Search

Author(s): Chiu, David T.; Lavoie, Ronald; Nathanson, Larry A.; Sanchez, Leon D. | Abstract: Introduction: Nearly 14% of US adults currently smoke cigarettes. Cigarette smoking causes more than 480,000 deaths each year in the United States. Emergency department (ED) patients are frequently asked for their use of tobacco. Manual selection of pre-formed discharge instructions is the norm for most ED. Providing tobacco cessation discharge instructions to ED patients presents another avenue to combat the tobacco use epidemic we face. The objective of the study is to evaluate the effectiveness of an automated discharge instruction system in increasing the frequency of discharging current tobacco users with instructions for tobacco cessation.Methods: The study was done at an urban academic tertiary care center. A before and after study was used to test the hypothesis that use of an automated discharged instruction system would increase the frequency that patients who use tobacco were discharged with tobacco cessation instructions. Patients that were admitted, left against medical advice, eloped or left without being seen were excluded. The before phase was from 09/21/14-10/21/14 and the after phase was from the same dates one year later, 09/21/15-10/21/15. This was done to account for confounding by time of year, ED volume and other factors. A Fisher’s Exact Test was calculated to compare these two groups.Results: Tobacco cessation DC instructions were received 2/486 (0.4%) of tobacco users in the pre-implementation period compared to 357/371 (96%) in the post-implementation period (p l 0.05).Conclusions: The automated discharge instructions system increases the proportion of tobacco users who receive cessation instructions. Given the public health ramifications of tobacco use, this could prove to be a significant piece in decreasing tobacco use in patients who go to the emergency department.

Background Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals. Objective To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated. Methods c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.). Results Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part. Conclusion HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep–wake cycle by engaging the hypothalamus.

Introduction: Considering the need for information regarding approaches to prevention and treatment of coronavirus disease 2019 (COVID-19), we sought to determine publication lag times of COVID19-related original research articles published in top general medicine and emergency medicine (EM) journals. We further sought to characterize the types of COVID-19 publications within these journals. Methods: We reviewed 125 top-ranked general medicine journals and 20 top-ranked EM-specific journals for COVID-19-related publications. We abstracted article titles and manuscript details for each COVID-19-related article published between January 1–June 30, 2020, and categorized articles as one of the following: original research;case report;review;or commentary. We abstracted data for preprint publications over the same time period and determined whether articles from the general medicine and EM journals had been previously published as preprint articles. Our primary outcomes were the following: 1) lag time (days) between global cumulative World Health Organization (WHO)-confirmed cases of COVID-19 and publications;2) lag times between preprint article publication and peerreviewed journal publication;and 3) lag times between submission and publication in peer-reviewed journals. Our secondary outcome was to characterize COVID-19-related publications. Results: The first original research publications appeared in a general medicine journal 20 days and in an EM journal 58 days after the first WHO-confirmed case of COVID-19. We found median and mean lag times between preprint publications and journal publications of 32 days (19, 49) and 36 days (22) for general medicine journals, and 26 days (16, 36) and 25 days (13) for EM journals. Median and mean lag times between submission and publication were 30 days (19, 45) and 35 days (13) for general medicine journals, and 23 days (11, 39) and 27 days (19) for EM journals. Of 2530 general medicine journal articles and 351 EM journal articles, 28% and 23.6% were original research. We noted substantial closing of the preprint to peer-reviewed publication (160 days pre-pandemic) and peer-reviewed journal submission to publication (194 days pre-pandemic) lag times for COVID-19 manuscripts. Conclusion: We found a rapid and robust response with shortened publication lag times to meet the need for the publication of original research and other vital medical information related to COVID-19 during the first six months of 2020. [ABSTRACT FROM AUTHOR] Copyright of Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health is the property of Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Absence seizures are generalized nonmotor epileptic seizures with abrupt onset and termination. Transient impairment of consciousness and spike-slow wave discharges (SWDs) in EEG are their characteristic manifestations. This type of seizure is severe in two common pediatric syndromes: childhood (CAE) and juvenile (JAE) absence epilepsy. The appearance of low-cost, portable EEG devices has paved the way for long-term, remote monitoring of CAE and JAE patients. The potential benefits of this kind of monitoring include facilitating diagnosis, personalized drug titration, and determining the duration of pharmacotherapy. Herein, we present a novel absence detection algorithm based on the properties of the complex Morlet continuous wavelet transform of SWDs. We used a dataset containing EEGs from 64 patients (37 h of recordings with almost 400 seizures) and 30 age and sex-matched controls (9 h of recordings) for development and testing. For seizures lasting longer than 2 s, the detector, which analyzed two bipolar EEG channels (Fp1-T3 and Fp2-T4), achieved a sensitivity of 97.6% with 0.7/h detection rate. In the patients, all false detections were associated with epileptiform discharges, which did not yield clinical manifestations. When the duration threshold was raised to 3 s, the false detection rate fell to 0.5/h. The overlap of automatically detected seizures with the actual seizures was equal to ~96%. For EEG recordings sampled at 250 Hz, the one-channel processing speed for midrange smartphones running Android 10 (about 0.2 s per 1 min of EEG) was high enough for real-time seizure detection.

Author(s): Leroux, Eric J.; Kaufman, Elizabeth A.; Kontaxis, Christian N.; Lipman, Grant S. | Abstract: Introduction: Pain control is an essential component of musculoskeletal injury treatment in the emergency department (ED). We evaluated the most effective type of cryotherapy for analgesia of acute musculoskeletal injury and the impact on opioid utilization.Methods: This was a prospective, randomized, single-blind controlled trial of adult ED patients who presented with acute musculoskeletal pain. Patients were randomized to either intensive targeted cryotherapy (crushed wetted ice in a plastic bag) or agitated chemical cold pack applied to the injury site for 20 minutes. All other diagnostic and therapeutic orders were at the discretion of the treating physician. Visual analog pain scores were measured at the time of cryotherapy application, at 20 minutes (time of cryotherapy removal), and at 60 minutes (40 minutes after removal).Results: We enrolled 38 patients, 17 randomized to intensive targeted cryotherapy and 21 to chemical cold packs, with well-matched demographics. The intensive targeted cryotherapy group achieved significantly greater pain relief at 20 minutes (2.1 [95% confidence interval (CI), 1.3 – 2.9] vs 0.9 [95% CI, 0.3 – 1.5], P l 0.05) and at 60 minutes (2.7 [95% CI, 1.6 – 3.7] vs 1.2 [95% CI, 0.6 – 1.7], P l 0.05), number need to trial (NNT) = 3.2. Opioid administration in the ED was significantly lower in the intensive targeted cryotherapy group (1 [6%] vs 7 [33%], P l 0.05), NNT = 3.6. Those who received a discharge opiate prescription had significantly higher 60-minute pain scores (7.3 ± 2.2 vs 4.1 ± 2.7, P l 0.05).Conclusion: Intensive targeted cryotherapy provided more effective analgesia than chemical cold packs for acute musculoskeletal injuries in the ED and may contribute to lower opioid usage.

Study Objectives: The surge and long tail of patients in acute respiratory distress during the coronavirus-19 (CoVID19) pandemic has inspired new innovations in diagnosing, treating and dispositioning patients during high census conditions with constrained resources During the first wave of the pandemic, we deployed an artificial intelligence (AI) algorithm for assisted interpretation of chest x-ray for use by radiologists and emergency department (ED) physicians We report first experiences of physician interaction with this novel AI algorithm designed to enhance physician abilities to identify ground glass and consolidation on chest radiographs Methods: Design: We created a fully-automated pipeline into the clinical environment to provide AI augmentation of chest x-rays, utilizing a previously developed deep learning-based AI algorithm Trained with 22,000 annotations by radiologists, the algorithm overlays X-rays with color-coded maps that indicate pneumonia probability This was provided alongside standard chest x-ray images for physicians to use in real-time at the point of care with existing imaging software For this prospective observational study, we developed a 3-point survey to characterize experiences with the tool regarding ease of use and impact on clinical decision-making Setting: Surveys were conducted during a one-month period surrounding the projected CoVID-19 surge locally (April 8-May 9) at two academic hospitals in Southern California A federal declaration of emergency occurred March 13, 2020 and the tool was urgently deployed on March 25 Types of Participants: Emergency medicine resident and attending physicians surveyed in real time by telephone Results: Of the 5,125 total visits and 1,960 chest radiographs obtained in the ED during the study period, 1,855 were analyzed by the algorithm Among these, emergency physicians were surveyed for their experiences on 202 Real-time computation and delivery of the tool took four minutes on average Overall, 86% either strongly agreed or somewhat agreed that the intervention was easy to use in the existing workflow 20% of all respondents reported that the algorithm impacted their clinical decision making In general, resident physicians found the AI implementation easier to use than attendings (Mann Whitney U, p=0 005) Descriptive statistics regarding further impact are summarized below (table 1) Conclusion: This AI technology was rapidly deployed in a large academic health system in the first wave of a global pandemic Surveyed ED physicians found this implementation easy to use within existing workflows Twenty percent of physicians reported that the tool changed clinical decision making, and approximately one third of those found that it impacted diagnostic testing decisions and treatment plans Several physicians reported ordering COVID-19 PCR testing as a direct result of the AI, resulting in positive tests and subsequent quarantining of patients who otherwise might not have been appropriately diagnosed To our knowledge, this is the first published study evaluating the impact of medical imaging AI on clinical decision making in the ED setting and may prove to be a powerful tool during the pandemic response [Formula presented]

