Increased periodontal attachment loss in patients with systemic sclerosis

Background: Patients with inflammatory rheumatic diseases and periodontitis share common pathogenetic characteristics, such as pro-inflammatory traits causative for tissue degradation and loss of function. Aim of the present case control study was to investigate the association between systemic sclerosis (SSc) and periodontitis. Methods: The association between SSc and periodontitis was examined in 58 SSc patients and 52 control patients, matched for age and gender. Periodontal examination included periodontal attachment loss, probing pocket depth, bleeding on probing, plaque index and gingival index. Potential risk factors of periodontitis were assessed through patients' questionnaires. Results: In unadjusted analyses, patients with SSc had a significant 0.61 mm higher periodontal attachment loss (95 % confidence interval (CI), 0.24 - 0.97; p = 0.002) when compared to controls. In a stepwise logistic regression, including SSc status, age, gender, education, smoking, alcohol consumption and BMI, only SSc status, age, and gender remained significantly associated with periodontitis. Adjusted for age and gender, patients with SSc had 0.52 mm higher periodontal attachment loss compared to controls (95 % CI, 0.16 - 0.88; p = 0.005). The strength of the association of SSc with periodontal attachment loss remained statistically significant after further adjustment for plaque index (0.44 mm; 95 % CI 0.02 - 0.86; p = 0.038) or gingival index (0.61 mm; 95 % CI, 0.24 - 0.97 p = 0.001). Conclusions: The study demonstrates higher periodontal clinical attachment loss in SSc patients, which remained significant following adjustment. The study indicates a possible relationship between SSc and periodontitis

Nanocoating with plant-derived pectins activates osteoblast response in vitro

Abstract: A new strategy to improve osseointegration of implants is to stimulate adhesion of bone cells, bone matrix formation, and mineralization at the implant surface by modifying surface coating on the nanoscale level. Plant-derived pectins have been proposed as potential candidates for surface nanocoating of orthopedic and dental titanium implants due to 1) their osteogenic stimulation of osteoblasts to mineralize and 2) their ability to control pectin structural changes. The aim of this study was to evaluate in vitro the impact of the nanoscale plant-derived pectin Rhamnogalacturonan-I (RG-I) from potato on the osteogenic response of murine osteoblasts. RG-I from potato pulps was isolated, structurally modified, or left unmodified. Tissue culture plates were either coated with modified RG-I or unmodified RG-I or – as a control – left uncoated. The effect of nanocoating on mice osteoblast- like cells MC3T3-E1 and primary murine osteoblast with regard to proliferation, osteogenic response in terms of mineralization, and gene expression of Runt-related transcription factor 2 (Runx2), alkaline phosphate (Alpl), osteocalcin (Bglap), α-1 type I collagen (Col1a1), and receptor activator of NF-κB ligand (Rankl) were analyzed after 3, 7, 14, and 21 days, respectively. Nanocoating with pectin RG-Is increased proliferation and mineralization of MC3T3-E1 and primary osteoblast as compared to osteoblasts cultured without nanocoating. Moreover, osteogenic transcriptional response of osteoblasts was induced by nanocoating in terms of gene induction of Runx2, Alpl, Bglap, and Col1a1 in a time-dependent manner – of note – to the highest extent under the PA-coating condition. In contrast, Rankl expression was initially reduced by nanocoating in MC3T3-E1 or remained unaltered in primary osteoblast as compared to the uncoated controls. Our results showed that nanocoating of implants with modified RG-I beneficially 1) supports osteogenesis, 2) has the capacity to improve osseointegration of implants, and is therefore 3) a potential candidate for nanocoating of bone implants

