The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis

<p>Abstract</p> <p>Background</p> <p>Ultrasonography of temporal arteries is not commonly used in the approach of patients with suspected giant cell arteritis (GCA) in clinical practice. A meta-analysis of primary studies available through April 2004 concluded that ultrasonography could indeed be helpful in diagnosing GCA. We specifically re-examined the diagnostic value of the ultrasonography-derived halo sign, a dark hypoechoic circumferential thickening around the artery lumen, indicating vasculitic wall edema, in GCA.</p> <p>Methods</p> <p>Original, prospective studies in patients with suspected GCA that examined ultrasonography findings of temporal arteries using the ACR 1990 classification criteria for GCA as reference standard, published through 2009, were identified. Only eight studies involving 575 patients, 204 of whom received the final diagnosis of GCA, fulfilled technical quality criteria for ultrasound. Weighted sensitivity and specificity estimates of the halo sign were assessed, their possible heterogeneity was investigated and pooled diagnostic odds ratio was determined.</p> <p>Results</p> <p>Unilateral halo sign achieved an overall sensitivity of 68% (95% CI, 0.61-0.74) and specificity of 91% (95% CI, 0.88-0.94) for GCA. The values of inconsistency coefficient (I²) of both sensitivity and specificity of the halo sign, showed significant heterogeneity concerning the results between studies. Pooled diagnostic odds ratio, expressing how much greater the odds of having GCA are for patients with halo sign than for those without, was 34 (95% CI, 8.21-138.23). Diagnostic odds ratio was further increased to 65 (95% CI, 17.86-236.82) when bilateral halo signs were present (sensitivity/specificity of 43% and 100%, respectively). In both cases, it was found that DOR was constant across studies.</p> <p>Conclusion</p> <p>Temporal artery edema demonstrated as halo sign should be always looked for in ultrasonography when GCA is suspected. Providing that currently accepted technical quality criteria are fulfilled, halo sign's sensitivity and specificity are comparable to those of autoantibodies used as diagnostic tests in rheumatology. Validation of revised GCA classification criteria which will include the halo sign may be warranted.</p

Identification of Clinically Relevant Protein Targets in Prostate Cancer with 2D-DIGE Coupled Mass Spectrometry and Systems Biology Network Platform

Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies

Atlantic Deep-water Response to the Early Pliocene Shoaling of the Central American Seaway

The early Pliocene shoaling of the Central American Seaway (CAS), ~4.7–4.2 million years ago (mega annum-Ma), is thought to have strengthened Atlantic Meridional Overturning Circulation (AMOC). The associated increase in northward flux of heat and moisture may have significantly influenced the evolution of Pliocene climate. While some evidence for the predicted increase in North Atlantic Deep Water (NADW) formation exists in the Caribbean and Western Atlantic, similar evidence is missing in the wider Atlantic. Here, we present stable carbon (δ13C) and oxygen (δ18O) isotope records from the Southeast Atlantic-a key region for monitoring the southern extent of NADW. Using these data, together with other δ13C and δ18O records from the Atlantic, we assess the impact of the early Pliocene CAS shoaling phase on deep-water circulation. We find that NADW formation was vigorous prior to 4.7 Ma and showed limited subsequent change. Hence, the overall structure of the deep Atlantic was largely unaffected by the early Pliocene CAS shoaling, corroborating other evidence that indicates larger changes in NADW resulted from earlier and deeper shoaling phases. This finding implies that the early Pliocene shoaling of the CAS had no profound impact on the evolution of climate

The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), outcome of patients remains poor due to the development of drug resistance. Thus, new drugs are urgently needed. We investigated efficacy, toxicity and mechanism of action of marine triterpene glycoside frondoside A (FrA) using CRPC cell lines in vitro and in vivo. FrA revealed high efficacy in human prostate cancer cells, while non-malignant cells were less sensitive. Remarkably, proliferation and colony formation of cells resistant to enzalutamide and abiraterone (due to the androgen receptor splice variant AR-V7) were also significantly inhibited by FrA. The marine compound caused cell type specific cell cycle arrest and induction of caspase-dependent or -independent apoptosis. Up-regulation or induction of several pro-apoptotic proteins (Bax, Bad, PTEN), cleavage of PARP and caspase-3 and down-regulation of anti-apoptotic proteins (survivin and Bcl-2) were detected in treated cells. Global proteome analysis revealed regulation of proteins involved in formation of metastases, tumor cell invasion, and apoptosis, like keratin 81, CrkII, IL-1β and cathepsin B. Inhibition of pro-survival autophagy was observed following FrA exposure. In vivo, FrA inhibited tumor growth of PC-3 and DU145 cells with a notable reduction of lung metastasis, as well as circulating tumor cells in the peripheral blood. Increased lymphocyte counts of treated animals might indicate an immune modulating effect of FrA. In conclusion, our results suggest that FrA is a promising new drug for the treatment of mCRPC. Induction of apoptosis, inhibition of pro-survival autophagy, and immune modulatory effects are suspected modes of actions. This article is protected by copyright. All rights reserved

