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For diversity to exist in the medical graduate workforce, students from all backgrounds should have equitable opportunities of employment. Specialties have utilized a minimal threshold for USMLE Step 1 score when screening applicants for residency interviews. The OHSU SOM class of 2021 completed a 14-question voluntary survey on their Step 1 score and the following non-modifiable risk factors: Adverse Childhood Experience score (ACEs), sex, gender, Underrepresented in Medicine status (URiM), family income during adolescence, highest degree held by a guardian, discrimination experience during medical school, federal/state assistance use, and rural versus urban primary home. Descriptive statistics and unadjusted risk ratios were applied to study the relation between Step 1 score and non-modifiable risk factors as well as certain non-modifiable risk factors and ACEs ≥ 3. The mean Step 1 score was 230 (213, 247). Of the students, 28.2% identified ACEs ≥ 3, 13.6% were considered URiM, and 65.4% were female. URiM were 2.34 (1.30, 4.23),females were 2.77 (1.06-7.29), and those who experienced discrimination in medical school were 4.25 (1.85, 9.77) times more likely to have ACEs ≥ 3. Students who had ACEs ≥ 3 were 3.58 (1.75, 7.29) times less likely to meet a minimal threshold for residency interviews of 220. These are the first results to demonstrate a relationship between Step 1 score and ACEs. Those who identified as URiM, females, and those who experienced discrimination in medical school were at a higher risk of ACEs of ≥ 3. Step 1 transitioned to pass/fail in January 2022. However, the first application cycle that residencies will see pass/fail scoring is 2023-2024, and fellowships will continue to see scored Step 1 until, at the earliest, the 2026-2027 application cycle. These data contribute to a foundation of research that could apply to Step 2CK testing scores, and help to inform decisions about the diversity and equity of the residency interview process.

Background: Introverted individuals comprise up to half of the population, but are often overlooked in a culture that privileges extraversion. This misunderstanding of introversion has downstream effects for introverts in academic medicine, including lower grades on clinical rotations, increased stress, and under-representation in leadership positions., Aims: To increase support for and awareness of the unique strengths of introverted individuals at all stages of a career in academic medicine., Description: This article offers twelve tips, based in the educational, business, and personality literature, to empower introverted students, residents, and faculty members for success in academic medicine. While many of the tips apply broadly, certain tips may be more relevant to those in a particular career stage., Conclusion: Increased understanding of the natural tendencies and strengths of introversion will promote a more inclusive working environment for all personality types in medicine and allow introverts at all levels of training and practice to thrive.

Purpose: To examine the stability and switching patterns of student career interests over the course of medical school., Method: From 2001 through 2004, during the first two weeks of classes, a survey on career interest was distributed to first-year students in 15 classes at eight Canadian medical schools. Students indicated interest in eight broad career paths (emergency medicine, family medicine, internal medicine, obstetrics-gynecology, pediatrics, psychiatry, surgery, and "other") and ranked their top three. Following these students' residency match three to four years later, student residency career choice was linked to their career interest at medical school entry. For students whose career interests switched be-tween medical school entry and exit, switching patterns were examined in terms of careers' matching difficulty scores (MDSs)., Results: Of 1,941 eligible students, 1,542 contributed to the final analysis. Family medicine, internal medicine, and surgery had the greatest student interest at both the beginning and end of medical school. Family medicine, surgery, obstetrics-gynecology, psychiatry, and "other" careers showed a net gain of student interest during medical school with the remaining careers showing a loss of interest. The most stable careers were family medicine, surgery, and internal medicine. The least stable were pediatrics and obstetrics-gynecology. Students tended to switch between careers with similar MDSs., Conclusions: Student career choice is relatively stable with a number of careers showing approximately 50% of stability from the entrance to the exit of medical school. Students tend to switch to careers with similar MDS, but some specific switching patterns exist.

Background: Poor communication between referring clinicians and specialists may lead to inefficient use of specialist services. San Francisco General Hospital implemented an electronic referral system (eReferral) that facilitates iterative pre-visit communication between referring and specialty clinicians to improve the referral process., Objective: The purpose of the study was to determine the impact of eReferral (compared with paper-based referrals) on specialty referrals., Design: The study was based on a visit-based questionnaire appended to new patient charts at randomly selected specialist clinic sessions before and after the implementation of eReferral., Participants: Specialty clinicians., Main Measures: The questionnaire focused on the self-reported difficulty in identifying referral question, referral appropriateness, need for and avoidability of follow-up visits., Key Results: We collected 505 questionnaires from speciality clinicians. It was difficult to identify the reason for referral in 19.8% of medical and 38.0% of surgical visits using paper-based methods vs. 11.0% and 9.5% of those using eReferral (p-value 0.03 and <0.001). Of those using eReferral, 6.4% and 9.8% of medical and surgical referrals using paper methods vs. 2.6% and 2.1% were deemed not completely appropriate (p-value 0.21 and 0.03). Follow-up was requested for 82.4% and 76.2% of medical and surgical patients with paper-based referrals vs. 90.1% and 58.1% of eReferrals (p-value 0.06 and 0.01). Follow-up was considered avoidable for 32.4% and 44.7% of medical and surgical follow-ups with paper-based methods vs. 27.5% and 13.5% with eReferral (0.41 and <0.001)., Conclusion: Use of technology to promote standardized referral processes and iterative communication between referring clinicians and specialists has the potential to improve communication between primary care providers and specialists and to increase the effectiveness of specialty referrals.

Objective: Development and validation of a questionnaire that measures patients' experiences of collaboration between general practitioners (GPs) and specialists., Methods: A questionnaire was developed using the method of the consumer quality index and validated in a cross-sectional study among a random sample of patients referred to medical specialists in the Netherlands. Validation included factor analysis, ascertain internal consistency, and the discriminative ability., Results: The response rate was 65% (1404 patients). Exploratory factor analysis indicated that four domains could be distinguished (i.e. GP Approach; GP Referral; Specialist; Collaboration). Cronbach's alpha coefficients ranged from 0.51 to 0.93 indicating sufficient internal consistency to make comparison of groups of respondents possible. The Pearson correlation coefficients between the domains were <0.4, except between the domains GP Approach and GP Referral. All domains clearly produced discriminating scores for groups with different characteristics., Conclusions: The Consumer Quality Index (CQ-index) Continuum of Care can be a useful instrument to assess aspects of the collaboration between GPs and specialists from patients' perspective., Practice Implications: It can be used to give feedback to both medical professionals and policy makers. Such feedback creates an opportunity for implementing specific improvements and evaluating quality improvement projects., (2009 Elsevier Ireland Ltd.)

