thf) adduct. While the macrocyclic ligand assures square-planar coordination in the uncomplexed form, the labile thf donors provide robustness for isolation on a multigram scale. Unique properties of a low-lying acceptor orbital imparted to germanium(IV) can be verified, e.g., by isolating an elusive anionic hydrido germanate and exploiting it for challenging bond activations. Aldehydes, water, alcohol, and a CN triple bond are activated for the first time by germanium-ligand cooperativity. Unexpected behaviors against fluoride ion donors disclose critical interferences of a putative redox-coupled fluoride ion transfer during the experimental determination of Lewis acidity. Overall, we showcase how ligand lability grants access to the uncharted chemistry of anti-van't Hoff-Le Bel germanium(IV) and line up this element as a member in the emerging class of structurally constrained p-block elements.

We demonstrate that a sodium dimer, Na&#95;{2}(1^{3}Σ&#95;{u}^{+}), residing on the surface of a helium nanodroplet, can be set into rotation by a nonresonant 1.0 ps infrared laser pulse. The time-dependent degree of alignment measured, exhibits a periodic, gradually decreasing structure that deviates qualitatively from that expected for gas-phase dimers. Comparison to alignment dynamics calculated from the time-dependent rotational Schrödinger equation shows that the deviation is due to the alignment dependent interaction between the dimer and the droplet surface. This interaction confines the dimer to the tangential plane of the droplet surface at the point where it resides and is the reason that the observed alignment dynamics is also well described by a 2D quantum rotor model.

Background: In droplet-based single-cell and single-nucleus RNA-seq experiments, not all reads associated with one cell barcode originate from the encapsulated cell. Such background noise is attributed to spillage from cell-free ambient RNA or barcode swapping events., Results: Here, we characterize this background noise exemplified by three scRNA-seq and two snRNA-seq replicates of mouse kidneys. For each experiment, cells from two mouse subspecies are pooled, allowing to identify cross-genotype contaminating molecules and thus profile background noise. Background noise is highly variable across replicates and cells, making up on average 3-35% of the total counts (UMIs) per cell and we find that noise levels are directly proportional to the specificity and detectability of marker genes. In search of the source of background noise, we find multiple lines of evidence that the majority of background molecules originates from ambient RNA. Finally, we use our genotype-based estimates to evaluate the performance of three methods (CellBender, DecontX, SoupX) that are designed to quantify and remove background noise. We find that CellBender provides the most precise estimates of background noise levels and also yields the highest improvement for marker gene detection. By contrast, clustering and classification of cells are fairly robust towards background noise and only small improvements can be achieved by background removal that may come at the cost of distortions in fine structure., Conclusions: Our findings help to better understand the extent, sources and impact of background noise in single-cell experiments and provide guidance on how to deal with it., (© 2023. The Author(s).)

This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS) treatment. It was a double-blind, randomized trial of 300 mg oral micronized progesterone@bedtime versus placebo for 3-months (m) after a 1-m untreated baseline during 2012/1-2017/4. We randomized untreated, non-depressed, screen- and baseline-eligible by VMS, perimenopausal women (with flow within 1-year), ages 35-58 (n = 189). Participants aged 50 (± SD = 4.6) were mostly White, educated, minimally overweight with 63% in late perimenopause; 93% participated remotely. The 1° outcome was 3rd-m VMS Score difference. Participants recorded VMS number and intensity (0-4 scale)/24 h on a VMS Calendar. Randomization required VMS (intensity 2-4/4) of sufficient frequency and/or ≥ 2/week night sweat awakenings. Baseline total VMS Score (SD) was 12.2 (11.3) without assignment difference. Third-m VMS Score did not differ by therapy (Rate Difference - 1.51). However, the 95% CI [- 3.97, 0.95] P = 0.222, did not exclude 3, a minimal clinically important difference. Women perceived progesterone caused decreased night sweats (P = 0.023) and improved sleep quality (P = 0.005); it decreased perimenopause-related life interference (P = 0.017) without increased depression. No serious adverse events occurred. Perimenopausal night sweats ± hot flushes are variable; this RCT was underpowered but could not exclude a minimal clinically important VMS benefit. Perceived night sweats and sleep quality significantly improved., (© 2023. The Author(s).)

