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1.
Gut ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168600

RESUMO

OBJECTIVE: The intestinal microbiome affects the prevalence and pathophysiology of a variety of diseases ranging from inflammation to cancer. A reduced taxonomic or functional diversity of the microbiome was often observed in association with poorer health outcomes or disease in general. Conversely, factors or manifest diseases that determine the long-term stability or instability of the microbiome are largely unknown. We aimed to identify disease-relevant phenotypes associated with faecal microbiota (in-)stability. DESIGN: A total of 2564 paired faecal samples from 1282 participants of the population-based Study of Health in Pomerania (SHIP) were collected at a 5-year (median) interval and microbiota profiles determined by 16S rRNA gene sequencing. The changes in faecal microbiota over time were associated with highly standardised and comprehensive phenotypic data to determine factors related to microbiota (in-)stability. RESULTS: The overall microbiome landscape remained remarkably stable over time. The greatest microbiome instability was associated with factors contributing to metabolic syndrome such as fatty liver disease and diabetes mellitus. These, in turn, were associated with an increase in facultative pathogens such as Enterobacteriaceae or Escherichia/Shigella. Greatest stability of the microbiome was determined by higher initial alpha diversity, female sex, high household income and preserved exocrine pancreatic function. Participants who newly developed fatty liver disease or diabetes during the 5-year follow-up already displayed significant microbiota changes at study entry when the diseases were absent. CONCLUSION: This study identifies distinct components of metabolic liver disease to be associated with instability of the intestinal microbiome, increased abundance of facultative pathogens and thus greater susceptibility toward dysbiosis-associated diseases.

2.
Sci Rep ; 10(1): 19111, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154486

RESUMO

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = - 0.17 to 0.76, I2 = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval = - 0.67 to 0.48, I2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

3.
PLoS One ; 15(11): e0230035, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33186364

RESUMO

BACKGROUND: Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome. METHODS AND RESULTS: Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. CONCLUSION: This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33205518

RESUMO

Physical activity (PA) may influence cardio-respiratory fitness (CRF). Yet, PA takes place in different domains (i.e. sports related physical activity [SPA], leisure time related physical activity [LTPA] and work-related physical activity [WPA]) and not all domain-specific PA may help to maintain high CRF levels throughout life. We assessed the relationship between changes in domain specific PA and the age-related decline in CRF. We analyzed data of 353 men (median age 50 years; inter-quartile range [IQR] 40 to 60) and 335 women (median age 50 years; IQR 41 to 59) with data for domain-specific PA as well as CRF testing measured ten years apart. CRF was assessed with cardiorespiratory exercise testing. Domain specific PA was measured using the Baecke questionnaire. During the 10 year follow-up CRF decreased in men from 29.3 (IQR 25.0 to 34.7) ml/min/kg to 24.3 (IQR 20.8 to 27.3) ml/min/kg. In women CRF declined from 26.0 (IQR 21.0 to 30.9) to 21.4 (IQR 18.3 to 25.6) ml/min/kg. A one point higher SPA at baseline was related to a 1.14 (95% confidence interval [CI] -1.50 to -0.53) ml/min/kg greater decrease in VO2peak . A one point greater SPA and LTPA over time was associated with a 1.68 (95% CI 1.06 to 2.29) ml/min/kg and 1.24 (95% CI 0.57 to 1.90) ml/min/kg lower decrease in VO2peak , respectively. Neither baseline values nor changes of WPA were associated with CRF. Sports and leisure time related PA may attenuate the age related decline in CRF.

