265 research outputs found

    Combining transplant professional's psychosocial donor evaluation and donor self-report measures to optimise the prediction of HRQoL after kidney donation:an observational prospective multicentre study

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    OBJECTIVES: Living donor kidney transplantation is currently the preferred treatment for patients with end-stage renal disease. The psychosocial evaluation of kidney donor candidates relies mostly on the clinical viewpoint of transplant professionals because evidence-based guidelines for psychosocial donor eligibility are currently lacking. However, the accuracy of these clinical risk judgements and the potential added value of a systematic self-reported screening procedure are as yet unknown. The current study examined the effectiveness of the psychosocial evaluation by transplant professionals and the potential value of donor self-report measures in optimising the donor evaluation. Based on the stress-vulnerability model, the predictive value of predonation, intradonation and postdonation factors to impaired longer term health-related quality of life (HRQoL) of kidney donors was studied. DESIGN: An observational prospective multicentre study. SETTING: Seven Dutch transplantation centres. PARTICIPANTS: 588 potential donors participated, of whom 361 donated. Complete prospective data of 230 donors were available. Also, 1048 risk estimation questionnaires were completed by healthcare professionals. METHODS: Transplant professionals (nephrologists, coordinating nurses, social workers and psychologists) filled in risk estimation questionnaires on kidney donor candidates. Furthermore, 230 kidney donors completed questionnaires (eg, on HRQoL) before and 6 and 12 months after donation. PRIMARY AND SECONDARY OUTCOME MEASURES: HRQoL, demographic and preoperative, intraoperative and postoperative health characteristics, perceived support, donor cognitions, recipient functioning and professionals risk estimation questionnaires. RESULTS: On top of other predictors, such as the transplant professionals’ risk assessments, donor self-report measures significantly predicted impaired longer term HRQoL after donation, particularly by poorer predonation physical (17%–28% explained variance) and psychological functioning (23%). CONCLUSIONS: The current study endorses the effectiveness of the psychosocial donor evaluation by professionals and the additional value of donor self-report measures in optimising the psychosocial evaluation. Consequently, systematic screening of donors based on the most prominent risk factors provide ground for tailored interventions for donors at risk

    Overview of In Situ X-ray Studies of Light Alloy Solidification in Microgravity

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    Gravity has significant effects on alloy solidification, primarily due to thermosolutal convection and solid phase buoyancy. Since 2004, the European Space Agency has been supporting investigation of these effects by promoting in situ X-ray monitoring of the solidification of aluminium alloys on microgravity platforms, on earth, and in periodically varying g conditions. The first microgravity experiment – investigating foaming of liquid metals – was performed on board a sounding rocket, in 2008. In 2012 the first ever X-ray-monitored solidification of a fully dense metallic alloy in space was achieved: the focus was columnar solidification of an Al-Cu alloy. This was followed in 2015 by a similar experiment, investigating equiaxed solidification. Ground reference experiments were completed in all cases. In addition, experiments have been performed on board parabolic flights – where the effects of varying gravity have been studied. We review here the technical and scientific progress to date, and outline future perspectives

    Predictors of Intraspinal Pressure and Optimal Cord Perfusion Pressure After Traumatic Spinal Cord Injury.

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    BACKGROUND/OBJECTIVES: We recently developed techniques to monitor intraspinal pressure (ISP) and spinal cord perfusion pressure (SCPP) from the injury site to compute the optimum SCPP (SCPPopt) in patients with acute traumatic spinal cord injury (TSCI). We hypothesized that ISP and SCPPopt can be predicted using clinical factors instead of ISP monitoring. METHODS: Sixty-four TSCI patients, grades A-C (American spinal injuries association Impairment Scale, AIS), were analyzed. For 24 h after surgery, we monitored ISP and SCPP and computed SCPPopt (SCPP that optimizes pressure reactivity). We studied how well 28 factors correlate with mean ISP or SCPPopt including 7 patient-related, 3 injury-related, 6 management-related, and 12 preoperative MRI-related factors. RESULTS: All patients underwent surgery to restore normal spinal alignment within 72 h of injury. Fifty-one percentage had U-shaped sPRx versus SCPP curves, thus allowing SCPPopt to be computed. Thirteen percentage, all AIS grade A or B, had no U-shaped sPRx versus SCPP curves. Thirty-six percentage (22/64) had U-shaped sPRx versus SCPP curves, but the SCPP did not reach the minimum of the curve, and thus, an exact SCPPopt could not be calculated. In total 5/28 factors were associated with lower ISP: older age, excess alcohol consumption, nonconus medullaris injury, expansion duroplasty, and less intraoperative bleeding. In a multivariate logistic regression model, these 5 factors predicted ISP as normal or high with 73% accuracy. Only 2/28 factors correlated with lower SCPPopt: higher mean ISP and conus medullaris injury. In an ordinal multivariate logistic regression model, these 2 factors predicted SCPPopt as low, medium-low, medium-high, or high with only 42% accuracy. No MRI factors correlated with ISP or SCPPopt. CONCLUSIONS: Elevated ISP can be predicted by clinical factors. Modifiable factors that may lower ISP are: reducing surgical bleeding and performing expansion duroplasty. No factors accurately predict SCPPopt; thus, invasive monitoring remains the only way to estimate SCPPopt