Microbiota in health and disease-potential clinical applications

Within the last two decades tremendous efforts in biomedicine have been undertaken to understand the interplay of commensal bacteria living in and on our human body with our own human physiology. It became clear that (1) a high diversity especially of the microbial communities in the gut are important to preserve health and that (2) certain bacteria via nutrition-microbe-host metabolic axes are beneficially affecting various functions of the host, including metabolic control, energy balance and immune function. While a large set of evidence indicate a special role for small chain fatty acids (SCFA) in that context, recently also metabolites of amino acids (e.g., tryptophan and arginine) moved into scientific attention. Of interest, microbiome alterations are not only important in nutrition associated diseases like obesity and diabetes, but also in many chronic inflammatory, oncological and neurological abnormalities. From a clinician's point of view, it should be mentioned, that the microbiome is not only interesting to develop novel therapies, but also as a modifiable factor to improve efficiency of modern pharmaceutics, e.g., immune-therapeutics in oncology. However, so far, most data rely on animal experiments or human association studies, whereas controlled clinical intervention studies are spare. Hence, the translation of the knowledge of the last decades into clinical routine will be the challenge of microbiome based biomedical research for the next years. This review aims to provide examples for future clinical applications in various entities and to suggest bacterial species and/or microbial effector molecules as potential targets for intervention studies

Basal forebrain cholinergic system volume is associated with general cognitive ability in the elderly

OBJECTIVE: At the present, it is unclear whether association of basal forebrain cholinergic system (BFCS) volume with cognitive performance exists in healthy as well as in cognitively impaired elderly subjects. Whereas one small study reported an association of BFCS volume with general cognitive ability 'g' in healthy ageing, effects on specific cognitive domains have only been found in subjects with cognitive decline. Here we aim to clarify whether an association of BFCS volume and 'g' is present in a larger sample of elderly subjects without obvious symptoms of dementia and whether similar associations can also be observed in specific cognitive domains. METHODS: 282 pre-surgical patients from the BioCog study (aged 72.7±4.9 years with a range of 65-87 years, 110 women) with a median MMSE score of 29 points (range 24-30) were investigated. BFCS and brain volume as well as brain parenchymal fraction were assessed in T1-weighted MR images using SPM12 and a probabilistic map of the BFCS. Neuropsychological assessment comprised the CANTAB cognitive battery and paper-and-pencil based tests. For data analysis, generalised linear models and quantile regression were applied. RESULTS: Significant associations of BFCS volume with 'g' and several cognitive domains were found, with the strongest association found for 'g'. BFCS volume explained less variance in cognitive performance than brain volume. The association was not confounded by brain parenchymal fraction. Furthermore, the association of BFCS volume and 'g' was similar in high- and low-performers. CONCLUSION: Our results extend previous study findings on BFCS volume associations with cognition in elderly subjects. Despite the observed associations of BFCS volume and cognitive performance, this association seems to reflect a more general association of brain volume and cognition. Accordingly, a specific association of BFCS volume and cognition in non-demented elderly subjects is questionable

Investigating people’s attitudes towards participating in longitudinal health research: an intersectionality-informed perspective

BACKGROUND: Increasing evidence suggests that participation proportions in longitudinal health research vary according to sex/gender, age, social class, or migration status. Intersectionality scholarship purports that such social categories cannot be understood in isolation and makes visible the co-dependent nature of the social determinants of health and illness. This paper uses an intersectionality-informed approach in order to expand the understanding of why people participate in health research, and the impact of intersecting social structures and experiences on these attitudes. METHODS: A sample of 80 respondents who had previously either accepted or declined an invitation to participate in the German National Cohort (NAKO) participated in our interview study. Interviews were semi-structured and contained both narrative elements and more structured probes. Data analysis proceeded in two steps: first, the entire data set was analysed thematically (separately for participants and non-participants); second, key themes were compared across self-reported sex/gender, age group and migration status to identify differences and commonalities. RESULTS: Respondents' attitudes towards study participation can be categorised into four themes: wanting to make a contribution, seeking personalised health information, excitement and feeling chosen, and seeking social recognition. Besides citing logistical challenges, non-participants narrated adverse experiences with or attitudes towards science and the healthcare system that deterred them from participating. A range of social experiences and cultural value systems shaped such attitudes; in particular, this includes the cultural authority of science as an arbiter of social questions, transgressing social categories and experiences of marginalisation. Care responsibilities, predominantly borne by female respondents, also impacted upon the decision to take part in NAKO. DISCUSSION: Our findings suggest that for participants, health research constitutes a site of distinction in the sense of making a difference and being distinct or distinguishable, whereas non-participants inhabited an orientation towards science that reflected their subjective marginalisation through science. No clear relationship can thereby be presumed between social location and a particular attitude towards study participation; rather, such attitudes transgress and challenge categorical boundaries. This challenges the understanding of particular populations as more or less disadvantaged, or as more or less inclined to participate in health research