Virtual surgical planning (VSP) and computer-aided design/computer-aided manufacturing have become essential tools for planning orthognathic surgery. Despite widespread use, empirical gaps still exist in the literature regarding the logistics of the orthognathic planning session itself. More precisely, there is a need to explicate the VSP workflow on which specific parameters are needed for a translation into 3D software. Although each surgeon has his/her theoretical framework, none have been elucidated to properly communicate the necessary pieces of information needed to plan the correction of a variety of dentofacial deformities. The authors provide an outline for conducting a successful VSP planning session for orthognathic surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Abstract: Nonsyndromic unilateral coronal craniosynostosis (UCS) is a rare congenital disorder that results from premature fusion of either coronal suture. The result is growth restriction across the suture, between the ipsilateral frontal and parietal bones, leading to bony dysmorphogenesis affecting the calvarium, orbit, and skull base. Prior studies have reported associations between UCS and visual abnormalities. The present study utilizes a novel geometric morphometric analysis to compare dimensions of orbital foramina on synostotic versus nonsynostotic sides in patients with UCS. Computed tomography head scans of pediatric UCS patients were converted into 3-dimensional mesh models. Anatomical borders of left and right orbital structures were plotted by a single trained team member. Dimensions between synostotic and nonsynostotic sides were measured and compared. Medical records were examined to determine prevalence of visual abnormalities in this patient cohort. Visual abnormalities were reported in 22 of the 27 UCS patients (77.8%). Astigmatism (66.7%), anisometropic amblyopia (44.4%), and motor nerve palsies (33.3%) represented the 3 most prevalent ophthalmologic abnormalities. Orbits on synostotic sides were 11.3% narrower ( P < 0.001) with 21.2% less volume ( P = 0.028) than orbits on nonsynostotic sides. However, average widths, circumferences, and areas were similar between synostotic and nonsynostotic sides upon comparison of supraorbital foramina, infraorbital foramina, optic foramina, and foramina ovalia. Therefore, previously proposed compression or distortion of vital neurovascular structures within bony orbital foramina does not seem to be a likely etiology of visual abnormalities in UCS patients. Future studies will examine the role of ocular and/or neuro-ophthalmologic pathology in this disease process., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Allergic conditions, such as asthma, hay fever and eczema, are some of the most common conditions impacting children globally. There is a strong incentive to study their determinants to improve their prevention. Asthma, hay fever and eczema are influenced through the same immunological pathway and often copresent in children ('the atopic march'). Increasing evidence shows a link between infant antibiotic use and the risk of childhood atopic conditions, mediated through gut microbial dysbiosis during immune system maturation, however, the potential for confounding remains. This study will investigate the relationship between infant antibiotic use and risk of allergic conditions in British Columbian and Manitoban children born over 10 years, adjusting for relevant confounders., Methods and Analysis: Provincial administrative datasets will be linked to perform comparable retrospective cohort analyses, using Population Data BC and the Manitoba Population Research Data Repository. All infants born between 2001 and 2011 in BC and Manitoba will be included (approximately 460 000 and 162 500 infants, respectively), following up to age 7. Multivariable logistic regression will determine the outcome risk by the fifth birthday among children who did and did not receive antibiotics before their first birthday. Clinical, demographic and environmental covariates will be explored, and sensitivity analyses performed to reduce confounding by indication., Ethics and Dissemination: The University of British Columbia Research Ethics Board (H19-03255) and University of Manitoba Ethics Board (HS25156 (H2021:328)) have approved this study. Data stewardship committees for all administrative datasets have granted permissions, facilitated by Population Data BC and the Manitoba Centre for Health Policy. Permissions from the Canadian Health Infant Longitudinal Development Study are being sought for breastfeeding data (CP185). Findings will be published in scientific journals and presented at infectious disease and respiratory health conferences. A stakeholder committee will guide and enhance sensitive and impactful communication of the findings to new parents., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gastrointestinal (GI) motility is largely dependent upon activity within the enteric nervous system (ENS) and is an important part of the digestive process. Dysfunction of the ENS can impair GI motility as is seen in the case of constipation where gut transit time is prolonged. Animal models mimicking symptoms of constipation have been developed by way of pharmacological manipulations. Studies have reported an association between altered GI motility and gut microbial population. Little is known about the changes in gut microbiota profile resulting specifically from pharmacologically induced slowed GI motility in rats. Moreover, the relationship between gut microbiota and altered intestinal motility is based on studies using faecal samples, which are easier to obtain but do not accurately reflect the intestinal microbiome. The aim of this study was to examine how delayed GI transit due to opioid receptor agonism in the ENS modifies caecal microbiota composition. Differences in caecal microbial composition of loperamide-treated or control male Sprague Dawley rats were determined by 16S rRNA gene amplicon sequencing. The results revealed that significant differences were observed at both genus and family level between treatment groups. Bacteroides were relatively abundant in the loperamide-induced slowed GI transit group, compared to controls. Richness and diversity of the bacterial communities was significantly lower in the loperamide-treated group compared to the control group. Understanding the link between specific microbial species and varying transit times is crucial to design interventions targeting the microbiome and to treat intestinal motility disorders., Competing Interests: Author JD is employed by AgResearch, New Zealand. Author WY was employed by AgResearch, New Zealand. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Parkar, Dalziel, Spencer, Janssen, McNabb and Young.)

