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Abstract Background Some evidence suggests that fluid resuscitation with lactated Ringer’s solution (LR) may have an anti-inflammatory effect on acute pancreatitis (AP) when compared to normal saline (NS) and may be associated with a decrease in severity, but existing single-center randomized controlled trials showed conflicting results. The WATERLAND trial aims to investigate the efficacy and safety of fluid resuscitation using LR compared to NS in patients with AP. Methods The WATERLAND trial is an international multicenter, open-label, parallel-group, randomized, controlled, superiority trial. Patients will be randomly assigned in a 1:1 ratio to receive LR versus NS-based fluid resuscitation for at least 48 h. The primary outcome will be moderately severe or severe AP, according to the revision of the Atlanta classification. The secondary objectives of the WATERLAND trial are to determine the effect of LR versus NS fluid resuscitation on several efficacy and safety outcomes in patients with AP. A total sample of 720 patients, 360 in the LR group and 360 in the NS group, will achieve 90% power to detect a difference between the group proportions of 10%, assuming that the frequency of moderately severe or severe AP in the LR group will be 17%. A loss to follow-up of 10% of patients is expected, so the total sample size will be 396 patients in each treatment arm (792 patients overall). The test statistic used is the two-sided Z test with pooled variance set at a 0.05 significance level. Discussion The WATERLAND study aims to improve the early management of AP. Fluid resuscitation is an inexpensive treatment available in any hospital center worldwide. If a better evolution of pancreatitis is demonstrated in one of the treatment arms, it would have important repercussions in the management of this frequent disease. Trial registration ClinicalTrials.gov, NCT05781243. Registration date on January 4, 2023. EudraCT number 2023–000010-18, first posted March 23, 2023.

This paper develops a new measure of human capital, calculated as a cohort-weighted average of the quality of education (PISA scores) and the quantity of education (mean years of schooling). Contrary to the existing studies, the relative weights of quality and quantity are estimated (and not calibrated). The quality of education is estimated to be three to four times more important for education than the quantity of education. The new measure has a strong link to productivity, which materialises with long lags. Productivity gains are much greater from improvements in the quality than quantity component of human capital.

Abstract Background Human Papilloma Virus (HPV) infection is a significant public health concern in the Gulf Cooperation Council countries, being widely prevalent and the main risk factor for cervical cancer. We aimed to assess knowledge and perception towards HPV, acceptability of the HPV vaccine, and HPV vaccination rates among university students in Education City, Doha, Qatar. Methods This cross-sectional survey utilized proportional quota-sampling, with quotas based on university, sex, and nationality, to recruit students from seven universities between February and September 2022. The English language questionnaire requested socio-demographic information, knowledge, and attitudes about HPV infection and the vaccine. The chi-square test, Student t-test, Mann-Whitney-Wilcoxon tests and multivariable ordinal logistic regression were used to assess differences in proportion, mean, and median according to broad HPV knowledge categories. Results Three hundred and ninety-eight students were recruited (response rate = 82.3%), of whom 251 (63.1%) were female. Mean age was 21.7 years. Eighty-nine (22.4%, 95% CI 18.4–26.8%) students had poor knowledge about HPV, 220 (55.3%, 95% CI 50.2–60.2%) students had some awareness, and 89 (22.4%, 95% CI 18.4–26.8%) students were knowledgeable. Age, nationality, and field of study influenced the students’ knowledge about HPV. Only 25 (6.3%) students had previously been vaccinated against HPV. However, 71% of the unvaccinated students reported being willing to get vaccinated if recommended by their healthcare provider. Conclusions Overall, 77.7% of the student population had some-to-good levels of knowledge about HPV-related infection, cancer, and vaccination. There are gaps in the student population’s understanding and knowledge about HPV. Increasing knowledge can be key toward shared decision-making for HPV vaccination among eligible populations. Targeted public health campaigns and integration into childhood vaccination programs should be critical first steps, especially as most of the surveyed students had a positive outlook on getting vaccinated. Healthcare professionals should be incentivized to increase their HPV knowledge and communication skills, while policymakers can work toward easing barriers in integrating HPV vaccinations in the immunization schedule and encouraging overall HPV vaccination uptake.

