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Ruptures of the extensor apparatus can have different etiologies and be complicated by underlying situations. Direct repair is not always possible, and reconstruction procedures can be insufficient, which leads to the appearance of multiple augmentation techniques to improve the strength of these constructs. Despite the proven results of these techniques, numerous procedures are described without any gold standard. We present our augmentation method for repairing the knee extensor apparatus with a vascular prosthesis that facilitates healing, does not interfere with the primary procedure, has no donor morbidity or rejection risk, and allows earlier mobilization and rehabilitation. The technique was used in different cases with multiple etiologies that needed reinforcement, with promising results.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.

Abstract The fungus Parastagonospora nodorum causes septoria nodorum blotch on wheat. The role of the fungal Velvet-family transcription factor VeA in P. nodorum development and virulence was investigated here. Deletion of the P. nodorum VeA ortholog, PnVeA, resulted in growth abnormalities including pigmentation, abolished asexual sporulation and highly reduced virulence on wheat. Comparative RNA-Seq and RT-PCR analyses revealed that the deletion of PnVeA also decoupled the expression of major necrotrophic effector genes. In addition, the deletion of PnVeA resulted in an up-regulation of four predicted secondary metabolite (SM) gene clusters. Using liquid-chromatography mass-spectrometry, it was observed that one of the SM gene clusters led to an accumulation of the mycotoxin alternariol. PnVeA is essential for asexual sporulation, full virulence, secondary metabolism and necrotrophic effector regulation.

While the coronavirus disease 2019 (COVID-19) pandemic placed a heavy burden on healthcare systems worldwide, it also induced urgent mobilisation of research teams to develop treatments preventing or curing the disease and its consequences. It has, therefore, challenged critical care research to rapidly focus on specific fields while forcing critical care physicians to make difficult ethical decisions. This narrative review aims to summarise critical care research -from organisation to research fields- in this pandemic setting and to highlight opportunities to improve research efficiency in the future, based on what is learned from COVID-19. This pressure on research revealed, i.e., (i) the need to harmonise regulatory processes between countries, allowing simplified organisation of international research networks to improve their efficiency in answering large-scale questions; (ii) the importance of developing translational research from which therapeutic innovations can emerge; (iii) the need for improved triage and predictive scores to rationalise admission to the intensive care unit. In this context, key areas for future critical care research and better pandemic preparedness are artificial intelligence applied to healthcare, characterisation of long-term symptoms, and ethical considerations. Such collaborative research efforts should involve groups from both high and low-to-middle income countries to propose worldwide solutions. As a conclusion, stress tests on healthcare organisations should be viewed as opportunities to design new research frameworks and strategies. Worldwide availability of research networks ready to operate is essential to be prepared for next pandemics. Importantly, researchers and physicians should prioritise realistic and ethical goals for both clinical care and research.

Abstract Hypercholesterolemia is characterized by elevated low‐density lipoprotein (LDL)‐cholesterol levels and an increased risk of cardiovascular disease. The adipokine chemerin is an additional risk factor. Here we investigated whether cholesterol‐lowering with statins or proprotein convertase subtilisin‐kexin type 9 inhibitors (PCSK9i) affects chemerin. Both statins and PCKS9i lowered plasma LDL‐cholesterol, triglycerides and total cholesterol in hypercholesterolemic patients, and increased high‐density lipoprotein (HDL)‐cholesterol. Yet, only statins additionally reduced chemerin and high‐sensitivity C‐reactive protein (hsCRP). Applying PCSK9i on top of statins did not further reduce chemerin. Around 20% of chemerin occurred in the HDL2/HDL3 fractions, while >75% was free. Statins lowered both HDL‐bound and free chemerin. Pull‐down assays revealed that chemerin binds to the HDL‐component Apolipoprotein A‐I (ApoA‐I). The statins, but not PCSK9i, diminished chemerin secretion from HepG2 cells by upregulating LDL receptor mRNA. Furthermore, chemerin inhibited HDL‐mediated cholesterol efflux via its chemerin chemokine‐like receptor 1 in differentiated macrophages. In conclusion, statins, but not PCSK9i, lower circulating chemerin by directly affecting its release from hepatocytes. Chemerin binds to ApoA‐I and inhibits HDL‐mediated cholesterol efflux. Statins prevent this by lowering HDL‐bound chemerin. Combined with their anti‐inflammatory effect evidenced by hsCRP suppression, this represents a novel cardiovascular protective function of statins that distinguishes them from PCSK9i.

