Outcomes of elderly patients with traumatic brain injury associated with the pre-injury antithrombotic prophylaxis type - A systematic review and meta-analysis.

OBJECTIVE: Our review aims at comparing the morbidity and mortality-related risks associated with the pre-injury administration of VK-antagonists or DOACs in elderly patients with TBI. MATERIALS AND METHODS: We performed a systematic search of the academic literature across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE), following PRISMA guidelines. We conducted a random-effect meta-analysis to compare the influence of pre-injury VK-antagonists or DOACs administration on the overall intensive care unit and hospital stays of patients with TBI. We also evaluated the overall risks associated with VK-antagonists and with DOACs for intracranial hemorrhage progression, surgical intervention, and overall mortality in patients with TBI. RESULTS: From 973 studies, we found 11 eligible with 4,991 patients with traumatic brain injury (mean age, 77.82 ± 6.76 years). Our meta-analysis revealed insignificantly higher odds of surgical intervention (OR=1.72) and mortality (OR=1.07) associated with VK-antagonists administration than with DOACs administration. Similarly, we found that the intensive care unit (Hedge's g, 0.13) and hospital (g, 0.26) stays were insignificantly longer for individuals on VK-antagonists than for those on DOAC. Moreover, we observed insignificantly higher intracranial hemorrhage progression risks (OR=1.22) for individuals receiving DOACs than for those receiving VK-antagonists. CONCLUSIONS: This study provides evidence on the morbidity and mortality-related outcomes associated with the pre-injury administration of VK-antagonists or DOACs in patients with TBI. We found no significant differences between VK-antagonists and DOACs on the overall morbidity (hospital and intensive care unit stays, intracranial hemorrhage, and surgical intervention frequency) and mortality outcomes in elderly patients with TBI.

ATG4 promotes cell proliferation, migration and invasion in HCC and predicts a poor prognosis.

OBJECTIVE: ATG14, as an autophagy-related protein, has been shown to be implicated in the progression of tumors by modulating cell autophagy. We aimed at exploring ATG14 level in hepatocellular carcinoma (HCC) and its possible molecular mechanism. PATIENTS AND METHODS: ATG14 levels in HCC tissues and cell lines were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the relationship between ATG14 expression and clinical parameters was analyzed through clinical information analysis. The impacts of ATG14 on the proliferation and invasiveness of HCC cells were evaluated by performing Cell Counting Kit-8 (CCK-8) and transwell tests, respectively. We further explored the potential mechanism of ATG14 action using bioinformatics analysis and in vitro cell experiments. RESULTS: Our data showed that ATG14 levels were abnormally enhanced in HCC tissues and cell lines, which predicted a poor prognosis of HCC patients. Downregulation of ATG14 markedly blunted the proliferation and migratory capacities of HCC cells. Bioinformatics analysis suggested that XIST can regulate ATG14 by binding multiple miRNAs (miR-195-5p, miR-497-5p, miR-424-5p, and miR-16-5p). In addition, XIST promoted cell autophagy by elevating ATG14 expression, thereby providing possible mechanisms by which ATG14 and XIST could modulate the development of HCC. CONCLUSIONS: In summary, our data preliminary verified ATG14 levels were abnormally enhanced in HCC tissues and cell lines, which predicted a poor prognosis of HCC patients.

CircRNA_MYLK promotes malignant progression of ovarian cancer through regulating microRNA-652.