Biofilm formation is one of main causes of bacterial antimicrobial resistance infections. It is known that the soluble lectins LecA and LecB, produced by Pseudomonas aeruginosa, play a key role in biofilm formation and lung infection. Bacterial lectins are therefore attractive targets for the development of new antibiotic-sparing anti-infective drugs. Building synthetic glycoconjugates for the inhibition and modulation of bacterial lectins have shown promising results. Light-sensitive lectin ligands could allow the modulation of lectins activity with precise spatiotemporal control. Despite the potential of photoswitchable tools, few photochromic lectin ligands have been developed. We have designed and synthesized several O- and S-galactosyl azobenzenes as photoswitchable ligands of LecA and evaluated their binding affinity with isothermal titration calorimetry. We show that the synthesized monovalent glycoligands possess excellent photophysical properties and strong affinity for targeted LecA with Kd values in the micromolar range. Analysis of the thermodynamic contribution indicates that the Z-azobenzene isomers have a systematically stronger favorable enthalpy contribution than the corresponding E-isomers, but due to stronger unfavorable entropy, they are in general of lower affinity. The validation of this proof-of-concept and the dissection of thermodynamics of binding will help for the further development of lectin ligands that can be controlled by light.

BackgroundThe 16-item Meat Attachment Questionnaire (MAQ-16) assesses emotional and cognitive attachment to meat across four dimensions: hedonism, affinity, entitlement, and dependence. Recently validated in French, we aimed to develop and validate a shorter, four-item version (MAQf-4) to reduce participant burden.MethodsIn this 2023 observational study in the Rhône-Alpes region, 919 primary care patients were invited to complete the French MAQ-16 (MAQf-16). Classical test theory guided the development of the MAQf-4, and Spearman’s correlation coefficients assessed its correlation with the MAQf-16 (dimension and overall scores). We also evaluated the diagnostic performance of the MAQf-4 for identifying patients with high meat attachment (MAQf-16 score > 60).ResultsA total of 822 patients participated (65.3% women; median age = 52; participation rate = 89.5%). The MAQf-4 showed strong correlations with the MAQf-16 (rho = 0.83 for hedonism, 0.77 for affinity, 0.70 for entitlement, 0.79 for dependence, and 0.86 for the overall score, all p-values

Abstract Background Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world context is challenging. To develop strategies to improve its application, it is essential to understand the strengths and challenges of this design. This study thus aimed to explore the strengths, challenges, and strategies for improving the implementation of a pragmatic multicenter, prospective, two-arm RCT evaluating the effects of the Personalized Citizen Assistance for Social Participation (Accompagnement-citoyen Personnalisé d’Intégration Communautaire: APIC; weekly 3-h personalized stimulation sessions given by a trained volunteer over a 12-month period) on older adults’ health, social participation, and life satisfaction. Methods A multiple case study was conducted with 14 participants, comprising one research assistant, seven coordinators, and six managers of six community organizations serving older adults, who implemented the APIC in the context of a RCT. Between 2017 and 2023, qualitative data were extracted from 24 group meetings, seven semi-directed interviews, emails exchanged with the research team, and one follow-up document. Results Aged between 30 and 60 (median ± SIQR: 44.0 ± 6.3), most participants were women from organizations already offering social participation interventions for older adults and working with the public sector. Reported strengths of this RCT were its relevance in assessing an innovative intervention to support healthy aging, and the sharing of common goals, expertise, and strategies with community organizations. Challenges included difficulties recruiting older adults, resistance to potential control group assignments, design complexity, and efforts to mobilize and engage volunteers. The COVID-19 pandemic lockdown and health measures exacerbated challenges related to recruiting older adults and mobilizing volunteers and complicated delivery of the intervention. The strategies that mostly overcame difficulties in recruiting older adults were reducing sample size, simplifying recruitment procedures, emphasizing the health follow-up, extending partnerships, and recognizing and supporting volunteers better. Because of the lockdown and physical distancing measures, the intervention was also adapted for remote delivery, including via telephone or videoconferencing. Conclusion Knowledge of the strengths and challenges of pragmatic RCTs can contribute to the development of strategies to facilitate implementation studies and better evaluate health and social participation interventions delivered under real-life conditions. Trial registration NCT03161860; Pre-results. Registered on May 22, 2017.