Background: Gastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. One of the main therapeutic approaches is accelerating gastric emptying (GE) by means of prokinetic agents. Their efficacy has been demonstrated, although the association between symptom improvement and acceleration of emptying is less clear. Meta-analyses have found contradictory results. Differences in applied methodology and included trials might drive these contradictions., Objective: To provide a transparent meta-analysis update to elucidate the association between symptom improvement and acceleration of GE due to gastroprokinetic agents available for long-term use in patients with gastroparesis., Design: Two approaches from earlier meta-analyses were executed and compared. One analyzed the relative changes on active treatment versus baseline, the other compared the change from baseline on active treatment versus the change from baseline on placebo. Papers that reported sufficient numerical data for both analyses were selected. Both analyses included the same trials., Results: Overall, both approaches yield the same positive direction of association between symptom improvement and acceleration of emptying (0.291 (-0.391, 0.972), p = 0.4 and 0.453 (0.123, 0.782), p = 0.007 for the active-only and placebo-controlled analysis respectively). The association between symptom improvement and GE acceleration for studies using optimal GE tests was either 0.028 (p > 0.9) or 0.463 (p = 0.007), and for sub-optimal GE tests was either 0.370 (p = 0.4) or 0.052 (p > 0.9) depending on the used meta-analysis methodology., Conclusions: The applied methodology for GE testing, and the meta-analysis substantially impacts the conclusion. When considering the clinically relevant outcome of improvement from baseline, symptoms and emptying improve with prokinetics, but no correlation is found between both aspects. When the change over placebo is considered, limiting the analysis to scientifically more rigorous study approaches, changes in emptying rate and symptom improvement are positively associated., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Increased weight gain and decreased physical activity have been reported in some populations since the coronavirus disease 2019 (COVID-19) pandemic, but this has not been well characterized in pregnant populations., Objectives: Our objective was to characterize the impact of the COVID-19 pandemic and associated countermeasures on pregnancy weight gain and infant birthweight in a US cohort., Methods: Washington State pregnancies and births (1 January, 2016 to 28 December, 2020) from a multihospital quality improvement organization were examined for pregnancy weight gain, pregnancy weight gain z-score adjusted for pregestational BMI and gestational age, and infant birthweight z-score, using an interrupted time series design that controls for underlying time trends. We used mixed-effect linear regression models, controlled for seasonality and clustered at the hospital level, to model the weekly time trends and changes on 23 March, 2020, the onset of local COVID-19 countermeasures., Results: Our analysis included 77,411 pregnant people and 104,936 infants with complete outcome data. The mean pregnancy weight gain was 12.1 kg (z-score: -0.14) during the prepandemic time period (March to December 2019) and increased to 12.4 kg (z-score: -0.09) after the onset of the pandemic (March to December 2020). Our time series analysis found that after the pandemic onset, the mean weight gain increased by 0.49 kg (95% CI: 0.25, 0.73 kg) and weight gain z-score increased by 0.080 (95% CI: 0.03, 0.13), with no changes in the baseline yearly trend. Infant birthweight z-scores were unchanged (-0.004; 95% CI: -0.04, 0.03). Overall, the results were unchanged in analyses stratified by pregestational BMI categories., Conclusions: We observed a modest increase in weight gain after the onset of the pandemic among pregnant people but no changes in infant birthweights. This weight change could be more important in high BMI subgroups., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: Although increasing evidence suggests a central mechanism of action for sacral neuromodulation, the exact mechanism remains unclear. We set up a scanning paradigm to measure brain activation related to various stages of rectal filling using rectal balloon distention., Materials and Methods: Six healthy volunteers underwent rectal balloon distention during MRI scanning at a 1.5T scanner with a Tx/Rx head coil. MR images were collected at four levels of distention: empty balloon (EB), first sensation volume (FSV), desire to defecate volume (DDV), maximum tolerable volume (MTV). Data were analyzed using BrainVoyager 20.4. Whole brain and ROI-based fixed-effects general linear model analyses were performed on the fMRI time-course data from all participants., Results: Rectal filling until FSV evoked the most blood-oxygen-level-dependent responses in several clusters throughout the cortex, followed by the responses evoked by rectal filling until DDV. Interestingly, rectal filling until MTV evoked negative responses compared to baseline throughout the cortex. No negative side effects were found., Discussion: This study shows that a standardized paradigm for functional MRI combined with rectal filling is feasible and safe in healthy volunteers and is ready to be used in fecal incontinent patients to assess whether their brain activity differs from healthy controls., (© 2022. The Author(s).)

