A miniaturised semi-dynamic in-vitro model of human digestion.

Reliable in-vitro digestion models that are able to successfully replicate the conditions found in the human gastrointestinal tract are key to assess the fate and efficiency of new formulations aimed for oral consumption. However, current in-vitro models either lack the capability to replicate crucial dynamics of digestion or require large volumes of sample/reagents, which can be scarce when working with nanomaterials under development. Here, we propose a miniaturised digestion system, a digestion-chip, based on incubation chambers integrated on a polymethylmethacrylate device. The digestion-chip incorporates key dynamic features of human digestion, such as gradual acidification and gradual addition of enzymes and simulated fluids in the gastric phase, and controlled gastric emptying, while maintaining low complexity and using small volumes of sample and reagents. In addition, the new approach integrates real-time automated closed-loop control of two key parameters, pH and temperature, during the two main phases of digestion (gastric and intestinal) with an accuracy down to ± 0.1 °C and ± 0.2 pH points. The experimental results demonstrate that the digestion-chip successfully replicates the gold standard static digestion INFOGEST protocol and that the semi-dynamic digestion kinetics can be reliably fitted to a first kinetic order model. These devices can be easily adapted to dynamic features in an automated, sensorised, and inexpensive platform and will enable reliable, low-cost and efficient assessment of the bioaccessibility of new and expensive drugs, bioactive ingredients or nanoengineered materials aimed for oral consumption, thereby avoiding unnecessary animal testing.

Expectations and basic knowledge in ultrasound screening among pregnant women: A questionnaire survey.

OBJECTIVE: This study aimed to evaluate the disparity of the expectations and basic knowledge of prenatal ultrasound (US) screening among pregnant women and make a comparison with the current scientific knowledge and national recommendations. We hypothesize that sociodemographic factors, including age, education, and professional occupation, may be associated with different levels of knowledge. METHODS: This was a cross-sectional study performed in 2021 of 336 women aged 18 to 46 years in a maternity facility in a tertiary hospital in Portugal. The main outcome measures were questionnaire data from questions divided into four categories (sociodemographic, expectations, knowledge, and final considerations/suggestions). The data were grouped according to the sociodemographic factors (age, educational level, and professional occupation) and analyzed and compared as a function of the social groups as well as overall tendencies. RESULTS: Our data confirmed a significant discrepancy between the expectations and general knowledge of pregnant women regarding prenatal US when compared with the current scientific knowledge. Importantly, we found that both depended greatly on sociodemographic factors, particularly educational level. This reiterated the importance of conducting effective dissemination actions of current scientific knowledge, focusing on the main objectives of US screening as well as the limitations of the existing technology. CONCLUSION: This study will help in defining strategies for future dissemination actions aiming to improve current practice and lead to a higher synchrony of expectations towards US between couples and practitioners.

Factors associated with satisfaction and perceived helpfulness of mental healthcare: a World Mental Health Surveys report.

BACKGROUND: Mental health service providers are increasingly interested in patient perspectives. We examined rates and predictors of patient-reported satisfaction and perceived helpfulness in a cross-national general population survey of adults with 12-month DSM-IV disorders who saw a provider for help with their mental health. METHODS: Data were obtained from epidemiological surveys in the World Mental Health Survey Initiative. Respondents were asked about satisfaction with treatments received from up to 11 different types of providers (very satisfied, satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied) and helpfulness of the provider (a lot, some, a little, not at all). We modelled predictors of satisfaction and helpfulness using a dataset of patient-provider observations (n = 5,248). RESULTS: Most treatment was provided by general medical providers (37.4%), psychiatrists (18.4%) and psychologists (12.7%). Most patients were satisfied or very satisfied (65.9-87.5%, across provider) and helped a lot or some (64.4-90.3%). Spiritual advisors and healers were most often rated satisfactory and helpful. Social workers in human services settings were rated lowest on both dimensions. Patients also reported comparatively low satisfaction with general medical doctors and psychiatrists/psychologists and found general medical doctors less helpful than other providers. Men and students reported lower levels of satisfaction than women and nonstudents. Respondents with high education reported higher satisfaction and helpfulness than those with lower education. Type of mental disorder was unrelated to satisfaction but in some cases (depression, bipolar spectrum disorder, social phobia) was associated with low perceived helpfulness. Insurance was unrelated to either satisfaction or perceived helpfulness but in some cases was associated with elevated perceived helpfulness for a given level of satisfaction. CONCLUSIONS: Satisfaction with and perceived helpfulness of treatment varied as a function of type of provider, service setting, mental status, and socio-demographic variables. Invariably, caution is needed in combining data from multiple countries where there are cultural and service delivery variations. Even so, our findings underscore the utility of patient perspectives in treatment evaluation and may also be relevant in efforts to match patients to treatments.