Background: Given the looming shortage of physicians in Canada, we wished to determine how closely the career preference of students entering Canadian medical schools was aligned with the current physician mix in Canada., Methods: Career choice information was collected from a survey of 2,896 Canadian medical students upon their entry to medical school. The distribution of career choices of survey respondents was compared to the current physician specialty mix in Canada., Results: We show that there is a clear mismatch between student career choice at medical school entry and the current specialty mix of physicians in Canada. This mismatch is greatest in Urban Family Medicine with far fewer students interested in this career at medical school entry compared to the current proportion of practicing physicians. There are also fewer students interested in Psychiatry than the current proportion of practicing physicians., Conclusion: This mismatch between the student interest and the current proportion of practicing physicians in the various specialties in Canada is particularly disturbing in the face of the current sub-optimal distribution of physicians. If nothing is done to correct this mismatch of student interest in certain specialties, shortages and misdistributions of physicians will be further amplified. Studies such as this can give a window into the future health human resources challenges for a nation.

Data were gathered through a random national mail survey of 3000 US osteopathic physicians. Nine hundred and fifty-five questionnaires were usable for analysis. Through open-ended questions, osteopathic physicians identified philosophic and practice differences that distinguished them from their allopathic counterparts, and whether they believed the use of osteopathic manipulative treatment (OMT), a key identifiable feature of the osteopathic profession, was appropriate in their specialty. Seventy-five percent of the respondents to the question regarding philosophic differences answered positively, and 41 percent of the follow-up responses indicated that holistic medicine was the most distinguishing characteristic of their profession. In response to the question on practice differences, 59 percent of the respondents believed they practiced differently from allopathic physicians, and 72 percent of the follow-up responses indicated that the osteopathic approach to treatment was a primary distinguishing feature, mainly incorporating the application of OMT, a caring doctor-patient relationship, and a hands-on style. More respondents who specialized in osteopathic manipulative medicine and family practice perceived differences between them and their allopathic counterparts than did other practitioners. Almost all respondents believed OMT was an efficacious treatment, but 19 percent of all respondents felt use of OMT was inappropriate in their specialty. Thirty-one percent of the pediatricians and 38 percent of the non-primary care specialists shared this view. Eighty-eight percent of the respondents had a self-identification as osteopathic physicians, but less than half felt their patients identified them as such. When responses are considered in the context of all survey respondents (versus only those who provided open-ended responses) not a single philosophic concept or resultant practice behavior had concurrence from more than a third of the respondents as distinguishing osteopathic from allopathic medicine. Rank and file osteopathic practitioners seem to be struggling for a legitimate professional identification. The outcome of this struggle is bound to have an impact on health care delivery in the US., (Copyright 2002 Elsevier Science Ltd.)

Abstract Most published prediction models for Coronavirus Disease 2019 (COVID-19) were poorly reported, at high risk of bias, and heterogeneous in model performance. To tackle methodological challenges faced in previous prediction studies, we investigated whether model updating and extending improves mortality prediction, using the Intensive Care Unit (ICU) as a proxy. All COVID-19 patients admitted to seven ICUs in the Euregio-Meuse Rhine during the first pandemic wave were included. The 4C Mortality and SEIMC scores were selected as promising prognostic models from an external validation study. Five predictors could be estimated based on cohort size. TRIPOD guidelines were followed and logistic regression analyses with the linear predictor, APACHE II score, and country were performed. Bootstrapping with backward selection was applied to select variables for the final model. Additionally, shrinkage was performed. Model discrimination was displayed as optimism-corrected areas under the ROC curve and calibration by calibration slopes and plots. The mortality rate of the 551 included patients was 36%. Discrimination of the 4C Mortality and SEIMC scores increased from 0.70 to 0.74 and 0.70 to 0.73 and calibration plots improved compared to the original models after updating and extending. Mortality prediction can be improved after updating and extending of promising models.

Abstract Over 700,000 people die by suicide annually. Collecting longitudinal fine-grained data about at-risk individuals, as they occur in the real world, can enhance our understanding of the temporal dynamics of suicide risk, leading to better identification of those in need of immediate intervention. Self-assessment questionnaires were collected over time from 89 at-risk individuals using the EMMA smartphone application. An artificial intelligence (AI) model was trained to assess current level of suicidal ideation (SI), an early indicator of the suicide risk, and to predict its progression in the following days. A key challenge was the unevenly spaced and incomplete nature of the time series data. To address this, the AI was built on a missing value imputation algorithm. The AI successfully distinguished high SI levels from low SI levels both on the current day (AUC = 0.804, F1 = 0.625, MCC = 0.459) and three days in advance (AUC = 0.769, F1 = 0.576, MCC = 0.386). Besides past SI levels, the most significant questions were related to psychological pain, well-being, agitation, emotional tension, and protective factors such as contacts with relatives and leisure activities. This represents a promising step towards early AI-based suicide risk prediction using a smartphone application.

Abstract Reading requires the transformation of a complex array of visual features into sounds and meaning. For deaf signers who experience changes in visual attention and have little or no access to the sounds of the language they read, understanding the visual constraints underlying reading is crucial. This study aims to explore a fundamental aspect of visual perception intertwined with reading: the crowding effect. This effect manifests as the struggle to distinguish a target letter when surrounded by flanker letters. Through a two-alternative forced choice task, we assessed the recognition of letters and symbols presented in isolation or flanked by two or four characters, positioned either to the left or right of fixation. Our findings reveal that while deaf individuals exhibit higher accuracy in processing letters compared to symbols, their performance falls short of that of their hearing counterparts. Interestingly, despite their proficiency with letters, deaf individuals didn’t demonstrate quicker letter identification, particularly in the most challenging scenario where letters were flanked by four characters. These outcomes imply the development of a specialized letter processing system among deaf individuals, albeit one that may subtly diverge from that of their hearing counterparts.

Abstract Seaweed farming is widely promoted as an approach to mitigating climate change despite limited data on carbon removal pathways and uncertainty around benefits and risks at operational scales. We explored the feasibility of climate change mitigation from seaweed farming by constructing five scenarios spanning a range of industry development in coastal British Columbia, Canada, a temperate region identified as highly suitable for seaweed farming. Depending on growth rates and the fate of farmed seaweed, our scenarios sequestered or avoided between 0.20 and 8.2 Tg CO2e year−1, equivalent to 0.3% and 13% of annual greenhouse gas emissions in BC, respectively. Realisation of climate benefits required seaweed-based products to replace existing, more emissions-intensive products, as marine sequestration was relatively inefficient. Such products were also key to reducing the monetary cost of climate benefits, with product values exceeding production costs in only one of the scenarios we examined. However, model estimates have large uncertainties dominated by seaweed production and emissions avoided, making these key priorities for future research. Our results show that seaweed farming could make an economically feasible contribute to Canada’s climate goals if markets for value-added seaweed based products are developed. Moreover, our model demonstrates the possibility for farmers, regulators, and researchers to accurately quantify the climate benefits of seaweed farming in their regional contexts.