Background: Large-scale longitudinal studies with biological samples are needed to examine the associations between prenatal cannabis use and birth and developmental outcomes., Objectives: The aim of this study was to understand the feasibility and acceptability of collecting umbilical cord tissue for the purpose of cannabis use testing in a community sample., Design: This is a mixed methods research study consisted of a prospective cohort study and a qualitative descriptive study., Methods: This study was conducted in Vancouver, British Columbia between January 2021 and August 2022. Participants were recruited during pregnancy, and the umbilical cord tissues were collected at birth and tested for the presence of cannabinoids. After the completion of the study, participants completed an online open-ended questionnaire about their overall experience. Data were analyzed using descriptive and thematic analyses., Results: Among the 85 eligible individuals, 57 people (67%) consented to the study. The cord tissue was collected for 39 participants (68.4%). The collection rates for participants with vaginal, elective, and emergency cesarean delivery were 73.0%, 71.4%, and 53.8%, respectively, and for those with spontaneous and induced labor were 81.5% and 50%, respectively. Four (7.0%) and seven participants (12.3%) reported prenatal cannabis use in direct and probing self-report questions, respectively. The agreement between any self-report and cord tissue test was moderate (kappa 0.53, 95% confidence interval 0.06-0.99). Qualitative findings were classified into five themes., Conclusion: The collection of cord tissue was perceived acceptable by most participants. Implementation of collection protocols for complex labors, a central hospital unit to liaise direct communications and active participants' involvement might increase the feasibility of future studies.

Objective. Basic, translational and clinical neuroscience are increasingly focusing on large-scale invasive recordings of neuronal activity. However, in large animals such as nonhuman primates and humans-in which the larger brain size with sulci and gyri imposes additional challenges compared to rodents, there is a huge unmet need to record from hundreds of neurons simultaneously anywhere in the brain for long periods of time. Here, we tested the electrical and mechanical properties of thin, flexible multi-electrode arrays (MEAs) inserted into the primary visual cortex of two macaque monkeys, and assessed their magnetic resonance imaging (MRI) compatibility and their capacity to record extracellular activity over a period of 1 year. Approach. To allow insertion of the floating arrays into the visual cortex, the 20 by 100 µ m 2 shafts were temporarily strengthened by means of a resorbable poly(lactic-co-glycolic acid) coating. Main results . After manual insertion of the arrays, the ex vivo and in vivo MRI compatibility of the arrays proved to be excellent. We recorded clear single-unit activity from up to 50% of the electrodes, and multi-unit activity (MUA) on 60%-100% of the electrodes, which allowed detailed measurements of the receptive fields and the orientation selectivity of the neurons. Even 1 year after insertion, we obtained significant MUA responses on 70%-100% of the electrodes, while the receptive fields remained remarkably stable over the entire recording period. Significance. Thus, the thin and flexible MEAs we tested offer several crucial advantages compared to existing arrays, most notably in terms of brain tissue compliance, scalability, and brain coverage. Future brain-machine interface applications in humans may strongly benefit from this new generation of chronically implanted MEAs., (Creative Commons Attribution license.)

