Patients with mild cognitive impairment (MCI) showed a high probability to be diagnosed with Alzheimer dementia (AD) after 30 months. Subtypes of MCI were not useful in defining early stages of various types of dementia: Not only amnestic MCI but also nonamnestic MCI converted frequently to AD, and conversion to vascular dementia and dementia with Lewy bodies was not restricted to nonamnestic MCI.

Background Haemodialysis (HD) patients are exposed to a high risk due to the SARS-CoV-2 pandemic. They are prone to acquiring the infection and are threatened by high mortality rates in case of infection. However, HD patients were not included in the efficacy trials of the SARS-CoV-2 vaccines. Such efficacy data would have been critical because HD patients show decreased responses against various other vaccines and this could translate to the SARS-CoV-2 vaccines as well. Methods We conducted a prospective cohort study that contained a group of 81 HD patients and 80 healthy controls. All of them had been vaccinated with the BioNTech/Pfizer mRNA vaccine (two doses, as per the manufacturer’s recommendation). The anti-SARS-CoV-2 S antibody response was measured for all participants 21 days after the second dose. The groups were compared using univariate quantile regressions and a multivariate analysis. The adverse events (AEs) of the vaccination were assessed via a questionnaire. Finally, a correlation between the HBs-Antibody response and the SARS-CoV-2 antibody response in the HD patients was established. Results The HD patients had significantly lower Anti-SARS-CoV-2 S antibody titres than the control patients 21 days after vaccination (median was 171 U/ml for dialysis patients and 2,500 U/ml for the controls). Further, the HD group presented less AEs than the control group. No correlation was found between the antibody response to previous Hepatitis B vaccination and that of the SARS-CoV-2 vaccine. Conclusions HD patients present highly diminished SARS-CoV-2 S antibody titres compared to a cohort of controls. Therefore, they could be much less protected by SARS-CoV-2 mRNA vaccinations than expected. Further studies to test alternative vaccination schemes should be considered.

Key Points• Uridine diphospho glucuronosyltransferase 2B17 (UGT2B17) is overexpressed in poor prognostic chronic lymphocytic leukemia.Uridine diphospho glucuronosyltransferase 2B17 (UGT2B17) glucuronidates androgens and xenobiotics including certain drugs. The UGT2B17 gene shows a remarkable copy number variation (CNV), which predisposes for solid tumors and influences drug response. Here, we identify a yet undescribed UGT2B17 mRNA overexpression in poor-risk chronic lymphocytic leukemia (CLL). In total, 320 CLL patients and 449 healthy donors were analyzed. High (above median) UGT2B17 expression was associated with established CLL poor prognostic factors and resulted in shorter treatment-free and overall survival (hazard ratio ([death] 2.18; 95% CI 1.18-4.01; P ‫؍‬ .013). The prognostic impact of mRNA expression was more significant than that of UGT2B17 CNV. UGT2B17 mRNA levels in primary CLL samples directly correlated with functional glucuronidation activity toward androgens and the anticancer drug vorinostat (R > 0.9, P < .001). After treatment with fludarabine containing regimens UGT2B17 was up-regulated particularly in poor responders (P ‫؍‬ .030). We observed an exclusive involvement of the 2B17 isoform within the UGT protein family. Gene expression profiling of a stable UGT2B17 knockdown in the CLL cell line MEC-1 demonstrated a significant involvement in key cellular processes. These findings establish a relevant role of UGT2B17 in CLL with functional consequences and potential therapeutic implications. (Blood. 2013;121(7):1175-1183) IntroductionChronic lymphocytic leukemia (CLL) is characterized by a considerable heterogeneity regarding clinical presentation, need for treatment, and outcome. Many prognostic markers have been identified. 1 Although most of them provide information about risk of progression and survival, the functional role of these markers is often unclear and therapeutic consequences are therefore lacking. Apart from the clinical Rai and Binet staging systems and cytogenetics, 2-4 molecular markers, such as immunoglobulin heavy chain variable (IGHV) gene mutational status 5,6 and lipoprotein lipase (LPL) mRNA expression have strong prognostic value. 7,8 In a pilot gene expression study with 20 CLL patients, we identified a significant association of uridine diphospho (UDP) glucuronosyltransferase 2B17 (UGT2B17) with these prognostic factors. 9 Metabolizing phase 2 enzymes of the UGT2B super-family conjugate various endogenous compounds, in particular steroid hormones as well as several pharmaceutical drugs. 10,11 The UGT2B genes and pseudogenes are clustered on chromosome 4q13 and display up to 95% sequence homology among each other, which is reflected in some overlap in substrate specificity but often distinct expression profile. Isoform UGT2B17 is a major androgen inactivating enzyme playing a role in local tissuespecific regulation of it is substrates. 12 Importantly, antileukemic drugs, such as anthraquinones or the histone deacetylase (HDAC) inhibitor vorinostat, are also subject ...