5.
Sci Rep ; 10(1): 18285, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106555

RESUMO

The relation between thyroid function biomarkers and attention deficit hyperactivity disorder (ADHD) in children and adolescents is currently unclear. Cross-sectional data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Baseline) was analyzed to assess the association between thyroid function biomarkers and ADHD in a population-based, nationally representative sample. The study cohort included 11,588 children and adolescents with 572 and 559 having an ADHD diagnosis or symptoms, respectively. ADHD symptoms were assessed through the Inattention/Hyperactivity subscale of the Strength and Difficulties Questionnaire. ADHD diagnosis was determined by a physician or psychologist. Serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations were determined enzymatically. Adjusted regression models were used to relate serum TSH, fT3, and fT4 with risk for ADHD diagnosis or symptoms. In children, a 1 mIU/l higher TSH was related to a 10% lower risk (odds ratio [OR] 0.90; 95% confidence interval [CI] 0.81-1.00) of ADHD diagnosis. We found a significant positive association between fT3 and continuously assessed ADHD symptoms in children (ß 0.08; 95% CI 0.03-0.14). Our results suggest that physical maturity may influence the association between thyroid function biomarkers and risk for ADHD.

6.
Sleep ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017007

RESUMO

Advanced brain ageing is commonly regarded as a risk factor for neurodegenerative diseases, e.g. Alzheimer's dementia, and it was suggested that sleep disorders such as obstructive sleep apnoea (OSA) are significantly contributing factors to these neurodegenerative processes. To determine the association between OSA and advanced brain ageing, we investigated the specific effect of two indices quantifying OSA, namely the apnoea-hypopnea index (AHI) and the oxygen desaturation index (ODI), on brain age, a score quantifying age-related brain patterns in 169 brain regions, using magnetic resonance imaging and overnight polysomnography data from 690 participants (48.8% women, mean age 52.5±13.4 years) of the Study of Health in Pomerania. We additionally investigated the mediating effect of subclinical inflammation parameters on these associations via a causal mediation analysis. AHI and ODI were both positively associated with brain age (AHI std. effect [95% CI]: 0.07 [0.03; 0.12], p-value: 0.002; ODI std. effect [95% CI]: 0.09 [0.04; 0.13], p-value: <0.0003). The effects remained stable in the presence of various confounders such as diabetes and were partially mediated by the white blood cell count, indicating a subclinical inflammation process. Our results reveal an association between OSA and brain age, indicating subtle but widespread age-related changes in regional brain structures, in one of the largest general population studies to date, warranting further examination of OSA in the prevention of neurodegenerative diseases.

7.
Clin Transl Gastroenterol ; 11(9): e00232, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33094959

RESUMO

INTRODUCTION: Exocrine pancreatic function is a critical host factor in determining the intestinal microbiota composition. Diseases affecting the exocrine pancreas could therefore influence the gut microbiome. We investigated the changes in gut microbiota of patients with chronic pancreatitis (CP). METHODS: Patients with clinical and imaging evidence of CP (n = 51) were prospectively recruited and compared with twice the number of nonpancreatic disease controls matched for distribution in age, sex, body mass index, smoking, diabetes mellitus, and exocrine pancreatic function (stool elastase). From stool samples of these 153 subjects, DNA was extracted, and intestinal microbiota composition was determined by bacterial 16S ribosomal RNA gene sequencing. RESULTS: Patients with CP exhibited severely reduced microbial diversity (Shannon diversity index and Simpson diversity number, P < 0.001) with an increased abundance of facultative pathogenic organisms (P < 0.001) such as Enterococcus (q < 0.001), Streptococcus (q < 0.001), and Escherichia.Shigella (q = 0.002). The CP-associated changes were independent of exocrine pancreatic insufficiency. Short-chain fatty acid producers, considered protective for epithelia such as Faecalibacterium (q < 0.001), showed reduced abundance in patients with CP. Of 4 additional patients with CP previously treated with antibiotics (ceftriaxone and metronidazole), 3 patients were characterized by distinct Enterococcus overgrowth. DISCUSSION: CP is associated with marked gut microbiota dysbiosis, greatly reduced diversity, and increased abundance of opportunistic pathogens, specifically those previously isolated from infected pancreatic necrosis. Taxa with a potentially beneficial role in intestinal barrier function are depleted. These changes can increase the probability of complications from pancreatitis such as infected fluid collections or small intestinal bacterial overgrowth (see Graphical Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A383).