Tying seismic data to geologic information from core data: an example from ODP Leg 177

The integration of seismic data with core data provides ground-truth toa structural interpretation of seismic data.The most important difficulty that arises in an integration effort isthe correct translation between the different scales of the core dataand the seismic data.In the absence of check-shots, detailed knowledge of the velocitystructure at the drilling locations is required, either from downholelogging measurements, velocity analysis of the seismic data, or directmeasurements on core samples.Three of the seven drill-sites during ODP (Ocean Drilling Program) Leg177 in the south-eastern Atlantic were located on the Agulhas Ridge andconnected through eight seismic profiles.Synthetic seismograms created from velocity and density measurements onselected core samples generally show a good agreement with real seismicdata with respect to amplitude and waveform, whereas timing of theevents is troublesome.The use of velocity profiles with inaccurate sections along cores, afalse depth scale due to recovery problems, and inaccuracies in thepositioning during both seismic and coring operations are the mainshortcomings of this method.The main reflectors identified on seismic data correspond to hiatuses orperiods of reduced sedimentation rates, and correlate well with densityvariations.In this way the cored data provide a calibration tool for the overallgeological interpretation of the seismic sections

Expression of annexin AI in conventional renal cell carcinoma (CRCC) correlates with tumour stage, Fuhrman grade, amount of eosinophilic cells and clinical outcome

There is increasing evidence that Annexin AI (ANX AI) expression is dysregulated in several carcinomas and tumour cell lines. In order to gain insight into the putative role of ANX AI in tumorigenesis, clinical outcome and metastatic potential of conventional renal cell carcinomas (CRCCs) we investigated the expression of ANX AI in CRCCs and metastases. Furthermore, it was elucidated whether ANX AI overexpression affects migratory potential in Caki-1 cells. ANX AI immunohistochemistry was performed on 33 samples of CRCCs and 10 metastases. ANX AI expression was assessed in 12 samples by 2-dimensional gelelectrophoresis (2-DE), subsequent mass spectrometry and RT-PCR. Immunohistochemical data were statistically correlated with pathological parameters, amount of eosinophilic cells and clinical outcome. Furthermore, a haptotactic migration assay was done on Caki-1 cells transfected with ANX AI. Immunostaining for ANX AI was found in 18 tumours and all metastases investigated. Intensity of immunohistochemical staining correlated to Fuhrman grade, amount of eosinophilic cells and clinical outcome. 2-DE and RT-PCR confirmed the presence of ANX AI in neoplastic tissue. Overexpression of ANX AI did not significantly influence cell migration. From these findings ANX AI expression seems to be related to Fuhrman grade, clinical outcome and metastatic potential of CRCCs. Thus ANX AI could serve as a prognostic marker for tumour progression

Cross-country and regional Analyses on the effect of environmental accounting on financial profitability, liquidity, marketability, leverage, and firm value of environmentally sensitive industries across the ASEAN-5

As one of the environmental hubs of the world, the operations of Southeast Asian companies inevitably coincide with the environment which leads to calls for environmental accountability. The main objective of this empirical research is to determine the effects of environmental disclosures and environmental costs reporting to the financial profitability, liquidity, marketability, leverage, and firm value of listed chemical, energy, food, beverage and tobacco (FBT), metals and mining, and utilities companies in Malaysia, Indonesia, Philippines, Thailand and Singapore, and in the whole ASEAN-5 region. The researchers make use of voluntary disclosure, legitimacy, signaling, stakeholders, and institutional theories to explain, predict and understand relationships. Also, the moderating effects of the firm-specific characteristics on each of the relationships mentioned are likewise explored and tested. Panel regression analysis is used by the researchers. Results show that environmental accounting disclosure has a significant direct effect on NPM, ROE, MBR and TQ. Moreover, EAD has no significant effect on CR, QR, and PER, but when moderated by firm specific characteristics, it has a significant effect on CR, QR, PER, and DTE in some countries. Environmental costs, on the other hand, have a significant effect on NPM, PER, MBR, and TQ. Likewise, environmental costs have a significant effect on ROE, CR, QR, and PER in some countries, at some extent, when moderated by firm-specific characteristics. In the context of the ASEAN-5 region, findings of this study suggest that EAD has a significant effect only on firm value using Tobin’s Q. But when moderated by firm-specific characteristics except years of existence, EAD has a significant effect on NPM, ROE, CR, QR, and MBR. On the flip side, environmental cost has no significant effect on a company\u27s financial performance. But when moderated by auditor type, industry type, years as publicly listed, and years of existence, it has a significant effect on NPM, ROE, and TQ. Furthermore, numerous recommendations are directly addressed to the internal and external users of financial and non-financial information, regulatory bodies and the academe