Correlation between hMLH1/hMSH2 and p53 protein expression in sporadic colorectal cancer

BACKGROUND/AIMS: The aim of this study was to analyze expression of hMLH1 and hMSH2 mismatch repair proteins in terms of p53 protein expression and clinicopathological parameters in sporadic colorectal cancer. METHODOLOGY: Four hundred and two cases of curative colorectal surgery for primary colorectal cancer were included in this study (patients with a familial history of colorectal cancer and familial adenomatous polyposis were not included). Clinicopathological parameters were reviewed retrospectively. HMLH1, hMSH2 and p53 protein expression in tumor tissue sections was determined using immunohistochemical staining with specific monoclonal antibodies. RESULTS: Of the 402 cases, immunohistochemical analysis showed 35 (8.7%) had loss of expression of hMLH1, 19 (4.7%) had loss of expression of hMSH2, and three cases (0.7%) had loss of expression of both proteins. Multivariate analysis showed that early age of onset (p=0.023), right side dominance (p<0.001) and poorly differentiated or mucinous cell type (p<0.001) were associated with loss of expression of hMLH1 or hMSH2. Loss of expression of hMLH1 or hMSH2 correlated with low p53 expression (p<0.001). In terms of clinicopathological parameters, p53 expression was associated only with hMLH1 or hMSH2 expression. CONCLUSIONS: Colorectal cancers not expressing hMLH1 or hMSH2 may have distinct features from those expressing these mismatch repair proteins. p53 expression appears to be implicated in a compensatory pathway with mismatch repair proteins.     

Pilot study of interferon gamma for chronic hepatitis C

BACKGROUND/AIMS: Currently, there are no effective therapies available for patients with chronic hepatitis C who have failed to respond to optimal interferon alfa-based regimens. The aims of this pilot study were to assess the antiviral activity and safety of interferon gamma in chronic hepatitis C. METHODS: Patients with chronic hepatitis C, genotype 1, who had not responded to or who had relapsed after therapy with interferon alfa and ribavirin were enrolled in a trial of interferon gamma 1b given in doses of 100, 200 or 400 microg subcutaneously three times weekly for 4 weeks. Frequent blood samples were obtained for HCV RNA levels. RESULTS: Fourteen patients were enrolled. Geometric mean HCV RNA levels remained unchanged. Serum aminotransferase levels also did not change, while there were significant decreases in neutrophil counts (-41% from baseline) and hematocrit (-5%). Low grade fever and malaise were common with the first injection of interferon gamma, but no serious side effects were encountered. CONCLUSIONS: Although relatively well tolerated, interferon gamma in doses of 100-400 microg thrice weekly had no effect on HCV RNA levels in patients with chronic hepatitis C who had failed to achieve a sustained response to interferon alfa-based therapies.     

Prognostic significance of p53 overexpression after hepatic resection of hepatocellular carcinoma.

BACKGROUND/AIMS: p53 mutation is the most common genetic abnormality in human cancers. However, although it has been reported that p53 overexpression in hepatocellular carcinoma (HCC) is associated with the aggressive behavior of tumor, the prognostic significance of p53 overexpression in HCC remains controversial. The aims of the present study were to examine the correlations between p53 overexpression and the clinicopathologic parameters of HCCs, and to determine the prognostic significance of p53 overexpression in HCC. METHODS: Immunohistochemical analysis of p53 overexpression was performed in 105 consecutive cases of HCC who underwent curative hepatic resection. Survival curves were calculated using the Kaplan-Meier method and multivariate analysis of outcome predictors for HCCs was assessed by logistic regression analysis. RESULTS: p53 overexpression was observed in 20 of 105 HCCs (19.0%). Multivariate analysis identified significant correlations between p53 overexpression and microvascular invasion (p=0.027), liver cirrhosis (p=0.035), 1-year survival rate (p=0.016), multiple tumors (p=0.014), and the presence of tumor capsule (p=0.010). The 2-year survival rate was poorer in patients without tumor capsule (p=0.043). CONCLUSIONS: Our results show a positive association between p53 overexpression and microvascular invasion in HCC, and indicate that p53 overexpression is a poor prognostic factor of survival, especially within 1 year after liver resection in HCC patients.     

