Mortality and Cardiovascular Disease among Older Live Kidney Donors

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation

Xenon ventilation MRI in difficult asthma; initial experience in a clinical setting

Background: Hyperpolarised gas MRI can be used to assess ventilation patterns. Previous studies have shown the image derived metric of ventilation defect percent (VDP) to correlate with FEV1/FVC and FEV1 in asthma. Objectives: To explore the utility of hyperpolarised xenon-129 (129Xe) ventilation MRI in clinical care and examine its relationship with spirometry and other clinical metrics in people seen in a severe asthma service. Methods: 26 people referred from a severe asthma clinic for MRI scanning were assessed by contemporaneous 129Xe MRI and spirometry. A sub-group of 18 patients also underwent reversibility testing with spirometry and MRI. Quantitative MRI measures of ventilation were calculated; VDP and the ventilation heterogeneity index (VHI), and compared to spirometry, ACQ7 and blood eosinophil count. Images were reviewed by a multidisciplinary team. Results: VDP and VHI correlated with FEV1, FEV1/FVC and FEF25–75% but not with ACQ7 or blood eosinophil count. Discordance of MRI imaging and symptoms and/or pulmonary function tests also occurred, prompting diagnostic re-evaluation in some cases. Conclusion Hyperpolarised gas MRI provides a complementary method of assessment in people with difficult to manage asthma in a clinical setting. When used as a tool supporting clinical care in a severe asthma service, occurrences of discordance between symptoms, spirometry and MRI scanning indicate how MRI scanning may add to a management pathway

High-utilizing Crohn's disease patients under psychosomatic therapy*

<p>Abstract</p> <p>Objective</p> <p>Few studies have been published on health care utilization in Crohn's disease and the influence of psychological treatment on high utilizers.</p> <p>Methods</p> <p>The present sub study of a prospective multi center investigation conducted in 87 of 488 consecutive Crohn's disease (CD) patients was designed to investigate the influence of the course of Crohn's disease on health care utilization (hospital days (HD) and sick leave days (SLD) collected by German insurance companies) and to examine the conditions of high-utilizing patients. Predictors of health care utilization should be selected. Based on a standardized somatic treatment, high health care utilizing patients of the psychotherapy and control groups should be compared before and after a one-year treatment.</p> <p>Results</p> <p>Multivariate regression analysis identified disease activity at randomization as an important predictor of the clinical course (r²= 0.28, p < 0.01). Health care utilization correlated with duration of disease (p < 0.04), but the model was not significant (r²= 0.15, p = 0.09). The patients' level of anxiety, depression and lack of control at randomization predicted their health-related quality of life at the end of the study (r²= 0.51, p < 0.00001). Interestingly, steroid intake and depression (t1) predicted the combined outcome measure (clinical course, HRQL, health care utilization) of Crohn's disease at the end of the study (r²= 0.22, p < 0.001).</p> <p>Among high utilizers, a significantly greater drop in HD (p < 0.03) and in mean in SLD were found in the treatment compared to the control group.</p> <p>Conclusion</p> <p>The course of Crohn's disease is influenced by psychological as well as somatic factors; especially depression seems important here. A significant drop of health care utilization demonstrates the benefit of psychological treatment in the subgroup of high-utilizing CD patients. Further studies are needed to replicate the findings of the clinical outcome in this CD subgroup.</p

The rapid formation of functional monolayers on silicon under mild conditions

We report on an exceedingly mild chemical functionalization of hydrogen-terminated Si(100) with unactivated and unprotected bifunctional α,ω-dialkynes. Monolayer formation occurs rapidly in the dark, and at room temperature, from dilute solutions of an aromatic-conjugated acetylene. The method addresses the poor reactivity of p-type substrates under mild conditions. We suggest the importance of several factors, including an optimal orientation for electron transfer between the adsorbate and the Si surface, conjugation of the acetylenic function with a π-system, as well as the choice of a solvent system that favors electron transfer and screens Coulombic interactions between surface holes and electrons. The passivated Si(100) electrode is amenable to further functionalization and shown to be a viable model system for redox studies at non-oxide semiconductor electrodes in aqueous solutions

Byrsonima crassifolia

Angiosperm

USP1 Regulates TAZ Protein Stability Through Ubiquitin Modifications in Breast Cancer

The Hippo signaling pathway is an evolutionarily conserved pathway that was initially discovered in Drosophila melanogaster and was later found to have mammalian orthologues. The key effector proteins in this pathway, YAP/TAZ, are often dysregulated in cancer, leading to a high degree of cell proliferation, migration, metastasis and cancer stem cell populations. Due to these malignant phenotypes it is important to understand the regulation of YAP/TAZ at the protein level. Using an siRNA library screen of deubiquitinating enzymes (DUBs), we identified ubiquitin specific peptidase 1 (USP1) as a novel TAZ (WWTR1) regulator. We demonstrated that USP1 interacts with TAZ and increases TAZ protein stability. Conversely, loss of function of USP1 reduces TAZ protein levels through increased poly-ubiquitination, causing a decrease in cell proliferation and migration of breast cancer cells. Moreover, we showed a strong positive correlation between USP1 and TAZ in breast cancer patients. Our findings facilitate the attainment of better understanding of the crosstalk between these pathways and may lead to potential therapeutic interventions for breast cancer patients