Identification of novel genes whose expression in adipose tissue affects body fat mass and distribution: an RNA-Seq and Mendelian Randomization study

Many studies have shown that abdominal adiposity is more strongly related to health risks than peripheral adiposity. However, the underlying pathways are still poorly understood. In this cross-sectional study using data from RNA-sequencing experiments and whole-body MRI scans of 200 participants in the EPIC-Potsdam cohort, our aim was to identify novel genes whose gene expression in subcutaneous adipose tissue has an effect on body fat mass (BFM) and body fat distribution (BFD). The analysis identified 625 genes associated with adiposity, of which 531 encode a known protein and 487 are novel candidate genes for obesity. Enrichment analyses indicated that BFM-associated genes were characterized by their higher than expected involvement in cellular, regulatory and immune system processes, and BFD-associated genes by their involvement in cellular, metabolic, and regulatory processes. Mendelian Randomization analyses suggested that the gene expression of 69 genes was causally related to BFM and BFD. Six genes were replicated in UK Biobank. In this study, we identified novel genes for BFM and BFD that are BFM- and BFD-specific, involved in different molecular processes, and whose up-/downregulated gene expression may causally contribute to obesity

Low Adiponectin Levels Are an Independent Predictor of Mixed and Non-Calcified Coronary Atherosclerotic Plaques

Atherosclerosis is the primary cause of coronary artery disease (CAD). There is increasing recognition that lesion composition rather than size determines the acute complications of atherosclerotic disease. Low serum adiponectin levels were reported to be associated with coronary artery disease and future incidence of acute coronary syndrome (ACS). The impact of adiponectin on lesion composition still remains to be determined. We measured serum adiponectin levels in 303 patients with stable typical or atypical chest pain, who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. In bivariate analysis adiponectin levels were inversely correlated with total coronary plaque burden (r = -0.21, p = 0.0004), mixed (r = -0.20, p = 0.0007) and non-calcified plaques (r = -0.18, p = 0.003). No correlation was seen with calcified plaques (r = -0.05, p = 0.39). In a fully adjusted multivariate model adiponectin levels remained predictive of total plaque burden (estimate: -0.036, 95%CI: -0.052 to -0.020, p<0.0001), mixed (estimate: -0.087, 95%CI: -0.132 to -0.042, p = 0.0001) and non-calcified plaques (estimate: -0.076, 95%CI: -0.115 to -0.038, p = 0.0001). Adiponectin levels were not associated with calcified plaques (estimate: -0.021, 95% CI: -0.043 to -0.001, p = 0.06). Since the majority of coronary plaques was calcified, adiponectin levels account for only 3% of the variability in total plaque number. In contrast, adiponectin accounts for approximately 20% of the variability in mixed and non-calcified plaque burden. Adiponectin levels predict mixed and non-calcified coronary atherosclerotic plaque burden. Low adiponectin levels may contribute to coronary plaque vulnerability and may thus play a role in the pathophysiology of ACS

