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© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES The determinants of poor functioning and subsequent early exit from work are well established but very little is known about the positive determinants of maintaining good functioning among the ageing workforce. We investigated modifiable determinants of maintaining good mental and physical health functioning. METHODS We used prospective survey data collected across four waves among the midlife employees of the City of Helsinki, Finland, 2000-2017 (n=3342). Health functioning was repeatedly measured using the Short Form 36 (SF-36) inventory. Trajectories of mental and physical health functioning were separately examined using group-based trajectory analysis. Multinomial logistic regression models were fitted to examine determinants of each trajectory. RESULTS Four trajectory solutions for the developmental patterns in health functioning during the follow-up period were selected, with a slightly different shape of the first trajectory for mental and physical functioning (1) continuously low (mental), low and decreasing (physical), (2) increasing, (3) decreasing and (4) continuously high functioning. After adjustments, the employees in the continuously high mental health functioning group were more likely to have optimal job demands, high job control, no sleep problems and no binge drinking behaviour. Employees in the continuously high physical functioning group had more likely low levels of physically strenuous work and hazardous working environment and no sleep problems and normal weight. CONCLUSION High job control, good sleep and avoiding binge drinking may help maintain good mental health functioning. Low levels of physical or environmental work exposures, good sleep and recommended healthy weight may support maintenance of good physical health functioning among ageing employees. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. Entospletinib Syk inhibitor They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin-Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of wild-type PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor-like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights in ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.BACKGROUND We examine the association among five types of state regulations on electronic cigarettes (defining e-cigarettes, special tax, packaging, youth access and licensure) and initiation and current usage of e-cigarettes in 50 US states and the District of Columbia. METHODS Data came from the 2017 Behavioral Risk Factor Surveillance System and the US e-cigarette regulations - 50 state review by the Public Health Law Center. Logistic regressions were used to determine the odds of initiation and current use of e-cigarettes among individuals aged 18-24, 25-34 and the whole sample, adjusting for socio-demographic covariates. RESULTS Despite the short history of state laws on e-cigarettes, each of the five state laws was associated with lower odds of initiation and use of e-cigarettes in the whole sample. In the 18-24 age group, only the licensure was associated with lower initiation. In the 25-34 age group, the licensure and taxation were related to lower initiation and current usage. There were significant differences of e-cigarette initiation and usage based on the number of state laws regulating e-cigarettes. CONCLUSIONS Our analysis indicates the potential of states' policy efforts to regulate e-cigarettes comprehensively in leading significant changes to e-cigarette prevalence in their populations. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Spine surgery research has improved considerably over the last few decades. Its' most recent growth is in large part due to the mounting increase in studies conducted using national databases and registries. With easy access to a large number of patients, the benefit of these registries has become evident. However, as with any research, this type of data must be used responsibly with the appropriate strengths and limitations kept in mind. Inappropriate use of these registries continues to be a growing concern as potentially false or inaccurate conclusions can adversely impact clinical practice. It is, therefore, the author and the readers' responsibility to acknowledge and understand the limitations of this type of data. Knowledge of methodological requirements in the use and analyses of registry data is essential to ensuring quality evidence with proper interpretation. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

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