    Походження права законодавчої ініціативи Державної ради Російської імперії 1906-1916 років

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    Демократизація державного та громадського життя в Україні висуває вимоги вивчення історичного досвіду цього процесу, перш за все, в умовах переходу від авторитарного управління до парламентаризму, а також гальмуючої ролі пережитків минулого. Це зачіпає і питання про впливи, які визначили сутність права законодавчої ініціативи Державної ради Російської імперії 1906 – 1916 рр. Воно не знайшло висвітлення, за одиночним винятком – статті російського правознавця Б.Е.Нольде (3) ні в дорадянській, ні в радянській історіографії. Мету нашого дослідження складає спроба встановити і охарактеризувати джерело виникнення права законодавчої ініціативи Державної ради Російської імперії 1906 – 1916 рр. шляхом аналізу відповідних законодавчих актів. Головним завданням дослідження є аналіз Основних державних законів 23 квітня 1906 р., Запровадження Державної ради 24 квітня 1906 р., Запроваджень Державної думи 6 серпня 1905 та 20 лютого 1906 рр., а також підготовчих матеріалів щодо цих актів

    The role of CSF1R-dependent macrophages in control of the intestinal stem cell niche

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    Colony-stimulating factor 1 (CSF1) controls the growth and differentiation of macrophages.CSF1R signaling has been implicated in the maintenance of the intestinal stem cell niche and differentiation of Paneth cells, but evidence of expression of CSF1R within the crypt is equivocal. Here we show that CSF1R-dependent macrophages influence intestinal epithelial differentiation and homeostasis. In the intestinal lamina propria CSF1R mRNA expression is restricted to macrophages which are intimately associated with the crypt epithelium, and is undetectable in Paneth cells. Macrophage ablation following CSF1R blockade affects Paneth cell differentiation and leads to a reduction of Lgr5 intestinal stem cells. The disturbances to the crypt caused by macrophage depletion adversely affect the subsequent differentiation of intestinal epithelial cell lineages. Goblet cell density is enhanced, whereas the development of M cells in Peyer's patches is impeded. We suggest that modification of the phenotype or abundance of macrophages in the gut wall alters the development of the intestinal epithelium and the ability to sample gut antigens

    TorsinA and the TorsinA-Interacting Protein Printor Have No Impact on Endoplasmic Reticulum Stress or Protein Trafficking in Yeast

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    Early-onset torsion dystonia is a severe, life-long disease that leads to loss of motor control and involuntary muscle contractions. While the molecular etiology of the disease is not fully understood, a mutation in an AAA+ ATPase, torsinA, has been linked to disease onset. Previous work on torsinA has shown that it localizes to the endoplasmic reticulum, where there is evidence that it plays roles in protein trafficking, and potentially also protein folding. Given the high level of evolutionary conservation among proteins involved in these processes, the ability of human such proteins to function effectively in yeast, as well as the previous successes achieved in examining other proteins involved in complex human diseases in yeast, we hypothesized that Saccharomyces cerevisiae might represent a useful model system for studying torsinA function and the effects of its mutants. Since torsinA is proposed to function in protein homeostasis, we tested cells for their ability to respond to various stressors, using a fluorescent reporter to measure the unfolded protein response, as well as their rate of protein secretion. TorsinA did not impact these processes, even after co-expression of its recently identified interacting partner, printor. In light of these findings, we propose that yeast may lack an additional cofactor necessary for torsinA function or proteins required for essential post-translational modifications of torsinA. Alternatively, torsinA may not function in endoplasmic reticulum protein homeostasis. The strains and assays we describe may provide useful tools for identifying and investigating these possibilities and are freely available.Howard Hughes Medical InstituteBachmann-Strauss Dystonia and Parkinson Foundatio

    Silencing and Nuclear Repositioning of the λ5 Gene Locus at the Pre-B Cell Stage Requires Aiolos and OBF-1

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    The chromatin regulator Aiolos and the transcriptional coactivator OBF-1 have been implicated in regulating aspects of B cell maturation and activation. Mice lacking either of these factors have a largely normal early B cell development. However, when both factors are eliminated simultaneously a block is uncovered at the transition between pre-B and immature B cells, indicating that these proteins exert a critical function in developing B lymphocytes. In mice deficient for Aiolos and OBF-1, the numbers of immature B cells are reduced, small pre-BII cells are increased and a significant impairment in immunoglobulin light chain DNA rearrangement is observed. We identified genes whose expression is deregulated in the pre-B cell compartment of these mice. In particular, we found that components of the pre-BCR, such as the surrogate light chain genes λ5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclear repositioning of the λ5 gene is impaired in pre-B cells lacking OBF-1 and Aiolos. These studies uncover a novel role for OBF-1 and Aiolos in controlling the transcription and nuclear organization of genes involved in pre-BCR function
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