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS). Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time. Results: On the 1st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged

Purpose: This meta-analysis evaluates the mid- to long-term survival outcome of MAT (meniscal allograft transplantation). Potential prognosticators, with particular focus on chondral status and age of the patient at the time of transplantation, were also analysed. Study design: Meta-analysis. Methods: An online database search was performed using following search string: “meniscal allograft transplantation” and “outcome”. A total of 65 articles were analysed for a total of 3157 performed MAT with a mean follow-up of 5.4 years. Subjective and clinical data was analysed. Results: The subjective and objective results of 2977 patients (3157 allografts) were analysed; 70% were male, 30% were female. Thirty-eight percent received an isolated MAT. All other patients underwent at least one concomitant procedure. Lysholm, Knee injury and Osteoarthritis Outcome (KOOS), International Knee Documentation Committee (IKDC) and Visual Analogue Scale (VAS) scores were analysed. All scores showed a good patient satisfaction at long-term follow-up. The mean overall survival rate was 80.9%. Complication rates were comparable to standard meniscal repair surgery. There was a degenerative evolution in osteoarthritis with at least one grade in 1760 radiographically analysed patients. Concomitant procedures seem to have no effect on the outcome. Age at transplantation is a negative prognosticator. The body mass index (BMI) of the patient shows a slightly negative correlation with the outcome of MAT. Conclusions: MAT is a viable solution for the younger patient with chronic pain in the meniscectomised knee joint. The complications are not severe and comparable to meniscal repair. The overall failure rate at final follow-up is acceptable and the allograft heals well in most cases, but MAT cannot be seen as a definitive solution for post-meniscectomy pain. The correct approach to the chronic painful total meniscectomised knee joint thus requires consideration of all pathologies including alignment, stability, meniscal abnormality and cartilage degeneration. It requires possibly combined but appropriate action in that order.

Diversity in terms of class, sexual identity and migration background among medical students in high income countries has increased greatly in recent decades. Some research into the experiences of these new groups of doctors has been performed. However, no previous research into the experiences of psychiatry residents specifically, is known. This qualitative study investigates how psychiatry residents, from these minoritized groups, experience their training regarding inclusion. Inclusion is defined as the degree to which one's needs for connection and for being valued in one's uniqueness, is satisfied. In-depth interviews with 16 psychiatry residents were conducted. These interviews were transcribed and coded using MaxQDA software. Initial themes that were constructed, were explored further in subsequent interviews and linked to literature. Finally, the developed themes were ordered in a model conceptualizing inclusion. Participants reported high belongingness within psychiatry training. Their experienced value in uniqueness, however, was generally quite low. Participants reported to experience little interest in and sensitivity for their perspectives and lived experiences from their co-workers. When faced with stigmatization and discrimination, participants reported lack of support from their colleagues. Assimilation was found to be the most frequently used coping strategy in dealing with diversity. Participants seemed to conform to the 'neutral' norm and experienced barriers in expressing themselves. Through this mechanism of assimilation, the added value that participants might bring with their unique knowledge and lived experiences was not used, both in patient care and in creating an inclusive climate within the organization. Moreover, assimilation is associated with psychological strain.

Introduction Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective.Methods and analysis The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement.Ethics and dissemination The trial was approved by the London—Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.Trial registration number ISRCTN87336549.

Workplace health promotion (WHP) may be an appropriate way to support women with a low socioeconomic position (SEP) during midlife. Little is known about reaching and engaging women in WHP, particularly not at the intersection of midlife, low SEP, and ethnicity. We initiated the ProudWoman project, in which we implemented a WHP intervention aimed at supporting midlife women as a pilot in an academic hospital. We qualitatively evaluated the implementation using the RE-AIM framework. The pilot comprised multiple steps: tailoring the intervention to the needs of ethnically diverse group of midlife women with a low SEP, developing an implementation protocol, implementing the tailored intervention, and evaluating the implementation process. The main findings of our study are: (1) due to a wide range of recruitment activities that were actively deployed, we were able to "reach" an ethnically diverse group of midlife women with a low SEP; (2) regarding "adoption," awareness of the relevance of this topic as an occupational health challenge was not self-evident at the organizational level; (3) according to our participants, various facilitators and barriers should be taken into account in the "implementation" of the work-life program; and (4) our focus group discussion revealed as "maintenance" is relevant to these levels in different ways, awareness of midlife and menopause as an occupational health challenge should be raised at four professional levels. We conclude that elements, such as an active and personal recruitment approach, are important in the implementation of WHP for ethnically diverse midlife women with an SEP.

Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. The high-dimensional dataset was integrated into a multiomic model that predicted the time to spontaneous labor [R = 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 × 10-40, N = 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 × 10-7, N = 10, independent test set]. Coordinated alterations in maternal metabolome, proteome, and immunome marked a molecular shift from pregnancy maintenance to prelabor biology 2 to 4 weeks before delivery. A surge in steroid hormone metabolites and interleukin-1 receptor type 4 that preceded labor coincided with a switch from immune activation to regulation of inflammatory responses. Our study lays the groundwork for developing blood-based methods for predicting the day of labor, anchored in mechanisms shared in preterm and term pregnancies.