Future neuroscience and biomedical projects involving non-human primates (NHPs) remain essential in our endeavors to understand the complexities and functioning of the mammalian central nervous system. In so doing, the NHP neuroscience researcher must be allowed to incorporate state-of-the-art technologies, including the use of novel viral vectors, gene therapy and transgenic approaches to answer continuing and emerging research questions that can only be addressed in NHP research models. This perspective piece captures these emerging technologies and some specific research questions they can address. At the same time, we highlight some current caveats to global NHP research and collaborations including the lack of common ethical and regulatory frameworks for NHP research, the limitations involving animal transportation and exports, and the ongoing influence of activist groups opposed to NHP research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Importance: Continuous kidney replacement therapy (CKRT) is the preferred method of kidney support for children with critical illness in pediatric intensive care units (PICUs). However, there are no data on the current CKRT management practices in European PICUs., Objective: To describe current CKRT practices across European PICUs., Design, Setting, and Participants: This cross-sectional survey of PICUs in 20 European countries was conducted by the Critical Care Nephrology Section of the European Society of Pediatric and Neonatal Intensive Care from April 1, 2020, to May 31, 2022. Participants included intensivists and nurses working in European PICUs. The survey was developed in English and distributed using SurveyMonkey. One response from each PICU that provided CKRT was included in the analysis. Data were analyzed from June 1 to June 30, 2022., Main Outcome and Measures: Demographic characteristics of European PICUs along with organizational and delivery aspects of CKRT (including prescription, liberation from CKRT, and training and education) were assessed., Results: Of 283 survey responses received, 161 were included in the analysis (response rate, 76%). The attending PICU consultant (70%) and the PICU team (77%) were mainly responsible for CKRT prescription, whereas the PICU nurses were responsible for circuit setup (49%) and bedside machine running (67%). Sixty-one percent of permanent nurses received training to use CKRT, with no need for certification or recertification in 36% of PICUs. Continuous venovenous hemodiafiltration was the preferred dialytic modality (51%). Circuit priming was performed with normal saline (67%) and blood priming in children weighing less than 10 kg (56%). Median (IQR) CKRT dose was 35 (30-50) mL/kg/h in neonates and 30 (30-40) mL/kg/h in children aged 1 month to 18 years. Forty-one percent of PICUs used regional unfractionated heparin infusion, whereas 35% used citrate-based regional anticoagulation. Filters were changed for filter clotting (53%) and increased transmembrane pressure (47%). For routine circuit changes, 72 hours was the cutoff in 62% of PICUs. Some PICUs (34%) monitored fluid removal goals every 4 hours, with variation from 12 hours (17%) to 24 hours (13%). Fluid removal goals ranged from 1 to 3 mL/kg/h. Liberation from CKRT was performed with a diuretic bolus followed by an infusion (32%) or a diuretic bolus alone (19%)., Conclusions and Relevance: This survey study found a wide variation in current CKRT practice, including organizational aspects, education and training, prescription, and liberation from CKRT, in European PICUs. This finding calls for concerted efforts on the part of the pediatric critical care and nephrology communities to streamline CKRT education and training, research, and guidelines to reduce variation in practice.

Current approaches for measuring and assessing contributions of companies and their products to sustainability largely focus on reducing negative impacts. However, becoming "less bad" still means having adverse impacts on the environment. Various authors have therefore called for investigating how positive contributions can be made to further sustainable development. This systematic literature review explores how positive contributions to sustainability have been discussed in the environmental management literature dealing with sustainability performance measurement and assessment. Our review of 328 publications reveals an understanding of positive contributions to sustainability that is a mostly implicit or vague use. Inductive analysis, however, reveals three distinct understandings - an operationalization, a stakeholder and a transformation perspective - each of which is embedded in a different theoretical frame, namely decision, stakeholder and transition theory. These perspectives have so far been discussed separately in the literature. By drawing on theoretical foundations of performance measurement, we propose an integrated understanding of positive contributions to sustainability: A positive sustainability contribution has the goal of bringing about a sustainability transformation, considers the environmental, economic and social context through stakeholder participation, and is operationalized to facilitate decision-making and the implementation of effective sustainability measures. A clear definition is of key importance for both research and practice to both reduce negative and increase positive contributions to sustainable development., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To perform tasks like grasping, the brain has to process visual object information so that the grip aperture can be adjusted before touching the object. Previous studies have demonstrated that the posterior subsector of the Anterior Intraparietal area is connected to area 45B, and its anterior counterpart to F5a. However, the role of area 45B and F5a in visually-guided grasping is poorly understood. Here, we investigated the role of area 45B, F5a and F5p in object processing during visually-guided grasping in two monkeys. We tested whether the presentation of an object in near peripersonal space activated F5p neurons more than objects with the same retinal size presented beyond reachable distance and conversely, whether neurons in 45B and F5a-which may encode a purely visual object representation-were less affected by viewing distance when equalizing retinal size. Contrary to our expectations, we found that most neurons in area 45B were object- and viewing distance-selective, and preferred mostly Near presentations. Area F5a showed much weaker object selectivity compared to 45B, with a similar preference for objects presented at the Near position. Finally, F5p neurons were less object selective and frequently Far-preferring. In sum, area 45B-but not F5p- prefers objects presented in peripersonal space., (© 2022. The Author(s).)