This was a survey of the general non-healthcare-worker USA population regarding their knowledge and attitudes toward the COVID-19 pandemic. Almost everyone practiced social distancing. Women were significantly more likely to be worried about contracting the virus than men (65% vs. 43%, p = 0.0272). There was also a linear trend with age, with older Americans being more worried about contracting the virus. Women were also significantly likely to have received the influenza vaccine this past season compared to men (60% vs. 37%, p = .0167). Similarly, women were significantly more likely to get the influenza vaccine next season than men (77% vs. 46%, p = .0014.). Overall, across every age group, geographic part of the USA and gender, more (or the same) Americans plan on getting the influenza vaccine next season compared to last, but not fewer. This may reflect more awareness of preventative health brought on by the COVID-19 pandemic.

Background: Slow-wave activity (SWA) during non-rapid eye movement (NREM) sleep reflects synaptic potentiation during preceding wakefulness. Epileptic activity may induce increases in state-dependent SWA in human brains, therefore, localization of SWA may prove useful in the presurgical workup of epileptic patients. We analyzed high-density electroencephalography (HDEEG) data across vigilance states from a reflex epilepsy patient with a clearly localizable ictal symptomatogenic zone to provide a proof-of-concept for the testability of this hypothesis. Methods: Overnight HDEEG recordings were obtained in the patient during REM sleep, NREM sleep, wakefulness, and during a right facial motor seizure then compared to 10 controls. After preprocessing, SWA (i.e., delta power; 1–4 Hz) was calculated at each channel. Scalp level and source reconstruction analyses were computed. We assessed for statistical differences in maximum SWA between the patient and controls within REM sleep, NREM sleep, wakefulness, and seizure. Then, we completed an identical statistical comparison after first subtracting intrasubject REM sleep SWA from that of NREM sleep, wakefulness, and seizure SWA. Results: The topographical analysis revealed greater left hemispheric SWA in the patient vs. controls in all vigilance states except REM sleep (which showed a right hemispheric maximum). Source space analysis revealed increased SWA in the left inferior frontal cortex during NREM sleep and wakefulness. Ictal data displayed poor source-space localization. Comparing each state to REM sleep enhanced localization accuracy; the most clearly localizing results were observed when subtracting REM sleep from wakefulness. Conclusion: State-dependent SWA during NREM sleep and wakefulness may help to identify aspects of the potential epileptogenic zone. Future work in larger cohorts may assess the clinical value of sleep SWA to help presurgical planning.

Introduction: Our goal in this study was to estimate rates of emergency department (ED) visits for fever by children

Background Medical cannabis users report that their knowledge regarding cannabis is predominantly from their own personal experiences and the Internet. Objective We summarize and describe information found through Internet searches on medical cannabis in English language websites. Methods We used terms related to medical cannabis in the Google search engine between November and December 2019. Resulting websites were catalogued and coded for content, including mentions of health and medical conditions, pharmacology, dosage, harmful or adverse effects, harm reduction techniques, cautions or warnings, products for sale, and credentials. Results We coded 344 web pages on 179 unique websites. Cannabis was mentioned for the treatment of 151 different medical and health conditions, only four of the twenty most frequently mentioned conditions have received substantial empirical support for cannabis or cannabinoid treatment. Information content varied widely across sites, only a small proportion of sites included information on pharmacology, dosage, risks, and other aspects that are requirements for pharmaceutical drugs. Information provided was only moderately related to conclusions in the emerging scientific literature. Conclusions Given the rise in cannabis use within the U.S. and the reliance on the Internet as a source of information, considerable efforts are needed to provide accurate on-line cannabis education to minimize harms and maximize benefits for individuals and society.

Introduction SARS-CoV-2, a novel coronavirus, manifests as a respiratory syndrome (COVID-19) and is the cause of an ongoing pandemic. The response to COVID-19 in the United States has been hampered by an overall lack of diagnostic testing capacity. To address uncertainty about ongoing levels of SARS-CoV-2 community transmission early in the pandemic, we aimed to develop a surveillance tool using readily available emergency department (ED) operations data extracted from the electronic health record (EHR). This involved optimizing the identification of acute respiratory infection (ARI)-related encounters and then comparing metrics for these encounters before and after the confirmation of SARS-CoV-2 community transmission. Methods We performed an observational study using operational EHR data from two Midwest EDs with a combined annual census of over 80,000. Data were collected three weeks before and after the first confirmed case of local SARS-CoV-2 community transmission. To optimize capture of ARI cases, we compared various metrics including chief complaint, discharge diagnoses, and ARI-related orders. Operational metrics for ARI cases, including volume, pathogen identification, and illness severity, were compared between the preand post-community transmission timeframes using chi-square tests of independence. Results Compared to our combined definition of ARI, chief complaint, discharge diagnoses, and isolation orders individually identified less than half of the cases. Respiratory pathogen testing was the top performing individual ARI definition but still only identified 72.2% of cases. From the pre to post periods, we observed significant increases in ED volumes due to ARI and ARI cases without identified pathogen. Conclusion Certain methods for identifying ARI cases in the ED may be inadequate and multiple criteria should be used to optimize capture. In the absence of widely available SARS-CoV-2 testing, operational metrics for ARI-related encounters, especially the proportion of cases involving negative pathogen testing, are useful indicators for active surveillance of potential COVID-19 related ED visits.

Author(s): Mathews, Kusum S.; Rodriguez, Sandra M.; Nelson, Judith E.; Richardson, Lynne D. | Abstract: Introduction: We conducted a cross-sectional study at the Icahn School of Medicine at Mount Sinai to elicit emergency physician (EP) perceptions regarding intensive care unit (ICU) triage decisions and ongoing management for boarding of ICU patients in the emergency department (ED). We assessed factors influencing the disposition decision for critically ill patients in the ED to characterize EPs’ perceptions about ongoing critical care delivery in the ED while awaiting ICU admission.Methods: Through content expert review and pilot testing, we iteratively developed a 25-item written survey targeted to EPs, eliciting current ICU triage structure, opinions on factors influencing ICU admission decisions, and views on caring for critically ill patients “boarding” in the ED for g4-6 hours.Results: We approached 732 EPs at a large, national emergency medicine conference, achieving 93.6% response and completion rate, with 54% academic and 46% community participants. One-fifth reported having formal ICU admission criteria, although only 36.6% reported adherence. Common factors influencing EPs’ ICU triage decisions were illness severity (91.1%), ICU interventions needed (87.6%), and diagnosis (68.2%), while ICU bed availability (13.5%) and presence of other critically ill patients in ED (10.2%) were less or not important. While 72.1% reported frequently caring for ICU boarders, respondents identified high patient volume (61.3%) and inadequate support staffing (48.6%) as the most common challenges in caring for boarding ICU patients.Conclusion: Patient factors (eg, diagnosis, illness severity) were seen as more important than system factors (eg, bed availability) in triaging ED patients to the ICU. Boarding ICU patients is a common challenge for more than two-thirds of EPs, exacerbated by ED volume and staffing constraints.