Psychological support interventions for family caregivers should take gender-specific risk factors into account. Interventions focusing on keeping up hope while caring for a terminally ill family member may be a valuable addition to palliative services to improve support for family carers. Women may benefit from interventions that address adaptive coping and strategies to deal with the dual demands of employment and caring. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Background Coronavirus disease 2019 (COVID‐19) interferes with the vascular endothelium. It is not known whether COVID‐19 additionally affects arterial stiffness. Methods This case–control study compared brachial‐ankle pulse wave (baPWV) and carotid‐femoral pulse wave velocities (cfPWV) of acutely ill patients with and without COVID‐19. Results Twenty‐two COVID‐19 patients (50% females, 77 [67–84] years) were compared with 22 age‐ and sex‐matched controls. In COVID‐19 patients, baPWV (19.9 [18.4–21.0] vs. 16.0 [14.2–20.4], P = 0.02) and cfPWV (14.3 [13.4–16.0] vs. 11.0 [9.5–14.6], P = 0.01) were higher than in the controls. In multiple regression analysis, COVID‐19 was independently associated with higher cfPWV ( β = 3.164, P = 0.004) and baPWV ( β = 3.532, P = 0.003). PWV values were higher in nonsurvivors. In survivors, PWV correlated with length of hospital stay. Conclusion COVID‐19 appears to be related to an enhanced PWV reflecting an increase in arterial stiffness. Higher PWV might be related to an increased length of hospital stay and mortality.

DNA methylation is part of the epigenetic gene regulation complex, which is relevant for the pathogenesis of cancer. We performed a genome-wide search for methylated CpG islands in tumors and corresponding non-malignant lung tissue samples of 101 stages I-III non-small cell lung cancer (NSCLC) patients by combining methylated DNA immunoprecipitation and microarray analysis. Overall, we identified 2414 genomic positions differentially methylated between tumor and non-malignant lung tissue samples. Ninety-seven percent of them were found to be tumor-specifically methylated. Annotation of these genomic positions resulted in the identification of 477 tumor-specifically methylated genes of which many are involved in regulation of gene transcription and cell adhesion. Tumor-specific methylation was confirmed by a gene-specific approach. In the majority of tumors, methylation of certain genes was associated with loss of their protein expression determined by immunohistochemistry. Treatment of NSCLC cells with epigenetically active drugs resulted in upregulated expression of many tumor-specifically methylated genes analyzed by gene expression microarrays suggesting that about one-third of these genes are transcriptionally regulated by methylation. Moreover, comparison of methylation results with certain clinicopathological characteristics of the patients suggests that methylation of HOXA2 and HOXA10 may be of prognostic relevance in squamous cell carcinoma (SCC) patients. In conclusion, we identified a large number of tumorspecifically methylated genes in NSCLC patients. Expression of many of them is regulated by methylation. Moreover, HOXA2 and HOXA10 methylation may serve as prognostic parameters in SCC patients. Overall, our findings emphasize the impact of methylation on the pathogenesis of NSCLCs.

Component-based testing and the whole-allergen CAP are equally relevant in the diagnosis of grass-, birch- and cat-allergic patients. Although slightly less sensitive, the microarray is sufficient for the diagnosis of HDM-allergic patients, but needs alternative and/or additional components for detecting mugwort allergy.

Knowledge about the extent of total variation experienced between samples from different individuals is of great importance for the design of not only proteomics but every clinical study. This variation defines the smallest statistically significant detectable signal difference when comparing two groups of individuals. We isolated platelets from 20 healthy human volunteers aged 56 -100 years because this age group is most commonly encountered in the clinics. We determined the technical and total variation experienced in a proteome analysis using two-dimensional DIGE with IPGs in the pI ranges 4 -7 and 6 -9. Only spots that were reproducibly detectable in at least 90% of all gels (n ‫؍‬ 908) were included in the study. All spots had a similar technical variation with a median coefficient of variation (cv) of about 7%. In contrast, spots showed a more diverse total variation between individuals with a surprisingly low median cv of only 18%. Because most known biomarkers show an effect size in a 1-2-fold range of their cv, any future clinical proteomics study with platelets will require an analytical method that is able to detect such small quantitative differences. In addition, we calculated the minimal number of samples (sample size) needed to detect given protein expression differences with statistical significance. Molecular & Cellular Proteomics 7:193-203, 2008.Biomarkers are used to differentiate between different biological states and to monitor disease progress or the success of medical treatment. To fulfill these tasks, there are not only strict requirements for each biomarker candidate in terms of selectivity and specificity but also for the precision of the analytical process. Therefore knowledge on the extent of variation between the individuals within each group is crucial for the study design as well as the selection of the method of measurement. The total variation experienced between individuals within one group is the result of the biological variation caused by factors like sex, age, genetic background, lifestyle, or health status and the technical variation introduced by the applied sample handling and the method of measurement itself. This study investigated the extent of variation in human blood platelets. Platelets are responsible for the maintenance of vascular integrity and are also involved in inflammation and wound healing (1). They are anucleate cytoplasmic fragments released from megakaryocytes in the bone marrow. During platelet biogenesis, organelles, especially the mitochondria and the ␣-and dense granules, are actively transported into the platelets. Furthermore platelets receive a certain set of mRNAs during their biogenesis from the megakaryocytes and are still capable of protein synthesis and processing (2). Several proteomics studies have focused on different aspects in platelet research using 2D 1 electrophoresis followed by mass spectrometry. These studies provided 2D maps of the total platelet proteome (3, 4), the platelet secretome (5), and the processes during platelet activ...