Abstract Background Previous studies have produced conflicting results concerning the extent of magnitude representation deficit and its relationship with arithmetic achievement in children with 22q11.2 deletion syndrome. More specifically, it remains unclear whether deficits are restricted to visuospatial content or are more general and whether they could explain arithmetical impairment. Methods Fifteen 5- to 12-year-old children with 22q11.2 deletion syndrome and 23 age-matched healthy controls performed a non-symbolic magnitude comparison task. Depending on the trial, participants had to compare stimuli with high or low visuospatial load (visuospatial stimuli or temporal sequence of visual stimuli). The participants also completed a battery of arithmetic skills (ZAREKI-R) and a battery of global cognitive functioning (WISC-V or WPPSI-IV), from which working memory and visuospatial indices were derived. Results Children with 22q11.2DS responded as fast as healthy controls did but received fewer correct responses, irrespective of visuospatial load. In addition, their performance in the non-symbolic magnitude comparison task did not correlate with the ZAREKI total score, while the working memory index did. Conclusion Children with 22q11.2DS might suffer from a global magnitude representation deficit rather than a specific deficit due to visuospatial load. However, this deficit alone does not seem to be related to arithmetic achievement. Working memory might be a better concern of interest in favoring arithmetic skills in patients with 22q11.2 deletion syndrome. Trial registration Clinicaltrials, NCT04373226 . Registered 16 September 2020.

Background The zoonotic infection caused by tapeworms Echinococcus is a neglected tropical disease in poor regions with limited access to suitable sanitary conditions. Hydatid cysts produced by Echinococcus granulosus use fatty-acid-binding proteins (FABP) to obtain the fatty acids and cholesterol necessary for their survival from the host. In this work, we analyzed the behaviour of saturated, monounsaturated, and polyunsaturated fatty acids against EgFABP1. Methods We used computational biology and chemistry techniques and binding free energy estimations by molecular mechanics generalized Born surface area (MM/GBSA). Results This research has enabled us to clarify the EgFABP1 isoforms identified in the database, suggesting their potential involvement in diverse cellular activities of Echinococcus granulosus. Conversely, examining the global and local chemical reactivity of 14 fatty acids revealed that liposolubility is contingent upon the degree of unsaturation in the FAs. Additionally, FAs exhibited acceptable levels of oral absorption and bioavailability. The binding of EgFABP1 with FAs analyzed by molecular dynamics simulation showed us that these are highly stable, where the best affinity was with docosahexaenoic acid. Conclusions Our results suggest that the action of fatty acids could play an interesting role in detecting early Echinococcus granulosus.

Background Although the COVID-19 pandemic has diminished in intensity, the virus continues to circulate globally. The SARS-CoV-2 main protease (Mpro) is a key enzyme in the life cycle of the virus, making it important for the development of treatments against future variants of the virus. In this work, Peruvian natural compounds were evaluated against different mutations of the SARS-CoV-2 Mpro. Methods In silico techniques such as virtual screening, all-atom molecular dynamics simulations, and energy estimation analysis were applied. Results Of the tested compounds by virtual screening, rutin was identified as the best binding agent against the different proposed Mpro mutations. In addition, computational simulations and energy estimation analysis demonstrated the high structural and energetic stability between the Mpro-rutin systems. Conclusions Overall, our study identified rutin as the most promising compound with a strong affinity for various Mpro mutations, potentially playing a key role in the development of new treatments for emerging viral variants.

Introduction Home-based, virtually-supported care models may represent the most efficient and scalable approach to delivering prehabilitation services. However, virtual approaches to prehabilitation are understudied. This manuscript describes the protocol for an internal pilot randomised controlled trial of a virtually-delivered, multimodal prehabilitation intervention.Methods and analysis We will conduct a pragmatic, individual patient, internal pilot randomised controlled trial of home-based, virtually supported, multimodal prehabilitation compared with standard perioperative care in adults undergoing elective, inpatient thoracic, abdominal, pelvic and vascular surgery at five Canadian hospitals. Participants will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of 3–12 weeks of a home-based, multimodal (exercise, nutrition and psychosocial support) prehabilitation programme supported through an online platform. The primary feasibility outcomes and their progression targets are (1) monthly recruitment of>6 participants at each centre, (2) intervention adherence of>75%, (3) retention of>90% of participants at the patient-reported primary outcome point of 30-days after surgery and (4) elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial. A sample size of 144 participants will be adequate to estimate recruitment, adherence and retention rates with acceptable precision. All participants will be followed to either death or up to 1 year. As an internal pilot, if no substantive changes to the trial or intervention design are required, pilot participant outcome data will migrate, unanalysed by allocation, to the future full-scale trial.Ethics and dissemination Ethical approval has been granted by Clinical Trials Ontario (Project ID: 4479) and our ethics review board (Protocol Approval #20230399–01T). Results will be disseminated through presentations at scientific conferences, peer-reviewed publications, partner organisations and engagement of social and traditional media.Trial registration number ClinicalTrials.gov identifier NCT06042491. Protocol, V.1.2, dated 6 June 2024.

Sampling and sequencing marine environmental DNA (eDNA) provides a tool that can increase our ability to monitor biodiversity, but movement and mixing of eDNA after release from organisms before collection could affect our inference of species distributions. To assess how conditions at differing spatial scales influence the inferred species richness and compositional turnover, we conducted a paired eDNA metabarcoding and capture (beach seining) survey of fishes on the coast of British Columbia. We found more taxa were typically detected using eDNA compared to beach seining. eDNA identified more taxa with alternative habitat preferences, and this richness difference was greater in areas of high seawater movement, suggesting eDNA has a larger spatial grain influenced by water motion. By contrast, we found that eDNA consistently missed low biomass species present in seining surveys. Spatial turnover of communities surveyed using beach seining differed from that of the eDNA and was better explained by factors that vary at small (10–1000s meters) spatial scales. Specifically, vegetation cover and shoreline exposure explained most species turnover from seining, while eDNA turnover was not explained by those factors and showed a distance decay pattern (a change from 10% to 25% similarity from 2 km to 10 km of distance), suggesting unmeasured environmental variation at larger scales drives its turnover. Our findings indicate that the eDNA sample grain is larger than that of capture surveys. Whereas seining can detect differences in fish distributions at scales of 10s–100s of meters, eDNA can best summarize fish biodiversity at larger scales possibly more relevant to regional biodiversity assessments.

