Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B

<p>Abstract</p> <p>Background</p> <p>Development of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Recent studies demonstrated an increased oncogenic potential of this mutant in NIH3T3 cells. In this study, we aimed to investigate the clinical significance of this finding.</p> <p>Methods</p> <p>Serum samples from 123 LAM-resistant chronic hepatitis B patients were submitted for virological assays. A highly sensitive amplification created restriction enzyme site (ACRES) method was devised to detect small amounts of the rtA181T mutant in the serum. Virological factors including HBV-DNA level, genotype, precore G1896A, BCP A1762T/G1764A, rtM204I/V, rtA181T and pre-S internal deletion mutations as well as clinical variables including subsequent use of rescue drugs were submitted for outcome analysis.</p> <p>Results</p> <p>By use of the highly sensitive ACRES method, the rtA181T mutant was detectable in 10 of the 123 LAM-resistant patients. During the mean follow-up period of 26.2 ± 16.4 months (range 2 to 108 months), 3 of the 10 (30.0%) rtA181T-positive patients and 2 of the 113 (1.8%) rtA181T-negative patients developed hepatocellular carcinoma (HCC). Kaplan-Meier analysis indicated that the presence of rtA181T mutation (P < 0.001), age > 50 years (P = 0.001), and liver cirrhosis (P < 0.001) were significantly associated with subsequent occurrence of HCC. All 5 HCC patients belonged to the older age and cirrhosis groups.</p> <p>Conclusions</p> <p>Emergence of the rtA181T/sW172* mutant in LAM-resistant patients increased the risk of HCC development in the subsequent courses of antiviral therapy.</p

A global method for coupling transport with chemistry in heterogeneous porous media

Modeling reactive transport in porous media, using a local chemical equilibrium assumption, leads to a system of advection-diffusion PDE's coupled with algebraic equations. When solving this coupled system, the algebraic equations have to be solved at each grid point for each chemical species and at each time step. This leads to a coupled non-linear system. In this paper a global solution approach that enables to keep the software codes for transport and chemistry distinct is proposed. The method applies the Newton-Krylov framework to the formulation for reactive transport used in operator splitting. The method is formulated in terms of total mobile and total fixed concentrations and uses the chemical solver as a black box, as it only requires that on be able to solve chemical equilibrium problems (and compute derivatives), without having to know the solution method. An additional advantage of the Newton-Krylov method is that the Jacobian is only needed as an operator in a Jacobian matrix times vector product. The proposed method is tested on the MoMaS reactive transport benchmark.Comment: Computational Geosciences (2009) http://www.springerlink.com/content/933p55085742m203/?p=db14bb8c399b49979ba8389a3cae1b0f&pi=1

Update on the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus Infection

Chronic hepatitis B virus infection is an important cause of liver-related morbidity and mortality, with hepatocellular carcinoma being the most life-threatening complication. Because of the highly variable clinical course of the disease, enormous research efforts have been made with the aim of revealing the factors in the natural history that are relevant to hepatocarcinogenesis. These include epidemiological studies of predisposing risk groups, viral studies of mutations within the hepatitis B viral genome, and clinical correlation of these risk factors in predicting the likelihood of development of hepatocellular cancer in susceptible hosts. This update addresses these risks, with emphasis on the latest research relevant to hepatocarcinogenesis

Community-acquired Klebsiella pneumoniae meningitis in an alcoholic patient with an infected pancreatic pseudocyst; a case report and review of literature

We report a case of a 49-year-old male with a history of chronic alcoholism and evidence of a pancreatic pseudocyst on CT scanning. He presented with a 3-days history of fever, loss of appetite and upper abdominal pain. Blood cultures grew Klebsiella pneumoniae and he improved clinically with a seven-day course of intravenous co-amoxiclav and metronidazole. Two weeks later he was readmitted to hospital with impaired consciousness and septic shock, and died three days later in intensive care. Post mortem examination revealed bacterial meningitis and an infected pancreatic pseudocyst. Klebsiella pneumoniae was isolated from the pancreas and meninges

Multiplex Detection and SNP Genotyping in a Single Fluorescence Channel

Probe-based PCR is widely used for SNP (single nucleotide polymorphism) genotyping and pathogen nucleic acid detection due to its simplicity, sensitivity and cost-effectiveness. However, the multiplex capability of hydrolysis probe-based PCR is normally limited to one target (pathogen or allele) per fluorescence channel. Current fluorescence PCR machines typically have 4–6 channels. We present a strategy permitting the multiplex detection of multiple targets in a single detection channel. The technique is named Multiplex Probe Amplification (MPA). Polymorphisms of the CYP2C9 gene (cytochrome P450, family 2, subfamily C, polypeptide 9, CYP2C9*2) and human papillomavirus sequences HPV16, 18, 31, 52 and 59 were chosen as model targets for testing MPA. The allele status of the CYP2C9*2 determined by MPA was entirely concordant with the reference TaqMan® SNP Genotyping Assays. The four HPV strain sequences could be independently detected in a single fluorescence detection channel. The results validate the multiplex capacity, the simplicity and accuracy of MPA for SNP genotyping and multiplex detection using different probes labeled with the same fluorophore. The technique offers a new way to multiplex in a single detection channel of a closed-tube PCR

Sound Frequency and Aural Selectivity in Sound-Contingent Visual Motion Aftereffect

