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Background: Adequate pain management is important in patients’ recovery from total hip arthroplasty (THA) and total knee arthroplasty (TKA). Objective: To determine whether risk factors for prolonged opioid use are considered when discharge prescriptions for postoperative pain are written following THA and TKA. Methods: Opioid prescriptions written between June 14 and July 9, 2021, for patients who underwent THA or TKA were analyzed. Data were also collected on the patients’ age, sex, type of surgery, type of anesthesia (regional or general), preoperative use of opioids, and preoperative use of antidepressants. Results: Among the 59 patients included in the study, the most common prescriptions were for hydromorphone 2 mg (n = 15, 25%) and hydromorphone 1 mg (n = 15, 25%). At discharge, patients received a median of 400 morphine milligram equivalents (MMEs). There was no significant difference in the quantity of opioids (MMEs) prescribed at discharge in relation to surgery type (p = 0.63), sex (p = 0.44), preoperative antidepressant use (p = 0.22), or preoperative opioid use (p = 0.97). There also appeared to be no correlation between a patient’s age and MMEs at discharge (p = 0.21; r2 = 0.028). None of these variables could be used to predict which patients would receive more than 400 MMEs. Conclusions: Patient-specific factors appeared not to be taken into consideration when opioids were prescribed for postoperative pain among patients who underwent THA or TKA. RÉSUMÉ Contexte : Une gestion adéquate de la douleur est importante pour le rétablissement des patients après une arthroplastie totale de la hanche (ATH) et une arthroplastie totale du genou (ATG). Objectif : Déterminer si les facteurs de risque relatifs à l’utilisation prolongée d’opioïdes sont pris en compte lors de la rédaction d’ordonnances de congé pour douleurs postopératoires après une ATH et une ATG. Méthodes : Les prescriptions d’opioïdes rédigées entre le 14 juin et le 9 juillet 2021 pour les patients ayant subi une ATH ou une ATG ont été analysées. Des données ont également été recueillies sur l’âge, le sexe, le type de chirurgie, le type d’anesthésie (locale ou générale), l’utilisation préopératoire d’opioïdes et l’utilisation préopératoire d’antidépresseurs. Résultats : Parmi les 59 patients compris dans l’étude, les prescriptions les plus fréquentes étaient l’hydromorphone 2 mg (n = 15; 25 %) et l’hydromorphone 1 mg (n = 15; 25 %). Les patients recevaient une médiane de 400 équivalents milligrammes de morphine (MME) au moment du congé. Aucune différence significative quant à la quantité d’opioïdes (mesurée en MME) prescrits au moment du congé en fonction du type de chirurgie (p = 0,63), du sexe (p = 0,44), de l’utilisation préopératoire d’antidépresseurs (p = 0,22) ou de l’utilisation préopératoire d’opioïdes (p = 0,97) n’a été observée. Il ne semblait pas non plus y avoir de corrélation entre l’âge d’un patient et les MME au moment du congé (p = 0,21; r2 = 0,028). Aucune de ces variables ne pouvait être utilisée pour prédire quels patients recevraient plus de 400 MME. Conclusions : Les facteurs spécifiques au patient ne semblaient pas être pris en compte lors de la prescription d’opioïdes pour la douleur postopératoire chez les patients ayant subi une ATH ou une ATG.

Background: High-cost health care users use disproportionate amounts of health care resources relative to the typical patient. It is unclear to what extent poor-quality prescribing, including potentially inappropriate prescribing (PIP), may be contributing to their adverse outcomes and health utilization costs. Objectives: To evaluate the prevalence of PIP and to explore its impact in older adult high-cost health care users. Methods: The charts of older adult high-cost health care users admitted to 2 academic hospitals in Ontario, Canada, in fiscal year 2015/16 were reviewed. Eligible patients were at least 66 years old with at least 5 emergency department visits and 3 hospital admissions in the previous year. A total of 243 patients met these criteria, of whom 100 were randomly selected for review. Cases of PIP were identified using explicit prescribing quality indicators, including the STOPP/START criteria. Types of PIP included potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). Log–linear regression was used to characterize the relationship between PIP and future health care utilization. Medications were reconciled to determine the proportion of PIP addressed by the time of discharge. Results: Eighty-nine of the 100 patients had at least 1 instance of PIP. In total, 276 PIMs and 54 PPOs were identified. Of the 271 instances of PIP identified on admission, only 38 (14%) were resolved by the time of hospital discharge. Each additional PPO was associated with a 1.43-fold increase in the rate of future emergency department visits (p < 0.001). Conclusions: The rate of PIP among older adult high-cost health care users was high. Despite frequent interactions with the health care system, many opportunities to improve the quality of prescribing for this vulnerable population were missed. Greater attention to medication optimization is needed. RÉSUMÉ Contexte : Les grands utilisateurs de soins de santé consomment une proportion disproportionnée des ressources par rapport aux patients moyens. On ne sait pas vraiment dans quelle mesure la prescription de mauvaise qualité, notamment la prescription potentiellement inappropriée (PPI), contribue aux effets indésirables et aux coûts d’utilisation des soins de santé. Objectifs : Évaluer la prévalence des PPI et étudier ses effets chez les grands utilisateurs des soins de santé âgés. Méthodes : Les dossiers des grands utilisateurs de soins de santé âgés admis dans 2 hôpitaux universitaires en Ontario, au Canada, pendant l’exercice 2015-2016 ont été examinés. Les patients admissibles étaient âgés d’au moins 66 ans, avaient effectué au moins 5 visites à l’urgence et avaient été admis 3 fois à l’hôpital au cours de l’année précédente. Au total, 243 patients répondaient à ces critères, dont 100 ont été sélectionnés au hasard pour un examen. Les cas de PPI ont été identifiés à l’aide d’indicateurs explicites de la qualité de prescription, notamment les critères STOPP/START. Les types de PPI comprenaient des médicaments potentiellement inappropriés (MPI) et les omissions potentielles de prescription (OPP). La régression log-linéaire a été utilisée pour caractériser la relation entre la PPI et l’utilisation future des soins de santé. Un bilan comparatif des médicaments prescrits a été effectué pour déterminer la proportion de PPI traités au moment de la sortie de l’hôpital. Résultats : Quatre-vingt-neuf (89 %) des patients présentaient au moins 1 cas de PPI. Au total, 276 MPI et 54 OPP ont été identifiées. Sur les 271 cas de PPI identifiés au moment de l’admission, seuls 38 (14 %) étaient résolus au moment de la sortie de l’hôpital. Chaque OPP supplémentaire était associée à une augmentation de 1,43 fois du taux de futures visites à l’urgence (p < 0,001). Conclusions : Le taux de PPI chez les grands utilisateurs de soins de santé âgés était élevé. Malgré des interactions fréquentes avec le système de santé, de nombreuses occasions d’amélioration de la qualité des prescriptions pour cette population vulnérable ont été manquées. Une plus grande attention doit être portée à l’optimisation des médicaments.

Introduction: Head computed tomography (CT) interpretation is a vital skill for emergency physicians. Existing literature shows poor concordance between emergency physicians and radiologists in head CT interpretation. Prior studies have used passive learning methods to address this knowledge gap. We created an active learning curriculum for teaching head CT interpretation to emergency medicine (EM) residents and compared its effectiveness to a passive learning strategy. Methods: We conducted a prospective, randomized controlled study of EM residents at a single institution. Three educational sessions were delivered over a three-month period via video conference. The active learning cohort (ALC) scrolled through head CT teaching cases we designed on Pascbin, a web-based radiology picture archiving and communication system. The passive learning cohort (PLC) watched instructional videos that scrolled through the same cases. Both cohorts were given equal time to review the cases and ask an instructor questions. Residents took pre-intervention and post-intervention tests on head CT interpretation. We analyzed scores using paired and unpaired t-tests. Results: Forty-two residents took the pre-intervention test. Mean pre- and post-test scores for the ALC were 43.8% and 59.0% (P

Objective To categorize multiparametric MRI features of Bacillus Calmette–Guérin (BCG)-related granulomatous prostatitis (GP) and discover potential manifestations for its differential diagnosis from prostate cancer Materials and Methods The cases of BCG-related GP in 24 male (mean age ± standard deviation, 66.0 ± 9.4 years; range, 50–88 years) pathologically confirmed between January 2011 and April 2019 were retrospectively reviewed. All patients underwent intravesical BCG therapy followed by a MRI scan. Additional follow-up MRI scans, including diffusion-weighted imaging (DWI), were performed in 19 patients. The BCG-related GP cases were categorized into three: A, B, or C. The lesions with diffusion restriction and homogeneous enhancement were classified as type A. The lesions with diffusion restriction and a poorly enhancing component were classified as type B. A low signal intensity on high b-value DWI (b = 1000 s/mm2) was considered characteristic of type C. Two radiologists independently interpreted the MRI scans before making a consensus about the types. Results The median lesion size was 22 mm with the interquartile range (IQR) of 18–26 mm as measured using the initial MRI scans. The lesion types were A, B, and C in 7, 15, and 2 patients, respectively. Cohen’s kappa value for the inter-reader agreement for the interpretation of the lesion types was 0.837. On the last follow-up MRI scans of 19 patients, the size decreased (median, 5.8 mm; IQR, 3.4–8.5 mm), and the type changed from A or B to C in 11 patients. The lesions resolved in four patients. In five patients who underwent prostatectomy, caseous necrosis on histopathology matched with the non-enhancing components of type B lesions and the entire type C lesions. Conclusion BCG-related GP demonstrated three imaging patterns on multiparametric MRI. Contrast-enhanced T1-weighted imaging and DWI may play a role in its differential diagnosis from prostate cancer.

