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Summary: New, nontoxic and earth‐abundant materials for heat‐energy interconversion are urgently required to mitigate the over‐reliance on finite fossil fuels supply. Herein, using ab initio quantum mechanical calculations and Boltzmann theory, optimization of thermoelectric performances instable, mechanically robustCm‐SnSSe and P3m1‐SnSeS phases was performed. These phases exhibit an intrinsically low thermal conductivity of ~1.00 W m−1 K−1 at room temperature. Beyond 400 K, both phases display satisfactory thermoelectric performances, namely figure of merit ZT > 0.7 and power factor PF > 3.0 mW K−2 m−1. Better performances were obtained through holes doping at 1020 cm−3 concentration, where their ZT values reach 0.9 at 500 K and fluctuate minimally over broad temperature plateau, retaining the high PF over 3.0 mWK−2 m−1. Evolution into layered structure is also possible, with the calculated p‐type doping of P3m1‐SnSSe monolayer displaying decent ZT ~ 0.7 and very high PF > 6.0 mWK−2 m−1 beyond 300 K. In bulk form, the study specimens display superior machinability and mechanical properties, as evidenced by the approximately 8‐fold increase in their Vickers hardness when compared to PbTe and Bi2Te3 materials, while maintaining their plasticity characteristic. The computed E2D of 55.50 N m−1 is relatively low, which means Sn‐S‐Se alloy remains ductile when progressing to 2D state. Biaxial strain‐induced results show enhanced anharmonicity phonon scattering and thermopower increment, enabling maximum ZT ~ 1.0 and PF > 7.0 mW m−1 K−2 to be achieved in the appealing industrial waste heat akin 373 ≤ T ≤ 773 K range under 10% tensile strain. [ABSTRACT FROM AUTHOR]

Background Risks and benefits of protease inhibitor ( PI) (telaprevir or boceprevir) triple therapy in hepatitis C virus ( HCV)-infected patients with mildly decompensated cirrhosis, including those wait-listed for liver transplantation ( LT), are incompletely known. Aim To assess virological responses and safety of PI triple therapy in patients with mildly decompensated Child-Pugh ( CP) CP ≥6 vs. compensated ( CP = 5) cirrhosis. Methods Multicentre cohort of 160 adults with cirrhosis treated with peginterferon/ribavirin (peg- IFN/ RBV) plus telaprevir (69%) or boceprevir (31%), comparing outcomes between those with CP = 5 and CP ≥6. Results Patients, 47% with CP ≥6 cirrhosis ( CP range 6-10), received PI triple therapy for a targeted duration of 48 weeks. The cohort was median age 59 years, 32% female, 59% genotype 1a, 35% previous null/partial responders. Sustained virological response at 12 weeks ( SVR12) was achieved by 35% of patients with CP ≥6 vs. 54% of those with CP = 5 ( P = 0.02). CP = 5, achievement of rapid virological response and genotype 1b/other, independently predicted SVR12. Compared to those with CP = 5, patients with CP ≥6 had more peg- IFN dose reductions, eltrombopag use, transfusions and hospitalisations to manage adverse events (all P < 0.05). Overall, 67 (42%) discontinued treatment early. Nine wait-listed patients were treated for a median of 97 days ( IQR 60-160) prior to liver transplantation and five achieved post- LT SVR. Conclusions In the presence of mild decompensation (Child-Pugh ≥6), SVR12 rates with protease inhibitor triple therapy are significantly reduced and adverse events increased. Thus, treatment with protease inhibitor triple therapy, if judged as necessary, should be undertaken with close monitoring and awareness of the significant risks. [ABSTRACT FROM AUTHOR]

K-ras is an oncogenic GTPase responsible for at least 15-25% of all non-small cell lung cancer cases worldwide. Lung cancer of both types is increasing with an alarming rate due to smoking habits in Malaysia among men and women. Natural products always offer alternate treatment therapies that are safe and effective. Typhonium flagelliforme or Keladi Tikus is a local plant known to possess anticancer properties. The whole extract is considered more potent than individual constituents. Since K-ras is the key protein in lung cancer, our aim was to identify the constituents of the plant that could target the mutated K-ras. Using docking strategies, reported potentially active compounds of Typhonium flagelliforme were docked into the allosteric surface pockets and switch regions of the K-ras protein to identify possible inhibitors. The selected ligands were found to have a high binding affinity for the switch II and the interphase region of the ras-SOS binding surface. [ABSTRACT FROM AUTHOR]

