Public exhibit for demonstrating the quantum of electrical conductance

We present a new robust setup that explains and demonstrates the quantum of electrical conductance for a general audience and which is continuously available in a public space. The setup allows users to manually thin a gold wire of several atoms in diameter while monitoring its conductance in real time. During the experiment, a characteristic step-like conductance decrease due to rearrangements of atoms in the cross-section of the wire is observed. Just before the wire breaks, a contact consisting of a single atom with a characteristic conductance close to the quantum of conductance can be maintained up to several seconds. The setup is operated full-time, needs practically no maintenance and is used on different educational levels

The effect of treatment modifications by an onco-geriatric MDT on one-year mortality, days spent at home and postoperative complications

OBJECTIVES: Decision-making in older patients with cancer can be complex, as benefits of treatment should be weighed against possible side-effects and life-expectancy. A novel care pathway was set up incorporating geriatric assessment into treatment decision-making for older cancer patients. Treatment decisions could be modified following discussion in an onco-geriatric multidisciplinary team (MDT). We assessed the effect of treatment modifications on outcomes. MATERIALS AND METHODS: This retrospective study was performed in the surgical department of a University Hospital. Patients of 70 years and older with a solid malignancy were included. All patients underwent a nurse-led geriatric assessment (GA) and were discussed in an onco-geriatric MDT. This could result in a modified or an unchanged treatment advice compared to the regular tumor board. Primary outcome was one-year mortality. Secondary outcomes were post-operative complications and days spent in hospital in the first year after inclusion. RESULTS: For the 184 patients in the analyses, the median age was 77.5 years and 41.8% were female. For 46 patients (25%), the treatment advice was modified by the onco-geriatric MDT. There was no significant difference in one-year mortality between the unchanged and modified group (29.7% versus 26.1%, p = 0.7). There were, however, significantly fewer days spent in hospital (median 5 vs 8.5 days p = 0.02) and fewer grade II or higher postoperative complications (13.3% versus 35.5% p = 0.005) in the modified group. CONCLUSION: Incorporating geriatric assessment in decision-making did not lead to excess one-year mortality, but did result in fewer complications and days spent in hospital

Медико-психологическая характеристика и дифференциальная диагностика дезадаптивных состояний у военнослужащих

Діагностична і експертна оцінка дезадаптивних станів є актуальною проблемою сучасної психіатрії. У цієї роботі розглядаються дезадаптивні стани з погляду девіантної поведінки у акцентуйованих осіб. Результати дослідження підтверджувалися психологічними, нейрофізіологічними методами.Diagnostics and expert estimation of deadaptation states is a topical problem of modern psychiatry. This article represents an examination of deadaptation states from the point of view of deviant behavior of accentuated personalities. The research results were confirmed by psychological and neurophysiological methods

The association between the inflammatory response to surgery and postoperative complications in older patients with cancer; a prospective prognostic factor study

BACKGROUND: Accurate prognostic biomarkers would substantially improve surgical planning and decisions making yet no studies have been reported exploring the inflammatory response in surgically treated older patients with cancer. The aim of this study was to explore inflammatory biomarkers as potential prognostic factors for postoperative complications within 30 days in older patients with cancer. METHOD: Patients 65 years and older undergoing surgery for removal of a solid malignant tumour were included in an observational cohort study. All complications occurring up to 30 days postoperatively were documented prospectively. Inflammatory markers were measured in plasma samples pre- and postoperatively: C-reactive protein (CRP), Interleukin-1 beta (IL-1β), IL-6, IL-10, IL-12, and Tumour necrosis factor-alpha (TNF-α). Associations between inflammatory markers and postoperative complications were explored using logistic regression analysis. RESULTS: Between July 2010 and April 2014, plasma samples of 224 patients were collected. Median age was 72 (65-89) years and 116 (51.8%) patients were female. Approximately half of the patients developed postoperative complications (49.6%) of whom 62 patients (55.9%) developed >1 complication. An independent prognostic effect was observed for the inflammatory biomarkers IL-6 and IL-10 for the occurrence of postoperative complications. CONCLUSION: The perioperative inflammatory response is associated with complications, independently from patient and surgical factors which are also associated with outcome. Research is warranted towards further exploration of the perioperative inflammatory response with the aim to improve perioperative care and outcome, and might help to improve surgical planning and decision making for older patients with cancer