8.
Artigo em Inglês | MEDLINE | ID: mdl-33034626

RESUMO

CONTEXT: Osteoporosis and anemia are amongst the most common diseases in the aging population with a worldwide increasing prevalence. OBJECTIVE: As the bone-derived hormone fibroblast-growth factor-23 (FGF-23) was recently reported to regulate erythropoiesis, we examined age-related associations between hemoglobin levels and bone quality, bone turnover and FGF-23 concentrations. DESIGN: We used data from more than 5,000 adult subjects who participated in the population-based cohorts of the Study of Health in Pomerania (SHIP and SHIP-Trend). Bone quality was assessed by quantitative ultrasound at the heel, bone turnover by measurement of carboxy-terminal telopeptide of type I collagen (CTX) and intact amino-terminal propeptide of type I procollagen (P1NP) serum concentrations, respectively. Anemia was defined as hemoglobin <13 g/dl in men and <12 g/dl in women. C-terminal FGF-23 levels were measured in plasma in a subset of 852 subjects. RESULTS: Anemic subjects had poorer bone quality, higher fracture risk, and lower serum levels of P1NP than non-anemic individuals. Linear regression models revealed positive associations between hemoglobin and bone quality in subjects aged 40 or above and inverse associations with CTX in subjects aged 60 or above. Hemoglobin and FGF-23 concentrations were inversely associated, while FGF-23 was not related to bone quality or turnover. CONCLUSION: Our data corroborates a close link between FGF-23 and anemia, which is related to poor bone quality in the elderly. Yet, we observed no direct association of FGF-23 with bone parameters. Therefore, further studies are needed clarifying the role of FGF-23 on bone and red blood cell production.

9.
Brain Behav ; : e01884, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33052028

RESUMO

INTRODUCTION: Insufficient vitamin D levels were found to be related to various psychiatric disorders and particularly depression. The functional polymorphisms rs4588 and rs7041 of the vitamin D-binding protein (also group-specific component or Gc) influence vitamin D level and activity. Resilience is considered the individual predisposition to maintain psychological functioning in the face of adversities. We sought to investigate whether associations of vitamin D levels and genotypes of rs4588 and rs7041 were associated with trait resilience and symptoms of depression. METHODS: Serum levels of total 25(OH)D were measured in a general population sample (n = 1,908) of the Study of Health in Pomerania (SHIP-1). The Resilience Scale-25 (RS-25) was applied to assess trait resilience. Lifetime depressive symptoms were assessed using the CID-S, while current depressive symptoms were measured using the Beck Depression Inventory II (BDI-II). Study participants were genotyped for rs4588 and rs7041. RESULTS: Participants with vitamin D insufficiency had lower adjusted mean RS-25 scores as compared to vitamin D replete subjects (p = .002). Linear regression analyses revealed a positive association between 25(OH)D and RS-25 scores (ß = 2.782, p = .002). Additional adjustment for BDI-II scores slightly attenuated this result (ß = 1.830 and p = .026). Symptoms of depression and the lifetime diagnosis of MDD were not significantly associated with vitamin D concentrations. rs4588 and rs7041 showed strong associations with vitamin D concentrations (both p < .001), but not RS-25 scores. CONCLUSIONS: In contrast with previous studies, our findings do not provide evidence for a strong role of vitamin D in the psychopathology of depression. However, considering the role of trait resilience as a common protective factor to different psychiatric disorders, our results support the concept of low vitamin D as a general risk factor to stress-related psychopathologies.

