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Effects of hypoxia/reoxygenation stimuli on renal redox status and nuclear factor erythroid2-related factor 2 pathway in sickle cell SAD mice.

What is the central question of this study? Nuclear related factor 2 (Nrf2)-dependent antioxidant gene expression has been well investigated in renal ischemia/reperfusion models. Nevertheless, Nrf2 and oxidative stress balance regulation had never been explored in the kidney of transgenic SAD mice exposed to repeated subclinical vaso-occlusions. What is the main finding and its importance? In response to hypoxia/reoxygenation, nuclear Nrf2 protein expression decreased only in the kidney of SAD mice while heme-oxygenase transcripts were increased. This suggest that in SAD mice, other transcription factors than Nrf2 could be involved in renal antioxidant gene regulation in response to hypoxia/reoxygenation.

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Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men.

Intermittent hypoxia leads to long-lasting increases in muscle sympathetic nerve activity and blood pressure contributing to increased risk for hypertension in obstructive sleep apnoea patients. We determined whether augmented vascular responses to increasing sympathetic vasomotor outflow, termed sympathetic neurovascular transduction (sNVT), accompanied changes in blood pressure following acute intermittent hypercapnic hypoxia (IH) in men. Lower body negative pressure was utilized to induce a range of sympathetic vasoconstrictor firing while measuring beat-by-beat blood pressure and forearm vascular conductance. IH reduced vascular shear stress and steepened the relationship between diastolic blood pressure and sympathetic discharge frequency suggesting greater systemic sNVT. Our results indicate that recurring cycles of acute IH characteristic of obstructive sleep apnoea could promote hypertension by increasing sNVT.

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Comorbidities Associated with Large Abdominal Aortic Aneurysms.

 Abdominal aortic aneurysm has become increasingly important owing to demographic changes. Some other diseases, for example, cholecystolithiasis, chronic obstructive pulmonary disease, and hernias, seem to co-occur with abdominal aortic aneurysm. The aim of this retrospective analysis was to identify new comorbidities associated with abdominal aortic aneurysm.

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[Systems Biology in Ophthalmology - Innovative Drug Identification for the Specific Prevention of Postoperative Fibrosis].

The long-term success of fistulating therapies for the treatment of glaucoma is essentially limited by excessive scarring reactions (fibrosis). Cytostatic agents such as mitomycin C can prevent fibrosis, but are often associated with side effects. Specific antifibrotics are not currently in clinical use. Therefore, this study describes a systems biology approach using a dedicated bioinformatics technology platform, with which active substances can be identified and repositioned as antifibrotics.

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[Automated Cell Counting Using "Deep Learning" in Donor Corneas from Organ Culture Achieves High Precision and Accuracy].

Human corneal grafts from organ culture need to have more than 2000 endothelial cells/mm to be suitable for transplantation. Measurement of the endothelial cell density is complicated by invisible cell borders in phase contrast microscopy, as well as by limited areas for counting due to folds in the Descemet membrane of the swollen corneal grafts. To date, no automated counting method for measuring the endothelial cell density exists. The neuronal network U-Net has already proven itself in automated segmentation of specular microscopy images of human corneal endothelium. The aim of this study was the application of the U-Net in the quality control of human corneal grafts.

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Mobility Characteristics of Children with Spastic Paraplegia Due to a Mutation in the KIF1A Gene.

Several variants in the gene have been reported to cause a complicated form of hereditary spastic paraplegia. Additional symptoms include cognitive impairment and varying degrees of peripheral neuropathy, epilepsy, decreased visual acuity, and ataxia. We describe four patients (ages 10-18 years), focusing on their mobility and gait characteristics. Two patients were not able to walk without assistance and showed a severe abnormal gait pattern, crouch gait. At examination, severe contractures were found.In addition to describing the different phenotypes with specific attention to gait in our cases, we reviewed known mutations and summarized their associated phenotypes.We conclude that mobility and cognition are severely affected in children with spastic paraplegia due to mutations. Deterioration in mobility is most likely due to progressive spasticity, muscle weakness, and the secondary development of severe contractures, possibly combined with an additional progressive polyneuropathy. Close follow-up and treatment of these patients are warranted.

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Accuracy of a Robotic Endoscopic System in Cadaver Models with Simulated Tumor Targets: ACCESS Study.

Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear.

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Inhibition of NLRP3 Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Apoptosis by NF-κB Signaling.

To explore whether NLRP3 is involved in the development of cataract and to study the effect of NLRP3 on hydrogen peroxide (H2O2)-induced injury in human lens epithelial cells.

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Siglec-14 Enhances NLRP3-Inflammasome Activation in Macrophages.

Pathogenic microorganisms are sensed by the inflammasome, resulting in the release of the pro-immune and proinflammatory cytokine interleukin-1β (IL-1β). In humans, the paired sialic acid-binding Ig-like lectin receptors Siglec-5 (inhibitory) and Siglec-14 (activating) have been shown to have reciprocal roles in regulating macrophage immune responses, but their interaction with IL-1β signaling and the inflammasome has not been characterized. Here we show that in response to known inflammasome activators (ATP, nigericin) or the sialic acid-expressing human bacterial pathogen group B Streptococcus (GBS), the presence of Siglec-14 enhances, whereas Siglec-5 reduces, inflammasome activation and macrophage IL-1β release. Human THP-1 macrophages stably transfected with Siglec-14 exhibited increased caspase-1 activation, IL-1β release and pyroptosis after GBS infection, in a manner blocked by a specific inhibitor of nucleotide-binding domain leucine-rich repeat protein 3 (NLRP3), a protein involved in inflammasome assembly. Another leading pathogen, Streptococcus pneumoniae, lacks sialic acid but rather prominently expresses a sialidase, which cleaves sialic acid from macrophages, eliminating cis- interactions with the lectin receptor, thus attenuating Siglec-14 induced IL-1β secretion. Vimentin, a cytoskeletal protein released during macrophage inflammatory activation is known to induce the inflammasome. We found that vimentin has increased interaction with Siglec-14 compared to Siglec-5, and this interaction heightened IL-1β production by Siglec-14-expressing cells. Siglec-14 is absent from some humans because of a SIGLEC5/14 fusion polymorphism, and we found increased IL-1β expression in primary macrophages from SIGLEC14+/+ individuals compared to those with the SIGLEC14-/+ and SIGLEC14-/- genotypes. Collectively, our results identify a new immunoregulatory role of Siglec-14 as a positive regulator of NLRP3 inflammasome activation.

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