Platelet glycoprotein VI-dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets

Platelet activation and thrombus formation have been implicated to be detrimental for intraportal pancreatic islet transplants. The platelet-specific collagen receptor glycoprotein VI (GPVI) plays a key role in thrombosis through cellular activation and the subsequent release of secondary mediators. In aggregometry and in a microfluidic dynamic assay system modeling flow in the portal vein, pancreatic islets promoted platelet aggregation and triggered thrombus formation, respectively. While platelet GPVI deficiency did not affect the initiation of these events, it was found to destabilize platelet aggregates and thrombi in this process. Interestingly, while no major difference was detected in early thrombus formation after intraportal islet transplantation, genetic GPVI deficiency or acute anti-GPVI treatment led to an inferior graft survival and function in both syngeneic mouse islet transplantation and xenogeneic human islet transplantation models. These results demonstrate that platelet GPVI signaling is indispensable in stable thrombus formation induced by pancreatic islets. GPVI deficiency resulted in thrombus destabilization and inferior islet engraftment indicating that thrombus formation is necessary for a successful intraportal islet transplantation in which platelets are active modulators.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Impact of COVID-19 pandemic lockdown on myocardial infarction care

European Journal of Epidemiology - The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors...     

Long‐term tooth loss in periodontally compromised but treated patients according to the type of prosthodontic treatment. A retrospective study

If prosthodontic treatment is considered after periodontal therapy, the questions arise i) does prosthodontic treatment affect the treatment outcome of the dentition in general and ii) which type of prosthesis is related to best treatment outcome of abutment teeth? Our goal was to compare long‐term tooth loss after comprehensive periodontal therapy in patients with or without prosthodontic treatment. Ninety patients' charts with a total of 1937 teeth who had received comprehensive periodontal treatment 5–17 years ago by the same periodontist were retrospectively evaluated. Sixty‐five patients received fixed dental prostheses (FDP; n = 29) and/or removable partial dentures anchored with clips (RPDC; n = 25) or double crowns (RPDD; n = 25). Twenty‐five patients were also periodontally compromised but treated without prosthodontic treatment and served as a control group. A total of 317 teeth and 70 abutment teeth were lost during 9·7 ± 4·1 years of observation. Thereof, 273 teeth and 48 abutment teeth were lost due to periodontal reasons. Mean tooth loss amounted to 1·2 ± 1·5 (controls) and 4·4 ± 3·4 (partial dentures). Abutment tooth loss was 0·4 ± 1·1 (FDP), 1·0 ± 1·2 (RPDC) and 1·3 ± 1·0 (RPDD). Poisson regressions identified prosthodontic treatment, age, socio‐economic status, diabetes mellitus, mean initial bone loss and aggressive periodontitis as factors significantly contributing to tooth loss. Age, diabetes and non‐compliance contributed to abutment tooth loss. Not considering biomechanical factors, patients with prosthodontic reconstructions under long‐term supportive periodontal therapy were at higher risk for further tooth loss than patients without prostheses. Not only the type of partial denture but also the patient‐related risk factors were associated with abutment tooth loss.     

A boy with a one-sided red rash

We report on a boy with a sudden onset of unilateral skin lesions following tonsillar infection with fever 2 weeks before. The lesions consisted of erythematous macules with scaling affecting trunk, axillar, as well as inguinal region. CRP, blood differential, serum IgG and IgM antibodies (coxsackievirus, cytomegalovirus, parvovirus, herpes virus, varicella zoster virus, human herpesvirus-6/-7), and lesional swabs (bacteria, dermatophytes, yeasts) were uneventful.     

Is prevention of atopic eczema with hydrolyzed formulas cost-effective? A health economic evaluation from Germany

To cite this article: Mertens J, Stock S, Lüngen M, Berg AV, Kr?mer U, Filipiak-Pittroff B, Heinrich J, Koletzko S, Grübl A, Wichmann H-E, Bauer C-P, Reinhardt D, Berdel D, Gerber A. Is Prevention of Atopic Eczema with Hydrolyzed Formulas Cost-Effective? A Health Economic Evaluation from Germany. Pediatr Allergy Immunol 2012: 23: 597-604. ABSTRACT: Objective: The German Infant Nutritional Intervention (GINI) trial, a prospective, randomized, double-blind intervention, enrolled children with a hereditary risk for atopy. When fed with certain hydrolyzed formulas for the first 4?months of life, the risk was reduced by 26-45% in PP and 8-29% in intention-to-treat (ITT) analyses compared with children fed with regular cow's milk at age 6. The objective was to assess the cost-effectiveness of feeding hydrolyzed formulas. Patients and Methods: Cost-effectiveness was assessed with a decision tree model programmed in TreeAge. Costs and effects over a 6-yr period were analyzed from the perspective of the German statutory health insurance (SHI) and a societal perspective at a 3% effective discount rate followed by sensitivity analyses. Results: The extensively hydrolyzed casein formula would be the most cost-saving strategy with savings of 478?€ per child treated in the ITT analysis (CI95%: 12?€; 852?€) and 979?€ in the PP analysis (95%CI: 355?€; 1455?€) from a societal perspective. If prevented cases are considered, the partially whey hydrolyzed formula is cost-saving (ITT -5404?€, PP -6358?€). From an SHI perspective, the partially whey hydrolyzed formula is cost-effective, but may also be cost-saving depending on the scenario. An extensively hydrolyzed whey formula also included into the analysis was dominated in all analyses. Conclusions: For the prevention of AE, two formulas can be cost-effective or even cost-saving. We recommend that SHI should reimburse formula feeding or at least the difference between costs for cow's milk formula and the most cost-effective formula.     

Gender aspects in skin diseases

Gender differences in medicine have been recognized in anatomy, physiology, as well as in epidemiology and manifestations of various diseases. With respect to skin disorders, males are generally more commonly afflicted with infectious diseases while women are more susceptible to psychosomatic problems, pigmentary disorders, certain hair diseases, and particularly autoimmune as well as allergic diseases. Significantly, more female sex‐associated dermatoses can be identified than the male sex‐associated dermatoses. Dermatoses in the genital area differ between men and women. Gender differences also exist in the occurrence and prognosis of certain skin malignancies. The mechanisms underlying gender differences in skin diseases remain largely unknown. Differences in the skin structure and physiology, effect of sex hormones, ethnic background, sociocultural behaviour and environmental factors may interact to exert the influences. A better understanding of gender differences in human health and diseases will allow the development of novel concepts for prevention, diagnosis and therapy of skin diseases.