Abstract Objectives The vast majority of children with Attention-Deficit Hyperactivity Disorder (ADHD) do not have access to proper diagnosis and treatment in China. The goal of this project is to identify the challenges and facilitators in implementing a Canadian ADHD Shared Care Pathways program in pediatric settings in Shanghai region. Methods Purposive semi-structured focus groups were conducted on a total of 13 healthcare practitioners from the Shanghai Xinuha, Ninghai and Chongming hospitals. Two independent researchers conducted a thematic analysis of the data with themes emerging based on the Consolidated Framework for Implementation Research (CFIR). Results Notable barriers identified by participants included: (1) lack of knowledge in the management of ADHD, primarily among general practitioners; (2) lack of resources such as lack of staff, time, and medication for ADHD; (3) challenges in implementing an international multicentre intervention (such as communication difficulties between teams and integration of resources available in different hospitals); and (4) mental health stigma, difficulties in identifying ADHD patients, and logistical problems related to medication procurement rules put in place by provincial governments. Notable facilitators included: (1) the strong motivation of stakeholders and their confidence in their ability to learn and subsequently execute action plans to achieve the implementation goal; (2) the compatibility between the values and goals of the stakeholders and those of the program despite some cultural tension, a positive learning climate, strong tensions for change, and the high interest of organization leaders in engaging in the program (3) the perceived benefits of the program, such as standardization of the diagnostic and treatment process, and engaging primary care providers in ADHD management; and (4) the strong relationship between participating institutions and schools as well as provincial health initiatives available to support collaborative models of care. Mixed factors to implementation were also explored. Conclusions Appropriate training of health care providers, cultural adaptation of the program, increase public awareness about ADHD to decrease stigma, as well as strong project management and guidelines that clearly describe the role and expectations of each team member appeared essential to successful implementation.

In the past decade, significant European calls for research proposals have supported translational collaborative research on non-communicable and infectious diseases within the biomedical life sciences by bringing together interdisciplinary and multinational consortia. This research has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts’ societal impact. Research proposals should be thoughtfully designed to ensure that the research findings can be effectively translated into actionable policies. In addition, the choice of scientific methods plays a pivotal role in shaping the societal impact of research discoveries. Understanding the factors responsible for current unmet public health issues and medical needs is crucial for crafting innovative strategies for research policy interventions. A multistakeholder survey and a roundtable helped identify potential needs for consideration in the EU research and policy agenda. Based on survey findings, mental health disorders, metabolic syndrome, cancer, antimicrobial resistance, environmental pollution, and cardiovascular diseases were considered the public health challenges deserving prioritisation. In addition, early diagnosis, primary prevention, the impact of environmental pollution on disease onset and personalised medicine approaches were the most selected unmet medical needs. Survey findings enabled the formulation of some research-policies interventions (RPIs), which were further discussed during a multistakeholder online roundtable. The discussion underscored recent EU-level activities aligned with the survey-derived RPIs and facilitated an exchange of perspectives on public health and biomedical research topics ripe for interdisciplinary collaboration and warranting attention within the EU’s research and policy agenda. Actionable recommendations aimed at facilitating the translation of knowledge into transformative, science-based policies are also provided.

BackgroundSalutogenesis focuses on understanding the factors that contribute to positive health outcomes. At the core of the model lies the sense of coherence (SOC), which plays a crucial role in promoting well-being and resilience. ObjectiveUsing the validscale Stata command, we aimed to assess the psychometric properties of the French version of the 3-dimension 13-item SOC questionnaire (SOC-13), encompassing the comprehensibility, manageability, and meaningfulness dimensions. We also aimed to determine if a refined scale, assessed through this method, exhibits superior psychometric properties compared to the SOC-13. MethodsA sample of 880 consecutive primary care patients recruited from 35 French practices were asked to complete the SOC-13. We tested for internal consistency and scalability using the Cronbach α and Loevinger H coefficients, respectively, and we tested for construct validity using confirmatory factor analysis and goodness-of-fit indices (root mean square error of approximation [RMSEA] and comparative fit index [CFI]). ResultsOf the 880 eligible patients, 804 (91.4%) agreed to participate (n=527, 65.6% women; median age 51 years). Cronbach α and Loevinger H coefficients for the SOC-13 were all 0.06 (0.09) and