Author(s): Ramaekers, Rosa; Perry, Jeffrey; Leafloor, Cameron; Thiruganasambandamoorthy, Venkatesh | Abstract: Introduction: There are currently no robust tools available for risk stratification of emergency department (ED) patients with lower gastrointestinal bleed (LGIB). Our aim was to identify risk factors and develop a preliminary model to predict 30-day serious adverse events among ED LGIB patients.Methods: We conducted a health records review including adult ED patients with acute LGIB. We used a composite outcome of 30-day all-cause death, recurrent LGIB, need for intervention to control the bleeding, and severe adverse events resulting in intensive care unit admission. One researcher collected data for variables and a second researcher independently collected 10% of the variables for inter-observer reliability. We used backward multivariable logistic regression analysis and SELECTION=SCORE option to create a preliminary risk-stratification tool. We assessed the diagnostic accuracy of the final model.Results: Of 372 patients, 48 experienced an adverse outcome. We found that age ≥75 years, hemoglobin ≤100 g/L, international normalized ratio ≥2.0, ongoing bleed in the ED, and a medical history of colorectal polyps were statistically significant predictors in the multivariable regression analysis. The area under the curve (AUC) for the model was 0.83 (95% confidence interval, 0.77-0.89). We developed a scoring system based on the logistic regression model and found a sensitivity 0.96 (0.90-1.00) and specificity 0.53 (0.48-0.59) for a cut-off score of 1.Conclusion: This model showed good ability to differentiate patients with and without serious outcomes as evidenced by the high AUC and sensitivity. The results of this study could be used in the prospective derivation of a clinical decision tool.

Author(s): Walter, Lauren A.; Leader, Elizabeth; Galbraith, James W. | Abstract: Introduction: A vaccine targeting high-risk human papillomavirus (HPV) strains can effectively prevent HPV-associated cervical cancer risk. However, many girls and women do not receive the vaccine, more often those impacted by health disparities associated with race and/or socioeconomic status. This same disparate population has also been shown to be at higher risk for cervical cancer. Many of these women also rely on the emergency department (ED) as a safety net for their healthcare. This study sought to gather information pertaining to HPV and cervical cancer risk factors, awareness of HPV and the vaccine, as well as HPV vaccine uptake in female patients presenting to an ED.Methods: We obtained 81 surveys completed by female ED patients. Demographics included age, race, income, insurance status, primary care provider status, and known cervical-cancer risk factors. Subsequent survey questions explored respondents’ knowledge, familiarity, and attitudes regarding HPV, cervical cancer, and the HPV vaccine, including vaccination uptake rates. We analyzed data using descriptive statistics and Fisher’s exact test.Results: Approximately one in seven respondents (14.8%) had never previously heard of HPV and 32.1% were unaware of the existence of a HPV vaccine. Minority patients, including those who were Black and Hispanic patients, low income patients, and uninsured and publicly insured patients were less likely to be aware of HPV and the vaccine and likewise were less likely to be offered and receive the vaccine. More than 60% of all respondents (61.3%) had never previously been offered the vaccine, and only 24.7% of all respondents had completed the vaccine series.Conclusion: Female ED patients may represent an at-risk cohort with relatively low HPV awareness and low HPV vaccine uptake. The ED could represent a novel opportunity to access and engage high-risk HPV populations.

De nombreuses études ont examiné la manière dont l'adhésion à un club sportif peut engendrer des résultats affectifs bénéfiques. La littérature scientifique a également montré que les sports d'équipe, les sports intensifs et les sports pratiqués en milieu naturel de manière fréquente peuvent entraîner un accroissement des affects positifs. Cependant, à notre connaissance, aucune étude n'a examiné l'influence de certains sports sur les affects positifs et négatifs. Sur la base de la littérature, nous avons supposé que certains sports qui répondant aux critères définis précédemment apporteront de plus grands bénéfices affectifs. Cette étude à grande échelle a examiné les données d'adolescents (N = 12 849, femmes = 5 812, âgés de 10 à 18 ans, moyenne = 12,56 ± 2,00 ans) et visait à répondre à cette hypothèse. Nos résultats ont montré que, bien que des différences d'affects puissent être trouvées entre l'absence d'adhésion à un club et la plupart des adhésions à un club sportif, ces différences entre les sports spécifiques sont moins frappantes. Les sports qui sont associés au plus haut niveau d'affectivité positive et au plus bas niveau d'affectivité négative ne sont pas nécessairement ceux auxquels nous nous attendions. Enfin, les adolescents pratiquant l'athlétisme ont rapporté plus d'affects positifs et moins d'affects négatifs comparés aux adolescents pratiquant d'autres sports. Nos résultats suggèrent également que le football en tant que sport le plus pratiqué par les adolescents français était associé à des affects plus positifs que la majorité des 10 sports français les plus licenciés pratiqués par les adolescents entre 2008 et 2019. D'autres sports, comme la danse, le badminton, la boxe ou encore l'équitation sont associés à moins de bénéfices affectids. La pratique sportive en club engendre une augmentation des bénéfices affectifs et sports spécifiques peuvent engendrer des bénéfices supplémentaires. Prior studies extensively examined the way sports club membership can lead to beneficial affective outcomes. Prior experiments also found that team sports, intensive sports, and sports that are frequently pursued can lead to even more affective benefits. However, no prior studies examined the differences between the affective benefits of specific sports. Based on prior results, we supposed that certain sports that meet all the previously set criteria-will provide the greatest affective benefits. The present large-scale investigation examined the data of adolescents ( = 12,849, female = 5,812, aged between 10 and 18, = 12.56 years, and = 2.00) and aimed to fill this gap. Firstly, the results showed that-although differences in affect can be found between the lack of club membership and most of the sports club memberships-the differences between the specific sports are less striking. Secondly, the sports that are associated with the highest level of positive and the lowest level of negative affectivity are not necessarily the ones expected. Finally, adolescents who practice athletics, reported the lowest means of negative, and the highest means of positive affect. However, it did not differ significantly from the results regarding the most practiced sport in France: soccer. Our results suggest that soccer as the most practice sport among French adolescents was associated with more positive affects than the majority of the 10 most licensed members French sports practiced by teens between 2008 and 2019. All in all, being a member of a sports club is associated with affective benefits, and some specific sports clubs can have some extra benefits. 12

Andersen-Tawil Syndrome (ATS) is a rare disease defined by the association of cardiac arrhythmias, periodic paralysis and dysmorphic features, and is caused by KCNJ2 loss-of-function mutations. However, when extracardiac symptoms are atypical or absent, the patient can be diagnosed with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a rare arrhythmia at high risk of sudden death, mostly due to RYR2 mutations. The identification of KCNJ2 variants in CPVT suspicion is very rare but important because beta blockers, the cornerstone of CPVT therapy, could be less efficient. We report here the cases of two patients addressed for CPVT-like phenotypes. Genetic investigations led to the identification of p. Arg82Trp and p. Pro186Gln de novo variants in the KCNJ2 gene. Functional studies showed that both variants forms of Kir2.1 monomers act as dominant negative and drastically reduced the activity of the tetrameric channel. We characterize here a new pathogenic variant (p.Pro186Gln) of KCNJ2 gene and highlight the interest of accurate cardiologic evaluation and of attention to extracardiac signs to distinguish CPVT from atypical ATS, and guide therapeutic decisions. We also confirm that the KCNJ2 gene must be investigated during CPVT molecular analysis.

Deep neural networks, inspired by information processing in the brain, can achieve human-like performance for various tasks. However, research efforts to use these networks as models of the brain have primarily focused on modeling healthy brain function so far. In this work, we propose a paradigm for modeling neural diseases in silico with deep learning and demonstrate its use in modeling posterior cortical atrophy (PCA), an atypical form of Alzheimer’s disease affecting the visual cortex. We simulated PCA in deep convolutional neural networks (DCNNs) trained for visual object recognition by randomly injuring connections between artificial neurons. Results showed that injured networks progressively lost their object recognition capability. Simulated PCA impacted learned representations hierarchically, as networks lost object-level representations before category-level representations. Incorporating this paradigm in computational neuroscience will be essential for developing in silico models of the brain and neurological diseases. The paradigm can be expanded to incorporate elements of neural plasticity and to other cognitive domains such as motor control, auditory cognition, language processing, and decision making.