Study Objectives Lumbar spinal stenosis is an age-related spine condition that contributes to pain and disability. Decompressive laminectomy (DL) is regularly performed to alleviate symptoms. Insomnia symptoms are common among people living with chronic pain and may affect key DL outcomes, such as healthcare utilization. We examined associations of insomnia symptom severity with post-DL healthcare utilization in veterans with lumbar spinal stenosis. Methods Veterans (N = 200) with lumbar spinal stenosis undergoing DL were recruited into a prospective cohort study and self-reported insomnia symptom severity on the Insomnia Severity Index prior to DL. Post-DL, veterans reported on pain and non-pain-related monthly healthcare office visits, emergency room visits, hospitalizations, and mental health visits for 1 year. Incident rate ratios (IRRs) obtained via negative binomial regression evaluated associations of insomnia symptom severity with healthcare utilization rates. Results Approximately 51% of participants endorsed insomnia symptoms of at least mild severity. Participants who reported at least mild insomnia symptoms had more healthcare office visits (IRR = 1.23, p = .04), general mental health visits (IRR = 3.98, p < .0001), and pain-related mental health visits (IRR = 9.55, p = .01) than those without insomnia symptoms. Adjusting for covariates, rates of mental health visits, overall (IRR = 3.13, p = .001) and pain-related (IRR = 6.93, p = .02), remained statistically significantly higher. Conclusions Insomnia symptoms are associated with postoperative healthcare utilization lending support for future work to examine the value of assessing and intervening on insomnia symptoms prelaminectomy.

BACKGROUND: This study investigated whether neurotypical individuals' judgments that they dislike a person are more common when viewing autistic individuals than when viewing neurotypical individuals. METHODS: Videos of autistic and neurotypical targets were presented to a group of perceivers (neurotypical adults) who were asked whether or not they liked each target and why. RESULTS: It was more common for perceivers to “like” neurotypical than autistic targets. The number of “likes” each target received correlated highly with perceiver ratings of target social favorability. Perceivers cited perceived awkwardness and lack of empathy as being reasons for deciding they disliked targets. CONCLUSIONS: The findings shed light on how neurotypical people (mis)perceive autistic people. Such perceptions may act as a barrier to social integration for autistic people. LAY SUMMARY: WHY WAS THIS STUDY DONE? Previous research has found that nonautistic people tend to form less positive first impressions of autistic people than they do of other nonautistic people. These studies have tended to present questions such as “How trustworthy is this person?” or “How attractive is this person?” along with ratings scales. However, although it is known that nonautistic people tend to give lower ratings on these scales, we do not know whether this amounts to a dislike for autistic people or just lower levels of liking. WHAT WAS THE PURPOSE OF THIS STUDY? This study aimed to find out whether nonautistic people are less likely to say they like (and more likely to say they dislike) autistic people than other nonautistic people. WHAT DID THE RESEARCHERS DO? The researchers presented videos of autistic and nonautistic people to other nonautistic adults. The people watching the videos were not told that some of the people in the videos were autistic. They were asked to decide whether they liked or disliked the person in each video and to say why they had made their decision by choosing from a range of options. WHAT WERE THE RESULTS OF THE STUDY? Nonautistic people were more likely to say they disliked the person in the video if they were autistic, even though they did not know the diagnosis. The most common reasons for disliking a person was that they appeared awkward, and that they appeared to lack empathy. WHAT DO THESE FINDINGS ADD TO WHAT WAS ALREADY KNOWN? It was already known that nonautistic people tend to rate autistic people less positively on ratings scales. This study suggests that when making judgments—of either liking or disliking—they will sometimes go so far as to say they dislike autistic people. WHAT ARE POTENTIAL WEAKNESSES IN THE STUDY? All of the people in the video clips were male, while those watching the videos were mainly female. Therefore, we do not know whether the same observations would be made for perceptions of autistic females. The number of participants watching the videos was relatively small: a larger sample would give more reliable findings. HOW WILL THESE FINDINGS HELP AUTISTIC ADULTS NOW OR IN THE FUTURE? The findings add to previous research showing nonautistic people's misperceptions of autistic people could be a barrier to social integration for autistic people. They highlight the need for interventions at the societal level aimed at reducing misunderstanding and promoting tolerance.

Lockdowns and other preventive measures taken to curb the spread of diseases such as COVID-19 have restricted the use of face-to-face cognitive assessment. Remote testing may be an alternative, but it should first be shown to be comparable to in-person assessment before being used more widely, during and after the pandemic. Our aim was to evaluate the suitability of online, examiner-mediated administration of an open-access battery of executive function tests (the Free Research Executive Evaluation battery, or FREE) that can be adapted considering various characteristics of diverse populations and therefore used worldwide. A total of 96 9–15-year olds (42 girls) were tested, half of whom online through video calls mediated by an examiner. Their performance was compared to that of the other 48 individuals tested face-to-face, who were matched against the online-tested participants for age, pubertal status, sex, and parental schooling. The battery consists of two tests of the following executive domains: Updating (2-Back and Number Memory tests), Inhibition (Stroop Victoria and Stroop Happy-Sad), and Switching (Color Shape and Category Switch). Answers were vocal and self-paced, and the examiner recorded accuracy and time taken to complete in-person and online tasks. Only free software is needed for the assessment. Executive measures obtained from the tasks did not differ statistically between online and in-person tested participants and effects sizes of group effects were small, thus showing that the FREE test battery holds promise for online cognitive assessment, pending confirmation in different samples and further validation studies.

Heparan sulfate (HS) is a glycosaminoglycan found mainly in its protein-conjugated form at the cell surface and the extracellular matrix. Its high sulfation degree mediates functional interactions with positively charged amino acids in proteins. 2-O sulfation of iduronic acid and 3-O sulfation of glucosamine in HS are mediated by the sulfotransferases HS2ST and HS3ST, respectively, which are dysregulated in several cancers. Both sulfotransferases regulate breast cancer cell viability and invasion, but their role in cancer stem cells (CSCs) is unknown. Breast CSCs express characteristic markers such as CD44+/CD24−/low, CD133 and ALDH1 and are involved in tumor initiation, formation, and recurrence. We studied the influence of HS2ST1 and HS3ST2 overexpression on the CSC phenotype in breast cancer cell lines representative of the triple-negative (MDA-MB-231) and hormone-receptor positive subtype (MCF-7). The CD44+/CD24−/low phenotype was significantly reduced in MDA-MB-231 cells after overexpression of both enzymes, remaining unaltered in MCF-7 cells. ALDH1 activity was increased after HS2ST1 and HS3ST2 overexpression in MDA-MB-231 cells and reduced after HS2ST1 overexpression in MCF-7 cells. Colony and spheroid formation were increased after HS2ST1 and HS3ST2 overexpression in MCF-7 cells. Moreover, MDA-MB-231 cells overexpressing HS2ST1 formed more colonies and could not generate spheres. The phenotypic changes were associated with complex changes in the expression of the stemness-associated notch and Wnt-signaling pathways constituents, syndecans, heparanase and Sulf1. The results improve our understanding of breast CSC function and mark a subtype-specific impact of HS modifications on the CSC phenotype of triple-negative and hormone receptor positive breast cancer model cell lines.