Objective: We aimed to investigate the association between university students' dietary patterns, their demographics and lifestyle in a cross-sectional study in Qatar. Participants: 370 students in eight universities in Qatar enrolled between February 2017 and February 2018. Methods: Based on a structured questionnaire, dietary patterns were identified using principal component analysis, and their associations with student characteristics were assessed using logistic regression. Results: Four dietary patterns were identified. The "fast food" pattern was associated with being younger and male (p-values = 0.1). The "traditional diet" pattern was associated with not skipping meals or eating when bored (p-values = 0.1). The "healthy diet" pattern was associated with regular exercise and having time to eat healthy foods (p-values = 0.01). The "protein shake" pattern was associated with being male and engaging in more vigorous physical activity (p-values = 0.01). Conclusions: Our findings provide a roadmap for the prioritization of population-specific interventions in university students within Qatar and the region.

BACKGROUND: In the context of an ageing population and increasing health needs, primary care reform is needed and several new models have emerged, including the introduction of case managers in general practitioner practices. AIM: To describe the frequency of case managers in general practices in eleven Western countries between 2012 and 2019 and to investigate the characteristics of general practitioners and their practices associated with case manager frequency. METHODS: A secondary analysis of the Commonwealth Fund International Health Policy Surveys of Primary Care Physicians, which were international cross-sectional studies conducted in 2012, 2015 and 2019. Random samples of general practitioners were selected in 11 Western countries (2012: n = 9776; 2015: n = 12,049; 2019: n = 13,200). The use of case managers in general practitioner practices was determined with the question “Does your practice use personnel, such as nurses or case managers, to monitor and manage care for patients with chronic conditions that need regular follow-up care?”, with possible answers “Yes, within the practice”, “Yes, outside the practice”, “Yes, both within and outside the practice” or “No”. Other variables characterising general practitioners and their practices were considered. Mixed-effects logistic regression was performed. RESULTS: The frequency of case managers within general practitioner practices varied greatly by country, with an overall trend towards an increase from 2012 to 2019. In the multivariate analysis, more case managers were found in practices located in small towns (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.2–1.7) and in rural areas (OR 1.9; 95% CI 1.5–2.4) compared to cities. The frequency of case managers was higher in larger practices, as shown in comparisons of practices in the second, third and fourth quartile of full-time equivalent employee counts compared to those in the first quartile (Q2: OR 1.7, 95% CI 1.4–1.9; Q3: OR 2.1, 95% CI 1.6–2.9; Q4: OR 3.8, 95% CI 3.0–4.9). There was no significant difference in frequency with respect to the age and sex of the general practitioners. CONCLUSION: The use of case managers in general practitioner practices is a promising approach, but its practice varies greatly. This practice has been developing in Western countries and is tending to increase. The implementation of case managers seems to be associated with certain characteristics linked to general practitioner practices (practice location, practice size), whereas it does not seem to depend on the personal characteristics of general practitioners, such as age or sex.

Summary: Background: Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. Methods: We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. Findings: A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9–82.2) and 57.3% (51.7–63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6–80.2) and 50.7% (45.0–56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3–84.2) and 65.3% (59.8–70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0–83.1) and 61.5% (55.9–67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age

IntroductionUsing the conservation of resources (COR) theory, our study explores the interaction between role ambiguity and leader-member exchange (LMX) quality on burnout using work addiction as a mediator among Canadian first-level healthcare managers.MethodsCross-sectional data was collected among 165 first-level managers working in healthcare with the support of interprofessional associations in Canada. Linear regression was used to test the presented hypotheses.ResultsWork addiction fully mediated the positive relationship between role ambiguity and burnout among first-level managers. In addition, high LMX exacerbated both the direct and indirect effects of role ambiguity.ConclusionOur study contributes by identifying role ambiguity as a context under which LMX can have adverse effects for first-level managers in healthcare. Moreover, work addiction acted as a mediator, theorized as a risky resource investment which depletes managers’ resources. Having a good relationship with their team further entices managers to develop a pathological relationship with their work to protect its members, which in turn is related to higher levels of burnout.