Perisinusoidal hepatic stellate cells (HSC) are the principal fibrogenic cells in the liver. In animal models, HSC apoptosis is the predominant clearance mechanism of activated HSC, although data evaluating whether the same processes occur in humans are limited. We conducted a cross-sectional study to evaluate the association between HSC apoptosis and fibrosis stage in subjects with chronic hepatitis C virus (HCV) infection ( n = 44) and HCV-negative controls with normal liver histology ( n = 9). We used immunohistochemical techniques to identify activated (α-smooth muscle actin+), proliferative (Ki-67+) and apoptotic (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end-labelling+) HSC in liver biopsy specimens from all subjects. The same pathologist enumerated positive cells per high-power field (HPF, ×200) in 20 periportal/lobular areas. HSC apoptosis was decreased in HCV-positive subjects compared with controls (median 0.4, range 0.0–3.1 vs 1.1, 0.2–3.5 cells/HPF, P = 0.02). Among HCV-positive subjects, HSC apoptosis was decreased in those with moderate to advanced fibrosis ( P = 0.04) compared with those with mild fibrosis. By multivariate analysis, HSC apoptosis decreased by an average of 0.14 cells/HPF (95% confidence interval 0.01–0.28 cells/HPF) per increase in fibrosis stage ( P = 0.04). While the number of activated and proliferative HSC was significantly increased in HCV-infected subjects compared with that in uninfected controls, the numbers of these cells did not differ between HCV-infected subjects with mild vs moderate/advanced fibrosis. In conclusion, the number of apoptotic HSC was significantly decreased in HCV-infected subjects with advanced fibrosis. In chronic HCV infection, inhibition of HSC apoptosis may be one mechanism by which fibrosis progresses. [ABSTRACT FROM AUTHOR]

The model for end stage liver disease (MELD)-based organ allocation system is designed to prioritize orthotopic liver transplantation (OLT) for patients with the most severe liver disease. However, there are no published data to confirm whether this goal has been achieved or whether the policy has affected long-term post-OLT survival.To compare pre-OLT liver disease severity and long-term (1 year) post-OLT survival between the pre- and post-MELD eras.Using the United Network of Organ Sharing database, we compared two cohorts of adult patients undergoing cadaveric liver transplant in the pre-MELD (n = 3857) and post-MELD (n = 4245) eras. We created multivariable models to determine differences in: (i) pre-OLT liver disease severity as measured by MELD; and (ii) 1-year post-OLT outcomes.Patients undergoing OLT in the post-MELD era had more severe liver disease at the time of transplantation (mean MELD = 20.5) vs. those in the pre-MELD era (mean MELD = 17.0). There were no differences in the unadjusted patient or graft survival at 1 year post-OLT. This difference remained insignificant after adjusting for a range of prespecified recipient, donor, and transplant centre-related factors in multivariable survival analysis.Although liver disease severity is higher in the post- vs. pre-MELD era, there has been no change in long-term post-OLT patient or graft survival. These results indicate that the MELD era has achieved its primary goals by allocating cadaveric livers to the sickest patients without compromising post-OLT survival. [ABSTRACT FROM AUTHOR]

McCutcheon JA, Yee H, Hayashi R, Licari B, Lombardo D, Rosenberg PA, Phelan J. Identification of γδT lymphocytes in human periapical lesions. Oral Microbiol Immunol 2004: 19: 106–110. © Blackwell Munksgaard, 2004. Endodontic (root canal) therapy is required when the pulp of a tooth becomes necrotic due to a bacterial infection or trauma. A proportion of patients who receive endodontic therapy subsequently have periapical (around the tooth root) lesions detected by radiolucency. Currently, there are no means to identify susceptible patients. Although tissue from periapical lesions has been described as inflammatory, inflammatory cell types and their functions have been poorly characterized. For example, T lymphocytes were identified using pan specific anti-CD3 mAb, which recognizes both αβ and γδT cells. Using the current model of γδT cells as immunoregulatory cells; γδT cells can mediate protective or destructive milieus. We postulated that patients who have a periapical lesion, as identified by radiographic bone loss, mount a γδT cell response. We collected specimens removed by surgery from both periapical lesions and other oral tissues, generated total RNA and performed reverse-transcriptase polymerase chain reaction to identify rearranged δ genes. Results were confirmed with semi-nested polymerase chain reaction. In addition, we demonstrate that these lesions contain a population of CD3+ cells that are αβT cell receptor negative, implying that these cells are γδT cells. Here we show that 36/37 of periapical lesions and only 2/11 of other lesions contain γδT cells ( P < 0.0001). Vδ2+ T cells were the most common subtype identified (30/36) in these samples. This is the first report in the literature of the presence of γδT cells in human periapical lesions. [ABSTRACT FROM AUTHOR]