Male germ cells share a common origin across animal species, therefore they likely retain a conserved genetic program that defines their cellular identity. However, the unique evolutionary dynamics of male germ cells coupled with their widespread leaky transcription pose significant obstacles to the identification of the core spermatogenic program. Through network analysis of the spermatocyte transcriptome of vertebrate and invertebrate species, we describe the conserved evolutionary origin of metazoan male germ cells at the molecular level. We estimate the average functional requirement of a metazoan male germ cell to correspond to the expression of approximately 10,000 protein-coding genes, a third of which defines a genetic scaffold of deeply conserved genes that has been retained throughout evolution. Such scaffold contains a set of 79 functional associations between 104 gene expression regulators that represent a core component of the conserved genetic program of metazoan spermatogenesis. By genetically interfering with the acquisition and maintenance of male germ cell identity, we uncover 161 previously unknown spermatogenesis genes and three new potential genetic causes of human infertility. These findings emphasize the importance of evolutionary history on human reproductive disease and establish a cross-species analytical pipeline that can be repurposed to other cell types and pathologies.

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults, but it can also cause childhood-onset complications. The presentation and clinical course of young adults who present due to BAV complications are relatively uncharacterized. In a multicenter study, we found that young people who experience significant complications related to BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early-onset BAV complications.

Abstract Dengue virus (DENV), mainly transmitted by Aedes aegypti mosquitoes, is the most prevalent arbovirus worldwide, representing a public health problem in tropical and subtropical countries. In these areas, antibiotic consumption rises which may impact both mosquito microbiota and dengue transmission. Here, we assessed how the ingestion by Ae. aegypti of therapeutic concentrations of amoxicillin–clavulanic Acid association (Amox/Clav), a broad-spectrum antibiotic used to treat febrile symptoms worldwide, impacted its microbiota. We also evaluated whether simultaneous ingestion of antibiotic and DENV impacted Ae. aegypti ability to transmit this virus. We found that Amox/Clav ingestion impacted microbiota composition in Ae. aegypti and we confirmed such impact in field-collected mosquitoes. Furthermore, we observed that Amox/Clav ingestion enhanced DENV dissemination and transmission by this mosquito at 21 days post-DENV exposure. These findings increase our understanding of factors linked to human hosts that may influence dengue transmission dynamics in regions with mass-drug administration programs.

Objectives Cancer is a leading cause of death in unhoused adults. We sought to examine the association between housing status, stage at diagnosis and all-cause survival following cancer diagnosis at a public hospital.Design Retrospective cohort study examining new cancer diagnoses between 1 July 2011 and 30 June 2021.Setting A public hospital in San Francisco.Exposure Housing status (housed, formerly unhoused, unhoused) was ascertained via a county-wide integrated dataset that tracks both observed and reported homelessness.Methods We reported univariate analyses to investigate differences in demographic and clinical characteristics by housing group. We then constructed Kaplan-Meier curves stratified by housing group to examine unadjusted all-cause mortality. Finally, we used multivariable Cox proportional hazards models to compare the hazard rate of mortality for each housing status group, adjusting for demographic and clinical factors.Results Our cohort included 5123 patients with new cancer diagnoses, with 4062 (79%) in housed patients, 623 (12%) in formerly unhoused patients and 438 (9%) in unhoused patients. Unhoused and formerly unhoused patients were more commonly diagnosed with stage 4 disease (28% and 27% of the time, respectively, vs 22% of housed patients). After adjusting for demographic and clinical characteristics, unhoused patients with stage 0–3 disease had a 50% increased hazard of death (adjusted HR (aHR) 1.5, 95% CI 1.1 to 1.9; p

Objectives To assess the seroprevalence of infection-acquired SARS-CoV-2 and the mental health of school/daycare staff in the months after reopening of schools in Montreal, Quebec (Canada) in the Fall of 2020 and whether these varied by school and participant characteristics.Design A cross-sectional design based on a convenience sample of schools/daycares and staff was used as the originally planned longitudinal design was no longer feasible due to obstacles in recruitment, for example, teacher’s strike.Setting Forty-nine schools/daycares in four Montreal neighbourhoods from March to October 2021.Participants Three-hundred and sixty-two participants completed both questionnaires and serology tests.Primary and secondary outcome measures SARS-CoV-2 seroprevalence and prevalence of anxiety, depression, resilience and burnout/emotional exhaustion.Results The seroprevalence estimate made representative to the Quebec population of educators was 8.6% (95% CI 5.2 to 13.0). The adjusted seroprevalence in high school was 20% that of elementary school (aRR=0.20, 95% CI 0.07 to 0.58). Thirty per cent of seropositive staff were exposed to a household member with confirmed COVID-19. Prevalence of high emotional exhaustion/burnout was 35%, 44% and 53% in daycare, elementary school and high school staff, respectively. However, moderate/severe anxiety and depression and low resilience did not exceed 18%. After adjusting for confounders, being very afraid of catching COVID-19 at school was associated with moderate–severe anxiety, moderate–severe depression and high emotional exhaustion (aRR=4.4, 95% CI 2.2 to 8.9; aRR=2.8, 95% CI 1.5 to 5.4; aRR=2.2, 95% CI 1.6 to 3.0, respectively).Conclusion The seroprevalence, anxiety and depression among school/daycare staff were comparable to the reported levels in the adult population of Quebec. The prevalence of emotional exhaustion/burnout was high across all school levels and exceeding the average across all occupations in the USA and in teachers in Germany.

Abstract Urinary incontinence is a common complication following radical prostatectomy, as the surgery disturbs critical anatomical structures. This study explored how pudendal nerve (PN) injury affects urinary continence in male rats. In an acute study, leak point pressure (LPP) and external urethral sphincter electromyography (EMG) were performed on six male rats with an intact urethra, the urethra exposed (UE), the PN exposed (NE), and after PN transection (PNT). In a chronic study, LPP and EMG were tested in 67 rats 4 days, 3 weeks, or 6 weeks after sham PN injury, PN crush (PNC), or PNT. Urethras were assessed histologically. Acute PNT caused a significant decrease in LPP and EMG amplitude and firing rate compared to other groups. PNC resulted in a significant reduction in LPP and EMG firing rate 4 days, 3 weeks, and 6 weeks later. EMG amplitude was also significantly reduced 4 days and 6 weeks after PNC. Neuromuscular junctions were less organized and less innervated after PNC or PNT at all timepoints compared to sham injured animals. Collagen infiltration was significantly increased after PNC and PNT compared to sham at all timepoints. This rat model could facilitate preclinical testing of neuroregenerative therapies for post-prostatectomy incontinence.