Abstract This study focused on children treated for mental health problems during the pandemic. The present study examined how parent’s difficulties in managing COVID-19 restrictions increased children's behavioral problems (internalizing and externalizing) and parent–child conflict through parental mental health and parental stress. Family functioning, particularly problem-solving ability, was tested as a resilience factor. were collected using online surveys from 337 parents with a child between the ages of 4 and 18 years who was receiving active outpatient mental health treatment at a pediatric tertiary care center. Parents who reported a greater impact of COVID-19 reported more behavioral difficulties in their children. This relationship was significantly mediated by parental mental health (general stress, anxiety, and depression) and parental stress. Similar indirect pathways were observed when examining internalizing and externalizing problems in children, where the most significant pathway had parental stress as the sole mediator. Furthermore, the effect of COVID-19 impact on parent–child conflict through parental stress was significantly moderated by problem-solving skills within the family. Parenting stress mediates the impact of COVID-19 on parent–child conflict. Interventions improving within family problem solving-skills may decrease the effect of parental stress on parent–child conflict.

A measurement campaign was conducted in the Paris region, focusing on the evolution of chemical composition of wet deposition during rainfall events from sequential sampling. A total of eight rain events were documented and characterized by varying meteorological conditions, atmospheric dynamics, and aerosol particle concentrations representative of urban conditions and influenced by long-range mineral dust transport. The intra-event evolution of the chemical composition of wet deposition revealed the predominant role of meteorological parameters and local sources in the observed mass concentration variability. From selected case studies, the washout ratios (WRs) and scavenging coefficients were quantified by conducting simultaneous measurements of aerosol particle composition and wet deposition. The results highlighted a variability of the WR and scavenging coefficients depending on the rainfall rate and on the chemical species. Scavenging coefficients estimated from WR ranged from 5.4×10-8 to 1.1×10-5 s−1 for chemical elements, and they are within the range of values reported in the literature for 0.2–2 µm particle diameters. Our results pointed out that the scavenging coefficient increases with rainfall rate according to a power law, as previously shown in the literature, indicating a stronger removal of particles from the atmosphere with greater precipitation intensity. Quantitative analysis of the data allowed us to estimate the relative contributions of in-cloud scavenging (ICS) for selected rain events. The ICS relative contributions ranged on average from 23 % to 62 % depending on the rain events, and they varied according to the chemical species within the same rain event. This highlights the variability and complexity of the wet deposition process and the influence of specific factors on the contribution of ICS, such as aerosol particle size and hygroscopicity. Overall, this study highlights the variability of wet deposition and its chemical composition and the need to consider the specificities of each event to fully understand the underlying mechanisms.

Abstract Background Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration ISRCTN27483786. Registered on August 2, 2023

IntroductionManagers assume a pivotal role during periods of organizational change, yet there exists a notable gap in our understanding of how their emotional exhaustion may impact their capacity to generate readiness to change within their teams. Grounded in the conservation of resources theory (COR), this study explores the crossover effect of managers’ emotional exhaustion on team readiness to change. We expect this to occur through higher levels of laissez-faire leadership, which impacts the teams’ psychological safety.MethodologyData was gathered within a Canadian governmental organization undergoing two significant changes—cultural change and digitalization—with a specific focus on leadership as a pivotal factor in preparing teams for change. Employing surveys from 372 team members and 62 managers affected by this change, we conducted path analysis to empirically test the proposed model across 74 teams and their respective managers.ResultsManagers’ emotional exhaustion has a negative indirect effect on team readiness to change. The double mediation pathway implies a positive relationship on laissez-faire leadership, which hinders psychological safety. In turn, psychological safety hampers team readiness to change.ConclusionManagers must invest significant resources to fulfill their roles and responsibilities during strategic change. Those who feel exhausted during change may look for ways to protect some of their resources by reducing the time and energy they invest leading their team. This self-preserving resource strategy has detrimental consequences on teams’ effectiveness during change due to an indirect crossover effect that affects the levels of psychological safety on the team.