Background: Three large cardiovascular outcome trials have investigated the safety of sodium glucose cotransporter 2 (SGLT2) inhibitors. Objective: To analyze the nationwide dispensing of SGLT2 inhibitors before and after the publication of these trials. Methods: A cross-sectional study was conducted of monthly prescription dispensing of SGLT2 inhibitors from May 23, 2014, to April 30, 2019, using nationwide data for Canada. An autoregressive integrated moving average (ARIMA) model was fitted to the monthly number of tablets dispensed for each SGLT2 inhibitor; the model included a ramp intervention function at the publication dates of interest to estimate the impact on SGLT2 inhibitor dispensing patterns. Results: The rate of canagliflozin and dapagliflozin dispensing declined after publication of results of the empagliflozin cardiovascular trial in September 2015. After publication of results of the canagliflozin trial in June 2017, which indicated a reduction in cardiovascular events and an increase in the risk of lower-limb amputation, canagliflozin remained the most commonly dispensed SGLT2 inhibitor, but its rate of dispensing declined further. In contrast, the rate of empagliflozin dispensing increased, while the rate of dapagliflozin dispensing was unchanged. After publication of the dapagliflozin trial in November 2018, which indicated no clear reduction in cardiovascular events, short-term trends in dispensing of canagliflozin, empagliflozin, and dapagliflozin were largely unaffected. Conclusions: The cardiovascular outcome trials appeared to have an important impact on the dispensing of SGLT2 inhibitors in Canada. RÉSUMÉ Contexte : Trois grands essais portant sur les résultats cardiovasculaires avaient pour objet l’étude de l’innocuité des inhibiteurs du cotransporteur sodium-glucose de type 2 (SGLT2). Objectif : Analyser la délivrance nationale des inhibiteurs du SGLT2 avant et après la publication de ces essais. Méthodes : Une étude transversale a été menée sur la délivrance d’ordonnances mensuelles d’inhibiteurs du SGLT2 du 23 mai 2014 au 30 avril 2019, à l’aide de données nationales pour le Canada. Un modèle de moyenne mobile intégrée autorégressive (ARIMA) a été adapté au nombre mensuel de comprimés distribués pour chaque inhibiteur du SGLT2; le modèle comprenait une fonction d’intervention progressive aux dates de publication d’intérêt pour estimer l’effet sur les schémas de délivrance d’inhibiteurs du SGLT2. Résultats : Le taux de délivrance de canagliflozine et de dapagliflozine a diminué après la publication des résultats de l’essai cardiovasculaire empagliflozine en septembre 2015. Après la publication des résultats de l’essai cardiovasculaire canagliflozine en juin 2017, qui indiquaient une réduction des événements cardiovasculaires et une augmentation du risque d’amputation des membres inférieurs, la canagliflozine est restée l’inhibiteur du SGLT2 le plus couramment délivré, mais son taux de délivrance a encore diminué. En revanche, le taux d’empagliflozine délivré a augmenté, tandis que le taux de délivrance de dapagliflozine est resté identique. Après la publication de l’essai sur la dapagliflozine en novembre 2018, qui n’indiquait aucune réduction nette des événements cardiovasculaires, les tendances à court terme de la délivrance de la canagliflozine, de l’empagliflozine et de la dapagliflozine n’ont pratiquement pas changé. Conclusions : Les essais portant sur les résultats cardiovasculaires semblaient avoir un effet important sur la délivrance des inhibiteurs du SGLT2 au Canada.

Background: Many antimicrobials given by the intravenous (IV) route have oral (PO) formulations with high oral bioavailability. The advantages of using the PO rather than the IV formulation include lower risk of adverse reactions, shorter length of hospital stay, and lower health care costs. Objectives: The primary objective was to determine the proportions of patients who received the IV and PO formulations of antimicrobials with high oral bioavailability. The secondary objectives were to determine the proportion of patients who were eligible to receive PO antimicrobials from the start of treatment, the proportion who qualified for IV-to-PO step-down, and areas of improvement to increase use of PO antimicrobials. Methods: A retrospective chart review was conducted in hospitals in the Fraser Health Authority, British Columbia, between October 18, 2019, and March 5, 2020. Two hundred charts were randomly selected for patients who had received either azithromycin, ciprofloxacin, clindamycin, fluconazole, levofloxacin, linezolid, moxifloxacin, metronidazole, sulfamethoxazole–trimethoprim, or voriconazole. Results: Of the 200 patients, 124 (62.0%) received the PO formulations, while 76 (38.0%) received the IV formulations. Of the 76 patients receiving IV antimicrobials, 39 (51.3%; 95% confidence interval 44.7%–57.9%) were eligible to receive PO antimicrobials from the start of treatment or could have been stepped down from IV to PO administration. Conclusions: More than half of patients who received IV therapy were eligible to receive the PO formulation of antimicrobials known to have high oral bioavailability; relative to earlier studies, this proportion has not improved over time. This finding highlights the need for continued vigilance in encouraging the use of PO rather than IV formulations for hospitalized patients. RÉSUMÉ Contexte : De nombreux antimicrobiens administrés par voie intraveineuse (IV) ont des formulations orales (PO) avec une biodisponibilité orale élevée. Les avantages de l’utilisation de cette formulation plutôt que de la formulation IV comprennent un risque moins élevé d’effets indésirables, une durée d’hospitalisation plus courte et des coûts de soins de santé inférieurs. Objectifs : L’objectif principal visait à déterminer les proportions de patients ayant reçu les formulations IV et PO d’antimicrobiens à haute biodisponibilité orale. Les objectifs secondaires consistaient, quant à eux, à déterminer la proportion de patients pouvant recevoir des antimicrobiens par voie orale dès le début du traitement, la proportion de patients qualifiés pour passer de l’administration IV à l’administration par voie orale et les domaines d’amélioration pour augmenter l’utilisation des antimicrobiens par voie orale. Méthodes : Un examen rétrospectif des dossiers a été effectué dans les hôpitaux de la Fraser Health Authority, en Colombie-Britannique, entre le 18 octobre 2019 et le 5 mars 2020. Deux cents dossiers ont été sélectionnés au hasard pour les patients qui avaient reçu soit de l’azithromycine, de la ciprofloxacine, de la clindamycine, du fluconazole, de la lévofloxacine, du linézolide, de la moxifloxacine, du métronidazole, de la sulfaméthoxazole-triméthoprime ou du voriconazole. Résultats : Sur les 200 patients, 124 (62,0 %) ont reçu les formulations PO, tandis que 76 (38,0 %) ont reçu les formulations IV. Sur les 76 patients recevant des antimicrobiens par voie intraveineuse, 39 (51,3 %; intervalle de confiance à 95 % 44,7 % à 57,9 %) étaient admissibles pour recevoir des antimicrobiens par voie orale dès le début du traitement ou auraient pu passer de l’administration IV à l’administration par voie orale. Conclusions : Plus de la moitié des patients ayant reçu une thérapie IV étaient admissibles pour recevoir la formulation PO d’antimicrobiens connus pour avoir une biodisponibilité orale élevée; par rapport aux études antérieures, cette proportion ne s’est pas améliorée avec le temps. Cette découverte souligne la nécessité d’une vigilance continue pour encourager l’utilisation de formulations PO plutôt que IV pour les patients hospitalisés.

Introduction Leadership positions occupied by women within academic emergency medicine have remained stagnant despite increasing numbers of women with faculty appointments. We distributed a multi-institutional survey to women faculty and residents to evaluate categorical characteristics contributing to success and differences between the two groups. Methods An institutional review board-approved electronic survey was distributed to women faculty and residents at eight institutions and were completed anonymously. We created survey questions to assess multiple categories: determination; resiliency; career support and obstacles; career aspiration; and gender discrimination. Most questions used a Likert five-point scale. Responses for each question and category were averaged and deemed significant if the average was greater than or equal to 4 in the affirmative, or less than or equal to 2 in the negative. We calculated proportions for binary questions. Results The overall response rate was 55.23% (95/172). The faculty response rate was 54.1% (59/109) and residents’ response rate was 57.1% (36/63). Significant levels of resiliency were reported, with a mean score of 4.02. Childbearing and rearing were not significant barriers overall but were more commonly reported as barriers for faculty over residents (P

The prediction of the estrogen receptor (ER) and androgen receptor (AR) activity of a compound is quite important to avoid the environmental exposures of endocrine-disrupting chemicals. The Estrogen and Androgen Receptor Database (EARDB, http://eardb.schanglab.org.cn/) provides a unique collection of reported ERα, ERβ, or AR protein structures and known small molecule modulators. With the user-uploaded query molecules, molecular docking based on multi-conformations of a single target will be performed. Moreover, the 2D similarity search against known modulators is also provided. Molecules predicted with a low binding energy or high similarity to known ERα, ERβ, or AR modulators may be potential endocrine-disrupting chemicals or new modulators. The server provides a tool to predict the endocrine activity for compounds of interests, benefiting for the ER and AR drug design and endocrine-disrupting chemical identification.

IntroductionNon-cystic fibrosis bronchiectasis is a respiratory health condition with many possible aetiologies, some of which are potentially reversible in childhood with early diagnosis and appropriate treatment. It is important to understand factors which contribute to progression or potential resolution of bronchiectasis. It is evident that respiratory exacerbations are a key feature of bronchiectasis disease progression. In this pilot study we document how the microbiota of the upper and lower airways presents during the course of an exacerbation and treatment.MethodsWe recruited children (aged 1-15) undergoing antibiotic treatment for bronchiectasis exacerbations at Starship Children’s Hospital and outpatient clinics. Sputum and nasal swabs were taken before and after antibiotic treatment. Sample DNA was extracted, then bacterial 16S rRNA genes amplified and sequenced via Illumina MiSeq.ResultsThirty patients were recruited into this study with 81 samples contributing to the final dataset, including 8 patients with complete sets of upper and lower airway samples at both (before and after antibiotics) timepoints. Changes in alpha-diversity over the course of an exacerbation and treatment were non-significant. However, sample composition did alter over the course of an exacerbation, with most notably a reduction in the relative abundance of amplicon sequence variants assigned to Haemophilus.DiscussionHaemophilus has been associated with more severe symptoms in respiratory infections and a reduction in its relative abundance may represent a positive shift in a patient’s microbiota. Current treatments for bronchiectasis may preserve bacterial diversity while altering microbiota composition.