Theta-burst transcranial magnetic stimulation (TBS) has become a standard non-invasive technique to induce offline changes in cortical excitability in human volunteers. Yet, TBS suffers from a high variability across subjects. A better knowledge about how TBS affects neural activity in vivo could uncover its mechanisms of action and ultimately allow its mainstream use in basic science and clinical applications. To address this issue, we applied continuous TBS (cTBS, 300 pulses) in awake behaving rhesus monkeys and quantified its after-effects on neuronal activity. Overall, we observed a pronounced, long-lasting, and highly reproducible reduction in neuronal excitability after cTBS in individual parietal neurons, with some neurons also exhibiting periods of hyperexcitability during the recovery phase. These results provide the first experimental evidence of the effects of cTBS on single neurons in awake behaving monkeys, shedding new light on the reasons underlying cTBS variability., Competing Interests: MR, LM, PJ, MD No competing interests declared, (© 2022, Romero et al.)

Objective: To identify determinants of cesarean delivery (CD) and examine associations between mode of delivery (MOD) and maternal and perinatal outcomes., Methods: We conducted a retrospective analysis of a Canadian multicentre birth cohort derived from provincial data collected in 2008/2009. Maternal and perinatal characteristics and outcomes were compared between vaginal and cesarean birth and between the following MOD subgroups: spontaneous vaginal delivery (VD), assisted VD, planned cesarean delivery (CD), and intrapartum CD. Multivariate regression identified determinants of CD and the effects of MOD and previous CD on maternal and perinatal outcomes., Results: The cohort included 264 755 births (72.1% VD and 27.9% CD) from 91 participating institutions. Determinants of CD included maternal age, parity, previous CD, chronic hypertension, diabetes, urinary tract infection or pyelonephritis, gestational hypertension, vaginal bleeding, labour induction, pre-term gestational age, low birth weight, large for gestational age, malpresentation, and male sex. CD was associated with greater risk of maternal and perinatal morbidity and mortality. Subgroup analysis demonstrated higher risk of adverse pregnancy outcomes with assisted VD and intrapartum CD than spontaneous VD. Planned CD reduced the risk of obstetric wound hematoma and perinatal mortality but increased maternal and neonatal morbidity. Previous CD increased the risk of maternal and neonatal morbidity among multiparous women., Conclusions: The CD rate in Canada is consistent with global trends reflecting demographic and obstetric intervention factors. The risk of adverse pregnancy outcomes with CD warrants evaluation of interventions to safely prevent nonessential cesarean birth., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Asthma encompasses a spectrum of heterogenous immune-mediated respiratory disorders sharing a similar clinical pattern characterized by cough, wheeze and exercise intolerance. In horses, equine asthma can be subdivided into severe or moderate asthma according to clinical symptoms and the extent of airway neutrophilic inflammation. While severe asthmatic horses are characterized by an elevated neutrophilic inflammation of the lower airways, cough, dyspnea at rest and high mucus secretion, horses with moderate asthma show a milder neutrophilic inflammation, exhibit intolerance to exercise but no labored breathing at rest. Yet, the physiopathology of different phenotypes of equine asthma remains poorly understood and there is a need to elucidate the underlying mechanisms tailoring those phenotypes in order to improve clinical management and elaborate novel therapeutic strategies. In this study, we sought to quantify the presence of neutrophil extracellular traps (NETs) in bronchoalveolar lavage fluids (BALF) of moderate or severe asthmatic horses and healthy controls, and assessed whether NETs correlated with disease severity. To this end, we evaluated the amounts of NETs by measuring cell-free DNA and MPO-DNA complexes in BALF supernatants or by quantifying NETs release by BALF cells by confocal microscopy. We were able to unequivocally identify elevated NETs levels in BALF of severe asthmatic horses as compared to healthy controls or moderate asthmatic horses. Moreover, we provided evidence that BALF NETs release was a specific feature seen in severe equine asthma, as opposed to moderate asthma, and correlated with disease severity. Finally, we showed that NETs could act as a predictive factor for severe equine asthma. Our study thus uniquely identifies NETs in BALF of severe asthmatic horses using three distinct methods and supports the idea that moderate and severe equine asthma do not rely on strictly similar pathophysiological mechanisms. Our data also suggest that NETs represent a relevant biomarker, a putative driver and a potential therapeutic target in severe asthma disease., 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 © 2022 Janssen, Tosi, Hego, Maréchal, Marichal and Radermecker.)

