Search

Dementia is the greatest global challenge for health and social care in the 21st century. About 47 million people were living with dementia worldwide in 2015, and this number is projected to triple by 2050. Genome-wide association studies (GWAS) have identified more than 20 loci that affect the risk of Alzheimer’s disease (AD), one of the most common forms of dementia. Several environmental factors that seem to increase the risk of AD have been identified. However, most such findings are prone to bias by reverse causation. Identification of new risk and causal factors is essential for prevention. Previous observational studies and randomized controlled trials have shown inconclusive results for a link between low serum vitamin D and impaired cognitive function. A recent experimental study indicated that a periodontitis-causing bacterium might be a causal factor for AD. However, evidence for a causal association of periodontitis with cognitive impairment and risk of AD is limited in humans. We therefore aim to investigate the interrelationship between vitamin D, oral health and cognitive function/dementia in The Trøndelag Health Study (HUNT) population. First, we will study the association between vitamin D status in HUNT3 and oral health (risk of dental caries and periodontitis etc.) in HUNT4 Dental Health (n≈1800). Second, the relationship between temporal change of vitamin D and cognitive function/dementia will be examined in a prospective study. Vitamin D levels that were repeatedly measured in HUNT2 and HUNT3 will be linked to cognitive function assessments in HUNT4 70+ (n≈1500). Genetic variants influencing vitamin D status will be used to clarify the directionality of the association. Interaction of genetic risk of AD (ApoE alleles) and vitamin D status will also be assessed. Third, we will investigate the relationship between oral health and cognitive function using data from the HUNT4 70+ and Trondheim 70+ (n≈3700).

Additional file 1: Supplementary Table S1. The association of BMI in HUNT2 with incidence of lung cancer overall and different histologic types after excluding the first five years’ follow-up, the HUNT Study, 1995-97 to2017 (N = 59,711). Supplementary Table S2. The associations of BMI in HUNT2 with lung cancer incidence taking account of competing risk due to death, the HUNT Study, 1995-97 to 2017 (N = 62,453). Supplementary Text 1. Analysis using negative control exposure. Supplementary Figure 1. DAG for body mass index(BMI) (as the main exposure), migraine (as the negative control exposure) and incidence of lung cancer (as the outcome). Supplementary Table S3. Negative control using migraine as an alternative exposure to address residual confounding by smoking for the association of BMI in HUNT2 with lung cancer incidence across different lung cancer subtypes, the HUNT Study, 1995-97 to 2017(N = 49,969). Supplementary Table S4. Comparison of baseline characteristics of participants with complete and missing information on 75 BMI SNPs in HUNT2. Supplementary Text 2. Univariable Mendelian randomization (MR) analyses using the 61 single-nucleotide polymorphisms only for body mass index (BMI-Only SNPs). Supplementary Table S5. Associations of externally weighted BMI GRS1 based on 61 BMI-Only SNPs with potential confounders in HUNT2, 1995-1997 (N = 54,511). Supplementary Table S6. The association of BMI with incidence of lung cancer overall and different histologic types based on the univariable MR analyses using 61 BMI-Only SNPs,the HUNT Study, 1995-97 to 2017 (N = 54,511).

Background Bone marrow mesenchymal stem cells (BM-MSCs) are multipotential stem cells that have been used for a broad spectrum of indications. Several investigations have used BM-MSCs to promote photoreceptor survival and suggested that BM-MSCs are a potential source of cell replacement therapy for some forms of retinal degeneration. Purpose To investigate the expression of the MER proto-oncogene, tyrosine kinase (Mertk), involved in the disruption of RPE phagocytosis and the onset of autosomal recessive retinitis pigmentosa in rat BM-MSCs and to compare phagocytosis of the photoreceptor outer segment (POS) by BM-MSCs and RPE cells in vitro. Methods MSCs were isolated from the bone marrow of Brown Norway rats. Reverse transcription-PCR (RT–PCR) and western blot analyses were used to examine the expression of Mertk. The phagocytized POS was detected with double fluorescent labeling, transmission electron microscopy, and scanning electron microscopy. Results Mertk expression did not differ among the first three passages of BM-MSCs. Mertk gene expression was greater in the BM-MSCs than the RPE cells. Mertk protein expression in the BM-MSCs was similar to that in the RPE cells in the primary passage and was greater than that in the RPE cells in the other two passages. BM-MSCs at the first three passages phagocytized the POS more strongly than the RPE cells. The process of BM-MSC phagocytosis was similar to that of the RPE cells. Conclusions BM-MSCs may be an effective cell source for treating retinal degeneration in terms of phagocytosis of the POS.

Background: Prolonged sitting as a major sedentary behavior potentially contributes to illness, but its relation with lung cancer risk is unclear. Prolonged sitting can be presented in physically active or inactive individuals. Those who are extendedly seated and also physically inactive may represent the most sedentary people. We therefore aimed to prospectively examine if total sitting time daily itself or in combination with physical activity is associated with lung cancer incidence overall and histologic types. Methods: We included 45,810 cancer-free adults who participated in the second survey of HUNT Study in Norway (1995–97), with a median follow-up of 18.3 years. Total sitting time daily and physical activity were self-reported at baseline. Lung cancer cases were ascertained from the Cancer Registry of Norway. Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: In total, 549 participants developed lung cancer during the follow-up. Total sitting time daily was not associated with the incidence of lung cancer overall and histologic subtypes. Compared with participants sitting < 8 h daily and being physically active, those sitting ≥8 h daily (prolonged sitting) and being physically inactive had an increased incidence of lung cancer (overall: adjusted HR = 1.44, 95% CI: 1.07–1.94; small cell lung cancer: adjusted HR = 2.58, 95% CI: 1.23–5.41). Prolonged sitting only or physical inactivity only was not associated with the incidence of lung cancer. Conclusions: Our study suggested that prolonged sitting was not independently associated with lung cancer incidence. The combination of prolonged sitting and physical inactivity might increase the risk of lung cancer. However, residual confounding by smoking cannot be excluded completely even though smoking was adjusted for with detailed information. Copyright © 2019 Jiang, Sun, Brumpton, Langhammer, Chen, Nilsen and Mai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Objective To investigate the shape of the causal relation between body mass index (BMI) and mortality. Design Linear and non-linear mendelian randomisation analyses. Setting Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom). Participants Middle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank. Main outcome measures All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality. Results 12 015 and 10 344 participants died during a median of 18.5 and 7.0 years of follow-up in the HUNT Study and UK Biobank, respectively. Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. An increase of 1 unit in genetically predicted BMI led to a 5% (95% confidence interval 1% to 8%) higher risk of mortality in overweight participants (BMI 25.0-29.9) and a 9% (4% to 14%) higher risk of mortality in obese participants (BMI ≥30.0) but a 34% (16% to 48%) lower risk in underweight (BMI