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome.Objective: To assess the safety of inulin and sinistrin use in France.Methods: We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin.Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign.Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.

Background: Persistent physical symptoms are common after a coronavirus disease 2019 (COVID-19) episode, but their pathophysiological mechanisms remain poorly understood. In this study, we aimed to explore the association between anxiety and depression at 1-month after acute infection and the presence of fatigue, dyspnea, and pain complaints at 3-month follow-up.Methods: We conducted a prospective study in patients previously hospitalized for COVID-19 followed up for 3 months. The Hospital Anxiety and Depression Scale (HAD-S) was administered by physicians at 1-month follow-up, and the presence of fatigue, dyspnea, and pain complaints was assessed at both 1 month and 3 months. Multivariable logistic regressions explored the association between anxiety and depression subscores and the persistence of each of the physical symptom at 3 months.Results: A total of 84 patients were included in this study (Median age: 60 years, interquartile range: 50.5–67.5 years, 23 women). We did not find any significant interaction between anxiety and the presence of fatigue, dyspnea, or pain complaints at 1 month in predicting the persistence of these symptoms at 3 months (all p ≥ 0.36). In contrast, depression significantly interacted with the presence of pain at 1 month in predicting the persistence of pain at 3 months (OR: 1.60, 95% CI: 1.02–2.51, p = 0.039), with a similar trend for dyspnea (OR: 1.51, 95% CI: 0.99–2.28, p = 0.052).Discussion and Conclusion: Contrary to anxiety, depression after an acute COVID-19 episode may be associated with and increased risk of some persistent physical symptoms, including pain and dyspnea.

Professional and colloquial sleep hygiene guidelines advise against evening physical activity, despite meta-analyses of laboratory studies concluding that evening exercise does not impair sleep. This study is the first to investigate the association between objectively measured evening physical activity and sleep within a real-world big-data sample. A total of 153,154 nights from 12,638 individuals aged 18–60 years (M = 40.1 SD = 10.1; 44.5% female) were analyzed. Nighttime sleep and minutes of physical activity were assessed using Polar wearable devices for 14 consecutive days. Thirty minutes or more of moderate-to-near maximal physical activity during the 3 h before sleep onset were recorded in 12.4% of evenings, and were more frequent on weekdays than weekends (13.3 vs. 10.2% respectively, p < 0.001). Linear mixed modeling revealed that sleep efficiency was not significantly associated with evening physical activity, and that sleep duration was 3.4 min longer on average on nights following evenings in which participants engaged in 30 min or more of moderate-intense physical activity. Effects were found for sleep timing metrics, as evening physical activity was linked with earlier sleep onset and offset times (−13.7 and −9.3 min, respectively). Overall, these effects were greater– but still very small– on weekdays compared to weekends. The present study provides further evidence for the lack of meaningful links between sleep duration or quality and physical activity in the hours preceding sleep. Taken together with recent meta-analytic findings, these findings suggest that changes in public health recommendations are warranted regarding evening physical activity and its relation to sleep.

Erenumab is the first human monoclonal antibody to be approved as a selective therapy for migraine prophylaxis in adults. This study assessed, in a real-world setting, the efficacy of erenumab and its impact on the quality of life (QoL) of Cypriot migraine patients who had failed several treatments in the past. Erenumab was prescribed as a stand-alone or as an add-on therapy to 16 patients with chronic migraine. The first component of the study examined migraine parameters before and after erenumab therapy and included an interim 3-month subjective assessment. In the second component, the patients were asked to complete the validated Migraine-Specific Quality-of-Life Questionnaire—Version 2.1 (MSQ V2.1) during the last month of their individual treatment as a measure of the QoL. The results showed a statistically significant improvement in almost all migraine parameters following erenumab treatment. In the 3-month-interval assessment, 81.3% of the patients reported an improvement in their mental well-being, anxiety, and depression levels, with more than 80% of the patients reporting an improvement in almost all assessed migraine parameters. MSQ V2.1 indicated a good health status in all three domains (mean values > 60 on a scale 0–100), with the “role function preventative” domain having the highest health scores (85). Over a period of 6 months, erenumab was safe, well-tolerated, and effective in preventing migraine symptoms and improving HR-QoL. We conclude that this novel medication, which is not yet part of the national formulary in Cyprus, may be a cost-effective solution in reducing the disease burden of chronic migraine.

Reducing added sugars in non-alcoholic beverages is an important public health goal, which can result in increased use of low- and no-calorie sweeteners (LNCS). The aim of this study was to investigate recent changes in the use of LNCS in non-alcoholic beverages in the Slovenian food supply. The national branded foods dataset was updated with beverages available in 2020, and compared with previous datasets. The data were extracted from food labels. In 2020, N = 1,650 unique beverages were found in shops from five different retailers, covering the majority of the national market. The use of LNCS increased from 13.2% in 2017 and 15.5% in 2019 to 20.2% in 2020, with a major growth in soft drinks (16.8, 19.6, and 26.7%, respectively). We observed a significant growth of beverages containing both LNCS and added sugar. Results were also consistent with sales data, which showed that increased offer of beverages with LNCS also resulted in similarly increased sales of such beverages. The average energy and total sugar content in non-alcoholic beverages decreased, which reflects both the higher percentage of beverages with LNCS, and also the reduction of the sugar content in beverages with only added sugar. Analyses of product-specific reformulation practices highlighted reduced sugar content in 16.8% of products, and in 3.6% with the use of LNCS. The most commonly used LNCS are acesulfame K, sucralose, and aspartame. Typically, combinations are used, however steviol glycosides, sucralose and saccharin are also used alone, in most cases combined with added sugar. The results indicated rapid changes in the use of LNCS in non-alcoholic beverages in the Slovenian food supply, making further monitoring of this area highly relevant.

The egg plays a pivotal role in the reproduction of our species. Nevertheless, its fundamental biology remains elusive. Transmission electron microscopy is traditionally used to inspect the ultrastructure of female gametes. However, two-dimensional micrographs contain only fragmentary information about the spatial organization of the complex oocyte cytoplasm. Here, we employed the Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) to explore human oocyte intracellular morphology in three dimensions (3D). Volume reconstruction of generated image stacks provided an unprecedented view of ooplasmic architecture. Organelle distribution patterns observed in nine donor oocytes, representing three maturational stages, documented structural changes underlying the process by which the egg acquires developmental competence. 3D image segmentation was performed to extract information about distinct organelle populations, and the following quantitative analysis revealed that the mitochondrion occupies ∼ 4.26% of the maturing oocyte cytoplasm. In summary, this proof-of-concept study demonstrates the potential of large volume electron microscopy to study rare samples of delicate female gametes and paves the way for applying the FIB-SEM technique in human oocyte research.

International audience; The COVID-19 pandemic deeply affected how schools and families functioned through most of 2020. In particular, school closures meant parents took on a more central role in their children’s learning. This study analyzed social class variations in the quantity and quality of homeschooling during the lockdown. Through an online questionnaire, 360 parents reported (1) their digital equipment and use, (2) the perceptions of their ability to homeschool their children, (3) how they handled homeschooling and (4) the extent to which they supported other activities considered more or less “profitable” from an educational point of view (e.g., reading, watching television). A social position index was used as a proxy of social class. The results indicated that all parents were highly involved in setting up homeschooling and that the lower the parents’ social position, the more they spent time homeschooling their children. However, in line with the digital divide literature, the lower the parents’ social position, the lower the digital equipment and the less the parents felt capable of homeschooling. Finally, the higher the social position of the families, the more children spent time doing activities considered to be “educationally profitable,” and the less they spent time doing “unprofitable activities.” Thus, even if all parents were highly involved in homeschooling, higher social position parents were better equipped both materially and psychologically to face the challenge of homeschooling. The long-term impact of these processes on the perpetuation of social class inequalities are discussed.

Topoisomerase 2 (TOP2) inhibitors are drugs widely used in the treatment of different types of cancer. Processing of their induced-lesions create double-strand breaks (DSBs) in the DNA, which is the main toxic mechanism of topoisomerase inhibitors to kill cancer cells. It was established that the Nucleotide Excision Repair pathway respond to TOP2-induced lesions, mainly through the Cockayne Syndrome B (CSB) protein. In this paper, we further define the mechanism and type of lesions induced by TOP2 inhibitors when CSB is abrogated. In the absence of TOP2, but not during pharmacological inhibition, an increase in R-Loops was detected. We also observed that CSB knockdown provokes the accumulation of DSBs induced by TOP2 inhibitors. Consistent with a functional interplay, interaction between CSB and TOP2 occurred after TOP2 inhibition. This was corroborated with in vitro DNA cleavage assays where CSB stimulated the activity of TOP2. Altogether, our results show that TOP2 is stimulated by the CSB protein and prevents the accumulation of R-loops/DSBs linked to genomic instability.