OBJECTIVE: The purpose of this study was to investigate circRNA_MYLK level in ovarian cancer (OC), and to further investigate whether it could promote the malignant progression of OC via regulating microRNA-652. PATIENTS AND METHODS: quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine circRNA_MYLK level in 46 tumor tissue specimens and paracancerous normal ones collected from OC patients, and the interplay between circRNA_MYLK expression and clinical indicators of OC and patient prognosis was analyzed. Meanwhile, qPCR was also used to further verify circRNA_MYLK level in OC cell lines. In addition, circRNA_MYLK knockdown model was constructed using lentivirus in OC cell lines including A2780 and CAOV3, and the impacts of circRNA_MYLK on the biological functions of OC cells was evaluated using Cell Counting Kit-8 (CCK-8) and cloning experiments. Finally, Luciferase reporting assay and recovery experiment were performed to investigate the regulatory interplay between circRNA_MYLK and microRNA-652. RESULTS: qPCR results indicated that circRNA_MYLK level in OC patients was remarkably higher than that in adjacent ones, and the difference was statistically significant. Compared with patients with low expression of circRNA_MYLK, patients with high expression of circRNA_MYLK had a higher pathological staging and a lower overall survival rate. Compared with the control group (sh-NC), the OC cell proliferation ability was remarkably attenuated in the circRNA_MYLK knockdown group (sh-circRNA). In addition, qPCR verification revealed that the expression levels of microRNA-652 and circRNA_MYLK were negatively correlated in OC tissues. At the same time, bioinformatics analysis and Luciferase reporter gene assay results confirmed that circRNA_MYLK can be targeted by microRNA-652. Finally, it was found that simultaneous knockdown of circRNA_MYKK and microRNA-652 could reverse the enhanced OC cell proliferative capacity induced by downregulation of circRNA_MYLK alone. CONCLUSIONS: CircRNA_MYLK may promote the malignant progression of OC via regulating microRNA-652, and its expression was remarkably associated with pathological staging and poor prognosis in patients with OC.

Serum Cyr61 as a potential biomarker for diagnosis of colorectal cancer

Purpose. To determine the sensitivity and specificity of serum Cyr61 as a potential biomarker for the diagnosis of colorectal cancer (CRC) and to assess the association between serum Cyr61 level and CRC clinicopathological status. Methods. We used an enzyme-linked immunosorbent assay to measure serum Cyr61 in patients with CRC, patients with colorectal adenomas, and healthy controls. We also analyzed the relationship between serum Cyr61 and clinicopathological features of CRC patients. The levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were quantified using the Roche Cobas 6000 Analyzer. The sensitivity and specificity of Cyr61, CEA, CA19-9 and CEA + CA19-9 were evaluated by receiver operating characteristic (ROC) analysis. Results. The serum level of Cyr61 was significantly increased in CRC patients compared with colorectal adenoma patients and healthy controls (p < 0.001). Furthermore, the area under the ROC curve for Cyr61 was 0.935 (95 % confidence interval 0.902-0.968), higher than that for CEA + CA19-9 (0.827, 95 % confidence interval: 0.783-0.871). Use of a Cyr61 cutoff value of 92.0 pg/mL allowed distinguishing CRC patients and healthy controls with a sensitivity of 83 % and a specificity of 97 %. Among CRC patients, an elevated level of serum Cyr61 was significantly associated with more advanced TNM stage (p < 0.0042), lymph node metastasis (p < 0.0088), and vascular invasion (p = 0.0027). Conclusion. Cyr61 has potential as a serum biomarker for the diagnosis of CRC and for assessment of the clinicopathological status of CRC (AU)

No disponible

Gravitational waves from binary supermassive black holes missing in pulsar observations.

Gravitational waves are expected to be radiated by supermassive black hole binaries formed during galaxy mergers. A stochastic superposition of gravitational waves from all such binary systems would modulate the arrival times of pulses from radio pulsars. Using observations of millisecond pulsars obtained with the Parkes radio telescope, we constrained the characteristic amplitude of this background, A(c,yr), to be <1.0 × 10(-15) with 95% confidence. This limit excludes predicted ranges for A(c,yr) from current models with 91 to 99.7% probability. We conclude that binary evolution is either stalled or dramatically accelerated by galactic-center environments and that higher-cadence and shorter-wavelength observations would be more sensitive to gravitational waves.

Gpr177-mediated Wnt Signaling Is Required for Secondary Palate Development.

