Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.</p> <p>Results</p> <p>From hESCs, we derived NESs, the <it>in-vitro </it>version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of <it>in-vivo</it>-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their <it>in-vivo </it>counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.</p> <p>Conclusion</p> <p>Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an <it>in-vitro </it>model for <it>in-vivo </it>neurogenesis.</p

Two levels above and one level below pedicle screw fixation for the treatment of unstable thoracolumbar fracture with partial or intact neurology

<p>Abstract</p> <p>Background</p> <p>Treatment of unstable thoracolumbar fractures is controversial regarding short or long segment pedicle screw fixation. Although long level fixation is better, it can decrease one motion segment distally, thus increasing load to lower discs.</p> <p>Methods</p> <p>We retrospectively analyzed 31 unstable thoracolumbar fractures with partial or intact neurology. All patients were operated with posterior approach using pedicle screws fixed two levels above and one level below the fracture vertebra. No laminectomy, discectomy or decompression procedure was done. Posterior fusion was achieved in all. Post operative and at final follow-up radiological evaluation was done by measuring the correction and maintenance of kyphotic angle at thoracolumbar junction. Complications were also reported including implant failure.</p> <p>Results</p> <p>Average follow-up was 34 months. All patients had full recovery at final follow-up. Average kyphosis was improved from 26.7° to 4.1° postoperatively and to 6.3° at final follow-up. And mean pain scale was improved from 7.5 to 3.9 postoperatively and to 1.6 at final follow-up, All patients resumed their activity within six months. Only 4 (12%) complications were noted including only one hardware failure.</p> <p>Conclusion</p> <p>Two levels above and one level below pedicle screw fixation in unstable thoracolumbar burst fracture is useful to prevent progressive kyphosis and preserves one motion segment distally.</p

KNOW-Ped CKD (KoreaN cohort study for outcomes in patients with pediatric CKD): Design and methods

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background The global prevalence of chronic kidney disease (CKD) is increasing. In children, CKD exhibits unique etiologies and can have serious impacts on childrens growth and development. Therefore, an aggressive approach to preventing the progression of CKD and its complications is imperative. To improve the understanding and management of Asian pediatric patients with CKD, we designed and launched KNOW-Ped CKD (KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease), a nationwide, prospective, and observational cohort study of pediatric CKD with funding from the Korean government. Methods/design From seven major centers, 450 patients <20 years of age with CKD stages I to V are recruited for the comprehensive assessment of clinical findings, structured follow-up, and bio-specimen collection. The primary endpoints include CKD progression, defined as a decline of estimated glomerular filtration rate by 50 %, and a requirement for renal replacement therapy or death. The secondary outcomes include the development of left ventricular hypertrophy or hypertension, impairment of growth, neuropsychological status, behavioral status, kidney growth, and quality of life. Discussion With this study, we expect to obtain more information on pediatric CKD, which can be translated to better management for the patients. Trial registration NCT02165878(ClinicalTrials.gov), submitted on June 11, 2014

Increased urinary Angiotensinogen/Creatinine (AGT/Cr) ratio may be associated with reduced renal function in autosomal dominant polycystic kidney disease patients

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney diseases that frequently result in renal failure. In this cross-sectional observational cohort study, we evaluated urinary angiotensinogen (AGT) as a potential biomarker to assess renal function in ADPKD. Methods Urinary AGT was measured in 233 ADPKD patients and its association with estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV) were evaluated. The localization of AGT and other renin-angiotensin system (RAS)-related molecules were identified using immunohistochemistry in human ADPKD tissues. Results Baseline urinary AGT/Cr was negatively correlated with CKD-EPI eGFR (r 2= 0.162, P < 0.001) and positively correlated with htTKV (r2 = 0.107, P < 0.001). Both urinary AGT/Cr and plasma renin activity levels were significantly elevated in hypertensive ADPKD patients. Among hypertensive subjects, urinary AGT/Cr was significantly increased in the advanced CKD stages (III-V) compared to early CKD stages (I-II) (28.6 ± 60.3 vs. 93.2 ± 139.3 μg/g, P < 0.001). Immunohistochemical study showed strong expression of AGT along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. Conclusions Our results suggested that urinary AGT/Cr may be a valuable biomarker for renal damage in ADPKD since intrarenal ischemic insults induced by cyst growth and subsequent intrarenal RAS activation may play a potential role in the development of hypertension and renal dysfunction in ADPKD

Very Late Stent Thrombosis in a Drug-Eluting Stent due to Interruption of Anti-Platelet Agents in Patients With Acute Myocardial Infarction and Thrombocytosis

Stent thrombosis is a fatal complication in patients who have undergone percutaneous coronary intervention, and discontinuation of anti-platelet agent is a major risk factor of stent thrombosis. We report a rare case of very late stent thrombosis (VLST) following discontinuation of anti-platelet agents in a patient who experienced acute myocardial infarction and essential thrombocytosis. She had undergone implantation of a drug eluting stent (DES) and a bare metal stent (BMS) two and half years prior to her presentation. VLST developed in DES, not in BMS, following interruption of anti-platelet therapy

Sex-related impact on clinical outcomes of patients treated with drug-eluting stents according to clinical presentation: Patient-level pooled analysis from the GRAND-DES registry

Background: The contribution of sex and initial clinical presentation to the long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) is still debated. Methods: Individual patient data from 5 Korean-multicenter drug-eluting stent (DES) registries (The GRAND-DES) were pooled. A total of 17,286 patients completed 3-year follow-up (5216 women and 12,070 men). The median follow-up duration was 1125 days (interquartile range 1097–1140 days), and the primary endpoint was cardiac death at 3 years. Results: The clinical indication for PCI was stable angina pectoris (SAP) in 36.8%, unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI) in 47.4%, and STEMI in 15.8%. In all groups, women were older and had a higher proportion of hypertension and diabetes mellitus compared with men. Women presenting with STEMI were older than women with SAP, with the opposite seen in men. There was no sex difference in cardiac death for SAP or UAP/NSTEMI. In STEMI patients, the incidence of cardiac death (7.9% vs. 4.4%, p = 0.001), all-cause mortality (11.1% vs. 6.9%, p = 0.001), and minor bleeding (2.2% vs. 1.2%, p = 0.043) was significantly higher in women. After multivariable adjustment, cardiac death was lower in women for UAP/NSTEMI (HR 0.69, 95% CI 0.53–0.89, p = 0.005), while it was similar for STEMI (HR 0.97, 95% CI 0.65–1.44, p = 0.884). Conclusions: There was no sex difference in cardiac death after PCI with DES for SAP and UAP/NSTEMI patients. In STEMI patients, women had worse outcomes compared with men; however, after the adjustment of confounders, female sex was not an independent predictor of mortality