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New Findings: What is the topic of this review? We discuss tools available to access genome-wide data sets that harbour cell-specific, brain region-specific and tissue-specific information on exon usage for several species, including humans. In this Review, we demonstrate how to access this information in genome databases and its enormous value to physiology. What advances does it highlight? The sheer scale of protein diversity that is possible from complex genes, including those that encode voltage-gated ion channels, is vast. But this choice is critical for a complete understanding of protein function in the most physiologically relevant context. Many proteins of great interest to physiologists and neuroscientists are structurally complex and located in specialized subcellular domains, such as neuronal synapses and transverse tubules of muscle. Genes that encode these critical signalling molecules (receptors, ion channels, transporters, enzymes, cell adhesion molecules, cell-cell interaction proteins and cytoskeletal proteins) are similarly complex. Typically, these genes are large; human Dystrophin (DMD) encodes a cytoskeletal protein of muscle and it is the largest naturally occurring gene at a staggering 2.3 Mb. Large genes contain many non-coding introns and coding exons; human Titin (TTN), which encodes a protein essential for the assembly and functioning of vertebrate striated muscles, has over 350 exons and consequently has an enormous capacity to generate different forms of Titin mRNAs that have unique exon combinations. Functional and pharmacological differences among protein isoforms originating from the same gene may be subtle but nonetheless of critical physiological significance. Standard functional, immunological and pharmacological approaches, so useful for characterizing proteins encoded by different genes, typically fail to discriminate among splice isoforms of individual genes. Tools are now available to access genome-wide data sets that harbour cell-specific, brain region-specific and tissue-specific information on exon usage for several species, including humans. In this Review, we demonstrate how to access this information in genome databases and its enormous value to physiology., (© 2015 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

There are no standard guidelines to follow when a patient with chronic hepatitis B infection becomes pregnant or desires pregnancy. Topics to consider include which patients to treat, when to start treatment, what treatment to use and when to stop treatment. Without any prophylaxis or antiviral therapy, a hepatitis B surface antigen and E antigen positive mother has up to a 90% likelihood of vertical transmission of hepatitis B virus (HBV) to child. Standard of care in the United States to prevent perinatal transmission consists of administration of hepatitis B immune globulin and HBV vaccination to the infant. The two strongest risk factors of mother to child transmission (MTCT) of HBV infection despite immunoprophylaxis are high maternal HBV viral load and high activity of viral replication. The goal is to prevent transmission of HBV at birth by decreasing viral load and/or decreasing activity of the virus. Although it is still somewhat controversial, most evidence shows that starting antivirals in the third trimester is effective in decreasing MTCT without affecting fetal development. There is a growing body of literature supporting the safety and efficacy of antiviral therapies to reduce MTCT of hepatitis B. There are no formal recommendations regarding which agent to choose. Tenofovir, lamivudine and telbivudine have all been proven efficacious in decreasing viral load at birth without known birth defects, but final decision of which antiviral medication to use will have to be determined by physician and patient. The antivirals may be discontinued immediately if patient is breastfeeding, or within first four weeks if infant is being formula fed.

With sustained and rapid developments in the field of information technology, the issue of network security has become increasingly prominent. The theme of this study is network data security, with the test subject being a classified and sensitive network laboratory that belongs to the academic network. The analysis is based on the deficiencies and potential risks of the network's existing defense technology, characteristics of cyber attacks, and network security technologies. Subsequently, a distributed network security architecture using the technology of an intrusion prevention system is designed and implemented. In this paper, first, the overall design approach is presented. This design is used as the basis to establish a network defense model, an improvement over the traditional single-technology model that addresses the latter's inadequacies. Next, a distributed network security architecture is implemented, comprising a hybrid firewall, intrusion detection, virtual honeynet projects, and connectivity and interactivity between these three components. Finally, the proposed security system is tested. A statistical analysis of the test results verifies the feasibility and reliability of the proposed architecture. The findings of this study will potentially provide new ideas and stimuli for future designs of network security architecture.

Given the proliferation of internet connected devices, IPv6 has been proposed to replace IPv4. Aside from providing a larger address space which can be assigned to internet enabled devices, it has been suggested that the IPv6 protocol offers increased security due to the fact that with the large number of addresses available, standard IP scanning attacks will no longer become feasible. However, given the interest in attacking organizations rather than individual devices, most initial points of entry onto an organization's network and their attendant devices are visible and reachable through web crawling techniques, and, therefore, attacks on the visible application layer may offer ways to compromise the overall network. In this evaluation, we provide a straightforward implementation of a web crawler in conjunction with a benign black box penetration testing system and analyze the ease at which SQL injection attacks can be carried out.