The closure of in-person laboratories and decreased safety of face-to-face interactions resulting from the COVID-19 pandemic jeopardized the ability of many developmental researchers to continue data collection during this time. Disruptions in data collection are particularly damaging to longitudinal studies, in which the testing of different age groups occurs on a continuous basis, and data loss at one time point can have cascading effects across subsequent time points and threaten the viability of the study. In an effort to continue collecting data for a longitudinal study on emotion development started in-person pre-pandemic, we adapted two parent-infant interaction tasks (free-play task and toy removal task) for a remote testing framework. Our procedure for pivoting these tasks to a supervised, remote online testing framework is outlined and the associated strengths and challenges of testing in this format (e.g., feasibility and implementation, testing environment and task setup validity, and accessibility, recruitment, and diversity) are critically evaluated. Considerations for applying this framework to other behavioral tasks are discussed and recommendations are provided.

International audience; Daily activities can often be performed while listening to music, which could influence the ability to select relevant stimuli while ignoring distractors. Previous studies have established that the level of arousal of music (e.g., relaxing/stimulating) has the ability to modulate mood and affect the performance of cognitive tasks. The aim of this research was to explore the effect of relaxing and stimulating background music on selective attention. To this aim, 46 healthy adults performed a Stroop-type task in five different sound environments: relaxing music, stimulating music, relaxing music-matched noise, stimulating music-matched noise, and silence. Results showed that response times for incongruent and congruent trials as well as the Stroop interference effect were similar across conditions. Interestingly, results revealed a decreased error rate for congruent trials in the relaxing music condition as compared to the relaxing musicmatched noisecondition, and a similar tendency between relaxing music and stimulating musicmatched noise. Taken together, the absence of difference between background music and silence conditions suggest that they have similar effects on adult's selective attention capacities, while noise seems to have a detrimental impact, particularly when the task is easier cognitively. In conclusion, the type of sound stimulation in the environment seems to be a factor that can affect cognitive tasks performance.

A sentence such as We finished the paper is indeterminate with regards to what we finished doing with the paper. Indeterminate sentences constitute a test case for two major issues regarding language comprehension: (1) how we compose sentence meaning; and (2) what is retained in memory about what we read in context over time. In an eye-tracking experiment, participants read short stories that were unexpectedly followed by one of three recognition probes: (a) an indeterminate sentence (Lisa began the book), that is identical to the one in the story; (b) an enriched but false probe (Lisa began reading the book); and (c) a contextually unrelated probe (Lisa began writing the book). The probes were presented either at the offset of the original indeterminate sentence in context or following additional neutral discourse. We measured accuracy, probe recognition time, and reading times of the probe sentences. Results showed that, at the immediate time point, participants correctly accepted the identical probes with high accuracy and short recognition times, but that this effect reversed to chance-level accuracy and significantly longer recognition times at the delayed time point. We also found that participants falsely accept the enriched probe at both time points 50% of the time. There were no reading-time differences between identical and enriched probes, suggesting that enrichment might not be an early, mandatory process for indeterminate sentences. Overall, results suggest that while context produces an enriched proposition, an unenriched proposition true to the indeterminate sentence also lingers in memory.

Studies on simple language and simplification are often based on datasets of texts, either for children or learners of a second language. In both cases, these texts represent an example of simple language, but simplification likely involves different strategies. As such, this data may not be entirely homogeneous in terms of text simplicity. This study investigates linguistic properties and specific simplification strategies used in Russian texts for primary school children with different language backgrounds and levels of language proficiency. To explore the structure and variability of simple texts for young readers of different age groups, we have trained models for multiclass and binary classification. The models were based on quantitative features of texts. Subsequently, we evaluated the simplification strategies applied to readers of the same age with different linguistic backgrounds. This study is particularly relevant for the Russian language material, where the concept of easy and plain language has not been sufficiently investigated. The study revealed that the three types of texts cannot easily be distinguished from each other by judging the performance of multiclass models based on various quantitative features. Therefore, it can be said that texts of all types exhibit a similar level of accessibility to young readers. In contrast, binary classification tasks demonstrated better results, especially in the R-native vs. non R-native track (with 0.78 F1-score), these results may indicate that the strategies used for adapting or creating texts for each type of audience are different.

Introduction: Little is known on the effect of SARS-CoV-2 circulation on asthma daily symptoms in children. We compared asthma exacerbations, asthma symptom control and lung function before and after SARS-CoV-2 outbreak in children.Methods: Retrospective study of children with persistent asthma referred for lung function testing. The second quarter of 2020 being a period with nearly no activity, we compared the activity between the first, third and fourth quarters of 2019 and 2020 (Q1-2019 vs. Q1-2020, Q3-2019 vs. Q3-2020 and Q4-2019 vs. Q4-2020).Results: We retrieved 1,871 files in 2019 and 1,548 in 2020. The whole population [2,165 (63.3%) boys] had a median [IQR] age of 9.7 [6.8;13.1] years. There was no difference in age, sex, and ethnicity between 2019 and 2020 populations. Asthma was better controlled during Q4-2020 compared to Q4-2019 (P = 0.042), and there was a lower proportion of children with at least one exacerbation in the previous 3 months after the reopening, compared to the same period in 2019 (P < 0.0001). Baseline FEV1 (Z-score) recorded after the reopening was significantly higher (with less reversibility) compared to the same period before the epidemic (P < 0.0001). Baseline FEV1/FVC (Z-score) was significantly higher during Q3-2020 compared to Q3-2019 (P = 0.026), with fewer children having a significant reversibility (P = 0.035).Discussion: We demonstrated a trend toward increased exacerbations just before the recognition of the epidemic, and fewer exacerbations, better asthma symptom control and improvement in the lung function of asthmatic children after the reopening.

Background: Dance is a complex activity combining physical exercise with cognitive, social, and artistic stimulation.Objectives: We aimed to assess the effects of dance intervention (DI) on intra and inter-network resting-state functional connectivity (rs-FC) and its association to cognitive changes in a group of non-demented elderly participants.Methods: Participants were randomly assigned into two groups: DI and life as usual (LAU). Six-month-long DI consisted of supervised 60 min lessons three times per week. Resting-state fMRI data were processed using independent component analysis to evaluate the intra and inter-network connectivity of large-scale brain networks. Interaction between group (DI, LAU) and visit (baseline, follow-up) was assessed using ANOVA, and DI-induced changes in rs-FC were correlated with cognitive outcomes.Results: Data were analyzed in 68 participants (DI; n = 36 and LAU; n = 32). A significant behavioral effect was found in the attention domain, with Z scores increasing in the DI group and decreasing in the LAU group (p = 0.017). The DI as compared to LAU led to a significant rs-FC increase of the default mode network (DMN) and specific inter-network pairings, including insulo-opercular and right frontoparietal/frontoparietal control networks (p = 0.019 and p = 0.023), visual and language/DMN networks (p = 0.012 and p = 0.015), and cerebellar and visual/language networks (p = 0.015 and p = 0.003). The crosstalk of the insulo-opercular and right frontoparietal networks were associated with attention/executive domain Z-scores (R = 0.401, p = 0.015, and R = 0.412, p = 0.012).Conclusion: The DI led to intervention-specific complex brain plasticity changes that were of cognitive relevance.