ObjectiveFatigue after burns is often attributed to the hyperinflammatory and hypermetabolic response, while it may be best understood from a bio-psychological perspective, also involving the neuro-endocrine system. This longitudinal multi-center study examined the course of fatigue up to 18 months postburn. The contribution of bio-psychological factors, including burn severity, pain, and acute PTSD symptoms, to the course and persistence of fatigue was studied in a multifactorial model.MethodsParticipants were 247 adult burn survivors. Fatigue symptoms were assessed with the Multidimensional Fatigue Inventory during the acute phase and subsequently at 3, 6, 12, and 18 months postburn, and were compared to population norms. Age, gender, burn severity, acute PTSD symptoms and pain were assessed as potential predictors of fatigue over time in a latent growth model.ResultsAt 18 months postburn, 46% of the burn survivors reported fatigue, including 18% with severe fatigue. In the acute phase, higher levels of fatigue were related to multiple surgeries, presence of pain, and higher levels of acute PTSD symptoms. Fatigue gradually decreased over time with minor individual differences in rate of decrease. At 18 months, pain and acute PTSD symptoms remained significant predictors of fatigue levels.ConclusionsProtracted fatigue after burns was found in almost one out of five burn survivors and was associated with both pain and acute PTSD symptoms. Early detection of PTSD symptoms and early psychological interventions aimed at reducing PTSD symptoms and pain may be warranted to reduce later fatigue symptoms.

Objective Tissue plasminogen activator (tPA) is considered standard of care for acute ischemic stroke treatment, but some physicians withhold or delay this highly time‐dependent therapy from stroke patients because they do not think it works well or they are worried about the adverse effects or fear medico‐legal consequences. The authors sought to investigate whether litigation arises from physicians treating versus not treating acute ischemic stroke patients with tPA. Methods The authors examined closed cases from 1996 to 2020 in an online legal database, Westlaw, regarding alleged complaints for whether or not thrombolytic treatment was given for acute stroke. Results Sixty‐six relevant cases were identified. In all 66 cases, the plaintiffs sued for issues stemming from either failure to give tPA or a delay in giving tPA. In 77% of cases the verdict was in favor of the defendant. Only 1 lawsuit included intracerebral hemorrhage after tPA, but it was brought forth owing to delay in giving tPA; the verdict was in favor of the defendant. Conclusion It is more common for patients to sue physicians for not administering tPA in a timely fashion or at any point. Medicolegal risks of withholding or delaying tPA are clear, whereas we found no clear medicolegal risk to providing tPA when indicated.

BackgroundMusculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain.ObjectivesTo investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD.MethodsWe enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain.ResultsTwo hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07–2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63–6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life.ConclusionsThe lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

BackgroundSocial cognition and competence are a key part of daily interactions and essential for satisfying relationships and well-being. Pediatric neurological and psychological conditions can affect social cognition and require assessment and remediation of social skills. To adequately approximate the complex and dynamic nature of real-world social interactions, innovative tools are needed. The aim of this study was to document the performance of adolescents on two versions of a serious video game presenting realistic, everyday, socio-moral conflicts, and to explore whether their performance is associated with empathy or sense of presence, factors known to influence social cognition.MethodsParticipants (12–17 years, M = 14.39; SD = 1.35) first completed a pre-test measure of socio-moral reasoning based on three dilemmas from a previously validated computer task. Then, they either played an evaluative version (n = 24) or an adaptive (n = 33) version of a video game presenting nine social situations in which they made socio-moral decisions and provided justifications. In the evaluative version, participants’ audio justifications were recorded verbatim and coded manually to obtain a socio-moral reasoning maturity score. In the adaptive version (AV), tailored feedback and social reinforcements were provided based on participant responses. An automatic coding algorithm developed using artificial intelligence was used to determine socio-moral maturity level in real-time and to provide a basis for the feedback and reinforcements in the game. All participants then completed a three-dilemma post-test assessment.ResultsThose who played the adaptive version showed improved SMR across the pre-test, in-game and post-test moral maturity scores, F(1.97,63.00) = 9.81, pHF < 0.001, ϵ2 = 0.21, but those who played the Evaluative version did not. Socio-moral reasoning scores from both versions combined did not correlate with empathy or sense of presence during the game, though results neared significance. The study findings support preliminary validation of the game as a promising method for assessing and remediating social skills during adolescence.

ObjectiveThis study compared clinical, echocardiographic, and prognostic characteristics among patients with aortic dissection (AD) with (HypHist) and without (No-HypHist) hypertension history and evaluated the association of blood pressure (BP) at presentation with 1-year mortality, left ventricular (LV) remodeling and renal dysfunction.MethodsWe investigated clinical and echocardiographic characteristics and 1-year mortality among 367 patients with AD (81% HypHist, 66% Type-A) from three Brazilian centers.ResultsPatients with No-HypHist were more likely to have Marfan syndrome, bicuspid aortic valve, to undergo surgical therapy, were less likely to have LV hypertrophy and concentricity, and had similar mortality compared with HypHist patients. Adjusted restricted cubic spline analysis showed that systolic BP (SBP) and diastolic BP (DBP) at presentation had a J-curve association with mortality among patients with No-HypHist, but did not associate with death among patients with HypHist (p for interaction = 0.001 for SBP and = 0.022 for DBP). Conversely, the association between SBP at presentation and mortality was influenced by previous use of antihypertensive medications in the HypHist group (p for interaction = 0.002). Results of multivariable logistic regression analysis comprising the whole sample showed direct associations of SBP and DBP at presentation with LV hypertrophy (p = 0.009) and LV concentricity (p = 0.015), respectively, and an inverse association between pulse pressure at presentation and estimated glomerular filtration rate (eGFR) 2 (p = 0.008).ConclusionCombined information on BP at presentation, previous diagnosis of hypertension, and use of antihypertensive medications might be useful to predict mortality risk and to estimate extra-aortic end-organ damage among patients with AD.

BackgroundIn response to the COVID-19 pandemic, the French government took many measures, the most notable of which was a national lockdown on 17 March 2020. Its effects have been widely studied, but to our knowledge, no study has sought to determine how adolescents have adapted to cope with this situation. The present study set out to explore teenagers' stress levels, coping strategies, and substance use during this period.MethodsThis paper is a cross-sectional study that rides on an existing prevention program interviewed 348 French middle school students (209 girls and 139 boys) in grade 8 (Mage = 13.45; SDage = 0.54) using an online questionnaire between March 17 and May 11, 2020 (COVID-19 lockdown). The study examined the teenagers' perceived stress, coping strategies they had used, including recent use of tobacco, alcohol and cannabis, during COVID-19 lockdown.ResultsTeenagers reported lower perceived stress during lockdown than usually, with a significant decrease for girls. Those who perceived the least social support reported the highest levels of stress. The strategies of planning, behavioral disengagement, self-distraction, positive reframing, acceptance, and religion were used more than usual, while active coping and self-blame were used less. Acceptance was the most often used strategy and a source of decreased stress during lockdown. A significant decrease in recent tobacco, alcohol and cannabis use was also observed.ConclusionChanges in the use of coping strategies, withdrawal from the stressful school environment, and greater exposure to parents than to peers caused adolescents to be less stressed and to decrease their substance use during the lockdown.

The study aimed to examine the influence of personal characteristics on activity preferences using decision tree analysis and examine the effects of the variables using conventional approaches (logistic regression analysis). A descriptive study was conducted with 251 nursing home residents with dementia in Korea (76.9% female) to examine the relationship between their personal characteristics and activity preferences. Decision tree analysis was used to classify participants’ activity preferences, and preference levels were examined using logistic regression analysis. Activities were classified as either physical and social activities or cognitive and affective activities. This model showed an accuracy rate of 85.7% for positively predicting physical and social activity preference and 30.3% for positively predicting cognitive and affective activity preference. Gender was the strongest determinant of activity preference. The odds of preferring physical and social activities were 3.179 times higher among women, while the odds for preferring cognitive and affective activities were 0.412 times higher among men. Notably, cognitive and affective activity preference increased to 58.8% for married male participants. This study’s findings can contribute to the development of programs to decrease behavioral and psychological symptoms among older people with dementia residing in nursing homes and provide scientific evidence for integrating these activities into long-term services for this population.

Cryptosporidium spp. are responsible for moderate to severe diarrhea, mainly in children and immunocompromised patients. Using ELISA, the recognition of synthetic peptides generated from the sequences of the Cryptosporidium parvum gp40 and gp15 proteins by serum IgM and IgG antibodies from patients infected (cases) with Cryptosporidium hominis, C. parvum, and Cryptosporidium canis, and uninfected individuals (controls) was evaluated. A statistically significant difference (p = 0.0025) was found in terms of the recognition of peptides A133 and A32 between cases and controls. Additional studies are necessary to understand the potential of these peptides as vaccine candidates.