Over the years, human dependence on the Internet has increased dramatically. A large amount of information is placed on the Internet and retrieved from it daily, which makes web security in terms of online information a major concern. In recent years, the most problematic issues in web security have been e-mail address leakage and SQL injection attacks. There are many possible causes of information leakage, such as inadequate precautions during the programming process, which lead to the leakage of e-mail addresses entered online or insufficient protection of database information, a loophole that enables malicious users to steal online content. In this paper, we implement a crawler mining system that is equipped with SQL injection vulnerability detection, by means of an algorithm developed for the web crawler. In addition, we analyze portal sites of the governments of various countries or regions in order to investigate the information leaking status of each site. Subsequently, we analyze the database structure and content of each site, using the data collected. Thus, we make use of practical verification in order to focus on information security and privacy through black-box testing.

This study explored the participants' perceptions of using prayer and scripture in a Christian-based stress-coping support group (CSCSG). Twenty-eight church attendances were recruited from a Presbyterian Church in Taiwan. Based on the finding from qualitative analyses using a modified grounded theory approach, four themes related to the participants' learning experiences emerged. The four themes identified were stressful life events, stress-coping experiences, integration of Christian faith with life, and spiritual connection. A follow-up survey indicated that the participants perceived the experiences gained from the CSCSG as appropriate, important, functional, and constructive in coping with stress. Research questions and implications for church professionals are discussed.

Background/aims: Surgical management of gastric outlet obstruction may associate with significant morbidity and mortality. Few studies have documented surgical outcomes in elderly patients. The aim of this study was to review recent operative results of benign gastric outlet obstruction in elderly patients compared with younger patients., Methodology: Forty- seven consecutive patients from January 2000 through September 2008 were included. Preoperative, intraoperative data and early postoperative complications were analyzed., Results: Fifteen operations were performed in elderly patients and 32 in younger patients. More patients in the elderly group were assigned as ASA class 3 (p=0.037), but Charlson comorbidity index was similar. Procedure types included Finney or Jaboulay pyloroplasty (n=26), antrectomy (n=13) and gastrojejunostomy (n=8). The mean postoperative hospital stay was 14.9 days. A modest correlation between the length of stay and the patient's age (p=0.044; r=0.294) was observed. There were two in hospital mortalities and four patients had complications., Conclusions: Surgery for benign gastric outlet obstruction is safe in the elderly population and is not associated with any increase in morbidity or mortality.

Pancreatic cancer is the fourth leading cause of cancer related death in the US. Despite the advances in medical and surgical treatment, the 5-year survival rate for such cancer is only approximately 5% when considering all stages of disease. The lethal nature of pancreatic cancer stems from its high metastatic potential to the lymphatic system and distant organs. Lack of effective chemotherapies, which is believed to be due to drug-resistance, also contributes to the high mortality of pancreatic cancer. Recent evidence suggests that epithelial-mesenchymal transition of pancreatic cancer cells contributes to the development of drug resistance and an increase in invasiveness. Future strategies that specifically target against epithelial-mesenchymal transition phenotype could potentially reduce tumoral drug resistance and invasiveness and hence prolong the survival of patients with pancreatic cancer.

Aim: To estimate the prevalence of cardiovascular events in Primary biliary cirrhosis (PBC) and to determine whether this risk is higher within specific subgroups of patients with PBC., Methods: We included 180 patients with PBC (cases) and 151 patients seen for HCV infection (controls). Medical records were reviewed and statistical analyses were performed as appropriate., Results: When compared to controls, PBC patients were older, leaner and had higher serum levels of total cholesterol, high density lipoprotein and low density cholesterol. There were more females in the PBC group (91.7% vs 43%, P < 0.001). More control subjects had smoked than the PBC patients (63.6% vs 35%, P < 0.001). The prevalence of hypertension, diabetes, coronary artery disease and stroke was similar between the two groups. Seven percent of controls and 10% of cases developed any type of cardiovascular disease (P = 0.3). Only 36.7% were asymptomatic at diagnosis. Three cardiovascular events were documented among asymptomatic patients (4.5%) and fifteen among symptomatic patients (13.2%; P = 0.06). Among PBC patients with fatigue, 10 (13.5%) had a cardiovascular event compared to 7 (6.7%) among patients without fatigue (P = 0.1)., Conclusion: Asymptomatic PBC patients do not have a greater frequency of cardiovascular disease; nor do patients suffering with fatigue.

Sorafenib is an oral multiple kinase inhibitor that blocks Raf, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor. It has been approved in the US and Europe for the treatment of advanced hepatocellular carcinoma (HCC). Sorafenib has demonstrated a 44% increase in survival for advanced HCC patients, compared with best supportive care alone. We have reviewed the pharmacology, pivotal studies, and safety data for this agent. Sorafenib is the first systemic drug demonstrating a significant survival benefit, and is the standard of care for patients with advanced HCC for whom no potential curative option is available.