Cleft palate represents one of the major congenital birth defects in humans. Despite the essential roles of ectodermal canonical Wnt and mesenchymal Wnt signaling in the secondary palate development, the function of mesenchymal canonical Wnt activity in secondary palate development remains elusive. Here we show that Gpr177, a highly conserved transmembrane protein essential for Wnt trafficking, is required for secondary palate development. Gpr177 is expressed in both epithelium and mesenchyme of palatal shelves during mouse development. Wnt1(Cre)-mediated deletion of Gpr177 in craniofacial neural crest cells leads to a complete cleft secondary palate, which is formed mainly due to aberrant cell proliferation and increased cell death in palatal shelves. By BATGAL staining, we reveal an intense canonical Wnt activity in the anterior palate mesenchyme of E12.5 wild-type embryos but not in Gpr177(Wnt1-Cre) embryos, suggesting that mesenchymal canonical Wnt signaling activated by Gpr177-mediated mesenchymal Wnts is critical for secondary palate development. Moreover, phosphorylation of JNK and c-Jun is impaired in the Gpr177(Wnt1-Cre) palate and is restored by implantation of Wnt5a-soaked beads in the in vitro palate explants, suggesting that Gpr177 probably regulates palate development via the Wnt5a-mediated noncanonical Wnt pathway in which c-Jun and JNK are involved. Importantly, certain cellular processes and the altered gene expression in palates lacking Gpr177 are distinct from that of the Wnt5a mutant, further demonstrating involvement of other mesenchymal Wnts in the process of palate development. Together, these results suggest that mesenchymal Gpr177 is required for secondary palate development by regulating and integrating mesenchymal canonical and noncanonical Wnt signals.

Expression of vimentin and survivin in clear cell renal cell carcinoma and correlation with p53

Purpose. This study focuses on investigating the expression correlation of vimentin, survivin and p53 in clear cell renal cell carcinoma (ccRCC) and the clinical significance. Methods. The mRNA and protein expression levels of the vimentin, survivin and p53 were determined in ccRCC and adjacent normal renal tissues, using quantitative real-time-polymerase chain reaction (qRT-PCR) and Western blot. We detected the expression and localization of vimentin, survivin and p53 protein in ccRCC by immunohistochemistrical SP method and analyzed the relationships among clinical pathologic parameters and patient prognosis. Results. The expression of vimentin and survivin was significantly increased in ccRCC compared with adjacent normal renal tissues, which were positively correlated with the pathological grade and clinical stage (P < 0.05). p53 was highly expressed in ccRCC compared with normal tissues (P < 0.05), which was not positively correlated with the pathological grade and clinical stage (P > 0.05). Furthermore, univariate and multivariate analysis showed that high expression levels of vimentin and survivin were independent prognostic indicators for ccRCC. The levels of vimentin and survivin were positively correlated in ccRCC (r = 0.428, P < 0.01). Conclusions. Reliable basis about biological behavior and prognosis judgments of ccRCC can be provided by combining detection of vimentin and survivin. Foundation and new ideas for gene therapy of ccRCC may be provided by further studying the relationship among vimentin, survivin and p53 in ccRCC (AU)

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Expression of vimentin and survivin in clear cell renal cell carcinoma and correlation with p53.

PURPOSE: This study focuses on investigating the expression correlation of vimentin, survivin and p53 in clear cell renal cell carcinoma (ccRCC) and the clinical significance. METHODS: The mRNA and protein expression levels of the vimentin, survivin and p53 were determined in ccRCC and adjacent normal renal tissues, using quantitative real-time-polymerase chain reaction (qRT-PCR) and Western blot. We detected the expression and localization of vimentin, survivin and p53 protein in ccRCC by immunohistochemistrical SP method and analyzed the relationships among clinical pathologic parameters and patient prognosis. RESULTS: The expression of vimentin and survivin was significantly increased in ccRCC compared with adjacent normal renal tissues, which were positively correlated with the pathological grade and clinical stage (P < 0.05). p53 was highly expressed in ccRCC compared with normal tissues (P < 0.05), which was not positively correlated with the pathological grade and clinical stage (P > 0.05). Furthermore, univariate and multivariate analysis showed that high expression levels of vimentin and survivin were independent prognostic indicators for ccRCC. The levels of vimentin and survivin were positively correlated in ccRCC (r = 0.428, P < 0.01). CONCLUSIONS: Reliable basis about biological behavior and prognosis judgments of ccRCC can be provided by combining detection of vimentin and survivin. Foundation and new ideas for gene therapy of ccRCC may be provided by further studying the relationship among vimentin, survivin and p53 in ccRCC.

