Incidence of dementia after age 90 in a multiracial cohort

Introduction

Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence.

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Work hazards and workers’ mental health: an investigation based on the fifth European Working Conditions Survey

Background:Workplace hazards are a significant source of health impairment for workers and of financial losses for firms. EU directives on workers’ health and safety standards significantly contributed to reduce reported occupational injuries, yet the incidence and prevalence of work-related mental illness is still very high.Objectives:We investigated the association between work-related hazards and individuals’ perceived mental health. We reviewed the existing evidence on the channels through which task-related factors, adverse agents and psychosocial factors are expected to affect workers’ health, with specific regard to mental health.Methods:We used data from the fifth wave of the European Working Conditions Survey, covering over 40,000 face-to-face interviews with workers in 34 countries, which includes information on socio-demographic characteristics, firms and jobs attributes, employment status, as well as working conditions and health status. We carried out an empirical analysis with multivariate regression models in order to estimate the relationship between workers’ mental health problems and workplace risk factors.Results:21,020 interviews were used in the multivariate analysis. We found strong correlations between hazards and various indicators of mental health. Among hazardous agents, low temperatures (β=0.0287) and contact with infectious materials (β=0.0394) were positively associated with mental health outcomes. Among task/sequence-related factors, tiring or painful positions (β=0.0713), repetitive hand/arm movements (β=0.0255), working with VDUs (β=0.0301), repetitive tasks <10 min (β=0.0859) and working in evenings (β=0.00754) were positively associated with mental health. Various psychosocial risk factors related to both the content of the job (for example, frequent disruptive interruptions: β=0.219, working in free time: β=0.0759, poor work-life balance: β=0.228) as well as the job context (for example, bad employment prospects: β=0.177, low decisional autonomy: β=0.245, bad social relations: β=0.186, workplace violence: β=0.411) were positively associated with mental health. The main results of the decomposition show that an important contribution to workers’ overall mental distress at work is associated with psychosocial risk factors (up to 60% for depression/anxiety symptoms and sleep disorders), while the contribution of somatic factors is on average lower (up to 20% for overall fatigue).Conclusions:We argue that action is needed to improve workers’ mental well-being, and reduce the economic costs for both the national health system and employers. Regulations and traditional economic measures are unlikely to prove successful in providing adequate standards of primary and secondary preventive measures in the work place without an appropriate and reliable Risk Assessment Procedure.Key words: Work hazards, risk assessment, job content, mental health