Petrogenesis of synorogenic high-temperature leucogranites (Damara orogen, Namibia): Constraints from U–Pb monazite ages and Nd, Sr and Pb isotopes

Highlights: • Geochemical data from high-T leucogranites imply pure crustal melting. • New U–Pb monazite ages constrain intrusion time close to peak metamorphism. • Updated Sr–Nd–Pb isotope data imply metasedimentary sources. Two suites of leucogranites were emplaced at 508 ± 5.9 Ma in the Okombahe District of the Damara belt (Namibia) synchronous with the peak of regional high-temperature metamorphism. The Sr (87Sr/86Srinit: 0.707 to 0.711), Nd (εNdinit: − 4.5 to − 6.6), and Pb isotopic (206Pb/204Pb: 18.51–19.13; 207Pb/204Pb: 15.63–15.69; 208Pb/204Pb: 38.08–38.66) compositions indicate that these peraluminous S-type granites were derived from mid- to lower-crustal rocks, which are slightly different to the metapelitic rocks into which they intruded. Since the leucogranites are unfractionated and show no evidence for assimilation or contamination, they constrain the temperature and pressure conditions of their formation. Calculated Zr and LREE saturation temperatures of ca. 850 °C indicate high-temperature crustal melts. High Rb/Sr and low Sr/Ba ratios are consistent with biotite dehydration melting of pelitic source rocks. Qz–Ab–Or systematics reveal that melting and segregation for the least fractionated samples occurred at ca. 7 kbar corresponding to a mid-crustal level of ca. 26 km. However, there is no evidence for a mantle component that could have served as a local heat source for crustal melting. Therefore, the hot felsic magmas that formed close to the time of peak metamorphism are the result of long-lasting high temperature regional metamorphic conditions and intra-crustal collision

Treatment Methods and Early Neurologic Improvement After Endovascular Treatment of Tandem Occlusions in Acute Ischemic Stroke

Background and Purpose: A tandem occlusion of the intracranial circulation and the extracranial carotid artery (ICA) occurs in 10–20% of all strokes based on large vessel occlusion (LVO). The optimal treatment strategy for those patients is unknown. We report our management strategy and the outcome in these patients in a large single-center cohort.Materials and Methods: We retrospectively identified and analyzed all patients treated by Mechanical Thrombectomy (MT) for an intracranial LVO associated with an occlusion of the extracranial ICA between April 2009 and May 2016 (163/1,645, 9.9%). The following data was collected: Recanalization rate, occurrence of symptomatic intracranial hemorrhage (sICH), clinical result according to the early neurological improvement (ENI, NIHSS score improvement of ≥8 points after 24 h or NIHSS score of 0 or 1 after 3 days) and functional outcome and mortality during long term follow up. Secondary endpoints were the patency of the internal carotid artery at 24 h. Patient demographics and anti-aggregation regimen were recorded as co-variables.Results: 163/1,645 (9.9%) MT patients had a tandem occlusion. All thrombectomy procedures were performed with stent retrievers. PTA with or without additional placement of a stent was performed in 149 vs. 14 patients. The overall rate of TICI IIB/III recanalization was 91.4%. An early neurological improvement was found in 79 of 163 patients (48.4%), 51% (76/149) in the stent group and 21% (3/14) in the non stent group. 120/163 patients (73.6%) had a long term favorable outcome (mRS 0–2). The ICA re-occlusion rate at 24 h was 5.4% (8/149) in the stent group and 42% (6/14) in the non stent group. The rate of symptomatic hemorrhage was 4.9%.The regression analysis showed that only younger age (p = 0.002) and shorter recanalization times (p = 0.017) were associated with good outcome.Conclusion: Stent-PTA of the ICA in addition to MT with a stent retriever was safe and effective in tandem occlusion of the anterior brain circulation. PTA and MT without stenting in tandem lesions showed a higher early re-occlusion rate and lower rate of early neurological improvement. The technical approach should aim for the fastest possible recanalization of the intracranial vessels, either with stenting first or last

Time Point, Etiology, and Short-Term Outcome of Repeated Mechanical Thrombectomy Due to Recurrent Large Vessel Occlusion