The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update

This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria

This methods report describes the process of guideline development in detail. It is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) and is published in Allergy 2014; 69:868-887

Sixteen cases of pulmonary sclerosing haemangioma: CT findings are not definitive for preoperative diagnosis.

AIM: To describe and assess computed tomography (CT) imaging findings of pathologically confirmed pulmonary sclerosing haemangioma (PSH), a rare benign tumour, in 16 patients. MATERIALS AND METHODS: This study was approved by the human investigation committees of the two participating institutions, and the requirement of informed consent was waived. Findings from CT examinations in 16 patients with pathologically confirmed PSH were retrospectively reviewed. Two radiologists in consensus assessed the location, size, contour, and border of nodules, as well as the enhancement patterns. RESULTS: The study comprised 16 patients (two male and 14 female) aged 30-70 years. PSHs appeared as well-defined, round or ovoid masses with a diameter of 2.2±0.3cm, and were generally demonstrated as juxtapleural masses (94%) on CT. Calcification (13%), the air crescent sign (13%), and a prominent pulmonary artery (25%) in the tumours were also demonstrated in the cohort. The mean tumour attenuation value at CT was 30±3HU before intravenous administration of contrast media, and was significantly lower than that of the enhanced phase (79±3HU, p<0.05). Twelve tumours (75%) enhanced homogeneously compared with four tumours (25%) which enhanced heterogeneously. The diameters of the heterogeneously enhanced tumours were larger than those of the homogeneously enhanced tumours (p<0.05). CONCLUSION: The relatively characteristic CT findings include a markedly contrast-enhanced juxtapleural mass with homogeneous enhancement for the smaller tumours (<3cm in diameter) or heterogeneous enhancement for the larger tumours (>3cm). However, CT findings are not definitive for preoperative diagnosis of PSH.

Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic pemphigus.

BACKGROUND: Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. OBJECTIVES: To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. METHODS: Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. RESULTS: The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. CONCLUSIONS: The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus.

Four novel mutations in ATP2C1 found in Chinese patients with Hailey-Hailey disease.

BACKGROUND: Familial benign chronic pemphigus or Hailey-Hailey disease (HHD; OMIM 169600) is an autosomal dominant blistering disease. Pathogenic mutations in ATP2C1 encoding a novel Ca2+ pump have recently been identified. OBJECTIVES: To identify mutations in ATP2C1 in Chinese patients with HHD. METHODS: Eleven unrelated Chinese patients with HHD were subjected to mutation detection in ATP2C1. Eight of them had a family history of HHD. The 27 coding exons and their flanking sequences were amplified and sequenced. RESULTS: Five of the 11 patients were identified to have heterozygous mutations including three nonsense mutations and two splicing mutations in ATP2C1. CONCLUSIONS: Four novel mutations, nonsense mutations S887X and W795X and splicing mutations 118-1 g-->a and 1890+1del(gtgag)ins53, were found in this series of Chinese patients with HHD.

HLA-DR and DQ polymorphisms in bullous pemphigoid from northern China.

Bullous pemphigoid (BP) is an autoimmune disease mediated by autoantibodies against hemidesmosome components. This study used PCR-sequence-specific primers to genotype polymorphisms in HLA-DR and DQ in 25 BP patients and 57 normal controls from northern China. We found lower frequencies of DRB1*08 (DR8) and DRB1*08/DQB1*06 (DR8/DQ6) haplotypes in BP patients than in controls (4.08% vs. 15.19% and 1.54% vs. 13.82%, respectively; P < 0.05), suggesting a protective role for DR8 and DR8/DQ6 haplotypes in BP patients from northern China; there were no statistical differences among other alleles tested. This result is strikingly different from previous reports that DQB1*0301 is associated with BP in Caucasian patients and DRB1*1101, DQB1*0302, DRB1*04/DQA1*0301/DQB1*0302 and DRB1*1101/ DQA1*0505/DQB1*0302 with Japanese BP patients. Ethnic differences in the polymorphic composition of the HLA-DR and DQ genes may influence genetic susceptibility to BP.