Hypothesis: Increased cell motility is a hallmark of cancer cells. Proteins involved in cell motility may be used as molecular markers to characterize the malignant potential of tumors.Methods: Molecular biology and immunohistochemistry techniques were used to investigate the expression of a selected panel of motility-related proteins (Rho A, Rac 2, Cdc42, PI3K, 2E4, and Arp2) in normal, premalignant, and squamous cell cancer cell lines of human head and neck origin. To assess the clinical potential of these proteins as molecular markers for cancer, immunohistochemistry was performed on paraffin-fixed head and neck cancer specimens (n = 15).Results: All six motility-associated proteins were overexpressed in the premalignant and squamous cell cancer cell lines relative to normal keratinocytes. Immunohistochemistry with Rho A and Rac 2 showed increased staining in areas of cancer but not in normal tissue.Conclusion: Proteins involved in cell motility can be used as markers for head and neck squamous cell carcinoma. The head and neck cell lines used in this study may be used as a model to further investigate cell motility. Molecular markers of motility could have a significant impact on the diagnosis and staging of cancers originating from differentiated non-motile cells. [ABSTRACT FROM AUTHOR]

The structural and electronic properties of ternary AlxTiyNiz clusters, where x, y, and z are integers and x + y + z = 6, are investigated. Both Slater, Vosko, Wilks, and Nusair and B3LYP exchange‐correlation (XC) functionals are employed in a two‐stage density functional theory (DFT) calculations to generate these clusters. In the first stage, a minimum energy cluster structure is generated by an unbiased global search algorithm coupled with a DFT code using a light XC functional and small basis sets. In the second stage, the obtained cluster structure is further optimized by another round of global minimization search coupled with a DFT calculator using a heavier XC functional and more costly basis set. Electronic properties of the structures are illustrated in the form of a ternary diagram. Our DFT calculations find that the thermodynamic stability of the clusters increases with the increment in the number of constituent nickel atoms. These results provide a new insight to the structure, stability, chemical order, and electronic properties for the ternary alloy nanoclusters. [ABSTRACT FROM AUTHOR]

A cardiac varix is an unusual tumor of vascular origin that is rarely discovered antemortem. Here, we report the incidental finding of this lesion in the right atrium of a patient with concomitant prostate cancer., (© 2010 Wiley Periodicals, Inc.)

Aims: Hepatocyte proliferation (HP) is an adaptive response to liver injury. The relationships between HP and necroinflammation, fibrosis, and serum alpha-fetoprotein (AFP) levels in chronic hepatitis C virus (HCV) infection, however, are not well understood., Methods: Proliferative hepatocytes (Ki-67+) were identified using immunohistochemical staining in formalin-fixed, paraffin-embedded liver tissue from 156 HCV RNA-positive patients with different degrees of liver histopathology. Twenty high-power fields (HPFs) in lobular areas were counted in each specimen., Results: HP increased by 1.22 +/- 0.25 cells/HPF per increase in necroinflammation from grade 0 (median: 0.13; range: [0.1-0.5] cells/HPF) through grade 3 (median: 1.80; range: [0.0-25.2] cells/HPF; P=0.002). HP increased by 0.81 +/- 0.20 cells/HPF per increase in fibrosis from stage 0 (median: 0.33; range: [0.0-1.3] cells/HPF) through stage 3 (median: 1.70; range: [0.0-25.2] cells/HPF) and then decreased in stage 4 (to median: 0.90; range: [0.0-5.3] cells/HPF). HP also increased with advancing age (P=0.03). Among patients with advanced liver disease, HP was no higher in patients with elevated serum AFP levels (median: 1.68; range: [0.1-5.3] cells/HPF) than in those with normal serum AFP levels (median: 1.70; range: [0.0-25.2] cells/HPF; P=0.26)., Conclusions: In patients with chronic HCV infection, HP increases with histologic progression of liver disease, but is impaired in cirrhosis. HP was not increased in patients with elevated serum AFP levels., (Copyright 2004 Blackwell Munksgaard)

Acarbose is a novel oral anti-hyperglycemic agent approved for the treatment of noninsulin-dependent diabetes mellitus. It inhibits alpha-glucosidases in the small intestine, an action that delays the digestion and absorption of complex carbohydrates. Subsequently, there is a smaller rise in the postprandial plasma glucose levels and an overall decrease in the glycosylated hemoglobin by 0.5-1.0%. Potential advantages of acarbose include a greater effectiveness in controlling postprandial hyperglycemia, a low risk of hypoglycemia, and a possible delay in initiating insulin therapy. Acarbose can potentiate the hypoglycemic effects of sulfonylureas or insulin. It has not been associated with weight gain and hyperinsulinemia, both of which can occur with sulfonylureas or insulin. Gastrointestinal adverse effects are common with acarbose, and may decrease with continued treatment. Although rare, elevated serum transaminase levels have been reported.