Objective: University students face high levels of stress-related factors, such as an unfamiliar environment, challenging workload, and uncertainty about their ability to succeed. Participants: A total of 370 students in Qatar who consented to participate between February 2017 and February 2018. Methods: This cross-sectional study assessed perceived stress [using a validated 4-point perceived stress scale (PSS-4)], as well as diet, exercise, body mass index, sleep, and life satisfaction. Results: Among students aged 18-39 (mean = 20.1 ± 3.0 years), PSS-4 scores varied between 0 and 16 (mean = 7.4 ± 3.4). Elevated stress was significantly associated with female sex, country of origin, residing off-campus, eating when bored, lack of self-discipline, disturbed sleep, and low levels of life satisfaction. Furthermore, students with PSS-4 scores above the median level were 2.3 times likelier to report difficulty concentrating on academic work. Conclusion: Elevated stress levels are present in university students in Qatar. Strengthening coping skills may improve health and academic performance.

ABSTRACTClinical reasoning is the cornerstone to healthcare practice and teaching it appropriately is of utmost importance. Yet there is little formal training for clinical supervisors in supervising this reasoning process. Distance education provides interesting opportunities for continuous professional development of healthcare professionals. This mixed methods study aimed at gaining in-depth understanding about whether and how clinical teachers can develop complex pedagogical competencies through participation in a Massive Open Online Course on the supervision of clinical reasoning (MOOC SCR). Participants self-assed their clinical supervision skills before and after partaking in the MOOC SCR through the Maastricht Clinical Teachers Questionnaire. Item scores and the distribution of response proportions before and after participation were compared using paired t-tests and McNemar’s tests respectively. In parallel, the evolution of a subset of MOOC participants’ pedagogical practice and posture was explored via semi-structured interviews throughout and beyond their MOOC participation using simulated and personal situational recalls. The verbatim were analysed with standard thematic analysis. Quantitative and qualitative findings converged and their integration demonstrated that partaking in the MOOC SCR promoted the development of complex pedagogical competencies and reflexivity with the participants. This was quantitatively evidenced by significantly higher self-assessed supervision skills and corresponding attitudes after completing the MOOC. The qualitative data provided rich descriptions of how this progression in pedagogical practice and posture occurred in the field and how it was shaped by participants’ interaction with the MOOC’s content and their motivations to progress. Our findings provide evidence for the development of pedagogical skills and corresponding attitudes for the supervision of clinical reasoning through participation in the MOOC SCR and contribute to the literature body on the opportunities that distance learning provides for the development of pedagogical competencies. The extent to which the pedagogical underpinnings of the MOOC contributed to these developments remains to be determined.

Lung cancer screening by helical low-dose computed tomography detects nonsolid nodules that may be lung adenocarcinoma precursors. Aspirin's anti-inflammatory properties make it an attractive target for prevention of multiple cancers, including lung cancer. Therefore, we conducted a phase IIb trial (NCT02169271) to study the efficacy of low-dose aspirin to reduce the size of subsolid lung nodules (SSNs). A total of 98 current or former smokers (67.3% current) undergoing annual low-dose computed tomography screening with persistent SSNs were randomly assigned to receive aspirin 100 mg/day or placebo for 1 year. There was no difference in change in the sum of the longest diameters of target nodules in the placebo and aspirin arm after 12 months of treatment (-0.12 mm [SD = 1.55 mm] and +0.30 mm [SD= 2.54 mm], respectively; 2-sided P = .33 primary endpoint). There were no changes observed in subgroup analyses by individual characteristics or nodule type. One year of low-dose aspirin did not show any effect on lung SSNs. SSNs regression may not be the proper target for aspirin, and/or longer duration may be needed to see SSNs modifications.

Pathogens that infect plants and animals use a diverse arsenal of effector proteins to suppress the host immune system and promote infection. Identification of effectors in pathogen genomes is foundational to understanding mechanisms of pathogenesis, for monitoring field pathogen populations, and for breeding disease resistance. We identified candidate effectors from the lettuce downy mildew pathogen Bremia lactucae by searching the predicted proteome for the WY domain, a structural fold found in effectors that has been implicated in immune suppression as well as effector recognition by host resistance proteins. We predicted 55 WY domain containing proteins in the genome of B. lactucae and found substantial variation in both sequence and domain architecture. These candidate effectors exhibit several characteristics of pathogen effectors, including an N-terminal signal peptide, lineage specificity, and expression during infection. Unexpectedly, only a minority of B. lactucae WY effectors contain the canonical N-terminal RXLR motif, which is a conserved feature in the majority of cytoplasmic effectors reported in Phytophthora spp. Functional analysis of 21 effectors containing WY domains revealed 11 that elicited cell death on wild accessions and domesticated lettuce lines containing resistance genes, indicative of recognition of these effectors by the host immune system. Only two of the 11 recognized effectors contained the canonical RXLR motif, suggesting that there has been an evolutionary divergence in sequence motifs between genera; this has major consequences for robust effector prediction in oomycete pathogens.