Adverse reactions after intravascular administration of iodine contrast media are common and prophylactic regiments consisting of the use of steroids and low osmolality contrast media are highly effective in significantly decreasing the adverse reactions rate. The same type of contrast media are also used for opacification of the biliary tree and the pancreatic duct at the time of endoscopic retrograde cholangiopancreatography (ERCP). Systemic absorption of contrast media after ERCP routinely occurs. Although the adverse reaction rate appears to be very low the exact incidence remains unknown due to the retrospective nature of all reports. Despite the lack of formal recommendations, numerous prophylactic regiments are routinely used prior to ERCP in patients with history of prior reaction to intravascular contrast media. Moreover, the use of prophylaxis has even expanded to patients with no prior reaction to intravascular contrast media who are somehow perceived to be at increase risk (e.g. shellfish allergy). Recently, the first large scale prospective study reported exceedingly low incidence of adverse reaction to high oslmolality iodine-containing contrast media administered at the time of ERCP done without prophylactic premedication even in patients considered to be at the highest risk (prior severe reaction to intravascular contrast media administration). These data suggest that the use of prophylactic regiments prior to ERCP appears to be unnecessary.

Background/aims: Liver biopsy has been considered as the gold standard for assessing fibrosis in patients with chronic hepatitis. The objective of this study was to explore the feasibility of using serum tests to predict the presence of fibrosis in patients with chronic hepatitis B., Methodology: Fibrosis scores for 153 patients were established by examining liver biopsy specimens. Serum was obtained from each patient around the time of the biopsy and analyzed by standard laboratory techniques. Student's t test, univariate analysis, and multivariate logistic regression were employed to test the presence of statistical significance., Results: Only platelet count was an independent factor that could predict the presence of significant fibrosis. Platelet count was lower (p = 0.04) in the group with moderate/severe fibrosis. When platelet count was above 150 x 10(9)/L, the negative prediction value and specificity for the presence of significant fibrosis was 0.78 and 0.87 (AUC under ROC curve was 0.68). In this study, AST/ALT ratio was not associated with either activity or fibrosis., Conclusions: This study suggests that platelet count is an independent noninvasive marker for prediction of the presence of significant liver fibrosis in patients with chronic hepatitis B.

The role that transforming growth factor beta1 (TGF-beta1) plays in influencing growth of glioma cells is somewhat controversial. To further understand the potential growth-regulatory effects of TGF-beta1,we constructed an animal astroglial tumor model by injecting either wild-type or virally transduced human U-87 glioblastoma cells into nude rat brains. Wild type U-87 cells produced very low amounts of TGF-beta1 and were highly tumorigenic. In contrast, U-87 cells transduced to express high levels of TGF-beta1 showed reduced tumor size in vivo, in a dose-dependent manner. This reduction in tumor size was not due to either decreased vascularity or increased apoptosis. To test whether TGF-beta1 overproduction inhibited tumor growth through an autocrine mechanism, the highest TGF-beta1 producing cells were then double transduced with a vector expressing the kinase-truncated type II TGF-beta receptor. Cells expressing high levels of truncated TGF-beta receptor were less sensitive to TGF-beta1 mediated growth inhibition in vitro and produced more aggressive tumors in vivo. The data suggest that the degree of tumorigenicity of the U-87 high-grade glioblastoma cell line may be associated with correspondingly low level of production of TGF-beta1. These results also would tend to support the possibility that TGF-beta1 may be useful in treating some high-grade gliomas.

Background/aims: Wilson's disease has protean presentations. Most patients manifested as either hepatic or neurologic symptoms and signs initially. No study has investigated the predictor of presentation and differences in laboratory tests and survival between patients presented with hepatic or neurological disease so far., Methodology: Forty-one patients with Wilson's disease were diagnosed between 1981 and 2002 at our hospital. Their clinical features at presentation and laboratory findings were retrospectively collected. Survival was calculated using the Kaplan-Meier analysis., Results: Twelve patients initially presented with hepatic symptoms including chronic hepatitis, complications of cirrhosis, and fulminant hepatic failure. Twenty-nine patients presented with neurological symptoms including tremor, dysarthria, ataxia, and psychiatric diseases. No specific factor identified could predict the initial presentations. Compared to patients with neurological symptoms, patients with hepatic disease had significantly higher serum levels of aminotransferase, ceruloplasmin, copper, and 24-hour urine copper excretion. There was no significant difference in survival between these two groups. Among the patients who died, the most common causes of death were fulminant hepatic failure and complications of cirrhosis., Conclusions: Our results suggested that the overall survival did not differ significantly according to the initial presentations. There was no predictor found that could foretell the clinical course of Wilson's disease.