Bone scintigraphy of skeletal metastasis in hepatoma patients treated by TAE

BACKGROUND/AIMS: Skeletal metastasis in hepatocellular carcinoma patients has become clinically important as a result of advances in treatment modalities. However, the diagnostic accuracy of bone scintigraphy in hepatocellular carcinoma has been questioned. METHODOLOGY: 99mTc-MDP bone scintigraphy was performed in 63 unresectable hepatocellular carcinoma patients treated by transcatheter arterial embolization who either developed musculoskeletal pain (n = 43) or elevated serum alpha-fetoprotein levels (n = 20) during follow-up. Results were categorized as positive or negative for metastases, and their accuracy was evaluated by radiological studies, biopsy, and clinical follow-up. RESULTS: Bone scintigraphy was positive in 22/43 (51.2%) subjects with pain and 2/20 with alpha-feto-protein elevation. Among 24 bone scintigraphy(+) patients, metastasis was confirmed in 17 and excluded in 6. Frequent sites for metastatic bone scintigraphy lesions were the spine, pelvic bone and ribs. Although 8 metastatic lesions had low or mixed uptake, most had increased uptake on bone scintigraphy. Among 39 bone scintigraphy(-) patients, metastasis was excluded in 32 and confirmed in 1. The sensitivity and specificity of bone scintigraphy in this subset of patients was 94.4% and 84.2%, respectively. CONCLUSIONS: Transcatheter arterial embolization treated hepatocellular carcinoma patients with musculoskeletal pain have a high likelihood of bone metastasis, and bone scintigraphy is a highly reliable method for its detection.     

High-performance thin H:SiON OLED encapsulation layer deposited by PECVD at low temperature

Highly moisture permeation resistive and transparent single layer thin films for the encapsulation of hydrogenated silicon oxynitrides (H:SiON) were deposited by plasma-enhanced chemical vapor deposition (PECVD) using silane (SiH₄), nitrous oxide (N₂O), ammonia (NH₃), and hydrogen (H₂) at 100 °C for applications to a top-emission organic light-emitting diode (TEOLED). Addition of H₂ into the PECVD process of SiON film deposition afforded the hydrogenated SiON film, which showed not only improved optical properties such as transmittance and reflectance but also better barrier property to water permeation than PECVD SiON and even SiN_x. The H:SiON film with thickness of only 80 nm exhibited water vapor transmission rate (WVTR) lower than 5 × 10⁻⁵ g per m² per day in the test conditions of 38 °C and 100% humidity, where this WVTR is the measurement limit of the MOCON equipment. An additional coating of UV curable polymer enabled the H:SiON films to be flexible and to have very stable barrier property lower than 5 × 10⁻⁵ g per m² per day even after a number of 10k times bending tests at a curvature radius of 1R. The mild H:SiON film process improved the electrical properties of top-emission OLEDs without generating any dark spots. Furthermore, single H:SiON films having high water vapor barrier could maintain the original illumination features of TEOLED longer than 720 hours. These excellent properties of the H:SiON thin films originated from the structural changes of the SiON material by the introduction of hydrogen.

High-performance H:SiON single layer thin film encapsulation (TFE) was deposited by plasma enhanced chemical vapor deposition (PECVD) method. To control the characteristics of the SiON thin films, hydrogen gas was introduced during PECVD process.     

A study of the density of states of ZnCoO:H from resistivity measurements

Understanding the electronic band structure and density of states (DOS) of a material and their relationship to the associated electronic transport properties is the starting point for optimizing the performance of a device and its technological applications. In a hydrogenated Zn_0.8Co_0.2O (ZnCoO:H) film with an inverted thin-film transistor structure, we found ambipolar behavior, which is shown in many field-effect devices based on graphene, graphene nanoribbons, and organic semiconductors. In this study, to obtain information on the DOS of ZnCoO:H to explain the ambipolar behavior in terms of the carrier density and type, resistivity and magnetoresistance measurements of a ZnCoO:H film were performed at 5 K. Our proposed DOS representation of ZnCoO:H explains qualitatively the experimental observations of carrier density modulation and ambipolar behavior. First-principles calculations of the DOS of ZnCoO:H were in good agreement with the proposed DOS representation. Through a comparison of first-principles calculations and experimental data, evidence for the existence of Co–H–Co in ZnCoO:H is suggested.

Ambipolar behavior in a hydrogenated Zn_0.8Co_0.2O (ZnCoO:H) film is investigated via resistivity and magnetoresistance measurements and first-principles calculations of the DOS. Evidence for the existence of Co–H–Co in ZnCoO:H is suggested.     