10.
Clin Oral Investig ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32964310

RESUMO

OBJECTIVE: SLC22A4/5 single nucleotide polymorphisms (SNPs) have been reported to affect inflammatory diseases. We report the relationship of these polymorphisms with adiposity and tooth loss as elucidated in a 10-year follow-up study. METHODS: Participants of the Study of Health in Pomerania (SHIP, N = 4105) were genotyped for the polymorphisms c.1507C > T in SLC22A4 (rs1050152) and -207C > G in SLC22A5 (rs2631367) using allele-specific real-time PCR assays. A total of 1817 subjects, 934 female and 883 male aged 30-80 years, underwent follow-up 10 years later (SHIP-2) and were assessed for adiposity and tooth loss. RESULTS: The frequencies of the rarer SLC22A4 TT and SLC22A5 CC alleles were 16.7% and 20.3%, respectively. In women, tooth loss was associated with genotype TT vs. CC with incidence rate ratio IRR = 0.74 (95%C.I. 0.60-0.92) and CC vs. GG IRR = 0.79 (0.65-0.96) for SLC22A4 and SLC22A5 SNPs, respectively. In men, no such associations were observed. In the follow-up examination, the relationship between tooth loss and these SNPs was in parallel with measures of body shape such as BMI, body weight, waist circumference, or body fat accumulation. The association between muscle strength and body fat mass was modified by the genotypes studied. CONCLUSIONS: SLC22A4 c.150C > T and SLC22A5 -207C > G polymorphisms are associated with tooth loss and markers of body shape in women but not in men. CLINICAL RELEVANCE: Tooth loss may be related to obesity beyond inflammatory mechanisms, conceivably with a genetic background.

12.
Thyroid ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32912084

RESUMO

Background: Although substantial progress has been made in recent decades in eliminating iodine deficiency, iodine deficiency disorders (IDDs) are still prevalent in European countries. Challenges include ineffective public health programs and discontinuation of IDD prevention. However, the barriers against the implementation and continuation of prevention and monitoring of IDD remain unclear. Therefore, the objective of our study was to identify potential barriers against pan-European IDD prevention and monitoring programs and to find solutions for the different challenges. Methods: We conducted a Delphi study consisting of three rounds. We identified potential participants with expertise and experience in relevant fields from all European countries, including policy makers, health care professionals, health scientists, and patient representatives. The Delphi method was conducted with open-ended questions and item ranking to achieve group consensus on potential barriers against national and pan-European IDD prevention and monitoring programs and related solutions to overcome those barriers. The answers of the Delphi rounds were analyzed using qualitative content analysis and descriptive analysis methods. In addition, we conducted two expert interviews to analyze and discuss the study results. Results: Eighty experts from 36 countries and different fields of work participated in the first Delphi round, 52 in the second, and 46 in the third. Potential barriers include challenges in the fields of knowledge and information, implementation and management, communication and cooperation, political support, and differences between the European countries. Ranked solutions addressing these barriers include cooperation with different stakeholders, gaining knowledge, sharing information, the development of a European program with national specification, European guidelines/recommendations, and European monitoring. The ranking gives a first overview as to which of these barriers would need to be solved most urgently and which solutions may be most helpful. Conclusion: In our study, we derived key information and first insights with regard to barriers against IDD prevention programs from a broad range of stakeholders. Most barriers were found in the category of implementation and management. Also a lack of political support seems to play an important role. The findings of our study may help decision makers in health policy to develop more effective IDD prevention and monitoring strategies.

13.
Clin Oral Investig ; 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32827080

RESUMO

OBJECTIVES: We aimed at investigating whether the interaction between the local inflammation, periodontitis, and obesity is independently associated with systemic inflammation. METHODS: From the population-based Study of Health in Pomerania, 3366 participants, without (2366) and with (1000) obesity, were studied for the association of periodontitis, measured as probing depth (PD) and plaque together with body mass index (BMI) on C-reactive protein (CRP). Quantile regression was used to evaluate the association between periodontal, anthropometric, and inflammatory variables (outcomes). RESULTS: The overall prevalence of obesity in this adult population was 31.4% in men and 28.1% in women. Both PD and plaque were positively associated with CRP, revealing an increasing impact across the CRP concentration distribution. Adjusting the regression of CRP or fibrinogen on PD for waist circumference attenuated but did not abolish the PD coefficients. Dental plaque was similarly associated with these interrelations. Association between PD and a dental plaque was different among participants with low-, medium-, or high-risk CRP concentrations. CONCLUSION: Local and systemic sources of inflammation contribute to blood levels of inflammatory markers. The respective contributions depend on the relative rate in each of the inflammation-inducing risks and are dominated by adiposity. CLINICAL RELEVANCE: Keeping systemic inflammation low in order to prevent age-related disease sequelae.