Malonic acid is used as a common component of many products and processes in the pharmaceutical and cosmetic industries. Here, we designed a novel artificial synthetic pathway of malonic acid, in which oxaloacetate, an intermediate of cytoplasmic reductive tricarboxylic acid (rTCA) pathway, is converted to malonic semialdehyde and then to malonic acid, sequentially catalyzed by a-keto decarboxylase and malonic semialdehyde dehydrogenase. After the systematic screening, we discovered the enzyme oxaloacetate decarboxylase Mdc, catalyzing the first step of the artificially designed pathway in vitro. Then, this synthetic pathway was functionally constructed in cellulolytic thermophilic fungus Myceliophthora thermophila. After enhancement of glucose uptake, the titer of malonic acid achieved 42.5 mg/L. This study presents a novel biological pathway for producing malonic acid from renewable resources in the future.

[Background] The lack of the recovery of CD4+ T-cells (CD4+ recovery) among immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is not well known. We aimed to analyze the association between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4+ recovery in naïve HIV-infected patients who started ART with low baseline CD4+., [Methods] We conducted a retrospective study in 411 naïve individuals with plasma HIV load >200 copies/mL and CD4+, [Results] CD4+ recovery was higher in patients carrying DBP rs7041 AA genotype (AA versus CC/AC) and DHCR7 rs3829251 AA genotype (AA versus GG/AG) (p-value < 0.05). DBP rs7041 AA genotype was linked to increase in CD4+ (adjusted arithmetic mean ratio (aAMR) = 1.22; q-value = 0.011), increase in CD4+ ≥P75th [adjusted odds ratio (aOR) = 2.31; q-value = 0.005], slope of CD4+ recovery (aAMR = 1.25; q-value = 0.008), slope of CD4+ recovery ≥ P75th (aOR = 2.55; q-value = 0.005) and achievement of CD4+ ≥500 cells/mm3 (aOR = 1.89; q-value = 0.023). Besides, DHCR7 rs3829251 AA genotype was related to increase in CD4+ (aAMR = 1.43; q-value = 0.031), increase in CD4+ ≥P75th (aOR = 3.92; q-value = 0.030), slope of CD4+ recovery (aAMR = 1.40; q-value = 0.036), slope of CD4+ recovery ≥ P75th (aOR = 3.42; q-value = 0.031) and achievement of CD4+ ≥500 cells/mm3 (aOR = 5.68; q-value = 0.015)., [Conclusion] In summary, DHCR7 rs3829251 and DBP rs7041 polymorphisms were associated with CD4+ recovery in HIV-infected patients who started cART with low CD4+ T-cell counts., This study has been (partially) funded by grants from Instituto de Salud Carlos III (RD16/0025/0013 to JMB and RD16CIII/0002/0002 to SR) as part of the Health Research and Development Strategy, State Plan for Scientific and Technical Research and Innovation (2008–2011; 2013–2016) and co-financed by Institute of Health Carlos III, ISCIII – Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). The study was also funded by the Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas (CB21/13/00044, CB21/13/00020, and CB21/13/00063). MAJ-S is supported and funded by ISCIII (grant number CP17CIII/00007). NR is a Miguel Servet researcher from the ISCIII (grant number CPII19/00025).

Background:The effect of prone positioning (PP) on respiratory mechanics remains uncertain in patients with severe acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (VV-ECMO).Methods:We prospectively analyzed the effects of PP on respiratory mechanics from continuous data with over a thousand time points during 16-h PP sessions in patients with COVID-19 and ARDS under VV-ECMO conditions. The evolution of respiratory mechanical and oxygenation parameters during the PP sessions was evaluated by dividing each PP session into four time quartiles: first quartile: 0–4 h, second quartile: 4–8 h, third quartile: 8–12 h, and fourth quartile: 12–16 h.Results:Overall, 38 PP sessions were performed in 10 patients, with 3 [2–5] PP sessions per patient. Seven (70%) patients were responders to at least one PP session. PP significantly increased the PaO2/FiO2 ratio by 14 ± 21% and compliance by 8 ± 15%, and significantly decreased the oxygenation index by 13 ± 18% and driving pressure by 8 ± 12%. The effects of PP on respiratory mechanics but not on oxygenation persisted after supine repositioning. PP-induced changes in different respiratory mechanical parameters and oxygenation started as early as the first-time quartile, without any difference in PP-induced changes among the different time quartiles. PP-induced changes in driving pressure (−14 ± 14 vs. −6 ± 10%, p = 0.04) and mechanical power (−11 ± 13 vs. −0.1 ± 12%, p = 0.02) were significantly higher in responders (increase in PaO2/FiO2 ratio > 20%) than in non-responder patients.Conclusions:In patients with COVID-19 and severe ARDS, PP under VV-ECMO conditions improved the respiratory mechanical and oxygenation parameters, and the effects of PP on respiratory mechanics persisted after supine repositioning.

Background:Mast syndrome is a rare disorder belonging to the group of hereditary spastic paraplegias (HSPs). It is caused by bi-allelic mutations in the ACP33 gene, and is originally described in Old Order Amish. Outside this population, only one Japanese and one Italian family have been reported. Herein, we describe five subjects from the first three SPG21 families of German and Austrian descent.Methods:Five subjects with complicated HSP were referred to our centers. The workup consisted of neurological examination, neurophysiological and neuropsychological assessments, MRI, and genetic testing.Results:Onset varied from child- to adulthood. All patients exhibited predominant spastic para- or tetraparesis with positive pyramidal signs, pronounced cognitive impairment, ataxia, and extrapyramidal signs. Neurophysiological workup showed abnormal motor and sensory evoked potentials in all the patients. Sensorimotor axonal neuropathy was present in one patient. Imaging exhibited thin corpus callosum and global brain atrophy. Genetic testing revealed one heterozygous compound and two homozygous mutations in the ACP33 gene.Conclusion:Herein, we report the first three Austrian and two German patients with SPG21, presenting a detailed description of their clinical phenotype and disease course. Our report adds to the knowledge of this extremely rare disorder, and highlights that SPG21 must also be considered in the differential diagnosis of complicated HSP outside the Amish community.

There is emerging evidence that non-coding RNAs (ncRNAs) within maternal breast milk (MBM) impart unique metabolic and immunologic effects on developing infants. Most studies examining ncRNAs in MBM have focused on microRNAs. It remains unclear whether microRNA levels are related to other ncRNAs, or whether they are impacted by maternal characteristics. This longitudinal cohort study examined 503 MBM samples from 192 mothers to: 1) identify the most abundant ncRNAs in MBM; 2) examine the impact of milk maturity on ncRNAs; and 3) determine whether maternal characteristics affect ncRNAs. MBM was collected at 0, 1, and 4 months post-delivery. High throughput sequencing quantified ncRNAs within the lipid fraction. There were 3069 ncRNAs and 238 microRNAs with consistent MBM presence (≥10 reads in ≥10% samples). Levels of 17 ncRNAs and 11 microRNAs accounted for 80% of the total RNA content. Most abundant microRNAs displayed relationships ([R]>0.2, adj p< 0.05) with abundant ncRNAs. A large proportion of ncRNAs (1269/3069; 41%) and microRNAs (206/238; 86%) were affected by MBM maturity. The majority of microRNAs (111/206; 54%) increased from 0-4 months. Few ncRNAs and microRNAs were affected (adj p < 0.05) by maternal age, race, parity, body mass index, gestational diabetes, or collection time. However, nearly half of abundant microRNAs (4/11) were impacted by diet. To our knowledge this is the largest study of MBM ncRNAs, and the first to demonstrate a relationship between MBM microRNAs and maternal diet. Such knowledge could guide nutritional interventions aimed at optimizing metabolic and immunologic microRNA profiles within MBM.

The importance of self-regulated learning (SRL) has increased during the COVID-19 pandemic and measures for assessing students’ self-regulation skills and knowledge are greatly needed. We present the results of the first thorough adaptation of the Children’s Perceived use of Self-Regulated Learning Inventory (CP-SRLI). The inventory, consisting of 15 scales measuring nine components of SRL, was administered to a sample of 541 Slovenian ninth graders. Confirmatory factor analyses supported internal structure validity of most components, but two components required some structural modifications. Internal consistency coefficients were acceptable for the majority of scale scores and were highly comparable to the original ones. While metric invariance across gender was confirmed, the scalar invariance of some scales needs further examination. Meaningful correlations with relevant externally assessed and self-reported self-regulation and school performance variables indicated good criterion validity of the inventory. The Slovenian version of the CP-SRLI thus proved to be a sufficiently valid and reliable instrument for assessing pupils’ learning self-regulation.

Randomized trials supporting the benefit of endovascular treatment in acute ischemic stroke patients with a large early infarction are not yet available. Few retrospective studies exist that suggest a potential positive treatment effect on functional outcome, as well as procedural safety. However, potential benefit or harm of MT in patients with low initial ASPECTS is still a subject of current debate, and in particular, how to select these patients for treatment. The purpose of this pilot study was to evaluate how early tissue water uptake in acute ischemic brain might determine lesion fate and functional outcome in low ASPECTS patients undergoing MT. We observed that the degree of early water uptake measured by quantitative NWU was significantly associated with functional outcome in low ASPECTS patients, yielding a higher diagnostic power compared to other parameters such as ASPECTS, age, or NIHSS. No conclusive evidence of a beneficial effect of successful reperfusion was observed in patients with low ASPECTS and high NWU, which highlights the potential of NWU as a tool to specify patient selection.

In literature, indices of overall walking ability that are based on ground reaction forces have been proposed because of their ease of administration with patients. In this study, we analyzed the correlation between the indices of dynamic loading and propulsion ability of 40 chronic hemiparetic post-stroke patients with equinus foot deviation and a set of clinical assessments of ankle joint deviations and walking ability. Ankle passive and active range of motion (ROM) and triceps surae spasticity were considered, along with walking speed and three complementary scales of walking ability focusing respectively on the need for assistance on functional mobility, including balance and transfers, and the limitation in social participation. The correlation between the ground reaction force-based indices and both clinical and functional variables was carried out using the non-parametric Spearman correlation coefficient. Both indices were correlated to 8 of the 10 investigated variables, thus supporting their use. In particular, the dynamic propulsive ability was correlated with all functional scales (rho = 0.5, p < 0.01), and has the advantage of being a continuous variable. Among clinical assessments, limited ankle ROM affected walking ability the most, while spasticity did not. Since the acquisition of ground reaction forces does not require any patient prepping, the derived indices can be used during the rehabilitation period to quickly detect small improvements that, over time, might lead to the broad changes detectable by clinical scales, as well as to immediately highlight the lack of these improvements, thus suggesting adjustments to the ongoing rehabilitation approach.

African swine fever (ASF) is a highly detrimental viral disease caused by African swine fever virus (ASFV). The occurrence and prevalence of this disease have become a serious threat to the global swine industry and national economies. At present, the detection volume of African swine fever is huge, more sensitive and accurate detection techniques are needed for the market. pp62 protein, as a protein in the late stage of infection, has strong antigenicity and a high corresponding antibody titer in infected pigs. In this study, the CP530R gene was cloned into expression vector pET-28a to construct a prokaryotic expression plasmid, which was induced by IPTG to express soluble pp62 protein. Western blot analysis showed that it had great reactivity. Using the purified recombinant protein as an antigen, an indirect ELISA method for detecting ASFV antibody was established. The method was specific only to ASFV-positive serum, 1:1600 diluted positive serum could still be detected, and the coefficients of variation (CV) of the intra assay and inter assay were both

Public sequencing databases are invaluable resources to biological researchers, but assessing data veracity as well as the curation and maintenance of such large collections of data can be challenging. Genomes of eukaryotic organelles, such as chloroplasts and other plastids, are particularly susceptible to assembly errors and misrepresentations in these databases due to their close evolutionary relationships with bacteria, which may co-occur within the same environment, as can be the case when sequencing plants. Here, based on sequence similarities with bacterial genomes, we identified several suspicious chloroplast assemblies present in the National Institutes of Health (NIH) Reference Sequence (RefSeq) collection. Investigations into these chloroplast assemblies reveal examples of erroneous integration of bacterial sequences into chloroplast ribosomal RNA (rRNA) loci, often within the rRNA genes, presumably due to the high similarity between plastid and bacterial rRNAs. The bacterial lineages identified within the examined chloroplasts as the most likely source of contamination are either known associates of plants, or co-occur in the same environmental niches as the examined plants. Modifications to the methods used to process untargeted ‘raw’ shotgun sequencing data from whole genome sequencing efforts, such as the identification and removal of bacterial reads prior to plastome assembly, could eliminate similar errors in the future.

Aim: The aim of this study is to assess the knowledge of sexually transmitted infections (STIs), sexual habits, and behavior among students of medical and nonmedical students in Serbia.Methodology: The cross-sectional study of 1,273 university students of four undergraduate institutions in Serbia, two of medical and two of nonmedical orientation. A standardized questionnaire, prepared in line with the questionnaire of the European health research—the second wave (European Health Interview Survey—EHIS wave 2), according to defined internationally accepted indicators, was used as a survey instrument.Results: Statistically significant difference (p < 0.001) between medical and nonmedical student groups was determined for the following parameters: naming four of five STIs (29.1 vs. 13.4%), knowledge about vaccines against some STIs (26.0 vs. 17.0%), relationship between HPV infection and cervical malignancy (48.2 vs. 16.7%) engaged in the sexual relations (87.9 vs. 76.4%), never used a condom (15.2 vs. 10.4%), underwent gynecological or urological examination (66.7 vs. 44.1%), and tested to one of STIs (10.5 vs. 4.9%).Conclusion: Both student groups have limited knowledge on possible consequences that risky sexual behavior has for reproductive health. Promotion of knowledge about STIs, awareness of all complications, and consequences of these infections certainly affect the reduction of risky behavior.

In Alzheimer's disease (AD), amyloid β deposition-induced hippocampal synaptic dysfunction generally begins prior to neuronal degeneration and memory impairment. Lycium barbarum extracts (LBE) have been demonstrated to be neuroprotective in various animal models of neurodegeneration. In this study, we aimed to investigate the effects of LBE on the synapse loss in AD through the avenue of the retina in a triple transgenic mouse model of AD (3xTg-AD). We fed 3xTg-AD mice with low (200 mg/kg) or high (2 g/kg) dose hydrophilic LBE daily for 2 months from the starting age of 4- or 6-month-old. For those started at 6 month age, at 1 month (though not 2 months) after starting treatment, mice given high dose LBE showed a significant increase of a wave and b wave in scotopic ERG. After 2 months of treatment with high dose LBE, calpain-2, calpain-5, and the oxidative RNA marker 8-OHG were downregulated, and presynaptic densities in the inner plexiform layer but not the outer plexiform layer of the retina were significantly increased, suggesting the presynaptic structure of retina was preserved. Our results indicate that LBE feeding may preserve synapse stability in the retina of 3xTg-AD mice, probably by decreasing both oxidative stress and intracellular calcium influx. Thus, LBE might have potential as a neuroprotectant for AD through synapse preservation.

International audience; Objective: To understand awareness and fluctuations of awareness in Alzheimer’s disease (AD), it is fruitful to consider the objects of awareness, e.g., cognitive functioning or recognition of the disease, as well as the mechanisms and modes of expression underlying awareness. With a holistic and discourse-centered approach, we aimed to identify different awareness profiles and test whether these profiles were stable or whether transitions from one profile to another occurred over short time intervals. Methods: Twenty-eight residents of nursing homes with a diagnosis of AD participated in four semistructured interviews at biweekly intervals. These interviews were cluster analyzed to determine profiles of awareness. A Markov chain was applied to model their fluctuation. Results: Five awareness profiles were observed that differed in terms of objects and underlying processes. Awareness proved to be quite stable for four of the five profiles. Interindividual variability in awareness was also observed through numerous different trajectories that were identified. Discussion: Self-awareness and disease awareness are characterized by profiles that vary subtly between individuals. Fluctuations in awareness underscore the need to employ assessment intervals that closely reflect daily life in institutions.

With the advent of the industrial revolution, the use of toxic compounds has grown exponentially, leading to a considerable pollution of the environment. Consequently, the development of more environmentally conscious technologies is an urgent need. Industrial biocatalysis appears as one potential solution, where a higher demand for more robust enzymes aims to replace toxic chemical catalysts. To date, most of the commercially available enzymes are of mesophilic origin, displaying optimal activity in narrow ranges of temperature and pH (i.e., between 20°C and 45°C, neutral pH), limiting their actual application under industrial reaction settings, where they usually underperform, requiring larger quantities to compensate loss of activity. In order to obtain novel biocatalysts better suited for industrial conditions, an efficient solution is to take advantage of nature by searching and discovering enzymes from extremophiles. These microorganisms and their macromolecules have already adapted to thrive in environments that present extreme physicochemical conditions. Hence, extremophilic enzymes stand out for showing higher activity, stability, and robustness than their mesophilic counterparts, being able to carry out reactions at nonstandard conditions. In this brief research report we describe three examples to illustrate a stepwise strategy for the development and production of commercial extremozymes, including a catalase from an Antarctic psychrotolerant microorganism, a laccase from a thermoalkaliphilic bacterium isolated from a hot spring and an amine-transaminase from a thermophilic bacterium isolated from a geothermal site in Antarctica. We will also explore some of their interesting biotechnological applications and comparisons with commercial enzymes.

In this paper, we investigate the impact of sensory sensitivity during robot-assisted training for children diagnosed with Autism Spectrum Disorder (ASD). Indeed, user-adaptation for robot-based therapies could help users to focus on the training, and thus improve the benefits of the interactions. Children diagnosed with ASD often suffer from sensory sensitivity, and can show hyper or hypo-reactivity to sensory events, such as reacting strongly or not at all to sounds, movements, or touch. Considering it during robot therapies may improve the overall interaction. In the present study, thirty-four children diagnosed with ASD underwent a joint attention training with the robot Cozmo. The eight session training was embedded in the standard therapy. The children were screened for their sensory sensitivity with the Sensory Profile Checklist Revised. Their social skills were screened before and after the training with the Early Social Communication Scale. We recorded their performance and the amount of feedback they were receiving from the therapist through animations of happy and sad emotions played on the robot. Our results showed that visual and hearing sensitivity influenced the improvements of the skill to initiate joint attention. Also, the therapists of individuals with a high sensitivity to hearing chose to play fewer animations of the robot during the training phase of the robot activity. The animations did not include sounds, but the robot was producing motor noise. These results are supporting the idea that sensory sensitivity of children diagnosed with ASD should be screened prior to engaging the children in robot-assisted therapy.

Current treatments for giardiasis include drugs with undesirable side effects, which increase the levels of therapeutic desertion and promote drug resistance in the parasites. Herein, we describe the antigiardiasic evaluation on Giardia lamblia trophozoites of a structurally diverse collection of 74 molecules. Among these scaffolds, we discovered a benzopyrrolizidine derivative with higher antigiardiasic activity (IC50 = 11 µM) and lower cytotoxicity in human cell cultures (IC50 = 130 µM) than those displayed by the current gold-standard drugs (metronidazole and tinidazole). Furthermore, this compound produced morphologic modifications of trophozoites, with occasional loss of one of the nuclei, among other changes not observed with standard giardicidal drugs, suggesting that it might act through a novel mechanism of action.

AimTo compare hospital admissions across common respiratory tract infections (RTI) in 2017-21, and project possible hospital admissions for the RTIs among children aged 0-12 months and 1-5 years in 2022 and 2023.MethodsIn 644 885 children aged 0-12 months and 1-5 years, we plotted the observed monthly number of RTI admissions (upper- and lower RTI, influenza, respiratory syncytial virus (RSV), and COVID-19) from January 1st, 2017 until October 31st, 2021. We also plotted the number of RTI admissions with a need for respiratory support. We used the observed data to project four different scenarios of RTI admissions for the rest of 2021 until 2023, with different impacts on hospital wards: 1) “Business as usual”, 2) “Continuous lockdown”, 3) “Children’s immunity debt”, and 4) “Maternal and child immunity debt”.ResultsBy October 31st, 2021, the number of simultaneous RTI admissions had exceeded the numbers usually observed at the typical season peak in January, i.e. ∼900. Based on our observed data and assuming that children and their mothers (who transfer antibodies to the very youngest) have not been exposed to RTI over the last one and a half years, our scenarios suggest that hospitals should be prepared to handle two to three times as many RTI admissions, and two to three times as many RTI admissions requiring respiratory support among 0-5-year-olds as normal, from November 2021 to April 2022.ConclusionScenarios with immunity debt suggest that pediatric hospital wards and policy makers should plan for extended capacity.

In multi-talker listening environments, the culmination of different voice streams may lead to the distortion of each source’s individual message, causing deficits in comprehension. Voice characteristics, such as pitch and timbre, are major dimensions of auditory perception and play a vital role in grouping and segregating incoming sounds based on their acoustic properties. The current study investigated how pitch and timbre cues (determined by fundamental frequency, notated as F0, and spectral slope, respectively) can affect perceptual integration and segregation of complex-tone sequences within an auditory streaming paradigm. Twenty normal-hearing listeners participated in a traditional auditory streaming experiment using two alternating sequences of harmonic tone complexes A and B with manipulating F0 and spectral slope. Grouping ranges, the F0/spectral slope ranges over which auditory grouping occurs, were measured with various F0/spectral slope differences between tones A and B. Results demonstrated that the grouping ranges were maximized in the absence of the F0/spectral slope differences between tones A and B and decreased by 2 times as their differences increased to ±1-semitone F0 and ±1-dB/octave spectral slope. In other words, increased differences in either F0 or spectral slope allowed listeners to more easily distinguish between harmonic stimuli, and thus group them together less. These findings suggest that pitch/timbre difference cues play an important role in how we perceive harmonic sounds in an auditory stream, representing our ability to group or segregate human voices in a multi-talker listening environment.

Background: Patient-reported outcomes (PROs) can promote person-centered biopsychosocial health care by measuring outcomes that matter to patients, including functioning and well-being. Data support feasibility and acceptability of PRO administration as part of routine clinical care, but less is known about its effects on population health, including detection of unmet healthcare needs. Our objectives were to examine differences in rates of clinically significant depression across sociodemographic groups and clinical settings from universal depression screens in a large health system, estimate the number of patients with untreated depression detected by screenings, and examine associations between biopsychosocial PROs—physical, psychological, and social health.Methods: We analyzed data from over 200,000 adult patients who completed depression screens—either PROMIS (Patient Reported Outcomes Measurement Information System) or PHQ-2/9—as part of routine outpatient care.Results: Depression screens were positive in 14.2% of the sample, with more positive screens among younger vs. older adults, women vs. men, non-White vs. White, and Hispanics vs. non-Hispanics. These same sociodemographic indicators, as well as completing screening in primary care (vs. specialty care) were also associated with greater likelihood of detected depression in the medical record.Discussion: Universal screening for depression symptoms throughout a large health system appears acceptable and has the potential to detect depression in diverse patient populations outside of behavioral health. Expanded delivery of PROs to include physical and social health as well as depression should be explored to develop a clinically-relevant model for addressing patients' biopsychosocial needs in an integrated fashion across the health system.

Parents' use of food to soothe an infants' non-hunger related distress may impair an infants' development of appetite self-regulation. Parents tend to use food to soothe if their infant has more ‘difficult' temperamental tendencies. However, the role of infant appetite in this association is unclear. This study investigates the moderating effect of infant food responsiveness on cross-sectional and prospective associations between infant temperament and mothers' use of food to soothe. Mothers (n = 200) from low-income households reported their infants' temperament (i.e., surgency, negative affect and regulation) and food responsiveness at age 4 months, and their use of food to soothe at age 4 and 6 months. Temperament × food responsiveness interactions on mothers' use of food to soothe were examined using general linear models, adjusting for covariates. Cross-sectional associations showed that mothers used more food to soothe at 4 months for infants who were lower in negative affect and higher in food responsiveness (negative affect × food responsiveness interaction: p = 0.03). Prospective associations showed that mothers used more food to soothe at 6 months for infants who were lower in regulation and higher in food responsiveness (infant regulation × food responsiveness interaction: p = 0.009). Other interactions were not significant. Infant food responsiveness was consistently associated with mothers' use of food to soothe, independent of some temperamental dimensions. The findings highlight the salience of infant food responsiveness, both independent of and in association with temperament, on mothers' use of food to soothe.

Introduction: 3D printed trussed titanium interbody cages may deliver bone stimulating mechanobiological strains to cells attached at their surface. The exact size and distribution of these strains may depend on patient-specific factors, but the influence of these factors remains unknown. Therefore, this study aimed to determine patient-specific variations in local strain patterns on the surface of a trussed titanium interbody fusion cage.Materials and Methods: Four patients eligible for spinal fusion surgery with the same cage size were selected from a larger database. For these cases, patient-specific finite element models of the lumbar spine including the same trussed titanium cage were made. Functional dynamics of the non-operated lumbar spinal segments, as well as local cage strains and caudal endplate stresses at the operated segment, were evaluated under physiological extension/flexion movement of the lumbar spine.Results: All patient-specific models revealed physiologically realistic functional dynamics of the operated spine. In all patients, approximately 30% of the total cage surface experienced strain values relevant for preserving bone homeostasis and stimulating bone formation. Mean caudal endplate contact pressures varied up to 10 MPa. Both surface strains and endplate contact pressures varied more between loading conditions than between patients.Conclusions: This study demonstrates the applicability of patient-specific finite element models to quantify the impact of patient-specific factors such as bone density, degenerative state of the spine, and spinal curvature on interbody cage loading. In the future, the same framework might be further developed in order to establish a pipeline for interbody cage design optimizations.

Background: Visual hallucinations (VHs) in Parkinson's disease (PD) are the cardinal symptoms which declare the onset of PD psychosis (PDP). The anthropomorphic and zoomorphic VHs of PD resemble those of Charles Bonnet syndrome and temporal lobe epilepsy. In both of these disorders electroencephalography (EEG) abnormalities have been described. We therefore sought to examine whether VHs in PD were associated with similar EEG abnormalities.Methods: This retrospective observational study searched the medical records of 300 PD patients and filtered for those containing clinical 20-min scalp EEGs. Remaining records were separated into two groups: patients with reported VHs and those without. The prevalence of epileptiform discharges in the EEGs of both groups was identified.Results: Epileptiform discharges were present in 5 of 13 (38.5%) PD patients with VHs; all localized to the temporal lobe. No epileptiform discharges were observed in the EEGs of the 31 PD patients without VHs.Conclusion: The significantly high incidence of temporal lobe epileptiform discharges in PD patients with VHs as compared to those without VHs lends to the possibility of an association visual cortex epileptogenic focus. Accordingly, for treatment-refractory patients, antiepileptic drugs might be considered, as in the case of Charles Bonnet syndrome, temporal lobe epilepsy and migraine with visual aura. Future prospective studies involving larger samples and multi-center cohorts are required to validate these observational findings.