Abstract Optically pumped magnetometers (OPMs) offer a new wearable means to measure magnetoencephalography (MEG) signals, with many advantages compared to conventional systems. However, OPMs are an emerging technology, thus characterizing and replicating MEG recordings is essential. Using OPM-MEG and SQUID-MEG, this study investigated evoked responses, oscillatory power, and functional connectivity during emotion processing in 20 adults, to establish replicability across the two technologies. Five participants with dental fixtures were included to assess the validity of OPM-MEG recordings in those with irremovable metal. Replicable task-related evoked responses were observed in both modalities. Similar patterns of oscillatory power to faces were observed in both systems. Increased connectivity was found in SQUID-versus OPM-MEG in an occipital and parietal anchored network. Notably, high quality OPM-MEG data were retained in participants with metallic fixtures, from whom no useable data were collected using conventional MEG.

Abstract Background Many applied postgraduate pain training programs are monodisciplinary, whereas interdisciplinary training programs potentially improve interdisciplinary collaboration, which is favourable for managing patients with chronic pain. However, limited research exists on the development and impact of interdisciplinary training programs, particularly in the context of chronic pain. Methods This study aimed to describe the development and implementation of an interdisciplinary training program regarding the management of patients with chronic pain, which is part of a type 1 hybrid effectiveness-implementation study. The targeted groups included medical doctors, nurses, psychologists, physiotherapists, occupational therapists, dentists and pharmacists. An interdisciplinary expert panel was organised to provide its perception of the importance of formulated competencies for integrating biopsychosocial pain management with a cognitive behavioural approach into clinical practice. They were also asked to provide their perception of the extent to which healthcare professionals already possess the competencies in their clinical practice. Additionally, the expert panel was asked to formulate the barriers and needs relating to training content and the implementation of biopsychosocial chronic pain management with a cognitive behavioural approach in clinical practice, which was complemented with a literature search. This was used to develop and adapt the training program to the barriers and needs of stakeholders. Results The interdisciplinary expert panel considered the competencies as very important. Additionally, they perceived a relatively low level of healthcare professionals’ possession of the competencies in their clinical practice. A wide variety of barriers and needs for stakeholders were formulated and organized within the Theoretical Domain Framework linked to the COM-B domains; ‘capability’, ‘opportunity’, and ‘motivation’. The developed interdisciplinary training program, including two workshops of seven hours each and two e-learning modules, aimed to improve HCP’s competencies for integrating biopsychosocial chronic pain management with a cognitive behavioural approach into clinical practice. Conclusion We designed an interdisciplinary training program, based on formulated barriers regarding the management of patients with chronic pain that can be used as a foundation for developing and enhancing the quality of future training programs.

Abstract El Niño-Southern Oscillation (ENSO) teleconnections are an important predictability source for extratropical seasonal climate forecasts. Previous studies suggest that the ENSO teleconnection pattern depends on the ENSO phase (El Niño vs. La Niña) and/or Sea Surface Temperature (SST) pattern (central Pacific vs. eastern Pacific El Niño events). Observations and ensemble simulations with the CNRM-CM6.1 atmospheric general circulation model indicate that only extreme El Niño events (e.g. 1982–1983, 1997–1998, 2015–2016) display a statistically significant eastward shift relative to the well-known Pacific-North American teleconnection pattern that occurs during both central and eastern Pacific moderate El Niño or during La Niña. This specific teleconnection pattern emerges when equatorial SST anomalies are both eastward-shifted and sufficiently large to exceed the deep atmospheric convection threshold over most of the eastern Pacific, resulting in a basin-wide reorganization of tropospheric heat sources. It yields> 0.5 std wet conditions over Western United States (74% likelihood) as well as> 0.5 std warm anomalies over Canada and the Northern United States (71% likelihood), with more consistency across events and ensemble members than for any other El Niño or La Niña type. These findings hold important implications for the seasonal forecasting of El Niño’s impacts on the North American climate.

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform – optically pumped magnetometer-based magnetoencephalography (OPM-MEG) – to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.

El Instituto Nacional de Salud, ha llevado a cabo por primera vez el proceso de identificación de Prioridades Nacionales de Investigación en Salud Bucal a cargo de la Subdirección de Investigación y Laboratorios de Enfermedades No Transmisibles del Centro Nacional de Salud Pública con la asesoría técnica de la Dirección de Investigación e Innovación en Salud y en coordinación con la Dirección Ejecutiva de Salud Bucal de la Dirección General de Intervenciones Estratégicas en Salud Pública del Ministerio de Salud mediante metodología participativa de tres actores claves: investigadores/especialistas, expertos y decisores. El objetivo de este artículo es describir el proceso seguido para la identificación de estas prioridades, el cual comprendió cinco fases: i) identificación de objetivos estratégicos del MINSA, ii) identificación de necesidades de investigación en salud bucal, iii) revisión por expertos y valoración de las necesidades según criterios, iv) priorización (valoración de la lista de prioridades según calificación) y v) presentación de las prioridades. Como resultado se obtuvieron las 12 prioridades que posteriormente fueron aprobadas por Resolución Ministerial N.° 262-2022/MINSA, con un periodo de vigencia 2022–2026. Además, se brindaron recomendaciones para futuros procesos.

Abstract This study investigates the effects of including patients’ clinical information on the performance of deep learning (DL) classifiers for disease location in chest X-ray images. Although current classifiers achieve high performance using chest X-ray images alone, consultations with practicing radiologists indicate that clinical data is highly informative and essential for interpreting medical images and making proper diagnoses. In this work, we propose a novel architecture consisting of two fusion methods that enable the model to simultaneously process patients’ clinical data (structured data) and chest X-rays (image data). Since these data modalities are in different dimensional spaces, we propose a spatial arrangement strategy, spatialization, to facilitate the multimodal learning process in a Mask R-CNN model. We performed an extensive experimental evaluation using MIMIC-Eye, a dataset comprising different modalities: MIMIC-CXR (chest X-ray images), MIMIC IV-ED (patients’ clinical data), and REFLACX (annotations of disease locations in chest X-rays). Results show that incorporating patients’ clinical data in a DL model together with the proposed fusion methods improves the disease localization in chest X-rays by 12% in terms of Average Precision compared to a standard Mask R-CNN using chest X-rays alone. Further ablation studies also emphasize the importance of multimodal DL architectures and the incorporation of patients’ clinical data in disease localization. In the interest of fostering scientific reproducibility, the architecture proposed within this investigation has been made publicly accessible( https://github.com/ChihchengHsieh/multimodal-abnormalities-detection ).