Vitamin Status and the Development of Postoperative Cognitive Decline in Elderly Surgical Oncologic Patients

Background. This study aimed to evaluate the influence that serum levels of vitamin B12, folate, and homocysteine have on the development of short-term postoperative cognitive decline in the elderly surgical oncology patient. Methods. This study was part of a prospective cohort study focused on postoperative cognitive outcomes for patients 65 years of age or older undergoing surgery for a solid malignancy. Postoperative cognitive decline was defined as the change in the combined results of the Ruff Figural Fluency Test and the Trail-Making Test Parts A and B. Patients with the highest change in scores 2 weeks postoperatively compared with baseline were considered to be patients with cognitive decline. Patients with the lowest change were considered to be patients without cognitive decline. To analyze the effect of vitamin levels on the changes in postoperative cognitive scores, uni- and multivariate logistic regression analysis were performed. Results. The study enrolled 61 patients with and 59 patients without postoperative cognitive decline. Hyperhomocysteinemia was present in 14.2% of the patients. Patients with postoperative cognitive decline more often had hyperhomocysteinemia (27.9 vs 10.2%). Hyperhomocysteinemia was associated with a higher chance for the development of postoperative cognitive decline (odds ratio(adjusted), 11.9; 95% confidence interval, 2.4-59.4). Preoperative vitamin B12 or folate deficiency were not associated with the development of postoperative cognitive decline. Conclusion. Preoperative hyperhomocysteinemia is associated with the development of postoperative cognitive decline. The presence of preoperative hyperhomocysteinemia could be an indicator for an increased risk of postoperative cognitive decline developing in the elderly

Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration

Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes. To delineate how cellular consequences of NAE1 deficiency would lead to the clinical phenotype, we focused primarily on the rarest phenotypic features, based on the assumption that these would best reflect the pathophysiology at stake. Two of the rarest features, neuronal loss and lymphopenia worsening during infections, suggest that NAE1 is required during cellular stress caused by infections to protect against cell death. In support, we found that stressing the proteasome system with MG132—requiring upregulation of neddylation to restore proteasomal function and proteasomal stress—led to increased cell death in fibroblasts of individuals with NAE1 genetic variants. Additionally, we found decreased lymphocyte counts after CD3/CD28 stimulation and decreased NF-κB translocation in individuals with NAE1 variants. The rarest phenotypic feature—delayed closure of the ischiopubic rami—correlated with significant downregulation of RUN2X and SOX9 expression in transcriptomic data of fibroblasts. Both genes are involved in the pathophysiology of ischiopubic hypoplasia. Thus, we show that NAE1 plays a major role in (skeletal) development and cellular homeostasis during stress. Our approach suggests that a focus on rare phenotypic features is able to provide significant pathophysiological insights in diseases caused by mutations in genes with pleiotropic effects.</p

Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration

Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes. To delineate how cellular consequences of NAE1 deficiency would lead to the clinical phenotype, we focused primarily on the rarest phenotypic features, based on the assumption that these would best reflect the pathophysiology at stake. Two of the rarest features, neuronal loss and lymphopenia worsening during infections, suggest that NAE1 is required during cellular stress caused by infections to protect against cell death. In support, we found that stressing the proteasome system with MG132—requiring upregulation of neddylation to restore proteasomal function and proteasomal stress—led to increased cell death in fibroblasts of individuals with NAE1 genetic variants. Additionally, we found decreased lymphocyte counts after CD3/CD28 stimulation and decreased NF-κB translocation in individuals with NAE1 variants. The rarest phenotypic feature—delayed closure of the ischiopubic rami—correlated with significant downregulation of RUN2X and SOX9 expression in transcriptomic data of fibroblasts. Both genes are involved in the pathophysiology of ischiopubic hypoplasia. Thus, we show that NAE1 plays a major role in (skeletal) development and cellular homeostasis during stress. Our approach suggests that a focus on rare phenotypic features is able to provide significant pathophysiological insights in diseases caused by mutations in genes with pleiotropic effects.</p

Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration

Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes. To delineate how cellular consequences of NAE1 deficiency would lead to the clinical phenotype, we focused primarily on the rarest phenotypic features, based on the assumption that these would best reflect the pathophysiology at stake. Two of the rarest features, neuronal loss and lymphopenia worsening during infections, suggest that NAE1 is required during cellular stress caused by infections to protect against cell death. In support, we found that stressing the proteasome system with MG132—requiring upregulation of neddylation to restore proteasomal function and proteasomal stress—led to increased cell death in fibroblasts of individuals with NAE1 genetic variants. Additionally, we found decreased lymphocyte counts after CD3/CD28 stimulation and decreased NF-κB translocation in individuals with NAE1 variants. The rarest phenotypic feature—delayed closure of the ischiopubic rami—correlated with significant downregulation of RUN2X and SOX9 expression in transcriptomic data of fibroblasts. Both genes are involved in the pathophysiology of ischiopubic hypoplasia. Thus, we show that NAE1 plays a major role in (skeletal) development and cellular homeostasis during stress. Our approach suggests that a focus on rare phenotypic features is able to provide significant pathophysiological insights in diseases caused by mutations in genes with pleiotropic effects.</p

Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration

Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes. To delineate how cellular consequences of NAE1 deficiency would lead to the clinical phenotype, we focused primarily on the rarest phenotypic features, based on the assumption that these would best reflect the pathophysiology at stake. Two of the rarest features, neuronal loss and lymphopenia worsening during infections, suggest that NAE1 is required during cellular stress caused by infections to protect against cell death. In support, we found that stressing the proteasome system with MG132—requiring upregulation of neddylation to restore proteasomal function and proteasomal stress—led to increased cell death in fibroblasts of individuals with NAE1 genetic variants. Additionally, we found decreased lymphocyte counts after CD3/CD28 stimulation and decreased NF-κB translocation in individuals with NAE1 variants. The rarest phenotypic feature—delayed closure of the ischiopubic rami—correlated with significant downregulation of RUN2X and SOX9 expression in transcriptomic data of fibroblasts. Both genes are involved in the pathophysiology of ischiopubic hypoplasia. Thus, we show that NAE1 plays a major role in (skeletal) development and cellular homeostasis during stress. Our approach suggests that a focus on rare phenotypic features is able to provide significant pathophysiological insights in diseases caused by mutations in genes with pleiotropic effects.</p

Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration

Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes. To delineate how cellular consequences of NAE1 deficiency would lead to the clinical phenotype, we focused primarily on the rarest phenotypic features, based on the assumption that these would best reflect the pathophysiology at stake. Two of the rarest features, neuronal loss and lymphopenia worsening during infections, suggest that NAE1 is required during cellular stress caused by infections to protect against cell death. In support, we found that stressing the proteasome system with MG132—requiring upregulation of neddylation to restore proteasomal function and proteasomal stress—led to increased cell death in fibroblasts of individuals with NAE1 genetic variants. Additionally, we found decreased lymphocyte counts after CD3/CD28 stimulation and decreased NF-κB translocation in individuals with NAE1 variants. The rarest phenotypic feature—delayed closure of the ischiopubic rami—correlated with significant downregulation of RUN2X and SOX9 expression in transcriptomic data of fibroblasts. Both genes are involved in the pathophysiology of ischiopubic hypoplasia. Thus, we show that NAE1 plays a major role in (skeletal) development and cellular homeostasis during stress. Our approach suggests that a focus on rare phenotypic features is able to provide significant pathophysiological insights in diseases caused by mutations in genes with pleiotropic effects.</p