14.
Br J Ophthalmol ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859720

RESUMO

AIM: To assess whether cardiorespiratory fitness (CRF) and handgrip strength, two objective markers of physical fitness, are associated with age-related macular degeneration (AMD). METHODS: We analysed cross-sectional data from the population-based Study of Health in Pomerania (2008-2012) including 1173 adult men and women aged 20-79 years. Fundus photography of the central retina was recorded with a non-mydriatic camera, and images were graded according to an established clinical AMD classification scale by an experienced reader. CRF was measured using peak oxygen uptake (peakVO2), oxygen uptake at the anaerobic threshold (VO2@AT), and maximum power output (Wmax) from standardised cardiopulmonary exercise testing on a bicycle ergometer according to a modified Jones protocol. Handgrip strength was assessed using a handheld dynamometer. Adjusted prevalence ratios (PR) for the associations of peakVO2, VO2@AT, Wmax and handgrip strength with AMD were derived from multivariable Poisson regression models. RESULTS: PeakVO2, VO2@AT, Wmax and handgrip strength were not associated with AMD. Adjusted PR for AMD associated with a 1-SD increment in peakVO2, VO2@AT, Wmax and handgrip strength were 1.05 (95% CI 0.82 to 1.34), 0.96 (95% CI 0.78 to 1.18), 1.10 (95% CI 0.86 to 1.41) and 1.01 (95% CI 0.79 to 1.30), respectively. These associations were not modified by age, sex, smoking, body mass index and diabetes. Estimates in sensitivity analysis for confounding, selection bias and missing data were similar. CONCLUSION: In our study, CRF and handgrip strength were not associated with AMD. Nevertheless, longitudinal studies with bigger sample sizes are needed to furtherly examine these associations.

15.
Thyroid ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32847437

RESUMO

Background: Iodine deficiency is one of the most prevalent causes of intellectual disability and can lead to impaired thyroid function and other iodine deficiency disorders (IDDs). Despite progress made on eradicating iodine deficiency in the last decades in Europe, IDDs are still prevalent. Currently, evidence-based information on the benefit/harm balance of IDD prevention in Europe is lacking. We developed a decision-analytic model and conducted a public health decision analysis for the long-term net benefit of a mandatory IDD prevention program for the German population with moderate iodine deficiency, as a case example for a European country. Methods: We developed a decision-analytic Markov model simulating the incidence and consequences of IDDs in the absence or presence of a mandatory IDD prevention program (iodine fortification of salt) in an open population with current demographic characteristics in Germany and with moderate ID. We collected data on the prevalence, incidence, mortality, and quality of life from European studies for all health states of the model. Our primary net-benefit outcome was quality-adjusted life years (QALYs) predicted over a period of 120 years. In addition, we calculated incremental life years and disease events over time. We performed a systematic and comprehensive uncertainty assessment using multiple deterministic one-way sensitivity analyses. Results: In the base-case analysis, the IDD prevention program is more beneficial than no prevention, both in terms of QALYs and life years. Health gains predicted for the open cohort over a time horizon of 120 years for the German population (82.2 million inhabitants) were 33 million QALYs and 5 million life years. Nevertheless, prevention is not beneficial for all individuals since it causes additional hyperthyroidism (2.7 million additional cases). Results for QALY gains were stable in sensitivity analyses. Conclusions: IDD prevention via mandatory iodine fortification of salt increases quality-adjusted life expectancy in a European population with moderate ID, and is therefore beneficial on a population level. However, further ethical aspects should be considered before implementing a mandatory IDD prevention program. Costs for IDD prevention and treatment should be determined to evaluate the cost effectiveness of IDD prevention.