Abstract Pulmonary arterial hypertension is a rare but life-threatening and clinically heterogeneous disease. The diagnostic schedule of this disorder is complex, and no specific indicator of the arterial etiology has been explored. In this study, untargeted plasma metabolomics was applied to evaluate the metabolic fingerprints of pulmonary arterial hypertension patients. Plasma samples were prepared using a new approach, which applies proteinase K during the sample preparation procedure to increase the metabolite coverage. The metabolic fingerprints were determined via LC–MS and subsequently analyzed with the use of both uni- and multivariate statistics. A total of 21 metabolites were discovered to be significantly altered in pulmonary arterial hypertensive patients. The metabolites were mainly related to the phospholipid metabolic pathways. In this study, decreases were found in the phosphatidylcholines (PCs) [PC(32:0), PC(40:7), PC(42:7)], phosphatidylethanolamine PE(18:0/18:2), lysophosphatidylethanolamines (LPEs) [LPE(22:6), LPE(18:2), LPE(18:0), LPE(20:4), LPE(20:1), LPE(20:0)], lysophosphatidylcholine LPC(20:4) and lysophosphatidylserine LPS(19:0), as well as increase of sphingomyelin SM(36:2), in the plasma samples of pulmonary arterial hypertensive patients in comparison to the control group. Besides their function as components of the biological membranes, these metabolites are also involved in the intracellular signaling pathways that are related to cell proliferation and apoptosis. The results obtained during this study confirm the potential of (untargeted) metabolomics to identify the molecular characteristics of the pathophysiology of pulmonary arterial hypertension. The clinical relevance of this study constitutes the selection of a metabolic panel that can potentially detect and properly diagnose the disease.

Abstract Background Early diagnosis of Gaucher disease (GD) allows for disease-specific treatment before significant symptoms arise, preventing/delaying onset of complications. Yet, many endure years-long diagnostic odysseys. We report the development of a machine learning algorithm to identify patients with GD from electronic health records. Methods We utilized Optum’s de-identified Integrated Claims-Clinical dataset (2007–2019) for feature engineering and algorithm training/testing, based on clinical characteristics of GD. Two algorithms were selected: one based on age of feature occurrence (age-based), and one based on occurrence of features (prevalence-based). Performance was compared with an adaptation of the available clinical diagnostic algorithm for identifying patients with diagnosed GD. Undiagnosed patients highly-ranked by the algorithms were compared with diagnosed GD patients. Results Splenomegaly was the most important predictor for diagnosed GD with both algorithms, followed by geographical location (northeast USA), thrombocytopenia, osteonecrosis, bone density disorders, and bone pain. Overall, 1204 and 2862 patients, respectively, would need to be assessed with the age- and prevalence-based algorithms, compared with 20,743 with the clinical diagnostic algorithm, to identify 28 patients with diagnosed GD in the integrated dataset. Undiagnosed patients highly-ranked by the algorithms had similar clinical manifestations as diagnosed GD patients. Conclusions The age-based algorithm identified younger patients, while the prevalence-based identified patients with advanced clinical manifestations. Their combined use better captures GD heterogeneity. The two algorithms were about 10–20-fold more efficient at identifying GD patients than the clinical diagnostic algorithm. Application of these algorithms could shorten diagnostic delay by identifying undiagnosed GD patients.

Abstract Among evolutionary trends shaping phenotypic diversity over macroevolutionary scales, CREA (CRaniofacial Evolutionary Allometry) describes a tendency, among closely related species, for the smaller-sized of the group to have proportionally shorter rostra and larger braincases. Here, we used a phylogenetically broad cranial dataset, 3D geometric morphometrics, and phylogenetic comparative methods to assess the validity and strength of CREA in extinct and living felids. To test for the influence of biomechanical constraints, we quantified the impact of relative canine height on cranial shape evolution. Our results provided support to CREA at the family level. Yet, whereas felines support the rule, big cats, like Pantherinae and Machairodontinae, conform weakly if not at all with CREA predictions. Our findings suggest that Machairodontinae constitute one of the first well-supported exceptions to this biological rule currently known, probably in response to the biomechanical demands and developmental changes linked with their peculiar rostral adaptations. Our results suggest that the acquisition of extreme features concerning biomechanics, evo-devo constraints, and/or ecology is likely to be associated with peculiar patterns of morphological evolution, determining potential exceptions to common biological rules, for instance, by inducing variations in common patterns of evolutionary integration due to heterochronic changes under ratchet-like evolution.

Abstract A renewed interest in the use of psychedelics for treating obsessive compulsive disorder (OCD) has emerged in the last 20 years. But pre-clinical and clinical evidence remain scarce, and little is known about the factor determining the magnitude and persistence of the therapeutic effect. We therefore designed a retrospective online survey to explore, in the general population using psychoactive drugs, their impact on OCD symptoms. We also assessed the attitude of the participants towards the substance in term of frequency of intakes. In a sample of 174 participants, classic psychedelics were reported as the only substances effective at reducing OCD symptoms. In classic psychedelics users, symptoms reduction was associated with the intensity of acute effects, itself correlated to the dose. Reports on the persistence of the therapeutic effect varied from weeks to months, but we could not find any predicting factor. Finally, the occurrence and frequency of subsequent intakes, which seemed to be limited in our sample, were predicted by the magnitude and persistence of the therapeutic effect, respectively. Our observations support the hypothesis of classic psychedelics efficacy in reducing OCD symptoms but a careful evaluation of the persistence of this effect is still needed.

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control genotypes from the Database of Genotypes and Phenotypes were analyzed using identical methods. We filtered the data to select large genic CNVs that were detected by multiple algorithms. Findings were replicated in a BAV cohort with late onset sporadic disease (n = 5040). We identified 3 large and rare (< 1,1000 in controls) CNVs in EBAV probands. The burden of CNVs intersecting with genes known to cause BAV when mutated was increased in case-control analysis. CNVs intersecting with GATA4 and DSCAM were enriched in cases, recurrent in other datasets, and segregated with disease in families. In total, we identified potentially pathogenic CNVs in 9% of EBAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV.

Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007-2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57-0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77-0.78) and ICH models (0.77, 95%CI 0.75-0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data.

IntroductionSmall fiber neuropathy (SFN) is a common cause of neuropathic pain in peripheral neuropathies. Good accessibility of diagnostics and treatment is necessary for an accurate diagnosis and treatment of SFN. Evidence is lacking on the quality performance of the diagnostic SFN service in the Netherlands. Our aim was to determine the patient satisfaction and -accessibility of the diagnostic SFN service, and to identify areas for improvement.MethodsIn a single-center, prospective, survey-based cohort study, 100 visiting patients were asked to fill in the SFN patient satisfaction questionnaire (SFN-PSQ), with 10 domains and 51 items. Cut-off point for improvement was defined as ≥ 25% dissatisfaction on an item. A chi-square test and linear regression analyses was used for significant differences and associations of patient satisfaction.ResultsFrom November 2020 to May 2021, 98 patients with SFN-related complaints filled in the online SFN-PSQ within 20 minutes. In 84% of the patients SFN was confirmed, average age was 55.1 (52.5-57.8) years and 67% was female. High satisfaction was seen in the domains 'Waiting List Period', Chest X-ray', 'Consultation with the Doctor or Nurse Practitioner (NP)', 'Separate Consultation with the Doctor or NP about Psychological Symptoms', and 'General' of the SFN service. Overall average patient satisfaction score was 8.7 (IQR 8-10) on a 1-to-10 rating scale. Main area for improvement was shortening the 8-week period for receiving the results of the diagnostic testing (p < 0.05). General health status was statistically significant associated with patient satisfaction (p < 0.05).ConclusionA good reflection of the high patient satisfaction and -accessibility of the SFN-service is shown, with important points for improvement. These results could help hospitals widely to optimize the logistic and diagnostic pathway of SFN analysis, benchmarking patient satisfaction results among the hospitals, and to improve the quality of care of comparable SFN services.

To identify markers of oocyte competence, we compared the biochemical characteristics of fluid and cells from follicles containing oocytes with different capacities to form an embryo. Follicles (5-6 mm) were dissected, and follicular fluid (FF), granulosa cells (GC), cumulus cells (CC) from immature and mature cumulus-oocyte-complexes (COC) were individually collected. The oocytes were matured, fertilized, and cultured individually until day 8 (D8) of development. On D8, the samples were grouped according to embryo production into those that gave rise to blastocysts (EMB) and those that did not reach the blastocyst stage (NEMB). In CCs from immature and mature COCs and GCs, expression of CASP3, SERPINE2, VCAN, LUM, FSHR, EGFR, PGR, and GHR genes was quantified. Cell-free DNA (cfDNA), progesterone, and estradiol concentrations in the FF were determined. Data were analyzed by Mann-Whitney U test (GraphPad Prism 9). GHR was highly expressed in immature CCs from the EMB group, whereas CASP3 was highly expressed in mature CCs from the NEMB group (P

Introduction Uterine adenomyosis is a benign gynaecological disease that causes physical and psychological problems, impacting on relationships. It is poorly understood and consequently may be diagnosed late. This protocol describes the process of conducting a systematic scoping review to retrieve and describe literature examining the daily experience and impact of living with uterine adenomyosis. It will explore the journey to diagnosis (and perceptions of what this process is like); identify the main concepts currently used in the literature and highlight gaps in knowledge for future research in relevant populations.Methods and analysis Using the Joanna Briggs Institute methodology, the population–concept–context approach is used to form clear review questions. A three-phase search strategy will locate published and unpublished evidence from multiple sources. All articles reporting on the personal experiences of women diagnosed with uterine adenomyosis will be considered. Findings from qualitative, quantitative and mixed-method study designs from all settings will be included, not limited by geography but restricted to English. Documents will be screened by the primary researcher, supported by university supervisors. Search outputs will be presented using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flow diagram. No formal quality appraisal will be conducted. Review findings will be descriptively collated and reported consistent with the Scoping Review Extension of the PRISMA checklist. Patient and public involvement engagement reflected a positive response for the project that this protocol supports.Ethics and dissemination As primary data will not be collected, formal ethical approval is not required. Prepared as part of a professional doctorate thesis, the findings of this study will be disseminated via peer-reviewed publications, conference presentations, support groups and social media networks.

Abstract Background Formal education surrounding abortion care during pre-clinical years of medical school is limited and will likely decrease with the overturning of Roe v. Wade. This study describes and evaluates the impact of an original abortion didactic session implemented during the pre-clinical years of medical school. Methods We implemented a didactic session at the University of California Irvine outlining abortion epidemiology, pregnancy options counseling, standard abortion care, and the current legislative landscape surrounding abortion. The preclinical session also included an interactive, small group case-based discussion. Pre-session and post-session surveys were obtained to evaluate changes in participants’ knowledge and attitudes and to collect feedback for future sessions. Results 92 matched pre- and post-session surveys were completed and analyzed (response rate 77%). The majority of the respondents identified themselves as more “pro-choice” compared to “pro-life” on the pre-session survey. Results reflected significantly increased comfort discussing abortion care and significantly increased knowledge about abortion prevalence and techniques after the session. Qualitative feedback was overwhelmingly positive and reflected participants’ appreciation for the focus on the medical aspects of abortion care as opposed to an ethical discussion. Conclusions Abortion education targeted to preclinical medical students can be implemented effectively by a medical student cohort with institutional support.

OBJECTIVES/GOALS: A Mayo Clinic in Florida committee completes 100+ Scientific Reviews annually through manual e-mail and Excel tracking, placing a manual burden on reviewers and coordinators. REDCap, an electronic data capture system, was leveraged to reduce the administrative burden.#_ftn1 #_ftnref2 METHODS/STUDY POPULATION: Historically, emails were sent by a coordinator to physicians, requesting their initial review and following up with reminders. This process was tracked using Excel, presenting a need to make this process more efficient, so a workgroup was created. To ensure all perspectives were accounted for, the workgroup included the review coordinator, a physician reviewer, and study team members who submit development requests for studies. The process was mapped using the existing Excel spreadsheet, and email templates. Critical data elements were identified, ensuring the database would identify bottlenecks. Two REDCap instruments were then created: one to outline the coordinator workflow and a survey for physician reviewers to complete the scientific reviews. #_ftn2#_ftnref1 RESULTS/ANTICIPATED RESULTS: The workflow is live in REDCap and has effectively processed over 100 scientific reviews in

Abstract The generation of conditional alleles using CRISPR technology is still challenging. Here, we introduce a Short Conditional intrON (SCON, 189 bp) that enables the rapid generation of conditional alleles via one-step zygote injection. In this study, a total of 13 SCON mouse lines were successfully generated by 2 different laboratories. SCON has conditional intronic functions in various vertebrate species, and its target insertion is as simple as CRISPR/Cas9-mediated gene tagging.