Mental health conditions and utilisation of mental health services by survivors of physical intimate partner violence in Portugal: Results from the WHO world mental health survey.

The aim of this article is to study mental health conditions among survivors of severe physical intimate partner violence (IPV) and their utilisation of mental health services. This study is an integrated part of the World Mental Health Survey Initiative-Portugal, for which data was collected from a nationally representative adult sample using well-validated scales. Logistic regression models were used in the analysis. The most common statistically significant mental health conditions among IPV survivors were suicide ideation, PTSD, major depressive episode, and generalised anxiety disorder. More than one in three survivors developed PTSD. Suicide ideation was likely to occur after first experiencing IPV. Almost a half of survivors received specialised mental health treatment; in most cases, delivered by a psychiatrist. Over 60 % addressed their mental health issues consulting general physicians or other healthcare professionals. Those who experienced family violence in childhood had greater odds of also experiencing IPV; survivors of IPV with this experience were more likely to receive mental health treatment. The need to promote greater awareness and competencies of not only mental health professionals but also of general physicians and other healthcare professionals to provide support more effectively to survivors of any type of IPV deserves to be emphasised.

Recent Advances in Cell-Based In Vitro Models to Recreate Human Intestinal Inflammation.

Inflammatory bowel disease causes a major burden to patients and healthcare systems, raising the need to develop effective therapies. Technological advances in cell culture, allied with ethical issues, have propelled in vitro models as essential tools to study disease aetiology, its progression, and possible therapies. Several cell-based in vitro models of intestinal inflammation have been used, varying in their complexity and methodology to induce inflammation. Immortalized cell lines are extensively used due to their long-term survival, in contrast to primary cultures that are short-lived but patient-specific. Recently, organoids and organ-chips have demonstrated great potential by being physiologically more relevant. This review aims to shed light on the intricate nature of intestinal inflammation and cover recent works that report cell-based in vitro models of human intestinal inflammation, encompassing diverse approaches and outcomes.

From mouth to gut: microfluidic in vitro simulation of human gastro-intestinal digestion and intestinal permeability.

Reproducible in vitro studies of bioaccessibility, intestinal absorption, and bioavailability are key to the successful development of novel food ingredients or drugs intended for oral administration. There is currently a lack of methods that offer the finesse required to study these parameters for valuable molecules typically found in small volumes - as is the case of nanomaterials, which are often used to carry and protect bioactives. Here, we describe a modular microfluidic-based platform for total simulation of the human gastro-intestinal tract. Digestion-chips and cell-based gut-chips were fabricated from PDMS by soft lithography. On-chip digestion was validated using a fluorescently labelled casein derivative, which followed typical Michaelis-Menten kinetics and showed temporal resolution and good agreement with well-established bench-top protocols. Irreversible inhibition of serine proteases using Pefabloc® SC and a 1 : 6 dilution was sufficient to mitigate the cytotoxicity of simulated digestion fluids. Caco-2/HT29-MTX co-cultures were grown on-chip under a continuous flow for 7 days to obtain a differentiated cell monolayer forming a 3D villi-like epithelium with clear tight junction formation, and with an apparent permeability (Papp) of Lucifer Yellow closely approximating values reported ex vivo (3.7 × 10-6 ± 1.4 × 10-6vs. 4.0 × 10-6 ± 2.2 × 10-6). Digesta from the digestion-chips were flowed through the gut-chip, demonstrating the capacity to study sample digestion and intestinal permeability in a single microfluidic platform holding great promise for use in pharmacokinetic studies.