16.
J Am Heart Assoc ; 9(16): e015630, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32805196

RESUMO

Background Common carotid intima-media thickness (cIMT) is a biomarker for subclinical atherosclerosis and is associated with all-cause as well as cardiovascular mortality. Higher cIMT is accompanied by a compensatory increase in lumen diameter (LD) of the common carotid arteries. Whether cIMT or LD carry more information with regard to mortality is unclear. Methods and Results A total of 2751 subjects (median age 53 years; 52% female) were included. During a median follow-up of 14.9 years (range: 12.8-16.5) a total of 506 subjects died. At baseline, cIMT and LD were assessed by carotid ultrasound scans. Multivariable Cox regression models were used to relate cIMT, LD, LD adjusted for cIMT (LD+cIMT), and LD/cIMT ratio with all-cause, cardiovascular, and noncardiovascular mortality. All models were ranked using Akaike's information criterion. Harrel's c statistic was used to compare the models' predictive power for mortality. A 1-mm increase in LD was related to a higher risk for all-cause mortality (hazard ratio [HR], 1.29; 95% CI, 1.14-1.45, P<0.01). This association remained significant when cIMT was added to the model (HR, 1.26; 95% CI, 1.11-1.42; P<0.01). A 1-mm higher cIMT was also related with greater mortality risk (HR, 1.73; 95% CI, 1.09-2.75). The LD/cIMT ratio was not associated with all-cause mortality. LD had the lowest Akaike's information criterion regarding all-cause mortality and improved all-cause mortality prediction compared with the null model (P=0.01). CIMT weakened all-cause mortality prediction compared with the LD model. Conclusions LD provided more information for all-cause mortality compared with cIMT in a large population-based sample.

17.
Chronobiol Int ; 37(8): 1235-1243, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32654542

RESUMO

The association between shift work and the risk of colorectal cancer (CRC) is still unclear. Therefore, we studied the associations between exposure to shift or night work and incident CRC in two German population-based cohort studies, the Heinz Nixdorf Recall Study (HNR) and the Study of Health in Pomerania (SHIP). Including up to 6,903 participants, we analyzed the cohorts pooled and individually. We estimated incidence rate ratios (IRRs) with adjusted log-linear Poisson regression models with the natural logarithm of person-years as offset and performed subgroup analyses by sex and tumor localization in HNR. The pooled analysis revealed no increased risks for men working in night shifts (IRR: 1.03, 95% CI: 0.62; 1.71). In male HNR participants, we found an increased risk estimate for cancer of the distal colon in shift workers (IRR: 1.60, 95% CI: 0.53; 4.87) and in shift workers who did not perform night work (IRR: 3.93, 95% CI: 0.98; 15.70), but not in night workers. In SHIP, we observed elevated CRC risk estimates for rotating shift work including night work (IRR: 1.45, 95% CI: 0.72; 2.92) and for long-term exposure (IRR: 1.79, 95% CI: 0.81; 3.92) for men. In conclusion, night-shift work was not associated with CRC, although an increased risk was suggested for rotating shift work including nights in SHIP. The heterogeneity of shift-work jobs and schedules and associated lifestyle factors should be taken into account to disentangle a possible relationship between shift work and the risk for CRC in future investigations.