Abstract The 2019 global coronavirus (COVID-19) pandemic has brought the world to a grinding halt, highlighting the urgent need for therapeutic and preventive solutions to slow the spread of emerging viruses. The objective of this study was to assess the anti-SARS-CoV-2 effectiveness of 8 FDA-approved cationic amphiphilic drugs (CADs). SARS-CoV-2-infected Vero cells, Calu-3 cells and primary Human Nasal Epithelial Cells (HNEC) were used to investigate the effects of CADs and revealed their antiviral mode of action. Among the CADs tested, desloratadine, a commonly used antiallergic, well-tolerated with no major side effects, potently reduced the production of SARS-CoV-2 RNA in Vero-E6 cells. Interestingly, desloratadine was also effective against HCoV-229E and HCoV-OC43 showing that it possessed broad-spectrum anti-coronavirus activity. Investigation of its mode of action revealed that it targeted an early step of virus lifecycle and blocked SARS-CoV-2 entry through the endosomal pathway. Finally, the ex vivo kinetic of the antiviral effect of desloratadine was evaluated on primary Human Nasal Epithelial Cells (HNEC), showing a significant delay of viral RNA production with a maximal reduction reached after 72 h of treatment. Thus, this treatment could provide a substantial contribution to prophylaxis and systemic therapy of COVID-19 or other coronaviruses infections and requires further studies.

Objectives Depression is associated with problems in functioning in many aspects of life, including parenting. COVID-19 has increased risk factors for depression. We investigated the prevalence of depression among parents during the pandemic and the association with dysfunctional parenting.Design Canadian nationwide cross-sectional study.Setting and participants The 2020 and 2021 Surveys on COVID-19 and Mental Health (SCMH) and the Canadian Community Health Survey (CCHS) (2015‒2019). Responding sample sizes for parents were 3121 for the 2020-SCMH; 1574 for the 2021-SCMH and 6076 for the CCHS.Primary outcome measures All three surveys collected information on symptoms of major depressive disorder (MDD). The SCMH measured harsh parenting.Results Based on data from the 2021-SCMH collected during wave 3 of COVID-19, 14.4% of fathers and 21.2% of mothers screened positive for MDD. These prevalence estimates were similar to those from the 2020-SCMH during wave 2, but at least two times higher than pre-COVID-19 estimates from the CCHS. Multivariate analyses revealed a linear association between MDD and harsh parenting. COVID-19-related stressors were associated with harsh parenting. Among mothers, feeling lonely or isolated because of COVID-19 was a risk factor for harsh parenting; among fathers, being a front-line worker was a risk factor. Meditation was a protective factor for mothers.Conclusions After years of stability, the prevalence of MDD increased substantially among Canadian parents during the pandemic. Ongoing monitoring is vital to determine if elevated levels of depression persist because chronic depression increases the likelihood of negative child outcomes. Programmes aimed at addressing depression and bolstering parenting skills are needed as families continue to face stressors associated with COVID-19.

Background: Cancer patients are highly prone to infectious diseases. While undergoing antineoplastic treatment, the risk of severe symptoms upon infection increases, necessitating efficient protective measures, such as vaccination. For patients receiving radiotherapy, there is no specific information about humoral immunity. During the COVID-19 pandemic, serial antibody measurements were therefore offered to cancer patients, following SARS-CoV-2 vaccination while obtaining radiotherapy. Methods: Out of 74 enrolled patients, 46 met the inclusion criteria. Two cohorts were allocated, depending on an association with chemotherapy or pure radiotherapy. An additional healthy control cohort of 16 healthcare workers was enrolled. All participants followed a two-fold BNT162b2 vaccine schedule. SARS-CoV-2 binding antibodies were measured serially in a 7-day cycle for 35 days and over the long-term, using the Elecsys® Anti-SARS-CoV-2 immunoassay. Results: Cancer patients under pure radiotherapy have a comparable humoral vaccination response and long-term persistency of antibodies to healthy controls. Patients receiving additional chemotherapy show a significantly delayed immune response and decreased antibody titers. The vaccine was well tolerated in all cohorts. Conclusions: Pure radiotherapy in cancer patients does not interfere with the vaccine-induced humoral immune response or other immunogenetic aspects, whereas previous or simultaneous chemotherapy does. Findings are of particular relevance for future epidemic or pandemic scenarios.

Abstract Background Studies often evaluate mental health and well-being in association with individual health behaviours although evaluating multiple health behaviours that co-occur in real life may reveal important insights into the overall association. Also, the underlying pathways of how lifestyle might affect our health are still under debate. Here, we studied the mediation of different health behaviours or lifestyle factors on mental health and its effect on core markers of ageing: telomere length (TL) and mitochondrial DNA content (mtDNAc). Methods In this study, 6054 adults from the 2018 Belgian Health Interview Survey (BHIS) were included. Mental health and well-being outcomes included psychological and severe psychological distress, vitality, life satisfaction, self-perceived health, depressive and generalised anxiety disorder and suicidal ideation. A lifestyle score integrating diet, physical activity, smoking status, alcohol consumption and BMI was created and validated. On a subset of 739 participants, leucocyte TL and mtDNAc were assessed using qPCR. Generalised linear mixed models were used while adjusting for a priori chosen covariates. Results The average age (SD) of the study population was 49.9 (17.5) years, and 48.8% were men. A one-point increment in the lifestyle score was associated with lower odds (ranging from 0.56 to 0.74) for all studied mental health outcomes and with a 1.74% (95% CI: 0.11, 3.40%) longer TL and 4.07% (95% CI: 2.01, 6.17%) higher mtDNAc. Psychological distress and suicidal ideation were associated with a lower mtDNAc of − 4.62% (95% CI: − 8.85, − 0.20%) and − 7.83% (95% CI: − 14.77, − 0.34%), respectively. No associations were found between mental health and TL. Conclusions In this large-scale study, we showed the positive association between a healthy lifestyle and both biological ageing and different dimensions of mental health and well-being. We also indicated that living a healthy lifestyle contributes to more favourable biological ageing.