Clinical and Virological Features of SARS-CoV-2 Variants during the Four Waves of the Pandemic in the Mexican Southeast.

We conducted a retrospective study using a population of patients who were hospitalized at Dr. Juan Graham Casasus Hospital in Villahermosa (Tabasco, Mexico) and had a positive RT-PCR test for SARS-CoV-2 between June 2020 and January 2022. We analyzed all medical records, including demographic data, SARS-CoV-2 exposure history, underlying comorbidities, symptoms, signs at admission, laboratory findings during the hospital stay, outcome, and whole-genome sequencing data. Finally, the data were analyzed in different sub-groups according to distribution during waves of the COVID-19 pandemic regarding Mexican reports from June 2020 to January 2022. Of the 200 patients who tested positive via PCR for SARS-CoV-2, only 197 had samples that could be sequenced. Of the samples, 58.9% (n = 116) were males and 41.1% (n = 81) females, with a median age of 61.7 ± 17.0 years. Comparisons between the waves of the pandemic revealed there were significant differences in the fourth wave: the age of patients was higher (p = 0.002); comorbidities such as obesity were lower (p = 0.000), while CKD was higher (p = 0.011); and hospital stays were shorter (p = 0.003). The SARS-CoV-2 sequences revealed the presence of 11 clades in the study population. Overall, we found that adult patients admitted to a third-level Mexican hospital had a wide range of clinical presentations. The current study provides evidence for the simultaneous circulation of SARS-CoV-2 variants during the four pandemic waves.

Development and evaluation of a risk algorithm predicting alcohol dependence after early onset of regular alcohol use.

AIMS: Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost-effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD. DESIGN: A prediction model was developed for DSM-IV AD onset by age 25 years using an ensemble machine-learning algorithm known as 'Super Learner'. Shapley additive explanations (SHAP) assessed variable importance. SETTING AND PARTICIPANTS: Respondents reporting early onset of regular alcohol use (i.e. by 17 years of age) who were aged 25 years or older at interview from 14 representative community surveys conducted in 13 countries as part of WHO's World Mental Health Surveys. MEASUREMENTS: The primary outcome to be predicted was onset of life-time DSM-IV AD by age 25 as measured using the Composite International Diagnostic Interview, a fully structured diagnostic interview. FINDINGS: AD prevalence by age 25 was 5.1% among the 10 687 individuals who reported drinking alcohol regularly by age 17. The prediction model achieved an external area under the curve [0.78; 95% confidence interval (CI) = 0.74-0.81] higher than any individual candidate risk model (0.73-0.77) and an area under the precision-recall curve of 0.22. Overall calibration was good [integrated calibration index (ICI) = 1.05%]; however, miscalibration was observed at the extreme ends of the distribution of predicted probabilities. Interventions provided to the 20% of people with highest risk would identify 49% of AD cases and require treating four people without AD to reach one with AD. Important predictors of increased risk included younger onset of alcohol use, males, higher cohort alcohol use and more mental disorders. CONCLUSIONS: A risk algorithm can be created using data collected at the onset of regular alcohol use to target youth at highest risk of alcohol dependence by early adulthood. Important considerations remain for advancing the development and practical implementation of such models.

Diverse monogenic subforms of human spermatogenic failure.

Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human "knockouts", and, for the most part, have yet to be linked to a Mendelian trait. Integration with single-cell RNA sequencing data shows that azoospermia genes can be grouped into molecular subforms with synchronized expression patterns, and analogs of these subforms exist in mice. This analysis framework identifies groups of genes with known roles in spermatogenesis but also reveals unrecognized subforms, such as a set of genes expressed across mitotic divisions of differentiating spermatogonia. Our findings highlight NOA as an understudied Mendelian disorder and provide a conceptual structure for organizing the complex genetics of male infertility, which may provide a rational basis for disease classification.

Phasing of de novo mutations using a scaled-up multiple amplicon long-read sequencing approach.

De novo mutations (DNMs) play an important role in severe genetic disorders that reduce fitness. To better understand their role in disease, it is important to determine the parent-of-origin and timing of mutational events that give rise to these mutations, especially in sex-specific developmental disorders such as male infertility. However, currently available short-read sequencing approaches are not ideally suited for phasing, as this requires long continuous DNA strands that span both the DNM and one or more informative single-nucleotide polymorphisms. To overcome these challenges, we optimized and implemented a multiplexed long-read sequencing approach using Oxford Nanopore technologies MinION platform. We focused on improving target amplification, integrating long-read sequenced data with high-quality short-read sequence data, and developing an anchored phasing computational method. This approach handled the inherent phasing challenges of long-range target amplification and the normal accumulation of sequencing error associated with long-read sequencing. In total, 77 of 109 DNMs (71%) were successfully phased and parent-of-origin identified. The majority of phased DNMs were prezygotic (90%), the accuracy of which is highlighted by an average mutant allele frequency of 49.6% and standard error of 0.84%. This study demonstrates the benefits of employing an integrated short-read and long-read sequencing approach for large-scale DNM phasing.

The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans.

Infertility affects around 7% of the male population and can be due to severe spermatogenic failure (SPGF), resulting in no or very few sperm in the ejaculate. We initially identified a homozygous frameshift variant in FKBP6 in a man with extreme oligozoospermia. Subsequently, we screened a total of 2,699 men with SPGF and detected rare bi-allelic loss-of-function variants in FKBP6 in five additional persons. All six individuals had no or extremely few sperm in the ejaculate, which were not suitable for medically assisted reproduction. Evaluation of testicular tissue revealed an arrest at the stage of round spermatids. Lack of FKBP6 expression in the testis was confirmed by RT-qPCR and immunofluorescence staining. In mice, Fkbp6 is essential for spermatogenesis and has been described as being involved in piRNA biogenesis and formation of the synaptonemal complex (SC). We did not detect FKBP6 as part of the SC in normal human spermatocytes, but small RNA sequencing revealed that loss of FKBP6 severely impacted piRNA levels, supporting a role for FKBP6 in piRNA biogenesis in humans. In contrast to findings in piRNA-pathway mouse models, we did not detect an increase in LINE-1 expression in men with pathogenic FKBP6 variants. Based on our findings, FKBP6 reaches a "strong" level of evidence for being associated with male infertility according to the ClinGen criteria, making it directly applicable for clinical diagnostics. This will improve patient care by providing a causal diagnosis and will help to predict chances for successful surgical sperm retrieval.

Life History of Erotylina jaspidea (Erichson, 1847) (Coleoptera, Erotyloidea, Erotylidae, Erotylini).

The life history of Erotylina jaspidea (Erichson, 1847) (Coleoptera, Erotyloidea, Erotylidae, Erotylini) is described. A female specimen was found in an Atlantic Forest remnant in Northeast Brazil. After oviposition, individuals were reared in Petri dish and terrarium, feeding on basidiomes of Lentinus substrictus (Bolton) Zmitr. Kovalenko, Favolus tenuiculus P. Beauv (Polyporaceae) and an unidentified resupinate fungus. Growth and feeding behaviors were regularly observed. We provide information on the observed life history stages, together with morphological descriptions, and photographs of eggs, larvae, pupae and adults. We compared our description of the teneral E. jaspidea to species of similar color pattern. Furthermore, we discuss hypotheses about larval defensive behavior and total instar durations in E. jaspidea and other Erotylinae representatives. The present work is the first to provide a description for the life history of a species of the genus Erotylina.

Social anxiety disorder and childhood adversities in Portugal: Findings from the WHO world mental health survey initiative.

Social anxiety disorder (SAD) is one of the most underrecognized and undertreated common mental disorders. This study aimed to describe its epidemiology and to understand the association between childhood adversities and SAD in the context of Portugal's collectivist culture. Data about SAD, childhood adversities, socio-demographic variables were collected from a nationally representative sample using well-validated scales employed for the World Mental Health Survey. Logistic and linear regression models were carried out to explore the association between childhood adversities and SAD prevalence and age of onset. The estimated lifetime prevalence of SAD was 4.68% and the 12-month prevalence was 3.14%. The mean age of onset was 13.6 ± 8.79. People with a college education had 3.42 higher odds of having SAD compared to people with no education or a primary school education. Most childhood adversities significantly increased the odds of a lifetime prevalence of SAD. Parental Maladjustment increased the odds of SAD when gender, age, and education were adjusted. The study findings show a relatively high prevalence of SAD in Portugal and confirms that females, younger people, students, and single people are more likely to have SAD. The study highlights the need to address experiences of parental maladjustment in interventions for people with SAD in Portugal.

Large-scale analyses of the X chromosome in 2,354 infertile men discover recurrently affected genes associated with spermatogenic failure.

Although the evolutionary history of the X chromosome indicates its specialization in male fitness, its role in spermatogenesis has largely been unexplored. Currently only three X chromosome genes are considered of moderate-definitive diagnostic value. We aimed to provide a comprehensive analysis of all X chromosome-linked protein-coding genes in 2,354 azoospermic/cryptozoospermic men from four independent cohorts. Genomic data were analyzed and compared with data in normozoospermic control individuals and gnomAD. While updating the clinical significance of known genes, we propose 21 recurrently mutated genes strongly associated with and 34 moderately associated with azoospermia/cryptozoospermia not previously linked to male infertility (novel). The most frequently affected prioritized gene, RBBP7, was found mutated in ten men across all cohorts, and our functional studies in Drosophila support its role in germ stem cell maintenance. Collectively, our study represents a significant step towards the definition of the missing genetic etiology in idiopathic severe spermatogenic failure and significantly reduces the knowledge gap of X-linked genetic causes of azoospermia/cryptozoospermia contributing to the development of future diagnostic gene panels.

Advances in Microfluidics for the Implementation of Liquid Biopsy in Clinical Routine.

In recent years, we have seen major advances in the field of liquid biopsy and its implementation in the clinic, mainly driven by breakthrough developments in the area of molecular biology. New developments have seen an integration of microfluidics and also biosensors in liquid biopsy systems, bringing advantages in terms of cost, sensitivity and automation. Without a doubt, the next decade will bring the clinical validation and approval of these combined solutions, which is expected to be crucial for the wide implementation of liquid biopsy systems in clinical routine.

Determinants of effective treatment coverage for major depressive disorder in the WHO World Mental Health Surveys.

BACKGROUND: Most individuals with major depressive disorder (MDD) receive either no care or inadequate care. The aims of this study is to investigate potential determinants of effective treatment coverage. METHODS: In order to examine obstacles to providing or receiving care, the type of care received, and the quality and use of that care in a representative sample of individuals with MDD, we analyzed data from 17 WHO World Mental Health Surveys conducted in 15 countries (9 high-income and 6 low/middle-income). Of 35,012 respondents, 3341 had 12-month MDD. We explored the association of socio-economic and demographic characteristics, insurance, and severity with effective treatment coverage and its components, including type of treatment, adequacy of treatment, dose, and adherence. RESULTS: High level of education (OR = 1.63; 1.19, 2.24), private insurance (OR = 1.62; 1.06, 2.48), and age (30-59yrs; OR = 1.58; 1.21, 2.07) predicted effective treatment coverage for depression in a multivariable logistic regression model. Exploratory bivariate models further indicate that education may follow a dose-response relation; that people with severe depression are more likely to receive any services, but less likely to receive adequate services; and that in low and middle-income countries, private insurance (the only significant predictor) increased the likelihood of receiving effective treatment coverage four times. CONCLUSIONS: In the regression models, specific social determinants predicted effective coverage for major depression. Knowing the factors that determine who does and does not receive treatment contributes to improve our understanding of unmet needs and our ability to develop targeted interventions.

Dealing with the COVID-19 pandemic in Europe: five lessons from the European Society for Traumatic Stress Studies.

The paper provides insights into the mental health consequences of the coronavirus disease 2019 (COVID-19) pandemic from the Central, Eastern, Nordic, Southern, and Western subregions of Europe, represented by five member countries of the European Society for Traumatic Stress Studies (ESTSS). On the basis of the existing national research and experiences in these countries, we propose five lessons learned. (1) There is no evidence of a mental health pandemic so far in the countries in focus. No increase in severe mental disorders but some increase in the symptoms of common mental health disorders are observable. More high-quality longitudinal studies are needed to understand the mental health burden of the pandemic. (2) The pandemic affects countries (including the mental health situation) differently, depending on the level of the exposure, management policies, pre-pandemic structural characteristics, and healthcare resources. (3) The pandemic affects people differently: the exposure severity to pandemic-related stressors differs between individuals, as well as individual resources to cope with these stressors. There are winners and losers as well as identifiable at-risk groups that need particular attention. (4) Besides the negative consequences, the pandemic has had a positive impact. The rapidly applied innovations within the system of healthcare responses provide a window of opportunity for positive changes in mental healthcare policies, strategies, and practices. The increased focus on mental health during the pandemic may contribute to the prioritization of mental health issues at policy-making and organizational levels and may reduce stigma. (5) A stress- and trauma-informed response to COVID-19 is required. The European community of psychotraumatologists under the leadership of ESTSS plays an important role in promoting stress- and trauma-informed healthcare and policies of pandemic management. Based on the lessons learned, we propose a stepped-care public mental health model for the prevention of adverse mental health outcomes during pandemics. HIGHLIGHTS: Population mental health is affected differently in the COVID-19 pandemic: there are winners and losers, as well as identifiable at-risk groups that need particular attention.A stress- and trauma-informed public mental health stepped-care model can address pandemic-related mental health burden in a systematic way.

Este articulo proporciona información sobre las consecuencias para la salud mental de la pandemia por la COVID-19 en las subregiones Central, Oriental, Nórdica, Meridional y Occidental de Europa, representadas por cinco países miembros de la Sociedad Europea de Estudios del Estrés Traumático (ESTSS). Sobre la base de las investigaciones y experiencias nacionales existentes en estos países, proponemos cinco lecciones aprendidas: 1. No hay evidencia de una pandemia de salud mental hasta el momento en los países en estudio. No se observa un aumento de los trastornos mentales severos, pero sí un aumento de los síntomas de los trastornos de salud mental comunes. Se necesitan más estudios longitudinales de alta calidad para entender la carga de salud mental de la pandemia; 2. La pandemia afecta a los países (incluida la situación de salud mental) en forma diferente según el nivel de exposición, las políticas de gestión, las características estructurales previas a la pandemia y los recursos de atención en salud; 3. La pandemia afecta a las personas de distintas maneras: la severidad de exposición a los estresores relacionados con la pandemia difiere entre las personas, así como los recursos individuales para hacer frente a estos factores estresantes. Hay ganadores y perdedores así como grupos de riesgo identificables que necesitan atención especial; 4. Además de las consecuencias negativas, la pandemia ha tenido un impacto positivo. Las innovaciones aplicadas rápidamente dentro del sistema de respuestas de atención de la salud son una ventana de oportunidad para cambios positivos en las políticas, estrategias y prácticas de atención de la salud mental. El aumento del enfoque en la salud mental durante la pandemia puede contribuir a la priorización de problemas de salud mental en los niveles organizacionales y de formulación de políticas y podría reducir el estigma; 5. Se requieren respuestas frente a la COVID-19 informadas en estrés y en trauma. La comunidad europea de psicotraumatólogos, bajo el liderazgo de la ESTSS, juega un papel importante en la promoción de la atención en salud informada en estrés y trauma y las políticas de gestión de pandemias. Basados en las lecciones aprendidas, proponemos un modelo de salud mental pública de atención escalonada para la prevención de las consecuencias adversas de salud mental durante las pandemias.

Barriers and facilitators to implementing a continuing medical education intervention in a primary health care setting.

BACKGROUND: Continuing medical education (CME), as a systematic attempt to facilitate change in General Practitioners' (GPs) practices, is considered crucial, assuming that if physicians are up-to-date, they will change and improve their practice, resulting in better performance and ultimately better patient care. However, studies continue to demonstrate considerable gaps between the real and ideal performance and patient-related outcomes. The objective of this study was to explore GP's perception of the factors affecting the implementation of a CME digital platform in a primary health care setting in Portugal. METHODS: Our work is framed in a larger effectiveness-implementation hybrid type 1 study, where a Digital Behaviour Change Intervention (DBCI), called ePrimaPrescribe, was developed and implemented with the aim of changing benzodiazepines (BZD) prescribing patterns. Our design used mixed methodologies to obtain an enriched knowledge on GPs' perspectives on the facilitators and barriers to implementing a Digital Behaviour Change Intervention (DBCI) applied to CME. To do so, we used data coming from an onsite questionnaire, an adapted version of the Barriers and Facilitators Assessment Instrument (BaFAI) and in-depth interviews. RESULTS: From the 47 GPs successfully included in the intervention arm of our cluster-randomized effectiveness study, we collected 37 onsite questionnaires, 24 BaFAIs, and performed 12 in-depth interviews. GPs reported as the main barriers to CME a lack of time, a perception of work overload, a lack of digital competence, a lack of digital infrastructure, and motivational and emotional factors. They reported as facilitators to CME delivered through a DBCI the convenience of the delivery method, the practical and pragmatic characteristics of the content, and the possibility for CME to be mandatory. CONCLUSIONS: The perceptions of the barriers and facilitators reported by GPs represent an important contribution to improving knowledge regarding the factors influencing the implementation of CME in primary health care settings. We consider that our study might bring useful insights to other countries where primary health care plays a central role in the provision of care. TRIAL REGISTRATION: ClinicalTrials.gov number NCT04925596 .

Partitioning of Small Hydrophobic Molecules into Polydimethylsiloxane in Microfluidic Analytical Devices.

Polydimethylsiloxane (PDMS) is ubiquitously used in microfluidics. However, PDMS is porous and hydrophobic, potentially leading to small molecule partitioning. Although many studies addressed this issue and suggested surface/bulk modifications to overcome it, most were not quantitative, did not address which variables besides hydrophobicity governed molecule absorption, and no modification has been shown to completely obviate it. We evaluated qualitatively (confocal microscopy) and quantitatively (fluorescence spectroscopy) the effects of solute/solvent pairings, concentration, and residence time on molecule partitioning into PDMS. Additionally, we tested previously reported surface/bulk modifications, aiming to determine whether reduced PDMS hydrophobicity was stable and hindered molecule partitioning. Partitioning was more significant at lower concentrations, with the relative concentration of rhodamine-B at 20 µM remaining around 90% vs. 10% at 1 µM. Solute/solvent pairings were demonstrated to be determinant by the dramatically higher partitioning of Nile-red in a PBS-based solvent as opposed to ethanol. A paraffin coating slightly decreased the partitioning of Nile-red, and a sol-gel modification hindered the rhodamine-B diffusion into the PDMS bulk. However, there was no direct correlation between reduced surface hydrophobicity and molecule partitioning. This work highlighted the need for pre-assessing the absorption of test molecules into the microfluidic substrates and considering alternative materials for fabrication.

How do European Mature Adults and Elderly Perceive SARS-COV-2 and Associated Control Measures? A Cross-Country Analysis of Mental Health Symptoms in June and July 2020.

Objectives: Recent literature points out that elderly people are psychologically resilient to COVID-19, but the studies were performed in specific contexts. We measured the link between the worsening of mental health symptoms, the epidemiologic situation, and control measures among European people aged 50 or older. Methods: We used data from the 2020 wave of SHARE, merged with Oxford COVID-19 Government Response Tracker data (n = 38,358). We modeled the risk of worsening of depression, anxiety, sleeping trouble, and loneliness symptoms' self-perception, as functions of control measures and 7-days death incidence, using logistic regressions. Results: The worsening of anxiety and depression perception were more common (16.2 and 23.1%, respectively), compared to that of sleeping troubles and loneliness (8.1 and 11.5%, respectively). The worsening of depression and anxiety perception was negatively related to the rigor of control measures. The seven-days death incidence was positively linked to all symptoms except sleeping troubles. Conclusion: Older people were the most exposed to death risk and were affected psychologically by the COVID-19 epidemiological situation; yet control measures were protective (or neutral) to their mental health condition.