Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection

Hepatitis C virus (HCV) has a high propensity for persistence. To better define the immunologic determinants of HCV clearance and persistence, we examined the circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361 overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3-NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific type-1 T-cell response was significantly greater in average frequency (0.24% vs. 0.04% circulating lymphocytes, P =.001) and scope (14/36 vs. 4/36 pools, P =.002) among the recovered than the chronic subjects, and the T-cell response correlated inversely with HCV titer among the chronic subjects (R = -0.51, P =.049). Although highly antigenic regions were identified throughout the HCV genome, there was no apparent difference in the overall HCV-specific T-cell repertoire or type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells and with higher frequency of CD4(+)CD25(+) regulatory T cells (7.3% chronic vs. 2.5% recovered, P =.002) that could directly suppress HCV-specific type-1 CD8 T cells ex vivo. In conclusion, we found that HCV persistence is associated with a global quantitative and functional suppression of HCV-specific T cells but not differential antigenic hierarchy or cytokine phenotype relative to HCV clearance. The high frequency of CD4(+)CD25(+) regulatory T cells and their suppression of HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in HCV persistence.     

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.     

Androgen-repressed phenotype in human prostate cancer

An androgen-repressed human prostate cancer cell line, ARCaP, was established and characterized. This cell line was derived from the ascites fluid of a patient with advanced metastatic disease. In contrast to the behavior of androgen-dependent LNCaP and its androgen-independent C4-2 subline, androgen and estrogen suppress the growth of ARCaP cells in a dose-dependent manner in vivo and in vitro. ARCaP is tumorigenic and highly metastatic. It metastasizes to the lymph node, lung, pancreas, liver, kidney, and bone, and forms ascites fluid in athymic hosts. ARCaP cells express low levels of androgen receptor mRNA and prostate-specific antigen mRNA and protein. Immunohistochemical staining shows that ARCaP cells stain intensely for epidermal growth factor receptor, c-erb B2/neu, and c-erb B3. Staining is negative for chromogranin A and positive for bombesin, serotonin, neuron-specific enolase, and the c-met protooncogene (a hepatic growth factor/scatter factor receptor). ARCaP cells also secrete high levels of gelatinase A and B and some stromelysin, which suggests that this cell line may contain markers representing invasive adenocarcinoma with selective neuronendocrine phenotypes. Along with its repression of growth, androgen is also found to repress the expression of prostate-specific antigen in ARCaP cells as detected by a prostate-specific antigen promoter–β-galactosidase reporter assay. Our results suggest that the androgen-repressed state may be central to prostate cancer progression and that advanced prostate cancer can progress from an androgen-independent to an androgen-repressed state.     

Remediation of trichloroethene (TCE)-contaminated groundwater by persulfate oxidation: a field-scale study

This study uses a trichloroethene (TCE)-contaminated site to determine the efficacy of persulfate oxidation for the treatment of TCE-contaminated groundwater. The main objectives of this study are: (1) to evaluate the efficacy of TCE treatment using persulfate with different injection strategies; (2) to determine the persistence of persulfate in the aquifer; (3) to determine the radius of influence (ROI) and transport distance of persulfate and (4) to determine the impact of persulfate on indigenous microorganisms during remediation. TCE concentrations are 0.26 mg L⁻¹ in P143 and 0.361 mg L⁻¹ in P146 and the microbial numbers are 6.1 × 10³ CFU mL⁻¹ in P143 and 4.4 × 10⁴ CFU mL⁻¹ in P146, before persulfate is injected. The results of the pilot study show that persulfate eliminates TCE. 100% of TCE is removed in P146 and 95% in P143. Single injection of a total amount of 275 kg of 5% persulfate produces better TCE removal than two half persulfate injections in sequence. The transport distance of persulfate ranges from 3.6 to 4.5 m. Persulfate also persists for 14 days in the aquifer. After persulfate is injected, the total bacterial counts decrease slightly to 2.4 × 10³ CFU mL⁻¹ in P143 and 1.8 × 10³ CFU mL⁻¹ in P146. When persulfate is consumed, the total bacterial counts increase but there is no recovery of the microbial community. The results show that sequential injections of a large amount of persulfate are suggested to maintain good long-term performance for TCE treatment.