Abstract Background School dropout is a persisting problem with major socioeconomic consequences. Although poor health probably contributes to pathways leading to school dropout and health is likely negatively affected by dropout, these issues are relatively absent on the public health agenda. This emphasises the importance of integrative research aimed at identifying children at risk for school dropout at an early stage, discovering how socioeconomic status and gender affect health-related pathways that lead to dropout and developing a prevention tool that can be used in public health services for youth. Methods/design The SIODO study is a sequential mixed-methods study. A case–control study will be conducted among 18 to 24 year olds in the south of the Netherlands (n = 580). Data are currently being collected from compulsory education departments at municipalities (dropout data), regional public health services (developmental data from birth onwards) and an additional questionnaire has been sent to participants (e.g. personality data). Advanced analyses, including cluster and factor analyses, will be used to identify children at risk at an early stage. Using the quantitative data, we have planned individual interviews with participants and focus groups with important stakeholders such as parents, teachers and public health professionals. A thematic content analysis will be used to analyse the qualitative data. Discussion The SIODO study will use a life-course perspective, the ICF-CY model to group the determinants and a mixed-methods design. In this respect, the SIODO study is innovative because it both broadens and deepens the study of health-related determinants of school dropout. It examines how these determinants contribute to socioeconomic and gender differences in health and contributes to the development of a tool that can be used in public health practice to tackle the problem of school dropout at its roots.

Abstract Background To ascertain good and appropriate healthcare for both women and men implementation of gender perspectives in medical education is needed. For a successful implementation, knowledge about students' attitudes and beliefs about men, women, and gender is crucial. The aim of this study was to compare attitudes to gender and gender stereotyping among Dutch and Swedish male and female medical students. Methods In this cross-sectional study, we measured the attitudes and assumptions about gender among 1096 first year medical students (616 Dutch and 480 Swedish) with the validated Nijmegen Gender Awareness in Medicine Scale (N-GAMS). The response rate was 94% in the Netherlands and 93% in Sweden. Univariate analysis of variance (ANOVA) was used to compare the scores between Dutch and Swedish male and female students. Linear regressions were used to analyze the importance of the background variables. Results There were significant differences in attitudes to gender between Dutch and Swedish students. The Swedish students expressed less stereotypical thinking about patients and doctors and the Dutch were more sensitive to gender differences. The students' sex mattered for gender stereotyping, with male students in both countries agreeing more with stereotypical statements. Students' age, father's birth country and mother's education level had some impact on the outcome. Conclusions There are differences between cultures as well as between men and women in gender awareness that need to be considered when implementing gender in medical education. This study suggests that to arouse the students' interest in gender issues and make them aware of the significance of gender in medical work, the examples used in discussions need to be relevant and challenging in the context of the specific country. Due to different levels of knowledge and different attitudes within the student population it is important to create a climate for dialogue where students feel permitted to disclose their ideas and attitudes in order to become aware of what these are as well as their possible consequences on interaction and decision-making in medical work.

Abstract Background A good understanding of the aetiology and development of burnout facilitates its early recognition, prevention and treatment. Since the prevalence and onset of this health problem is thought to differ between men and women, sex must be taken into account. This study aims to assess the prevalence and development of burnout among General Practitioners (GPs). In this population the prevalence of burnout is high. Methods We performed a three-wave longitudinal study (2002, 2004, 2006) in a random sample of Dutch GPs. Data were collected by means of self-report questionnaires including the Maslach Burnout Inventory. Our final sample consisted of 212 GPs of which 128 were male. Data were analyzed by means of SPSS and LISREL. Results Results indicate that about 20% of the GPs is clinically burned out (but still working). For both sexes, burnout decreased after the first wave, but increased again after the second wave. The prevalence of depersonalization is higher among men. With regard to the process of burnout we found that for men burnout is triggered by depersonalization and by emotional exhaustion for women. Conclusions As regards the developmental process of burnout, we found evidence for the fact that the aetiological process of burnout, that is the causal order of the three burnout dimensions, differs between men and women. These sex differences should be taken into account in vocational training and policy development, especially since general practice is feminizing rapidly.

Abstract Background Being female is a strong predictor of health promoting behaviours. Workplaces show great potential for lifestyle interventions, but such interventions do not necessarily take the gendered background of lifestyle behaviours into account. A perspective analyzing how masculine gender norms affect health promoting behaviours is important. This study aims to explore men's health beliefs and attitudes towards health promotion; in particular, it explores workplace physical activity in relation to masculine ideals among male employees. Methods In the Fall of 2008, we interviewed 13 white Dutch male employees aged 23-56 years. The men worked in a wide range of professions and occupational sectors and all interviewees had been offered a workplace physical activity program. Interviews lasted approximately one to one-and-a-half hour and addressed beliefs about health and lifestyle behaviours including workplace physical activity, as well as normative beliefs about masculinity. Thematic analysis was used to analyze the data. Results Two normative themes were found: first, the ideal man is equated with being a winner and real men are prepared to compete, and second, real men are not whiners and ideally, not vulnerable. Workplace physical activity is associated with a particular type of masculinity - young, occupied with looks, and interested in muscle building. Masculine norms are related to challenging health while taking care of health is feminine and, hence, something to avoid. Workplace physical activity is not framed as a health measure, and not mentioned as of importance to the work role. Conclusions Competitiveness and nonchalant attitudes towards health shape masculine ideals. In regards to workplace physical activity, some men resist what they perceive to be an emphasis on muscled looks, whereas for others it contributes to looking self-confident. In order to establish a greater reach among vulnerable employees such as ageing men, worksite health promotion programs including workplace physical activity may benefit from greater insight in the tensions between health behaviours and masculinity.

Abstract Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness.