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The pericellular matrix (PCM) surrounding chondrocytes is essential for articular cartilage tissue engineering. As the current isolation methods to obtain chondrocytes with their PCM (chondrons) result in a heterogeneous mixture of chondrocytes and chondrons, regenerating the PCM using a tissue engineering approach could prove beneficial. In this study, we aimed to discern the behavior of articular chondrocytes (ACs) in regenerating the PCM in such an approach and whether this would also be true for articular cartilage-derived progenitor cells (ACPCs), as an alternative cell source. Bovine ACs and ACPCs were encapsulated in agarose microgels using droplet-based microfluidics. ACs were stimulated with TGF-β1 and dexamethasone and ACPCs were sequentially stimulated with BMP-9 followed by TGF-β1 and dexamethasone. After 0, 3, 5, and 10 days of culture, PCM components, type-VI collagen and perlecan, and ECM component, type-II collagen, were assessed using flow cytometry and fluorescence microscopy. Both ACs and ACPCs synthesized the PCM before the ECM. It was seen for the first time that synthesis of type-VI collagen always preceded perlecan. While the PCM synthesized by ACs resembled native chondrons after only 5 days of culture, ACPCs often made less well-structured PCMs. Both cell types showed variations between individual cells and donors. On one hand, this was more prominent in ACPCs, but also a subset of ACPCs showed superior PCM and ECM regeneration, suggesting that isolating these cells may potentially improve cartilage repair strategies.

Abstract Clonal growth and competition underlie processes of key relevance in etiology, progression and therapy response across all cancers. Here, we demonstrate a novel experimental approach, based on multi-color, fluorescent tagging of cell nuclei, in combination with picoliter droplet deposition, to study the clonal dynamics in two- and three-dimensional cell cultures. The method allows for the simultaneous visualization and analysis of multiple clones in individual multi-clonal colonies, providing a powerful tool for studying clonal dynamics and identifying clonal populations with distinct characteristics. Results of our experiments validate the utility of the method in studying clonal dynamics in vitro, and reveal differences in key aspects of clonal behavior of different cancer cell lines in monoculture conditions, as well as in co-cultures with stromal fibroblasts.

OBJECTIVES: This study aimed to examine whether (i) metabolic syndrome (MetS) increases the risk for premature employment exit and (ii) a dose–response relationship exists between an increasing number of MetS components and premature employment exit among middle-aged and older workers.METHODS: A sample of N=60 427 Dutch workers (40–64 years old) from the Lifelines Cohort Study and Biobank were examined using data from five measurement waves during a total median follow-up time of 4.2 years. MetS components were based on physical measures, blood markers, and medication use. Premature employment exit types (ie, unemployment, work disability, and early retirement) were determined using questionnaires. MetS and number of MetS components were examined as risk factors for premature employment exit using competing risk regression analysis.RESULTS: MetS significantly increased the risk for work disability [adjusted sub distribution hazard ratio (SHR) 1.78, 95% confidence interval (CI) 1.54–2.05] and unemployment (adjusted SHR 1.16, 95% CI 1.06–1.26). A clear dose–response relationship was found for an increasing number of MetS components and work disability. No associations were found between MetS (components) and early retirement after adjusting for sociodemographic factors.CONCLUSIONS: MetS was identified as a modifiable early-stage cardio-metabolic risk factor especially for work disability and, to a lesser extent, for unemployment. Further, a clear dose–response relationship was found between an increasing number of MetS components and work disability. MetS interventions and prevention might help to prolong working lives. More awareness is needed among employers and occupational health professionals about the premature employment exit risk faced by middle-aged and older workers with MetS.

OBJECTIVE: Jobs characterized by low job demands and high job resources are associated with better work outcomes, yet it remains unclear whether this is the case for workers with depression. This study examined whether depression moderates the relationship between job demands, job resources, and maintaining employment. METHODS: Data from the longitudinal population-based Lifelines cohort study were matched with register data on employment from Statistics Netherlands (N=55 950). Job demands included quantitative demands and work pace; job resources included influence at work and possibilities for development. The two-way interaction between job demands and depression and the three-way interaction between job demands, job resources and depression were examined in a zero-inflated Poisson regression model with path 1, including a binary employment outcome, and path 2, a count variable including months out of employment. RESULTS: The interaction effect of job demands and depression on being employed was significant [b=-0.22, 95% confidence interval (CI) -0.44‒0.01]. Workers without depression were more likely to be employed whereas workers with depression were less likely to be employed if they had high job demands. The three-way interaction between job demands, job resources, and depression was significant for months out of employment (b=0.15, 95% CI 0.01‒0.29), indicating that workers with depression had more months out of employment when reporting high job demands and high job resources compared to workers without depression. Discussion Although increasing influence at work and possibilities for development to prevent negative work outcomes may be beneficial for workers without depression, this approach might be limited for workers with depression.

Among Japanese film director Kurosawa Akira’s three Shakespeare films, Throne of Blood (1957), Ran (1985), and The Bad Sleep Well (1960), the latter has been relatively ignored in Anglophone Shakespeare criticism. This article investigates the Anglophone reception of The Bad Sleep Well and argues in favor of its re-appraisal as a Hamlet. On reception, it examines three explanations for the neglect: its modern setting, its deconstructive adaptation, and its cinematic quality. Considering the latter unconvincing, the article posits that the first two were only detrimental to the film’s reception because they respectively did not conform to Western expectations of essentially pre-modern ‘Oriental’ Japan and of ‘straight’ canonical Shakespeare. Considering changed attitudes in Shakespeare studies, neither of these should still be held against the film. On re-appraisal, The Bad Sleep Well may be reread in the 21st century as part of our continuing memory of our global Shakespeare discourse. Centering on the film’s innovative presentation of Claudius and The Mousetrap, the article argues for the porous border between ‘straight’ production and ‘crooked’ adaptation, and the value to the tradition of oblique approaches to familiar scenes and characters. By arguing for The Bad Sleep Well as a Hamlet worthy of study, the article furthers discussion on archival silences and new rhizomatic models of global Shakespeare that seek to move past the more reductive qualities of the ‘national Shakespeares’ mode of discourse that dominated in the 1990s and 2000s.

Mental health problems in the workforce present a major public and occupational health challenge and come with significant costs for the individuals, families, employers and society at large. It has been estimated that, globally, the 12-month prevalence of common mental health problems – such as depressive disorders, anxiety disorders, and stress-related disorders – is on average 17.6%, with often serious implications for employment, productivity, and wages (2, 3). The recent OECD report “Fitter Minds, Fitter Jobs” showed that in 2018, across OECD countries, people with mental health problems have 20% lower employment rates, are almost three times more likely to be unemployed, and almost one and a half times more likely to receive disability benefits as those without these problems (2). These key figures barely differ from those presented in 2013 (2). During the past decades, research on the highly complex phenomenon of (return to) work participation of people with common mental health problems has come a long way: many barriers and facilitators to (return to) working have been identified and interventions have been developed and tested for people with common mental health problems to participate in work (eg, 4, 5). To illustrate, facilitating factors concern, for example, an individual’s active coping style (keep a daily rhythm, exercise, stay in contact with work), high self-efficacy, and a supportive family context and social network (5-8); while the severity of mental health problems or the existence of other health problems are known barriers (5). A safe organizational climate (such as openness about mental health) and good psychosocial working conditions, including support from supervisors and colleagues, having decision authority, and no high workload, have been identified as facilitating workplace factors (5, 7, 8). Also, health and social systems may act as a barrier or facilitator with, eg, waiting lists for mental health treatment or the availability of integrative mental health and occupational rehabilitation/employment services (7, 9). It comes as no surprise that Corbière et al (10) identified 11 different stakeholder groups from the work, health and insurance systems and close to 200 relevant stakeholder actions in the return-to-work process of workers with common mental health problems. Despite extensive progress and a large body of evidence on factors to facilitate the (return to) work participation of workers with common mental health problems (for systematic reviews and meta-analyses, covering more than two decades of research, see, eg, 5, 9, 11), we must acknowledge that meta-analyses of intervention studies to date only have shown small effect sizes for sick leave reduction (4, 12–14) and no substantial effects for improved return-to-work (13) or being at work (14) rates. So, how to move the research field forward? Although people with common mental health problems have lower employment rates, the majority (60% on average across OECD countries) is working (OECD 2021), but knowledge about maintaining and improving at-work participation among this group is lacking. We see a great need for a focus shift towards a deeper understanding of at-work participation of people with common mental health problems. In the following, we focus on two challenges and avenues to move forward: (i) measuring at-work outcomes and (ii) examining the complex, interdependent relationship between common mental health problems and at-work participation with more intense, longitudinal real-time designs and a life course lens. Challenges and avenues to support people with common mental health problems at work Challenge 1: Measurement of at-work outcomes The first challenge concerns the measurement of how people with common mental health problems participate or function at work and what their needs are to enter and stay at work. To better support workers with common mental health problems at work, it is critical to further deepen our understanding of the strategies, work accommodation needs and functioning of these workers. To illustrate, in a qualitative study among workers suffering from common mental health problems, Danielsson et al (15) explored “strategies to keep working”. The authors showed that workers` strategies differed depending on the illness phase; ie, more reactive strategies to avoid strain were used in early phases and more reflective, solution-focused strategies were used in later phases. This knowledge on phase-specific work strategies may be used to better inform and tailor supportive interventions and work accommodation to help workers to maintain working. De Groot et al (16) recently provided first insights about how young adults with a history of mental health problems function at work. It was shown that young adults with both persistent high and elevated levels of mental health problems during childhood and adolescence, compared with those with low-level mental health problems, experience difficulties in meeting their work demands for more than one day a week given a full-time work week at age 29. Moreover, Arends et al (17) showed that many workers who returned to work after being absent with common mental health problems still experience impaired work functioning for up to 12 months. This study also demonstrated that workers recover at a different pace and at a different level in terms of mental health and work functioning. These findings highlight the importance of focusing on at-work strategies and functioning to support workers with common mental health problems as we need to capture early signs of maladaptive strategies or reduced functioning that may inform work accommodations to prevent a further decline in functioning or even more severe consequences as sick leave or work disability. Accommodating work for workers with (common) mental health problems may be especially challenging, as opposed to other health conditions, given the strong stigma attached to mental ill-health (18, 19). As discussed by LaMontagne et al (20), an integrated intervention approach to workplace mental health, combining knowledge from various disciplines (eg, occupational medicine, psychiatry, public health, -positive- psychology) and focusing on both protecting and promoting mental health as well as addressing mental health problems is essential (20). To assess and monitor the abilities to accomplish the work role, it is vital to consider at-work outcomes, such as health-related work functioning, work limitations, work instability, and work capabilities (21–24). Ideally, such outcomes – existing or to be developed – are at the intersection of a persons’ health and work performance, reflect the ability and/or need of a person to meet the work demands given the available personal and/or environmental resources, and provide information for the content and timing of work accommodations. We strongly encourage future research to (further) rigorously test the measurement properties of existing and to be developed at-work measures, in particular the responsiveness to change, within the population of workers with common mental health problems. Challenge 2: Examination of the complex, interdependent relationship between common mental health problems and at-work participation: novel designs and a life course lens The second challenge concerns the need to better understand the complex, interdependent relationship between common mental health problems and at-work participation. To provide adequate and timely support for workers with common mental health problems at work, it is critical to further unravel the underlying mechanisms and (environmental) conditions of this complex, dynamic relationship, as different support policies and programs need to be in place at different time periods to address either common mental health problems or at-work participation. We would like to encourage future longitudinal studies to not shy away from complexity but to use approaches that capture the dynamics of both common mental health problems and at-work participation by, eg, repeatedly and more intensively assessing both concepts over time. Not new, but to be considered in occupational health research and practice, may be the use of intensive, longitudinal real-time designs, as recently applied in single-subject time-series studies in psychiatry, addressing psychopathology as a complex system (eg, 25, 26). For example, to detect personalized early warning signals preceding the occurrence of a major depressive symptom transition, Wichers et al (26) conducted six single-subject time-series studies over a 3–6-month period, prospectively collecting frequent observations of momentary affective states (reported up to three times a day) during a time period when participants were at increased risk of a depressive symptom transition (reported weekly). The results showed (and replicated) the presence of rising early warning signals a month before the symptom transition occurred. To improve personalized support of workers with common mental health problems at work, this type of information is highly needed. What makes the relationship between common mental health problems and at-work participation even more complex is the fact that a person’s mental health does not start when work begins; ie, what happens before a person enters the workforce affects both the health resources a person brings to work and the work opportunities (27). As most research so far measured common mental health problems during working adults’ life, and not across the life course, knowledge on the impact of early life mental health experiences on at-work participation in later life is almost absent. Again, the findings of de Groot et al (16) highlight the importance of adopting a life course perspective by considering the concept of ‘accumulation of health risk or health advantages’ when connecting early life mental health experiences with work functioning. A life course perspective may also help advance future studies on the dynamics between different life domains (7), eg, the interplay between work and private life, as it recognizes an individual’s life course as a multi-level developmental process shaped by the social context. A focus shift towards supporting workers with common mental health problems at work also requires all key stakeholders in the healthcare system, the legal/administrative system, the work system and the personal and family system to work together – which may be a challenge in itself. However, in view of more inclusive workplaces and labor markets, we need to take the next steps to enable, maintain and improve at-work participation of workers with common mental health problems. References 1. Steel Z, Marnane C, Iranpour C, Chey T, Jackson JW, Patel V, Silove D. The global prevalence of common mental disorders: a systematic review and meta-analysis 1980-2013. 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Abstract Background Evidence on the association between the presence of fast-food outlets and Body Mass Index (BMI) is inconsistent. Furthermore, mechanisms underlying the fast-food outlet presence-BMI association are understudied. We investigated the association between the number of fast-food outlets being present and objectively measured BMI. Moreover, we investigated to what extent this association was moderated by neighbourhood socio-economic status (NSES) and healthy food outlets. Additionally, we investigated mediation by frequency of fast-food consumption and amount of fat intake. Methods In this cross-sectional study, we used baseline data of adults in Lifelines (N = 149,617). Geo-coded residential addresses were linked to fast-food and healthy food outlet locations. We computed the number of fast-food and healthy food outlets within 1 kilometre (km) of participants’ residential addresses (each categorised into null, one, or at least two). Participants underwent objective BMI measurements. We linked data to Statistics Netherlands to compute NSES. Frequency of fast-food consumption and amount of fat intake were measured through questionnaires in Lifelines. Multivariable multilevel linear regression analyses were performed to investigate associations between fast-food outlet presence and BMI, adjusting for individual and environmental potential confounders. When exposure-moderator interactions had p-value