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Little is known about the early pathogenic events by which mutant superoxide dismutase 1 (SOD1) causes amyotrophic lateral sclerosis (ALS). This lack of mechanistic understanding is a major barrier to the development and evaluation of efficient therapies. Although protein aggregation is known to be involved, it is not understood how mutant SOD1 causes degeneration of motoneurons (MNs). Previous research has relied heavily on the overexpression of mutant SOD1, but the clinical relevance of SOD1 overexpression models remains questionable. We used a human induced pluripotent stem cell (iPSC) model of spinal MNs and three different endogenous ALS-associated SOD1 mutations (D90Ahom, R115Ghet or A4Vhet) to investigate early cellular disturbances in MNs. Although enhanced misfolding and aggregation of SOD1 was induced by proteasome inhibition, Cells 2022, it was not affected by activation of the stress granule pathway. Interestingly, we identified loss of mitochondrial, but not lysosomal, integrity as the earliest common pathological phenotype, which preceded elevated levels of insoluble, aggregated SOD1. A super-elongated mitochondrial morphology with impaired inner mitochondrial membrane potential was a unifying feature in mutant SOD1 iPSC-derived MNs. Impaired mitochondrial integrity was most prominent in mutant D90Ahom MNs, whereas both soluble disordered and detergent-resistant misfolded SOD1 was more prominent in R115Ghet and A4Vhet mutant lines. Taking advantage of patient-specific models of SOD1-ALS in vitro, our data suggest that mitochondrial dysfunction is one of the first crucial steps in the pathogenic cascade that leads to SOD1-ALS and also highlights the need for individualized medical approaches for SOD1-ALS.

Purpose: The first objective was to contribute to a better understanding of the contrasting and paradoxical results in studies of work environment factors and sickness presence and sickness absence. A second objective was to examine if, and under what conditions, employees choose to replace sickness absence with sickness presence, i.e., so-called substitution. Methods: The study utilizes a large body of cross-sectional questionnaire data (n = 130,161) gathered in Sweden from 2002 to 2007 in connection with a comprehensive health promotion initiative. Health and motivation were analyzed as mediators of the effects of five job factors, job control, job support, job demand, role conflict and “work to family conflict” on sickness presence and absence. Results: The results concerning job demands indicate substitution in that increased job demands are associated with increased presenteeism and reduced absenteeism. The direct effect of higher job support was increased absenteeism, but via the health and motivation paths, the total effect of more social support was health-promoting and associated with a reduction in sickness absence and sickness presence. High job control emerged as the most pronounced health-promoting factor, reducing sickness presenteeism as well as absenteeism. More role conflicts and work-to-family conflicts were directly and indirectly associated with decreased health and increased absenteeism as well as presenteeism. earlier research. Conclusion: The mediation analyzes shed light on some of the paradoxes in research on sickness presenteeism and sickness absenteeism, especially regarding job demands and job support. The substitution effect is important for workplace policy and occupational health practice., The study was supported and financed by AFA Insurance. Dnr: 170100.

The relationship between whiplash trauma and chronic orofacial pain is unclear, especially with regard to the time elapsed from trauma to development of orofacial pain. The aim was to analyze prevalence of jaw pain and disability, as well as the relationship between pain and disability in the jaw and neck regions in the early nonchronic stage after whiplash trauma. In this case-control study, 70 individuals (40 women, 30 men, mean age 35.5 y) who visited an emergency department with neck pain following a car accident were examined within 3 wk of trauma (group 1) and compared with 70 individuals (42 women, 28 men, mean age 33.8 y), who declined to attend a clinical examination but agreed to fill in questionnaires (group 2). The 2 case groups were compared with a matched control group of 70 individuals (42 women, 28 men, mean age 37.6 y) without a history of neck trauma. All participants completed questionnaires regarding jaw pain and dysfunction, rating pain intensity in jaw and neck regions on the Numerical Rating Scale, the Neck Disability Index, and Jaw Disability Checklist. Compared with controls, individuals with a recent whiplash trauma reported more jaw pain and dysfunction. Furthermore, there was a moderate positive correlation between jaw and neck pain ratings for group 1 (r = 0.61, P < 0.0001) and group 2 (r = 0.59, P < 0.0001). In the logistic regression analysis, cases showed higher odds ratios (range, 6.1 to 40.8) for jaw and neck pain and disability compared with controls. Taken together, the results show that individuals with a recent whiplash trauma report more jaw pain and disability compared with controls without a history of neck trauma. Furthermore, the correlation between jaw and neck pain intensity implies that intensity of neck pain in the acute stage after whiplash trauma might be a possible risk factor also for development of chronic orofacial pain.

Temporomandibular disorders (TMD) are common but seem to be largely undetected within general dental care. To improve dentists' awareness of these symptoms, three screening questions (3Q/TMD) have been introduced. Our aim was to validate 3Q/TMD in relation to the diagnostic criteria for TMD (DC/TMD), while taking into account the severity level of the symptoms. The study population consisted of 7831 individuals 20-69 years old, who had their routine dental check-up at the Public Dental Health Service in Västerbotten, Sweden. All patients answered a health declaration, including the 3Q/TMD regarding frequent temporomandibular pain, pain on movement and catching/locking of the jaw. All 3Q-positives (at least one affirmative) were invited for examination in randomised order. For each 3Q-positive, a matched 3Q-negative was invited. In total, 152 3Q-positives and 148 3Q-negatives participated. At examination, participants answered 3Q/TMD a second time, before they were examined and diagnosed according to DC/TMD. To determine symptom's severity, the Graded Chronic Pain Scale and Jaw Functional Limitation Scale-20 (JFLS-20) were used. In total, 74% of 3Q-positives and 16% of 3Q-negatives met the criteria for DC/TMD pain or dysfunction (disc displacements with reduction and degenerative joint disorder were excluded). Fifty-five per cent of 3Q-positives had a TMD diagnosis and CPI score ≥3 or a JFLS-20 score ≥5, compared to 4% of 3Q-negatives. The results show that the 3Q/TMD is an applicable, cost-effective and valid tool for screening a general adult population to recognise patients in need of further TMD examination and management.

The 14th International Congress on Combustion By-Products and Their Health Effects was held in Umeå, Sweden from June 14th to 17th, 2015. The Congress, mainly sponsored by the National Institute of Environmental Health Sciences Superfund Research Program and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, focused on the “Origin, fate and health effects of combustion-related air pollutants in the coming era of bio-based energy sources”. The international delegates included academic and government researchers, engineers, scientists, policymakers and representatives of industrial partners. The Congress provided a unique forum for the discussion of scientific advances in this research area since it addressed in combination the health-related issues and the environmental implications of combustion by-products. The scientific outcomes of the Congress included the consensus opinions that: (a) there is a correlation between human exposure to particulate matter and increased cardiac and respiratory morbidity and mortality; (b) because currently available data does not support the assessment of differences in health outcomes between biomass smoke and other particulates in outdoor air, the potential human health and environmental impacts of emerging air-pollution sources must be addressed. Assessment will require the development of new approaches to characterize combustion emissions through advanced sampling and analytical methods. The Congress also concluded the need for better and more sustainable e-waste management and improved policies, usage and disposal methods for materials containing flame retardants.