At the start of the COVID-19 pandemic, early intubation was recommended on the basis of worldwide observations of severe hypoxemia. However, some patients were ultimately able to benefit from high-flow nasal cannula (HFNC) and thus avoid intubation. During the “second wave” (September to December 2020 in France), some emergency departments implemented HFNC in patients with severe COVID-19. The question then arose regarding the transfer of these most serious patients to intensive care units (ICU) and of the respiratory modalities to be used during this transfer. To assess the feasibility of interhospital transfers of COVID-19 patients needing HFNC, we conducted a bi-centric prospective observational study of all medical transfers of patients needing HFNC with the Chambéry and Angers (France) mobile emergency and intensive care service (SMUR) during the “second wave” of the COVID-19 pandemic in France. Analysis of these 42 patients showed no significant variation in the respiratory requirements during the transfer. Overall, 52% of patients were intubated during their stay in ICU, including three patients intubated before or during transfer. Interhospital transfer with HFNC is very high-risk, and intubation remains indicated in the most unstable patients. However, 48% of patients benefited from HFNC and were thus able to avoid intubation during their transfer and ICU stay; for these patients, intubation would probably have been indicated in the absence of available HFNC techniques.

Background: COVID-19 is a global pandemic and vaccination efforts may be impeded by vaccine hesitancy. The present study examined willingness to receive a COVID-19 vaccine, the associated reasons for willingness/unwillingness, and vaccine safety perceptions in a cross-sectional assessment of community adults in Ontario.Methods: One thousand three hundred sixty seven individuals (60.6% female, mean age = 37.5%) participated in this study between January 15, 2021 and February 15, 2021. Perceptions of vaccine safety and reasons for willingness/unwillingness to receive the COVID-19 vaccine were investigated using an online assessment. Perceptions were investigated in general and by age, sex and education using analysis of variance.Results: Overall, 82.8% of the sample reported they were willing to receive a COVID-19 vaccine and 17.2% reported they were unwilling. The three most common reasons for unwillingness were long-term side effects (65.5%), immediate side effects (60.5%), and lack of trust in the vaccine (55.2%). Vaccine willingness significantly differed by sex and education level, with female participants and those with less than a bachelor's degree being more likely to report unwillingness. Perception of COVID-19 vaccine safety was significantly lower (−10.3%) than vaccines in general and differed by age, sex and education, with females, older adults, and individuals with less than a bachelor's degree reporting lower perceived COVID-19 vaccine safety.Conclusion: In this sample of community adults, the COVID-19 vaccine hesitancy rate was less than one in five individuals, but with higher rates in population subgroups. Targeting public health messaging to females and individuals with less than bachelor's degree, and addressing concerns about long-term and immediate side effects may increase vaccine uptake.

Background: Cognitive complaints are frequent after COVID-19 but their clinical determinants are poorly understood. This study aimed to explore the associations of objective cognitive performances and psychological distress with cognitive complaints in COVID-19 survivors.Materials and Methods: Patients previously hospitalized for COVID-19 in a university hospital during the first wave of COVID-19 pandemic in France were followed-up at 1 month after their admission. Cognitive complaints were self-reported and standardized instruments were used to assess neuropsychological status (Digit Symbol Substitution Test, Semantic Verbal Fluency Test, Mini Mental Status Examination) and psychological distress (Hospital Anxiety and Depression Scale, HADS). Multivariable analyses were adjusted for age, sex, admission in intensive care unit (ICU) and need for oxygen and C-reactive protein.Results: One hundred patients (34% women, median age: 60 years [interquartile range: 49–72)] completed the neuropsychological assessment at follow-up. In multivariable analyses, cognitive complaints at 1-month were associated with greater HADS score (OR for one interquartile range: OR: 1.96, 95% CI: 1.08–3.57) and older age (OR: 1.05, 95% CI: 1.01–1.09) and, negatively, with admission in ICU (OR: 0.22, 95% CI: 0.05–0.90). In contrast, none of the objective neuropsychological test scores was significantly associated with cognitive complaints. Exploratory analysis showed that cognitive complaints were associated with both anxiety and depressive symptoms.Discussion: These preliminary results suggest that cognitive complaints at 1 month after a hospitalization for COVID-19 are associated with psychological distress, independently of objective neuropsychological status. Anxiety and depression symptoms should be systematically screened in patients presenting with cognitive complaints after a severe COVID-19 episode.

The voltage-dependent anion-selective channel (VDAC) is a porin in the mitochondrial outer membrane (MOM). Unlike bacterial porins, several mitochondrial β-barrels comprise an odd number of β-strands, as is the case for the 19-β-stranded VDAC. Previously, a variant of a VDAC from Neurospora crassa, VDAC-ΔC, lacking the predicted 19th β-strand, was found to form gated, anion-selective channels in artificial membranes. In vivo, the two C-terminal β-strands (β18 and β19) in VDAC form a β-hairpin necessary for import from the cytoplasm into mitochondria and the β-signal required for assembly in the mitochondrial outer membrane resides in β19. The current study demonstrated that the putative 18-stranded β-barrel formed by VDAC-ΔC can be imported and assembled in the MOM in vivo and can also partially rescue the phenotype associated with the deletion of VDAC from a strain of N. crassa. Furthermore, when expressed and purified from Escherichia coli, VDAC-ΔC can be folded into a β-strand-rich form in decyl-maltoside. Size exclusion chromatography (SEC) alone or combined with multi-angle light scattering (SEC-MALS) and analytical ultracentrifugation revealed that, unlike full-length VDACs, VDAC-ΔC can self-organize into dimers and higher order oligomers in the absence of sterol.

Research on dance interventions (DIs) in the elderly has shown promising benefits to physical and cognitive outcomes. The effect of DIs on resting-state functional connectivity (rs-FC) varies, which is possibly due to individual variability. In this study, we assessed the moderation effects of residual cognitive reserve (CR) on DI-induced changes in dynamic rs-FC and their association on cognitive outcomes. Dynamic rs-FC (rs-dFC) and cognitive functions were evaluated in non-demented elderly subjects before and after a 6-month DI (n = 36) and a control group, referred to as the life-as-usual (LAU) group (n = 32). Using linear mixed models and moderation, we examined the interaction effect of DIs and CR on changes in the dwell time and coverage of rs-dFC. Cognitive reserve was calculated as the residual difference between the observed memory performance and the performance predicted by brain state. Partial correlations accounting for CR evaluated the unique association between changes in rs-dFC and cognition in the DI group. In subjects with lower residual CR, we observed DI-induced increases in dwell time [t(58) = –2.14, p = 0.036] and coverage [t(58) = –2.22, p = 0.030] of a rs-dFC state, which was implicated in bottom-up information processing. Increased dwell time was also correlated with a DI-induced improvement in Symbol Search (r = 0.42, p = 0.02). In subjects with higher residual CR, we observed a DI-induced increase in coverage [t(58) = 2.11, p = 0.039] of another rs-dFC state, which was implicated in top-down information processing. The study showed that DIs have a differential and behaviorally relevant effect on dynamic rs-dFC, but these benefits depend on the current CR level.

The endocannabinoid system is responsible for regulating a spectrum of physiological activities and plays a critical role in the developing brain. During adolescence, the endocannabinoid system is particularly sensitive to external insults that may change the brain’s developmental trajectory. Cannabinoid receptor type 2 (CB2R) was initially thought to predominantly function in the peripheral nervous system, but more recent studies have implicated its role in the mesolimbic pathway, a network largely attributed to reward circuitry and reward motivated behavior, which undergoes extensive changes during adolescence. It is therefore important to understand how CB2R modulation during adolescence can impact reward-related behaviors in adulthood. In this study, adolescent male rats (postnatal days 28–41) were exposed to a low or high dose of the CB2R antagonist/inverse agonist SR144528 and Pavlovian autoshaping and instrumental conditional behavioral outcomes were measured in adulthood. SR144528-treated rats had significantly slower acquisition of the autoshaping task, seen by less lever pressing behavior over time [F(2, 19) = 5.964, p = 0.010]. Conversely, there was no effect of adolescent SR144528 exposure on instrumental conditioning. These results suggest that modulation of the CB2R in adolescence differentially impacts reward-learning behaviors in adulthood.

HighlightsInnate immune activation during Covid-19 infection is associated with pernicious clinical outcome.BackgroundCoronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.MethodsWe measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.ResultsSevere and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.ConclusionWe propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.