Background: The SARS-CoV-2 pandemic's unpredictability and ambiguity, combined with the lockdown, social distancing, containment measures, and economic impact could increase the risk of mental health issues., Objective: To assess the magnitude of mental health outcomes and risk factors among Moroccans, using an online survey, during the SARS-CoV-2 outbreak., Methods: This cross-sectional, survey-based study collected demographic data and mental health measurements from 11,123 participants. The degree of depression, anxiety, and insomnia symptoms were assessed by the 9-item Patient Health Questionnaire, the 7-items Generalized Anxiety disorder, and the 7-items Insomnia Severity Index., Results: The survey was completed by 11,123 individuals out of a total of 15,008 contacts. 7315 (65.8%) were women, and 7182 (64.6%) were aged 18 to 34. A significant proportion of respondents experienced depression (5894 [53%]), anxiety (5544 [49.8%]), and insomnia (4410 [39.6%]). Multivariable logistic regression analysis showed that being a woman, being married, and being a parent of children aged less than five years were associated with severe symptoms of depression and anxiety (e.g. severe depression among women vs. men (OR, 1.19; 95%CI, 1.06-1.33; P = .003), severe depression among married compared to unmarried respondents (OR, 1.92; 95%CI, 1.71-2.16; P < .000), e.g. severe anxiety among women vs. men (OR, 1.40; 95%CI, 1.24-1.58; <0.000), severe anxiety among married people compared to unmarried (OR, 1.14; 95%CI, 1.00-1.28; P < .003)., Conclusion: Our findings reported a significant mental health burden on the general public during the COVID-19 lockdown. In addition to efforts deployed to prevent the spread of the disease, timely and culturally-specific mental health care needs to be developed urgently., (Copyright © 2022. Published by Elsevier B.V.)

Chronic non-healing wounds are a major complication of diabetes, which affects 1 in 10 people worldwide. Dying cells in the wound perpetuate the inflammation and contribute to dysregulated tissue repair 1-3 . Here we reveal that the membrane transporter SLC7A11 acts as a molecular brake on efferocytosis, the process by which dying cells are removed, and that inhibiting SLC7A11 function can accelerate wound healing. Transcriptomics of efferocytic dendritic cells in mouse identified upregulation of several SLC7 gene family members. In further analyses, pharmacological inhibition of SLC7A11, or deletion or knockdown of Slc7a11 using small interfering RNA enhanced efferocytosis in dendritic cells. Slc7a11 was highly expressed in dendritic cells in skin, and single-cell RNA sequencing of inflamed skin showed that Slc7a11 was upregulated in innate immune cells. In a mouse model of excisional skin wounding, inhibition or loss of SLC7A11 expression accelerated healing dynamics and reduced the apoptotic cell load in the wound. Mechanistic studies revealed a link between SLC7A11, glucose homeostasis and diabetes. SLC7A11-deficient dendritic cells were dependent on aerobic glycolysis using glucose derived from glycogen stores for increased efferocytosis; also, transcriptomics of efferocytic SLC7A11-deficient dendritic cells identified increased expression of genes linked to gluconeogenesis and diabetes. Further, Slc7a11 expression was higher in the wounds of diabetes-prone db/db mice, and targeting SLC7A11 accelerated their wound healing. The faster healing was also linked to the release of the TGFβ family member GDF15 from efferocytic dendritic cells. In sum, SLC7A11 is a negative regulator of efferocytosis, and removing this brake improves wound healing, with important implications for wound management in diabetes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)