This study investigated relationships between inter-class variations in paranormal experience and executive functions. A sample of 516 adults completed self-report measures assessing personal encounter-based paranormal occurrences (i.e., Experience, Practitioner Visiting, and Ability), executive functions (i.e., General Executive Function, Working and Everyday Memory, and Decision Making) together with Emotion Regulation and Belief in the Paranormal. Paranormal belief served as a measure of convergent validity for experience-based phenomena. Latent profile analysis (LPA) combined experience-based indices into four classes based on sample subpopulation scores. Multivariate analysis of variance (MANOVA) then examined interclass differences. Results revealed that breadth of paranormal experience was associated with higher levels of executive functioning difficulties for General Executive Function, Working Memory, Decision Making, and Belief in the Paranormal. On the Everyday Memory Questionnaire, scores differed on Attention Tracking (focus loss) and Factor 3 (visual reconstruction), but not Retrieval (distinct memory failure). In the case of the Emotion Regulation Scale, class scores varied on Expressive Suppression (control), however, no difference was evident on Cognitive Reappraisal (reframing). Overall, inter-class comparisons identified subtle differences in executive functions related to experience. Since the present study was exploratory, sampled only a limited subset of executive functions, and used subjective, self-report measures, further research is necessary to confirm these outcomes. This should employ objective tests and include a broader range of executive functions.

Introduction: Cervical cancer is the second most prevalent cancer among women in Cameroon. In November 2020, the HPV vaccine was introduced into the expanded programme on immunisation. However, uptake of the vaccine has been slow in the Centre region as opposed to other regions in the country. We therefore sought to describe vaccinators' perception of HPV vaccination in Saa health district.Methods: A self-administered questionnaire with both open-ended and closed questions was used to assess the perception of HPV vaccination among 24 vaccinators from the Saa health district. Quantitative data were summarised as proportions while qualitative data were deductively and inductively coded and thematically analysed.Results: Most vaccinators (75%, n = 18) had a good knowledge about cervical cancer and HPV vaccination. Fourteen (58.3%, n = 14) vaccinators correctly reported the target group, number and spacing of doses for the HPV vaccine. Fourteen (58.3%) vaccinators favoured HPV vaccination while the others (n = 10) were sceptical. Sceptics felt manufacturers hadn't given enough proof of the safety of the vaccine and lacked confidence in government's assessment of the epidemiological situation. The COVID 19 pandemic, fear of infertility and the negative influence of social media were perceived as the main reasons for community hesitancy. Vaccinators criticised health authorities for failing to sensitise the population about the HPV vaccine before its introduction.Conclusion: Vaccinators' perceptions of HPV vaccination may influence the offer of HPV vaccination services. Measures to increase acceptance of HPV vaccination and ownership of the activity among vaccinators have to be put in place.

Follicular Lymphoma (FL) has a 10-year mortality rate of 20%, and this is mostly related to lymphoma progression and transformation to higher grades. In the era of personalized medicine it has become increasingly important to provide patients with an optimal prediction about their expected outcomes. The objective of this work was to apply machine learning (ML) tools on gene expression data in order to create individualized predictions about survival in patients with FL. Using data from two different studies, we were able to create a model which achieved good prediction accuracies in both cohorts (c-indexes of 0.793 and 0.662 in the training and test sets). Integration of this model with m7-FLIPI and age rendered high prediction accuracies in the test set (cox c-index 0.79), and a simplified approach identified 4 groups with remarkably different outcomes in terms of survival. Importantly, one of the groups comprised 27.35% of patients and had a median survival of 4.64 years. In summary, we have created a gene expression-based individualized predictor of overall survival in FL that can improve the predictions of the m7-FLIPI score.

Initially, the COVID-19 pandemic caused a continued pressure on professionals working in hospitals due to the increase of affected patients. At the moment, the pandemic continues but thanks to all kinds of measures (e.g., social distancing) workload seems to decrease at the hospitals. On the contrary, patients with long-lasting symptoms due to COVID-19 infection or the pandemic begin to merge at the mental healthcare institutions in the Netherlands but this also holds true for other countries. Furthermore, healthcare professionals are affected by safety measures such as working from home, which led to an increased feeling of stress and may have led to a misbalance in work and private life. As a result, the question whether healthcare employees in mental healthcare experience impaired mental health remains unclear and chances are fair that mental health problems such as exhaustion and burnout may be prevalent. This study describes an online survey in which mental health amongst mental healthcare professionals is investigated. About 1,300 professionals from a large number of mental healthcare institutions replied the survey. Around 50% of the respondents experienced increased levels of stress. Feelings of anxiety, anger, and sadness were also increasingly experienced due to the COVID-19 pandemic. Furthermore, 4.2% replied that they were considering resigning their jobs which is alarming considering the shortage of healthcare professionals in mental healthcare institutions. The results support the importance of treatment or support of professionals in mental healthcare that experience psychological ailments.

Background: During the first wave of the COVID-19 pandemic, coverage by critical care pharmacists (CCPs) was expanded in 2 medical–surgical intensive care units at the Queen Elizabeth II Health Sciences Centre, in Halifax, Nova Scotia, from 8 hours per day, 5 days per week, excluding holidays, to 8 hours per day, 7 days per week, including holidays. Objectives: To describe health care professionals’ opinions about and perceived impacts of the expanded CCP coverage on patient care, as well as their opinions about the role of the CCP as a member of the critical care team. Methods: An electronic 22-item survey was distributed to critical care health care professionals to capture opinions and perceived impacts of expanded CCP coverage. The perceived importance of 25 evidence-informed CCP activities was assessed using a 5-point Likert scale. Results: Thirty-eight complete responses were included (15% response rate, based on distribution of the survey to 249 health care professionals). Most respondents agreed or strongly agreed with the following statements: CCPs are integral members of the critical care team (34/38 [89%]), CCPs play an important role in improving patient outcomes (34/38 [89%]), the presence of CCPs on the unit and on patient care rounds allows other health care professionals to concentrate on their own professional responsibilities (33/38 [87%]), and the expanded CCP coverage improved patient care (29/35 [83%]). Respondents most frequently categorized 23 of the 25 CCP activities as very important. Conclusions: Expanded CCP coverage was perceived to have a positive effect on both patient care and members of the critical care team. Most CCP activities were perceived as very important. Given the findings of this quality project, novel staffing models are being explored to optimize CCP coverage. RÉSUMÉ Contexte : Au cours de la première vague de la pandémie de COVID-19, la couverture par les pharmaciens de soins intensifs (PSI) a été étendue dans 2 unités de soins intensifs médico-chirurgicaux du Queen Elizabeth II Health Sciences Centre, à Halifax (Nouvelle-Écosse) : de 8 heures par jour, 5 jours par semaine, hors jours fériés, la couverture est passée à 8 heures par jour, 7 jours par semaine, y compris les jours fériés. Objectifs : Décrire les opinions des professionnels de la santé sur la couverture élargie des PSI et leurs perceptions des incidences de celle-ci sur les soins aux patients, ainsi que le rôle des PSI en tant que membres de l’équipe de soins intensifs. Méthodes : Un sondage électronique comportant 22 questions a été distribué aux professionnels de la santé en soins intensifs pour recueillir les opinions et les impacts perçus de l›élargissement de la couverture des PSI. L’importance perçue des 25 activités des PSI fondées sur des données probantes a été évaluée à l’aide d’une échelle de Likert à 5 points. Résultats : Trente-huit réponses complètes ont été incluses (taux de réponse de 15 %, basé sur une distribution de l’enquête à 249 professionnels de la santé). La plupart des répondants étaient d’accord ou fortement d’accord avec les affirmations suivantes : « les PSI font partie intégrante de l’équipe de soins intensifs » (34/38, 89 %); « les PSI jouent un rôle important dans l’amélioration des résultats pour les patients » (34/38, 89 %); « la présence des PSI dans l’unité et lors des tournées de soins aux patients permet à d’autres professionnels de la santé de se concentrer sur leurs propres responsabilités professionnelles » (33/38, 87 %); et « la couverture élargie des PSI a amélioré les soins aux patients » (29/35, 83 %). Les répondants ont le plus souvent classé 23 des 25 activités du PSI comme « très importantes ». Conclusions : L’élargissement de la couverture des PSI était perçu comme ayant un effet positif à la fois sur les soins aux patients et sur les membres de l’équipe de soins intensifs. La plupart des activités des PSI étaient perçues comme très importantes. Compte tenu des résultats de ce projet de qualité, de nouveaux modèles de dotation en personnel sont à l’étude pour optimiser la couverture des PSI.