Aim: Stroke is a leading cause of disability; however, little is known about the outcomes of the utilization of long-term care (LTC) recipients in Taiwan. This study aimed to quantify the burdens of disease of stroke survivors receiving LTC by evaluating the outcomes of their utilization including mortality, readmissions, and re-emergency within 1 year after diagnoses of strokes.Methods: By interlinkages among the national mortality registry, LTC dataset (LTC-CM), and the National Health Insurance Research Dataset (NHIRD), the outcomes and the factors associated with receiving LTC up to 1 year were explored. Patients were aged 50 years and over with an inpatient claim of the first diagnosis of stroke of intracerebral hemorrhage (ICH) and ischemic stroke during 2011–2016. Outcomes of the healthcare utilization include rehospitalization and re-emergency.Results: There were 15,662 patients with stroke who utilized the LTC services in the dataset among the stroke population in NHIRD. Stroke survivors receiving LTC showed no difference in clinical characteristics and their expected years of life loss (EYLL = 7.4 years) among those encountered in NHIRD. The LTC recipients showed high possibilities to be rehospitalized and resent to emergency service within 1 year after diagnosis. Apart from the comorbidity and stroke severity, both the physical and mental functional disabilities and caregiving resources predicted the outcomes of the utilization.Conclusions: For stroke survivors, both severe functional impairments and cognitive impairments were found as important factors for healthcare utilizations. These results regarding reserving functional abilities deserve our consideration in making the decision on the ongoing LTC policy reform in the aged society of Taiwan.

To limit the spread of the SARS-CoV-2 (COVID-19) outbreak, humans have been significantly restricted in their ability to travel and interact with others worldwide. Consequently, dermatology conferences were forced to adapt to such changes. The aim of this study is to investigate the impact of COVID-19 on international dermatology conferences. We retrospectively investigated decisions made for international dermatology conferences scheduled for 2020. Thirty-three major conferences were analyzed. Their data were obtained from their respective websites (data was accessed 2 June 2021). Among 33 conferences analyzed, 13 (39.4%) were conducted as scheduled, nine (27.3%) were canceled, eight (24.3%) were postponed to 2021 or 2022, and three (9.1%) were delayed but conducted in 2020. The number of the cancellation (44.4%) and postponement (75%) was the largest in the second quarter of the year. During the fourth quarter, most conferences were held on schedule (70%) but were run virtually. Eight out of 13 virtual conferences shortened their duration (61.5%). Most (90.9%) conferences have decided on the schedule of their meetings for 2021 or 2022 while three (9.1%) remain undecided. Twelve (40%) are planned to run virtually, eight (26.7%) have opted for a hybrid form, five (16.7%) are planned to run in-person, four (13.3%) have not decided on the format, and one (3.3%) has been canceled. Virtual and hybrid conference formats have facilitated people to share knowledge despite the travel restrictions posed by the COVID-19 pandemic. Such formats are environmentally friendly, are able to attract a large audience, and save delegates time and costs involved in attending. Therefore, virtual platforms should continue to be integrated within conferences in the post-pandemic era.

One of the central landmarks of learning to read is the emergence of orthographic processing (i.e., the encoding of letter identity and letter order): it constitutes the necessary link between the low-level stages of visual processing and the higher-level processing of words. Regarding the processing of letter position, many experiments have shown worse performance in various tasks for the transposed-letter pair judge-JUDGE than for the orthographic control jupte-JUDGE. Importantly, 4-y.o. pre-literate children also show letter transposition effects in a same-different task: TZ-ZT is more error-prone than TZ-PH. Here, we examined whether this effect with pre-literate children is related to the cognitive and linguistic skills required to learn to read. Specifically, we examined the relation of the transposed-letter in a same-different task with the scores of these children in phonological, alphabetic and metalinguistic awareness, linguistic skills, and basic cognitive processes. To that end, we used a standardized battery to assess the abilities related with early reading acquisition. Results showed that the size of the transposed-letter effect in pre-literate children was strongly associated with the sub-test on basic cognitive processes (i.e., memory and perception) but not with the other sub-tests. Importantly, identifying children who may need a pre-literacy intervention is crucial to minimize eventual reading difficulties. We discuss how this marker can be used as a tool to anticipate reading difficulties in beginning readers.

Protein localization in cells has been analyzed by fluorescent labeling using indirect immunofluorescence and fluorescent protein tagging. However, the relationships between the localization of different proteins had not been analyzed using artificial intelligence. Here, we applied convolutional networks for the prediction of localization of the cytoskeletal proteins from the localization of the other proteins. Lamellipodia are one of the actin-dependent subcellular structures involved in cell migration and are mainly generated by the Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 2 (WAVE2) and the membrane remodeling I-BAR domain protein IRSp53. Focal adhesion is another actin-based structure that contains vinculin protein and promotes lamellipodia formation and cell migration. In contrast, microtubules are not directly related to actin filaments. The convolutional network was trained using images of actin filaments paired with WAVE2, IRSp53, vinculin, and microtubules. The generated images of WAVE2, IRSp53, and vinculin were highly similar to their real images. In contrast, the microtubule images generated from actin filament images were inferior without the generation of filamentous structures, suggesting that microscopic images of actin filaments provide more information about actin-related protein localization. Collectively, this study suggests that image translation by the convolutional network can predict the localization of functionally related proteins, and the convolutional network might be used to describe the relationships between the proteins by their localization.

Background: Most research in genomics of Parkinson’s disease (PD) has been done in subjects of European ancestry, leading to sampling bias and leaving Latin American populations underrepresented. We sought to clinically characterize PD patients of Costa Rican origin and to sequence familial PD and atypical parkinsonism-associated genes in cases and controls. Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, and motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, and ATP13A2. Results: Mean age of PD probands was 62.12 ± 13.51 years; 57.6% were male. The frequency of risk and protective factors averaged ∼45%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders, and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD; six were located between amino acids p.1620 and 1623 in the C-terminal-of-ROC (COR) domain of Lrrk2. Non-synonymous GBA variants (p.T369M, p.N370S, and p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R. Discussion: This is the first study that describes sociodemographics, risk factors, clinical presentation, and genetics of Costa Rican patients with PD, adding information to genomics research in a Latino population. Antecedentes: la mayor parte de la investigación en genómica de la enfermedad de Parkinson (EP) se ha realizado en sujetos de ascendencia europea, lo que provoca un sesgo de muestreo y deja a las poblaciones latinoamericanas infrarrepresentadas. Buscamos caracterizar clínicamente a los pacientes con EP de origen costarricense y secuenciar la EP familiar y los genes asociados con el parkinsonismo atípico en casos y controles. Métodos: Inscribimos a 118 pacientes con EP con 97 controles no relacionados. La información recopilada incluyó datos demográficos, exposición a factores de riesgo y de protección, y evaluaciones motoras y cognitivas. Se secuenciaron las regiones codificantes y no traducidas en la EP familiar y los genes asociados con el parkinsonismo atípico, incluidos GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C y ATP13A2. Resultados: La edad media de los probandos de EP fue de 62,12 ± 13,51 años; El 57,6% eran hombres. La frecuencia de los factores de riesgo y protección promedió ~ 45%. La actividad física se correlacionó significativamente con un mejor rendimiento motor a pesar de años de enfermedad. El aumento de años de educación se asoció significativamente con una mejor función cognitiva, mientras que las alucinaciones, las caídas, los trastornos del estado de ánimo y el consumo de café se correlacionaron con un peor rendimiento cognitivo. No identificamos una asociación entre los genes probados y la EP ni ninguna variante heterocigótica homocigótica o compuesta dañina. Las variantes raras en LRRK2 se asociaron nominalmente con la EP; seis estaban ubicados entre los aminoácidos p.1620 y 1623 en el dominio C-terminal-de-ROC (COR) de Lrrk2. Se identificaron variantes de GBA no sinónimas (p.T369M, p.N370S y p.L444P) en tres individuos sanos. Un paciente con EP portaba una variante patógena de GCH1, p.K224R. Universidad de Costa Rica/[837-B5-304]/UCR/Costa Rica Canadian Consortium on Neurodegeneration in Aging/[]/CCNA/Canadá Canada First Research Excellence Fund/[]/CFREF/Canadá Healthy Brains for Healthy Lives/[]/HBHL/Canadá UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN) UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicina

Using the COVID-19 database of Johns Hopkins University, this study examines the determinants of the case fatality rate of COVID-19. We consider various potential determinants of the mortality risk of COVID-19 in 120 countries. The Ordinary Least Squares (OLS) and the Kernel-based Regularized Least Squares (KRLS) estimations show that internal and external conflicts are positively related to the case fatality rates. This evidence is robust to the exclusion of countries across different regions. Thus, the evidence indicates that conflict may explain significant differences in the case fatality rate of COVID-19 across countries.