Background: Data on time point and etiology of repeated stroke caused by large brain vessel occlusion (LVO) resulting in repeated mechanical thrombectomy (MT) in acute stroke patients is very limited.Methods: We retrospectively reviewed all acute stroke patients treated with MT with stent retrievers or aspiration systems between January 2010 and June 2018 to identify patients who received two or more MT treatments due to recurrent LVO in our tertiary neurovascular center. Short-term outcome was assessed using the NIH stroke scale score at discharge.Results: We identified 35 out of 2,470 acute stroke patients treated with MT who had recurrent LVO and received repeated MT. Mean age at first MT was 69.3 (±15.8) years and the mean time interval between the first and second MT was 147 (±241) days, and 8 patients experienced short-term LVO recurrence within 3 days. Fifteen (43%) patients had cardioembolic, 9 (26%) arterioembolic, 4 (11%) mixed cardio-/arterioembolic, and 7 (20%) patients had unknown stroke etiology. Patients with cardioembolic stroke were substantially older, had no or insufficient oral anticoagulation at the time of the first and repeated LVO, and repeated LVO occurred very early in 50%. Seventeen (49%) patients had a NIHSS score of 0 or 1 at discharge and seven (20%) patients died in the hospital after repeated MT. No bleeding complications occurred.Conclusions: Repeated MT due to recurrent LVO is a rarely performed, safe, and effective procedure in acute stroke patients. Missing or insufficient anticoagulation is the most frequent cause for recurrent LVO

Разработка геоинформационной подсистемы для программного комплекса Scada Infinity

Объектом исследования является геоинформационная система, предназначенная для отображения технологических объектов и информации о состоянии технологического процесса на географической карте. Основная цель системы - повысить эффективность введения мониторинга территориально распределенных и мобильных объектов. В настоящей работе рассматриваются вопросы, возникающие при проектировании и реализации проектов по созданию геоинформационных систем, предназначенные для визуализации информации о состоянии технологического процесса, и ведения мониторинга территориально распределенных и мобильных технологических объектов. Особое внимание уделено определению архитектурного стиля, проектированию и реализации системы.The object of the study is a geoinformation system designed to display technological objects and information about the state of the technological process on a geographic map. The main goal of the system is to improve the efficiency of monitoring the geographically distributed and mobile objects. In this work, we consider issues arising in the design and implementation of projects for the creation of geoinformation systems designed to visualize information about the state of the technological process and to monitor the geographically distributed and mobile process facilities. Particular attention is paid to the definition of architectural style, design and implementation of the architectural solution of the system

Intracranial Stenting After Failed Thrombectomy in Patients With Moderately Severe Stroke: A Multicenter Cohort Study

Background and Purpose: Recently, acute intracranial stenting (ICS) has gained more interest as a potential bailout strategy for large vessel occlusions (LVO) that are refractory to thrombectomy. However, there are currently no reports on ICS in patients with moderately severe stroke discussing the question if implementing a permanent stent is feasible and leads to improved recanalization after failed thrombectomy. Methods: We analyzed a large multicenter database of patients receiving ICS for anterior circulation LVO after failed thrombectomy. Inclusion criteria were defined as: Moderately severe stroke (National Institute Health Stroke Scale (NIHSS) ≤9 on admission), anterior circulation LVO, acute ICS after failed stent retriever MT. Primary endpoint was the rate of improved successful recanalization after ICS defined as a modified Thrombolysis In cerebral Infarction (mTICI) score≥2b. Favorable neurological outcome was defined as an early neurological improvement (ENI) of 4 points or reaching 0 with respect to baseline NIHSS. Results: Forty-one patients met the inclusion criteria. A median of 2 retrievals were performed (IQR 1–4) prior decision-making for ICS. ICS led in 90.2% (37/41) of cases to a final mTICI≥2b with significant improvement (p < 0.001) after the last retrieval attempt. The median NIHSS decreased (p = 0.178) from 7 (IQR 3.5–8) on admission to 2.5 (IQR 0–8.25) at discharge. ENI was observed in 47.4% (18/38). sICH occurred in 4.8% (2/41). Conclusion: ICS after failed thrombectomy appears to effectively improve recanalization rates in patients with moderately severe strokes. Thus, ICS should be considered also for patients with baseline NIHSS ≤9 if thrombectomy fails

Feedback inhibition of the general phenylpropanoid and flavonol biosynthetic pathways upon a compromised flavonol-3-O-glycosylation