Membrane adaptation limitations in Enterococcus faecalis underlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes

The growing problem of antibiotic resistant bacteria, along with a dearth of new antibiotics, has redirected attention to the search for alternative antimicrobial agents. Conjugated oligoelectrolytes (COEs) are an emerging class of antimicrobial agents which insert into bacterial cell membranes and are inhibitory against a range of Gram-positive and Gram-negative bacteria. In this study, the extent of COE resistance that Enterococcus faecalis could achieve was studied. Enterococci are able to grow in hostile environments and develop resistance to membrane targeting antibiotics such as daptomycin in clinical settings. Herein we expand our knowledge of the antimicrobial mechanism of action of COEs by developing COE-resistant strains of E. faecalis OG1RF. Evolution studies yielded strains with a moderate 4–16 fold increase in antimicrobial resistance relative to the wild type. The resistant isolates accumulated agent-specific mutations associated with the liaFSR operon, which is a cell envelope-associated stress-response sensing and regulating system. The COE resistant isolates displayed significantly altered membrane fatty acid composition. Subsequent, exogenous supplementation with single fatty acids, which were chosen based on those dominating the fatty acid profiles of the mutants, increased resistance of the wild-type E. faecalis to COEs. In combination, genetic, fatty acid, and uptake studies support the hypothesis that COEs function through insertion into and disruption of membranes and that the mechanism by which this occurs is specific to the disrupting agent. These results were validated by a series of biophysical experiments showing the tendency of COEs to accumulate in and perturb adapted membrane extracts. Collectively, the data support that COEs are promising antimicrobial agents for targeting E. faecalis, and that there is a high barrier to the emergence of severely resistant strains constrained by biological limits of membrane remodeling that can occur in E. faecalis.

COEs are emerging antimicrobials to combat drug resistant infections and to which bacteria develop only limited resistance.     

Boron-doped diamond nanowire array electrode with high mass transfer rates in flow-by operation

We fabricated a boron-doped diamond nanowire (BDDNW) array electrode via soft lithography and metal-assisted chemical etching (MACE) of Si to provide a highly promoted effective surface area and increased mass transport during the electrochemical oxidation process. The effects of aligning the BDDNW on the electrochemical oxidation performance and the current efficiency of the electrode in phenol oxidation were examined. Although the effective surface area of the BDDNW array with an aligned nanowire configuration was smaller than that of the BDDNW with a random nanowire configuration, the BDDNW array electrode exhibited a higher mass transfer coefficient, resulting in a better performance in the removal of phenol. The enhanced mass transport exhibited by the BDDNW array electrode also greatly enhanced the chemical oxygen demand (COD) and current efficiency. Furthermore, because of its excellent oxidation performance, the BDDNW array electrode also exhibited much lower energy consumption during the phenol oxidation process.

We fabricated a boron-doped diamond nanowire (BDDNW) array electrode via lithography and metal-assisted chemical etching (MACE) to provide a highly promoted surface area and increased mass transport during the electrochemical oxidation process.     

Examining practical nursing experiences to discover ways in which to retain and invigorate the remaining functions of the elderly with a demented and complex disability in nursing homes

Aim

The bedridden elderly with moderate‐to‐severe dementia account for a large proportion of the residents in nursing homes and form a specialized group requiring customized care in order to encourage their remaining functions, which determine the quality of their residual life. The purpose of this study was to search for ways to invigorate and foster the remaining functions of this complex‐disability group, based on practical nursing strategies in nursing homes.

Methods

The qualitative thematic analysis was done by conducting in‐depth interviews with 29 nurses working at 11 different nursing homes in South Korea.

Results

This study proposed four main themes and 19 sub themes as keys for providing specialized nursing care to the elderly with physical and cognitive disabilities. The main themes encourage the residents' remaining functions: (i) accurate identification of an elderly resident's physical, cognitive, and behavioral baseline is necessary in order to determine their functional levels; (ii) nurses provide meticulous management to support the remaining functions in order to prevent further deterioration; (iii) optimized know‐how, based on accumulated experience and knowledge, is reflected in nursing strategies that maximize the effects of nursing interventions; and (iv) steady compliance with nursing guidelines and standards in nursing homes creates the best therapeutic environment and brings unexpected positive changes in the elderly's status.

Conclusion

A practical nursing strategy to target the group with a demented and complex disability in nursing homes was developed through thematic analysis of the empirical knowledge of nurses. The findings provide new insights for developing specialized nursing interventions and practical nursing models in long‐term care facilities.