Trail making test B in postoperative delirium: a replication study

BACKGROUND: The Trail Making Test B (TMT-B) is indicative of cognitive flexibility and several other cognitive domains. Previous studies suggest that it might be associated with the risk of developing postoperative delirium, but evidence is limited and conflicting. We therefore aimed to replicate the association of preoperative TMT-B results with postoperative delirium. METHODS: We included older adults (=65 yr) scheduled for major surgery and without signs of dementia to participate in this binational two-centre longitudinal observational cohort study. Presurgical TMT-B scores were obtained. Delirium was assessed twice daily using validated instruments. Logistic regression was applied and the area under the receiver operating characteristic curve calculated to determine the predictive performance of TMT-B. We subsequently included covariates used in previous studies for consecutive sensitivity analyses. We further analysed the impact of outliers, missing or impaired data. RESULTS: Data from 841 patients were included and of those, 151 (18%) developed postoperative delirium. TMT-B scores were statistically significantly associated with the incidence of postoperative delirium {odds ratio per 10-s increment 1.06 (95% confidence interval [CI] 1.02-1.09), P =0.001}. The area under the receiver operating characteristic curve was 0.60 ([95% CI 0.55-0.64], P <0.001). The association persisted after removing 21 outliers (1.07 [95% CI 1.03-1.07], P <0.001). Impaired or missing TMT-B data (n=88) were also associated with postoperative delirium (odds ratio 2.74 [95% CI 1.71-4.35], P <0.001). CONCLUSIONS: The TMT-B was associated with postoperative delirium, but its predictive performance as a stand-alone test was low. The TMT-B alone is not suitable to predict delirium in a clinical setting

Disease overarching mechanisms that explain and predict outcome of patients with high cardiovascular risk: rationale and design of the Berlin Long-term Observation of vascular events (BeLOVE) study

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of premature death worldwide. Effective and individualized treatment requires exact knowledge about both risk factors and risk estimation. Most evidence for risk prediction currently comes from population-based studies on first incident cardiovascular events. In contrast, little is known about the relevance of risk factors for the outcome of patients with established CVD or those who are at high risk of CVD, including patients with type 2 diabetes. In addition, most studies focus on individual diseases, whereas less is known about disease overarching risk factors and cross-over risk. AIM: The aim of BeLOVE is to improve short- and long-term prediction and mechanistic understanding of cardiovascular disease progression and outcomes in very high-risk patients, both in the acute as well as in the chronic phase, in order to provide the basis for improved, individualized management. STUDY DESIGN: BeLOVE is an observational prospective cohort study of patients of both sexes aged >18 in selected Berlin hospitals, who have a high risk of future cardiovascular events, including patients with a history of acute coronary syndrome (ACS), acute stroke (AS), acute heart failure (AHF), acute kidney injury (AKI) or type 2 diabetes with manifest target-organ damage. BeLOVE includes 2 subcohorts: The acute subcohort includes 6500 patients with ACS, AS, AHF, or AKI within 2-8 days after their qualifying event, who undergo a structured interview about medical history as well as blood sample collection. The chronic subcohort includes 6000 patients with ACS, AS, AHF, or AKI 90 days after event, and patients with type 2 diabetes (T2DM) and target-organ damage. These patients undergo a 6-8 hour deep phenotyping program, including detailed clinical phenotyping from a cardiological, neurological and metabolic perspective, questionnaires including patient-reported outcome measures (PROMs)as well as magnetic resonance imaging. Several biological samples are collected (i.e. blood, urine, saliva, stool) with blood samples collected in a fasting state, as well as after a metabolic challenge (either nutritional or cardiopulmonary exercise stress test). Ascertainment of major adverse cardiovascular events (MACE) will be performed in all patients using a combination of active and passive follow up procedures, such as on-site visits (if applicable), telephone interviews, review of medical charts, and links to local health authorities. Additional phenotyping visits are planned at 2, 5 and 10 years after inclusion into the chronic subcohort. FUTURE PERSPECTIVE: BeLOVE provides a unique opportunity to study both the short- and long-term disease course of patients at high cardiovascular risk through innovative and extensive deep phenotyping. Moreover, the unique study design provides opportunities for acute and post-acute inclusion and allows us to derive two non-nested yet overlapping sub-cohorts, tailored for upcoming research questions. Thereby, we aim to study disease overarching research questions, to understand crossover risk, and to find similarities and differences between clinical phenotypes of patients at high cardiovascular risk