The objective of this study was to describe pregnancy- and birth-related experiences of postpartum women during the third wave of the COVID-19 pandemic and their association with mental health outcomes. An online questionnaire was distributed in five European countries (Belgium, The Netherlands, Norway, Switzerland, UK) between June and August 2021. Participants were recruited though social media platforms including pregnancy- and motherhood-related websites, pregnancy fora, and apps. Postpartum women were asked eleven specific questions about pregnancy- and birth-related changes and the presence of support during delivery. The Edinburgh Depression Scale was used to assess depressive and anxiety symptoms. Covariates included sociodemographics, health and reproductive characteristics, and COVID-19 status. Associations were estimated with logistic regression. The study included 1730 postpartum women. Frequent changes included the exclusion of the partner from pregnancy care appointments (83.2%), changed prenatal care settings (64.4%), and cancellation of hospital information visits (42.7%). Few women, however, were without support apart from medical staff during delivery (1.4%). The number of pregnancy- and birth-related changes was associated with each woman’s mental health status, as well as the type of change. Experiencing changes related to delivery and cancellation or reduction of prenatal examination was associated with a doubling in the odds of symptoms of major depression and anxiety postpartum. These findings highlight the importance of ensuring adequate maternity care for women’s mental health postpartum, as well as during a pandemic.

The purpose of the present study was to determine whether the use of e-cigarettes to aid in quitting contributed to the increase in the pulmonary health of chronic smokers. The efficacy of e-cigarettes to support a successful smoking cessation attempt was also investigated. A total of 210 smokers (78 women) were enrolled in a screening program for the early detection of lung cancer and distributed in three arms: nicotine e-cigarette plus support, nicotine-free e-cigarette plus support, and support. Results showed that participants in the nicotine e-cigarette arm had a significant and fast decrease in daily cigarettes, but that later they resume smoking more than the other two groups. Conversely, participants in the other two arms showed similar daily consumption at the two evaluation points. Among abstinent participants, only 12.5% reported cough, while 48% of current smokers had pulmonary symptoms. Our study suggests that, in the long run, the use of a nicotine-free liquid may favor reducing smoking and could be considered a good option in a clinical setting.

Key points•Nucleotide binding oligomerization domain (Nod)-like receptors regulate cognition, anxiety and hypothalamic-pituitary-adrenal axis activation. •Nod-like receptors regulate central and peripheral serotonergic biology. •Nod-like receptors are important for maintenance of gastrointestinal physiology. •Intestinal epithelial cell expression of Nod1 receptors regulate behaviour.AbstractGut-brain axis signalling is critical for maintaining health and homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition and intestinal dysfunction. In the present study, we identified nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signalling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, and are important in the regulation of gastrointestinal physiology. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal cell proliferation and immature neurons, as well as reduced neural activation. In addition, NodDKO mice had increased gastrointestinal permeability and altered serotonin signalling in the gut following exposure to acute stress. Administration of the selective serotonin reuptake inhibitor, fluoxetine, abrogated behavioural impairments and restored serotonin signalling. We also identified that intestinal epithelial cell-specific deletion of Nod1 (VilCre+ Nod1f/f ), but not Nod2, increased susceptibility to stress-induced anxiety-like behaviour and cognitive impairment following exposure to stress. Together, these data suggest that intestinal epithelial NLR are novel modulators of gut-brain communication and may serve as potential novel therapeutic targets for the treatment of gut-brain disorders.

BackgroundGermline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls.MethodsIn this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger.FindingsWe analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants.InterpretationOur pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies.FundingSPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.