Recently hospitalized older people are at risk of falls and face barriers to undertaking fall prevention strategies after they return home from hospital. The authors examined the effects of tailored education delivered by physiotherapists on the knowledge (capability) and the motivation of older people to engage in fall prevention after hospital discharge. Utilizing data gathered from a recent trial, data was analyzed from 390 people who were 60 years and over without impaired cognition (>7/10 abbreviated mental test score) and discharged from three Australian hospitals. Motivation and capability were measured at baseline in the hospital and at 6-months after hospital discharge by blinded assistants using structured surveys. Bivariate analysis using generalized linear modeling explored the impact of education on the capability and motivation. Engagement in fall prevention strategies was entered as an independent variable during analysis to determine associations with capability and motivation. The education significantly improved capability [−0.4, 95% CI (−0.7, −0.2), p < 0.01] and motivation [−0.8, 95% CI (−1.1, −0.5), p < 0.01] compared with social-control at the time of hospital discharge. In contrast, social-control participants gained capability and motivation over the 6-months, and no significant differences were found between groups in capability [0.001, 95% CI (−0.2, 0.2), p = 0.9] and motivation [−0.01, 95% CI (−0.3, 0.3), p = 0.9] at follow-up. Tailored fall prevention education is recommended around hospital discharge. Participants still needed to overcome barriers to falls prevention engagement post hospitalization. Thus, tailored education along with direct clinical services such as physiotherapy and social supports is warranted for older people to avoid falls and regain function following hospitalization.

Nerve growth factor (NGF) stimulates numerous cellular physiological processes, including growth, differentiation, and survival, and maintains the phenotype of several neuronal types. Most of these NGF-induced processes require adaptation of the secretory pathway since they involve extensive remodeling of membranes and protein redistribution along newly formed neuritic processes. CREB3 transcription factors have emerged as signaling hubs for the regulation of numerous genes involved in the secretory pathway and Golgi homeostasis, integrating stimuli from multiple sources to control secretion, posttranslational modifications and trafficking of proteins. Although recent studies have focused on their role in the central nervous system, little is known about their participation in cell differentiation. Therefore, we aimed to analyze the expression and signaling mechanism of CREB3 transcription factor family members, using the NGF-induced PC12 cell differentiation model. Results show that NGF treatment causes Golgi enlargement and a parallel increased expression of proteins and mRNAs encoding for proteins required for membrane transport (transport factors). Additionally, a significant increase in CREB3L2 protein and mRNA levels is detected in response to NGF. Both MAPK and cAMP signaling pathways are required for this response. Interestingly, CREB3L2 overexpression hampers the NGF-induced neurite outgrowth while its inhibition enhances the morphological changes driven by NGF. In agreement, CREB3L2 overexpressing cells display higher immunofluorescence intensity of Rab5 GTPase (a negative regulator of PC12 differentiation) than control cells. Also, Rab5 immunofluorescence levels decrease in CREB3L2-depleted cells. Taken together, our findings imply that CREB3L2 is an important downstream effector of NGF-activated pathways, leading to neuronal differentiation.

Purpose: Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, yet glaucoma can continue to progress despite controlled IOP. Thus, development of glaucoma neurotherapeutics remains an unmet need. Scutellarin is a flavonoid that can exert neuroprotective effects in the eye and brain. Here, we investigated the neurobehavioral effects of scutellarin treatment in a chronic IOP elevation model.Methods: Ten adult C57BL/6J mice were unilaterally injected with an optically clear hydrogel into the anterior chamber to obstruct aqueous outflow and induce chronic IOP elevation. Eight other mice received unilateral intracameral injection of phosphate-buffered saline only. Another eight mice with hydrogel-induced unilateral chronic IOP elevation also received daily oral gavage of 300 mg/kg scutellarin. Tonometry, optical coherence tomography, and optokinetics were performed longitudinally for 4 weeks to monitor the IOP, retinal nerve fiber layer thickness, total retinal thickness, visual acuity, and contrast sensitivity of both eyes in all three groups.Results: Intracameral hydrogel injection resulted in unilateral chronic IOP elevation with no significant inter-eye IOP difference between scutellarin treatment and untreated groups. Upon scutellarin treatment, the hydrogel-injected eyes showed less retinal thinning and reduced visual behavioral deficits when compared to the untreated, hydrogel-injected eyes. No significant difference in retinal thickness or optokinetic measures was found in the contralateral, non-treated eyes over time or between all groups.Conclusion: Using the non-invasive measuring platform, oral scutellarin treatment appeared to preserve retinal structure and visual function upon chronic IOP elevation in mice. Scutellarin may be a novel neurotherapeutic agent for glaucoma treatment.

Objective: Investigate whether machine learning can predict pulmonary complications (PPCs) after emergency gastrointestinal surgery in patients with acute diffuse peritonitis.Methods: This is a secondary data analysis study. We use five machine learning algorithms (Logistic regression, DecisionTree, GradientBoosting, Xgbc, and gbm) to predict postoperative pulmonary complications.Results: Nine hundred and twenty-six cases were included in this study; 187 cases (20.19%) had PPCs. The five most important variables for the postoperative weight were preoperative albumin, cholesterol on the 3rd day after surgery, albumin on the day of surgery, platelet count on the 1st day after surgery and cholesterol count on the 1st day after surgery for pulmonary complications. In the test group: the logistic regression model shows AUC = 0.808, accuracy = 0.824 and precision = 0.621; Decision tree shows AUC = 0.702, accuracy = 0.795 and precision = 0.486; The GradientBoosting model shows AUC = 0.788, accuracy = 0.827 and precision = 1.000; The Xgbc model shows AUC = 0.784, accuracy = 0.806 and precision = 0.583. The Gbm model shows AUC = 0.814, accuracy = 0.806 and precision = 0.750.Conclusion: Machine learning algorithms can predict patients' PPCs with acute diffuse peritonitis. Moreover, the results of the importance matrix for the Gbdt algorithm model show that albumin, cholesterol, age, and platelets are the main variables that account for the highest pulmonary complication weights.

Innsbruck Medical University Hospital, Austria, provides the highest level of care for a region of approximately 1.8 million people. During the early COVID-19 outbreak in spring 2020 surgical activity was drastically reduced with the prime goal of preserving hospital capacities, especially intensive care beds. We conducted a retrospective analysis of surgical activities performed at Innsbruck Medical University Hospital during the lockdown period from March 15 to April 14, 2020 and compared these activities to the same period during the previous 5 years. Total surgical activity was reduced by 65.4% compared to the same period during the previous 5 years (p < 0.001); elective surgeries were reduced by 88.7%, acute surgeries by 35.3% and oncological surgeries by 47.8% compared to the previous 5 years (all p < 0.001). This dramatic decrease in acute and oncological surgeries can most likely be ascribed to the fact that many patients avoided health care facilities because of the strict stay-at-home policy and/or the fear of contracting SARS-CoV-2 in the hospital. In view of future waves, the population should be encouraged to seek medical help for acute symptoms and to attend cancer screening programs.

Emotional exhaustion in the context of vulnerability to burnout is a part of the universal narrative of high stress and systematically reported in healthcare professionals. The sense of coherence (SOC) is a salutogenic construct, operationalized by A. Antonovsky as a generalized resistance resource (GRR) to stress in three dimensions: meaningfulness (Me), the desire of a person to be motivated to cope; comprehensibility (C), the belief that the challenge is understood; and manageability (Ma), the belief that coping resources are available. The relation between SOC and the dimensions of burnout—Emotional Exhaustion (EE), Depersonalization (D), and Personal Accomplishment (PA)—is a part of salutogenic functioning, which reveals the inner motivation and self-organization of the psycho-emotional energetic resource. This study traces the salutogenic functioning of Bulgarian healthcare professionals during the pandemic. A general psychological background of coherence and exhaustion has been identified. All components of the SOC were positively correlated to Personal Accomplishment. Emotional Exhaustion and Depersonalization correlated negatively with coherence. SOC was validated as a possible determinant to predict the reduction of exhaustion and depersonalization as well as high levels of professional performance. The dimension of Meaningfulness in the coherence phenomenon was demonstrated to have the highest predictive value for professional burnout.