Flavonols, phenylalanine-derived secondary metabolites, have protective and regulatory functions in plants. In Arabidopsis thaliana, they are consecutively glycosylated at their 3-OH and 7-OH groups. UGT78D1 and UGT78D2 are the major flavonol 3-O-glycosyltransferases in Arabidopsis leaves. The ugt78d1 ugt78d2 double mutant, which was strongly compromised in the initial 3-O-glycosylation, showed a severe and specific repression of flavonol biosynthesis, retaining only one-third of the wild-type level. This metabolic phenotype was associated with a repressed transcription of several flavonol biosynthetic genes including the committed step chalcone synthase [(CHS) or TRANSPARENT TESTA 4 (TT4)]. Furthermore, the committed step of the upstream, general phenylpropanoid pathway, phenylalanine ammonia-lyase (PAL), was down-regulated in its enzyme activity and in the transcription of the flavonol-related PAL1 and PAL2. However, a complete blocking of flavonoid biosynthesis at CHS released PAL inhibition in a tt4 ugt78d1 ugt78d2 line. PAL activity was even enhanced in the flavonol synthase 1 mutant, which compromises the final formation of flavonol aglycones. The dependence of the PAL feedback inhibition on flavonols was confirmed by chemical complementation of tt4 ugt78d1 ugt78d2 using naringenin, a downstream flavonoid intermediate, which restored the PAL repression. Although aglycones were not analytically detectable, this study provides genetic evidence for a novel, flavonol-dependent feedback inhibition of the flavonol biosynthetic pathway and PAL. It was conditioned by the compromised flavonol-3-O-conjugation and a decrease in flavonol content, yet dependent on a residual, flavonol synthase 1 (FLS1)-related capacity to form flavonol aglycones. Thus, this regulation would not react to a reduced metabolic flux into flavonol biosynthesis, but it might prevent the accumulation of non-glycosylated, toxic flavonols

BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function

Podocyte loss and changes to the complex morphology are major causes of chronic kidney disease (CKD). As the incidence is continuously increasing over the last decades without sufficient treatment, it is important to find predicting biomarkers. Therefore, we measured urinary mRNA levels of podocyte genes NPHS1, NPHS2, PODXL and BDNF, KIM-1, CTSL by qRT-PCR of 120 CKD patients. We showed a strong correlation between BDNF and the kidney injury marker KIM-1, which were also correlated with NPHS1, suggesting podocytes as a contributing source. In human biopsies, BDNF was localized in the cell body and major processes of podocytes. In glomeruli of diabetic nephropathy patients, we found a strong BDNF signal in the remaining podocytes. An inhibition of the BDNF receptor TrkB resulted in enhanced podocyte dedifferentiation. The knockdown of the orthologue resulted in pericardial oedema formation and lowered viability of zebrafish larvae. We found an enlarged Bowman's space, dilated glomerular capillaries, podocyte loss and an impaired glomerular filtration. We demonstrated that BDNF is essential for glomerular development, morphology and function and the expression of BDNF and KIM-1 is highly correlated in urine cells of CKD patients. Therefore, BDNF mRNA in urine cells could serve as a potential CKD biomarker

Proline-Rich Tyrosine Kinase 2 (Pyk2) Promotes Cell Motility of Hepatocellular Carcinoma through Induction of Epithelial to Mesenchymal Transition

Aims: Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. Methodology/Principal Findings: We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. Conclusion: These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT. © 2011 Sun et al.published_or_final_versio

Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review

Background Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. Methods For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. Results We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m2 in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. Conclusions The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study result

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

Renal cell carcinoma (RCC) are frequently chemo- and radiation resistant. Thus, there is a need for identifying biological features of these cells that could serve as alternative therapeutic targets. We performed suppression subtractive hybridization (SSH) on patient-matched normal renal and RCC tissue to identify variably regulated genes. 11 genes were strongly up-regulated or selectively expressed in more than one RCC tissue or cell line. Screening of filters containing cancer-related cDNAs confirmed overexpression of 3 of these genes and 3 additional genes were identified. These 14 differentially expressed genes, only 6 of which have previously been associated with RCC, are related to tumour growth/survival (EGFR, cyclin D1, insulin-like growth factor-binding protein-1 and a MLRQ sub-unit homologue of the NADH:ubiquinone oxidoreductase complex), angiogenesis (vascular endothelial growth factor, endothelial PAS domain protein-1, ceruloplasmin, angiopoietin-related protein 2) and cell adhesion/motility (protocadherin 2, cadherin 6, autotaxin, vimentin, lysyl oxidase and semaphorin G). Since some of these genes were overexpressed in 80–90% of RCC tissues, it is important to evaluate their suitability as therapeutic targets. © 2001 Cancer Research Campaig