78 research outputs found

    Silent recovery of native kidney function after transplantation in a patient with membranous nephropathy

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    Recurrence of membranous nephropathy (MN) is frequently seen after transplantation. However, there are no published data about the course of MN in the native kidneys after transplantation. Disease progression in almost all cases is assumed to be the ‘natural' course after transplantation. We report on a patient suffering from end-stage renal disease due to MN. Eight years after transplantation, nephrectomy was performed due to chronic rejection and unexpectedly, partial recovery of native kidney function was noted. As far as we know, there is no other similar case reported in the literature. The potential impact of the immunosuppression, especially of calcineurin inhibitors, is discusse

    Rapid Detection of the Change in Surface Flow Patterns Near Fish Passages at Hydropower Dams With the Use of UAS Based Videos Under Controlled Discharge Conditions

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    The importance of keeping river environments healthy drives the scientific community towards the improvement of sustainable and validated environmental monitoring approaches. Accurate data on the state of the ecosystems provided rapidly are key in order to correctly assess, which interventions and management decisions are suitable, and which must be avoided. This paper analyses a rapid non-intrusive approach to change detection in surface flow patterns near fish passages at hydropower dams with the goal to improve the understanding of factors influencing fish passage discoverability. This, in turn, is of great relevance to the sustainability of migrating riverine fish populations from both ecological and economical perspectives. The present study includes three unique experiments performed at a large-scale hydropower dam site with an integrated fish passage under controlled discharge conditions. The analysis is performed with the use of the freely available KLT-IV software. The use of an Unmanned Aerial System (UAS) as a camera carrier platform provides the key flexibility in terms of any study site selection. The use of KLT-IV speeds up and simplifies flow pattern analysis, especially when compared to labour-intensive modelling relying on point-based ground truth data. In this paper, we demonstrate that the selected approach can be effectively applied to identify changes in surface flow patterns both in terms of flow velocity magnitudes and in terms of flow directions. It shows that the identification of actual flow patterns near the fish passage entrance provides more information on the potential discoverability of the fish passage than traditionally measured bulk discharge values alone

    Predictive preoperative clinical score for patients with liver-only oligometastatic colorectal cancer

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    BACKGROUND: Resection of liver metastases from colorectal cancer (CRC) in the oligometastatic stage improves survival and is a potentially curative treatment. Thus, predictive scores that reliably identify those patients who especially benefit from surgery are essential. PATIENTS AND METHODS: In this multicenter analysis, 512 patients had undergone surgery for liver metastases from CRC. We investigated distinct cancer-specific risk factors that are routinely available in clinical practice and developed a predictive preoperative score using a training cohort (TC), which was thereafter tested in a validation cohort (VC). RESULTS: Inflammatory response to the tumor, a right-sided primary tumor, multiple liver metastases, and node-positive primary tumor were significant adverse variables for overall survival (OS). Patients were stratified in five groups according to the cumulative score given by the presence of these risk factors. Median OS for patients without risk factors was 133.8 months [95% confidence interval (CI) 81.2-not reached (nr)] in the TC and was not reached in the VC. OS decreased significantly for each subsequent group with increasing number of risk factors. Median OS was significantly shorter (P < 0.0001) for patients presenting all four risk factors: 14.3 months (95% CI 10.5 months-nr) in the TC and 16.6 months (95% CI 14.6 months-nr) in the VC. CONCLUSIONS: Including easily obtainable variables, this preoperative score identifies oligometastatic CRC patients with prolonged survival rates that may be cured, and harbors potential to be implemented in daily clinical practice

    Long-term high-level exercise promotes muscle reinnervation with age.

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    The histologic features of aging muscle suggest that denervation contributes to atrophy, that immobility accelerates the process, and that routine exercise may protect against loss of motor units and muscle tissue. Here, we compared muscle biopsies from sedentary and physically active seniors and found that seniors with a long history of high-level recreational activity up to the time of muscle biopsy had 1) lower loss of muscle strength versus young men (32% loss in physically active vs 51% loss in sedentary seniors); 2) fewer small angulated (denervated) myofibers; 3) a higher percentage of fiber-type groups (reinnervated muscle fibers) that were almost exclusive of the slow type; and 4) sparse normal-size muscle fibers coexpressing fast and slow myosin heavy chains, which is not compatible with exercise-driven muscle-type transformation. The biopsies from the old physically active seniors varied from sparse fiber-type groupings to almost fully transformed muscle, suggesting that coexpressing fibers appear to fill gaps. Altogether, the data show that long-term physical activity promotes reinnervation of muscle fibers and suggest that decades of high-level exercise allow the body to adapt to age-related denervation by saving otherwise lost muscle fibers through selective recruitment to slow motor units. These effects on size and structure of myofibers may delay functional decline in late aging

    Distinct IL-1α-responsive enhancers promote acute and coordinated changes in chromatin topology in a hierarchical manner

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    How cytokine-driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)-1α induces acute and widespread changes in chromatin accessibility via the TAK1 kinase and NF-κB at regions that are highly enriched for inflammatory disease-relevant SNPs. Two enhancers in the extended chemokine locus on human chromosome 4 regulate the IL-1α-inducible IL8 and CXCL1-3 genes. Both enhancers engage in dynamic spatial interactions with gene promoters in an IL-1α/TAK1-inducible manner. Microdeletions of p65-binding sites in either of the two enhancers impair NF-κB recruitment, suppress activation and biallelic transcription of the IL8/CXCL2 genes, and reshuffle higher-order chromatin interactions as judged by i4C interactome profiles. Notably, these findings support a dominant role of the IL8 “master” enhancer in the regulation of sustained IL-1α signaling, as well as for IL-8 and IL-6 secretion. CRISPR-guided transactivation of the IL8 locus or cross-TAD regulation by TNFα-responsive enhancers in a different model locus supports the existence of complex enhancer hierarchies in response to cytokine stimulation that prime and orchestrate proinflammatory chromatin responses downstream of NF-κB
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