This study uses a trichloroethene (TCE)-contaminated site to determine the efficacy of persulfate oxidation for the treatment of TCE-contaminated groundwater.     

Synergetic effects of bimetals in modified beta zeolite for lactic acid synthesis from biomass-derived carbohydrates

An experimental study was carried out to convert carbohydrates using bimetal modified beta zeolite to obtain a maximum yield of lactic acid. The relationship between the properties and the catalytic performance of various bimetal modified beta zeolites was evaluated. The results showed that the maximum yield of lactic acid reached 52% with more than 99% glucose conversion over Pb–Sn-beta (0.3 mmol g⁻¹, Pb/Sn = 4 : 7) at 190 °C for 2 h under ambient air pressure. To evaluate the synergetic mechanism of lead and tin, key intermediates such as fructose, dihydroxyacetone, glyceraldehyde and pyruvaldehyde were used as probe reactants that were catalyzed by Pb-beta, Sn-beta and Pb–Sn-beta. The revealed key role of lead was to promote the isomerization of glucose to fructose and the retro-aldol condensation reaction from fructose to dihydroxyacetone and glyceraldehyde; meanwhile, tin had a superior catalytic performance in the dehydration of dihydroxyacetone, the hydration of pyruvaldehyde and the isomerization of pyruvic aldehyde hydrate.

An experimental study was carried out to convert carbohydrates using bimetal modified beta zeolite to obtain a maximum yield of lactic acid.     

Blood-based immunoassay of tau proteins for early diagnosis of Alzheimer's disease using surface plasmon resonance fiber sensors

We present the immunoassay of tau proteins (total tau and phosphorylated tau) in human sera using surface plasmon resonance (SPR) fiber sensors. This assay aimed at harvesting the advantages of using both SPR fiber sensors and a blood-based assay to demonstrate label-free point-of-care-testing (POCT) patient-friendly assay in a compact format for the early diagnosis of Alzheimer''s disease (AD). For conducting the assay, we used human sera of 40 subjects divided into halves, which were grouped into AD patients and control groups according to a number of neuropsychological tests. We found that on an average, the concentrations of both total tau and phosphorylated tau proteins (all known to be higher in cerebrospinal fluid (CSF) and the brain) turned out to be higher in human sera of AD patients than in controls. The limits of detection of total tau and phosphorylated tau proteins were 2.4 pg mL⁻¹ and 1.6 pg mL⁻¹, respectively. In particular, it was found that the AD group exhibited average concentration of total tau proteins 6-fold higher than the control group, while concentration of phosphorylated tau proteins was 3-fold higher than that of the control. We can attribute this inhomogeneity between both types of tau proteins (in terms of increase of control-to-AD in average concentration) to un-phosphorylated tau proteins being more likely to be produced in blood than phosphorylated tau proteins, which possibly is one of the potential key elements playing an important role in AD progress.

Blood-based early diagnosis of Alzheimer''s disease using a plasmonic fiber sensor that detects immunoreaction of tau proteins.     

Homogeneity and tolerance to heat of monolayer MoS2 on SiO2 and h-BN

We investigated the homogeneity and tolerance to heat of monolayer MoS₂ using photoluminescence (PL) spectroscopy. For MoS₂ on SiO₂, the PL spectra of the basal plane differ from those of the edge, but MoS₂ on hexagonal boron nitride (h-BN) was electron-depleted with a homogeneous PL spectra over the entire area. Annealing at 450 °C rendered MoS₂ on SiO₂ homogeneously electron-depleted over the entire area by creating numerous defects; moreover, annealing at 550 °C and subsequent laser irradiation on the MoS₂ monolayer caused a loss of its inherent crystal structure. On the other hand, monolayer MoS₂ on h-BN was preserved up to 550 °C with its PL spectra not much changed compared with MoS₂ on SiO₂. We performed an experiment to qualitatively compare the binding energies between various layers, and discuss the tolerance of monolayer MoS₂ to heat on the basis of interlayer/interfacial binding energy.

We investigated the homogeneity and tolerance to heat of monolayer MoS₂ using photoluminescence (PL) spectroscopy.     

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.