BACKGROUND: One possible strategy to evaluate whether signals in different modalities originate from a common external event or object is to form associations between inputs from different senses. This strategy would be quite effective because signals in different modalities from a common external event would then be aligned spatially and temporally. Indeed, it has been demonstrated that after adaptation to visual apparent motion paired with alternating auditory tones, the tones begin to trigger illusory motion perception to a static visual stimulus, where the perceived direction of visual lateral motion depends on the order in which the tones are replayed. The mechanisms underlying this phenomenon remain unclear. One important approach to understanding the mechanisms is to examine whether the effect has some selectivity in auditory processing. However, it has not yet been determined whether this aftereffect can be transferred across sound frequencies and between ears. METHODOLOGY/PRINCIPAL FINDINGS: Two circles placed side by side were presented in alternation, producing apparent motion perception, and each onset was accompanied by a tone burst of a specific and unique frequency. After exposure to this visual apparent motion with tones for a few minutes, the tones became drivers for illusory motion perception. However, the aftereffect was observed only when the adapter and test tones were presented at the same frequency and to the same ear. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the auditory processing underlying the establishment of novel audiovisual associations is selective, potentially but not necessarily indicating that this processing occurs at an early stage

HURP Expression-Assisted Risk Scores Identify Prognosis Distinguishable Subgroups in Early Stage Liver Cancer

Hepatoma up-regulated protein (HURP) is a component of the chromatin-dependent pathway for spindle assembly. We examined the prognostic predictive value of HURP in human hepatocellular carcinoma (HCC).HURP expression was evaluated by immunocytochemistry of fine needle aspirated hepatoma cells in 97 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage A. Subsequently, these patients underwent partial hepatectomy (n = 18) or radiofrequency ablation (n = 79) and were followed for 2 to 35 months. The clinicopathological parameters were submitted for survival analysis.HURP expression in aspirated HCC cells was detected in 19.6% patients. Kaplan-Meier survival analysis showed that positive HURP expression (P = 0.023), cytological grading ≥3 (P = 0.008), AFP ≥35 ng/mL (P = 0.039), bilirubin ≥1.3 mg/dL (P = 0.010), AST ≥50 U/L (P = 0.003) and ALT ≥35 U/L (P = 0.005) were all associated with a shorter disease-free survival. A stepwise multivariate Cox proportional hazard model revealed that positive HURP expression (HR, 2.334; 95% CI, 1.165-4.679, P = 0.017), AST ≥50 U/L (HR, 3.697; 95% CI, 1.868-7.319, p<0.001), cytological grade ≥3 (HR, 4.249; 95% CI, 2.061-8.759, P<0.001) and tumor number >1 (HR, 2.633; 95% CI, 1.212-5.722, P = 0.014) were independent predictors for disease-free survival. By combining the 4 independent predictors, patients with different risk scores (RS) showed distinguishable disease-free survival (RS≤1 vs. RS = 2, P = 0.001; RS = 2 vs. RS = 3, P<0.001). In contrast, the patients cannot be separated into prognosis distinguishable subgroups by using AJCC/UICC TNM staging system.HCC patients with BCLC stage A can be separated into three prognosis-distinguishable groups by use of a risk score that is based upon HURP expression in aspirated HCC cells, ALT, cytological grade and tumor number

Effect of Qigong on quality of life: a cross-sectional population-based comparison study in Taiwan

<p>Abstract</p> <p>Background</p> <p>Qigong, similar to Tai Chi Chuan, is beneficial to health. In Taiwan, Waitankung, a type of Qigong, is as popular as Tai Chi Chuan. This population-based comparison study compares the health-related quality of life between people practicing Waitankung and their comparable community residents.</p> <p>Methods</p> <p>A total of 165 individuals practicing Waitankung were matched by age and sex with 660 general individuals for comparison. Information about health-related quality of life, measured by the SF-36, and other basic and health conditions was obtained from the questionnaires. This study used the linear mixed-effect regression model to examine the association between health-related quality of life and the practice of Waitankung.</p> <p>Results</p> <p>Compared with either sedentary individuals or individuals practicing other types of exercise, the Waitankung group scored higher for eight and five out of ten SF-36 components, respectively. The Waitankung group scored better in general health, vitality, and physical component summary compared to individuals participating in other types of exercise, even when considering the energy expended by exercise.</p> <p>Conclusion</p> <p>The results suggest that Waitankung exercising is significantly associated with health-related quality of life. Waitankung may serve as an exercise choice for middle-aged and older people to improve overall quality of life.</p

Long-Term Mortality of Patients with Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess: A Population-Based Study

Background: Taiwan is endemic for pyogenic liver abscess (PLA). Septic ocular or central nervous system (CNS) complications derived from PLA can result in catastrophic disability. We investigated the epidemiology and long-term prognosis of PLA patients with septic ocular or CNS complications over an 8-year period. Methodology/Principal Findings: We extracted 21,307 patients with newly diagnosed PLA from a nationwide health registry in Taiwan between 2000 and 2007. The frequency of and risk factors for PLA with septic ocular or CNS complications were determined. The 2-year survival of these patients was compared between those with and without septic ocular or CNS complications. Septic ocular or CNS complications accounted for 2.1 % of all PLA patients. Age and the Charlson comorbidity index were significantly lower in PLA patients with ocular or CNS complications than those without. Diabetes and age,65 years were independent predictors of septic ocular or CNS complications. The 2-year mortality of patients with septic ocular or CNS complications was similar to those without complications (24.8 % vs. 27.5%, p = 0.502). However, among patients,65 years old and a Charlson index #1, the 2-year mortality was significantly higher in those with than without complications (18.6 % vs. 11.8%, p = 0.001). Conclusions/Significance: Physicians should recognize that catastrophic disability due to ocular or neurologica