18.
Obesity (Silver Spring) ; 28(8): 1550-1559, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32627926

RESUMO

OBJECTIVE: This study provides a comprehensive overview of the associations of five adipokines (adiponectin, chemerin, galectin-3, leptin, and resistin) with fat deposits, behavioral risk factors, and metabolic phenotypes. METHODS: Using multivariable linear and logistic regression models, cross-sectional data from 4,116 participants of the population-based Study of Health in Pomerania were analyzed. RESULTS: Participants with obesity showed higher chemerin, galectin-3, and leptin but showed lower adiponectin concentrations. Independently of other fat compounds, liver fat content, visceral adipose tissue, and subcutaneous adipose tissue (SAT) were inversely associated with adiponectin. Independent positive associations of liver fat content and SAT with chemerin as well as of SAT with galectin-3 and leptin were observed. Physically inactive participants had higher chemerin and leptin concentrations. Smokers had higher chemerin and galectin-3 as well as lower leptin. Alcohol consumption was associated with adiponectin (positive) and resistin (inverse). All adipokines were associated with at least one lipid marker. Associations with glucose metabolism were seen for adiponectin, chemerin, galectin-3, and leptin. CONCLUSIONS: High adiponectin concentrations were related to favorable metabolic conditions, whereas high chemerin, galectin-3, and leptin were associated with an unfavorable metabolic profile. High leptin seems to be primarily indicative of obesity, whereas high adiponectin and chemerin are associated with a broader range of metabolic phenotypes.

19.
Brain ; 143(7): 2312-2324, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32591831

RESUMO

Deep learning has emerged as a powerful approach to constructing imaging signatures of normal brain ageing as well as of various neuropathological processes associated with brain diseases. In particular, MRI-derived brain age has been used as a comprehensive biomarker of brain health that can identify both advanced and resilient ageing individuals via deviations from typical brain ageing. Imaging signatures of various brain diseases, including schizophrenia and Alzheimer's disease, have also been identified using machine learning. Prior efforts to derive these indices have been hampered by the need for sophisticated and not easily reproducible processing steps, by insufficiently powered or diversified samples from which typical brain ageing trajectories were derived, and by limited reproducibility across populations and MRI scanners. Herein, we develop and test a sophisticated deep brain network (DeepBrainNet) using a large (n = 11 729) set of MRI scans from a highly diversified cohort spanning different studies, scanners, ages and geographic locations around the world. Tests using both cross-validation and a separate replication cohort of 2739 individuals indicate that DeepBrainNet obtains robust brain-age estimates from these diverse datasets without the need for specialized image data preparation and processing. Furthermore, we show evidence that moderately fit brain ageing models may provide brain age estimates that are most discriminant of individuals with pathologies. This is not unexpected as tightly-fitting brain age models naturally produce brain-age estimates that offer little information beyond age, and loosely fitting models may contain a lot of noise. Our results offer some experimental evidence against commonly pursued tightly-fitting models. We show that the moderately fitting brain age models obtain significantly higher differentiation compared to tightly-fitting models in two of the four disease groups tested. Critically, we demonstrate that leveraging DeepBrainNet, along with transfer learning, allows us to construct more accurate classifiers of several brain diseases, compared to directly training classifiers on patient versus healthy control datasets or using common imaging databases such as ImageNet. We, therefore, derive a domain-specific deep network likely to reduce the need for application-specific adaptation and tuning of generic deep learning networks. We made the DeepBrainNet model freely available to the community for MRI-based evaluation of brain health in the general population and over the lifespan.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32420644

RESUMO

OBJECTIVES: To examine the association between third molars and orofacial pain. We hypothesized that impacted third molars are a cause of orofacial pain. METHODS: Magnetic resonance images of 1808 participants from two population-based cohorts from Northeastern Germany were analysed to define the status of third molars according to the Pell and Gregory classification. A self-reported questionnaire and a clinical dental examination were used to detect chronic and acute complaints of orofacial pain, masticatory muscle pain, migraine and other types of headache. Logistic regression models were used to analyse the associations between third molar status and orofacial pain. RESULTS: Individuals with impacted third molars in the maxilla had a higher chance of chronic orofacial pain than those with erupted third molars (odds ratio 2.19; 95% CI 1.19-4.02). No such association was detected for third molars in the lower jaw. Third molars were not associated with masticatory muscle pain, migraine or other types of headache. CONCLUSIONS: Impacted maxillary third molars might be a cause of chronic orofacial pain. Thus, physicians should consider the eruption/impaction status of third molars in their decision-making process when treating patients who complain of orofacial pain.

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