Abstract The in vitro modeling of human brain connectomes is key to exploring the structure-function relationship of the central nervous system. Elucidating this intricate relationship will allow better studying of the pathological mechanisms of neurodegeneration and hence result in improved drug screenings for complex neurological disorders, such as Alzheimer’s and Parkinson diseases. However, currently used in vitro modeling technologies lack the potential to mimic physiologically relevant neural structures. Herein, we present an innovative microfluidic design that overcomes one of the current limitations of in vitro brain models: their inability to recapitulate the heterogeneity of brain regions in terms of cellular density and number. This device allows the controlled and uniform deposition of any cellular population within unique plating chambers of variable size and shape. Through the fine tuning of the hydrodynamic resistance and cell deposition rate, the number of neurons seeded in each plating chamber can be tailored from a thousand up to a million. By applying our design to so-called neurofluidic devices, we offer novel neuro-engineered microfluidic platforms that can be strategically used as organ-on-a-chip platforms for neuroscience research. These advances provide essential enhancements to in vitro platforms in the quest to provide structural architectures that support models for investigating human neurodegenerative diseases.

Abstract Background Maternal mortality in the Middle East and North Africa (MENA) region decreased significantly between 1990 and 2017. This was uneven, however, with some countries faring much better than others. Methods We undertook a trend analysis of Maternal Mortality Ratios (MMRs) of countries in the region in order to understand differences in reduction across countries. Data were extracted from several databases for 23 countries and territories in the region on measures of women’s empowerment, availability of vehicles and human resources for health (as a proxy to the three delays model). We identified factors associated with MMR by grouping countries into five different Stages (I-V) of obstetric transition from high to low MMRs. Results Among the four Stage II countries, MMR is associated with “antenatal care coverage (% with at least one visit)” and “medical doctors per 10,000 population”. Among the eight Stage III countries, MMR is associated with “Gender Parity Index in primary and secondary level school enrolment” and with “nursing and midwifery personnel per 10,000 population”. Among the 10 countries and one territory in Stages IV and V, MMR is associated with “GDP per capita”, “nursing and midwifery personnel”, and “motor vehicle ownership/motorization rate”. Two factors were associated with changes in MMR from the period 2006–2010 to 2011–2015: 1) change in adolescent birth rate (r = 0.90, p = 0.005) and 2) Gender Parity Index in primary level school enrolment (r = − 0.51, p = 0.04). Conclusion Though impressive reductions in MMR have been achieved across countries in the MENA region since 1990, governments should realize that there exists an opportunity to learn from each other to bring MMRs as close to zero as possible. Immediate steps in the right direction would include investment in human resources for health, particularly nurses and midwives; measures to improve adolescent sexual and reproductive health; and greater investments in achieving gender equity in education.

Introduction Waterpipe smoking is common in the Eastern Mediterranean Region and is becoming more prevalent in Qatar. To better plan waterpipe smoking control strategies we aimed to: 1) determine the prevalence of waterpipe smoking and explore its patterns in Qatar; 2) describe the knowledge, attitudes, and practices related to smoking behaviors; 3) recognize locations of waterpipe smoking and symptoms experienced during waterpipe sessions; and 4) evaluate the frequency of waterpipe smoking and the initiation age. Methods We analyzed the data of a 7921 population-based survey of adults aged ≥18 years (nationals and expatriates), conducted in Qatar between March and December 2019. Out of 7105 surveys collected, 6904 were complete and included in the analysis. Results Of the 6904, 570 (8.3%; 95% CI: 7.7–9.0) were waterpipe tobacco smokers, 425 (10.6%) males and 145 (5.1%) females. The highest prevalence of waterpipe smoking was reported among people aged 18–24 years (10.6%). Of the 575 waterpipe smokers, 56.3% (n=324) were exclusive waterpipe smokers. Use of other tobacco products among waterpipe smokers was higher among Qataris (52.3%) than expatriates (37.7%). Waterpipe cafés were the most common location for waterpipe smoking, however, females preferred restaurants; 83.3% reported that waterpipe smoking is harmful, while 39.3% considered that it is less harmful than cigarette smoking. Conclusions Waterpipe smoking prevalence is considerably high in Qatar, the second form of tobacco used. The formulation of new policies and enforcement of regulatory restrictions on waterpipe smoking are essential to reduce its uptake. Expansion in tobacco cessation services for women and poly-tobacco users is needed.