Development and appropriateness of a scoring method for International Classification of Functioning, Disabilities, and Health assessment in older patients with heart failure: a Delphi survey of expert panel in Japan.

OBJECTIVE: The number of older patients with heart failure (HF) is increasing in Japan and has become a social problem. There is an urgent need to develop a comprehensive assessment methodology based on the common language of healthcare; the International Classification of Functioning, Disability and Health (ICF). The purpose of this study was to develop and confirm the appropriateness of a scoring methodology for 43 ICF categories in older people with HF. DESIGN: Cross-sectional survey. We applied the RAND/University of California at Los Angeles (UCLA) Appropriateness Method with a modified Delphi method. SETTING AND PARTICIPANTS: We included a panel of 26 multidisciplinary experts on HF care consisting of home physicians, cardiovascular physicians, care managers, nurses, physical therapists, a pharmacist, occupational therapist, nutritionist and a social worker. MEASURES: We conducted a literature review of ICF linking rules and developed a questionnaire on scoring methods linked to ICF categories in older people with HF. In the Delphi rounds, we sent the expert panel a questionnaire consisting of three questions for each of the 43 ICF categories. The expert panel responded to the questionnaire items on a 1 (very inappropriate) - 9 (very appropriate) Likert scale and repeated rounds until a consensus of 'Appropriate' and 'Agreement' was reached on all items. RESULTS: A total of 21 panel members responded to all the Delphi rounds. In the first Delphi round, six question items in four ICF categories did not reach a consensus of 'Agreement', but the result of our modifications based on panel members' suggestions reached to a consensus of 'Appropriate' and 'Agreement' on all questions in the second Delphi round. CONCLUSION: The ICF-based scoring method for older people with HF developed in this study was found to be appropriate. Future work is needed to clarify whether comprehensive assessment and information sharing based on ICF contributes to preventing readmissions.

Improvement of low temperature carbon combustion catalyst characteristic caused by mixing Bi2O3 with Tl2O3.

This study investigated the addition of various oxides to further improve the catalytic characteristics of Tl2O3, which offers a high carbon combustion catalytic capacity to lower the carbon combustion temperature of 660 °C by ~ 300 °C. Mixtures of carbon (2 wt%) with composite catalysts comprising 20 wt% Tl2O3-80wt% added oxide were analyzed using DSC. Bi2O3 offered the best improvement, where the exothermic peak temperatures for carbon combustion of carbon with various Tl2O3-x wt% Bi2O3 composites were lower than that of carbon with pure Tl2O3. Isothermal TG measurements were performed using a mixture of carbon and the Tl2O3‒95 wt% Bi2O3 composite catalyst, where a 2 wt% weight loss (i.e. removal of all carbon) was achieved above 230 °C. A porous alumina filter was coated with the composite catalyst and carbon was deposited on the filter surface. The filter was held at constant temperatures under air flow, which confirmed that carbon was completely removed at 230 °C. This study demonstrated the potential for using these composite catalysts in self-cleaning particulate filters to decompose and eliminate fine particulate matter and diesel particulate matter generated from steelworks, thermal power plants, and diesel vehicles simply using the heat of the exhaust gas in a factory flue-gas stack or vehicle muffler.

Effect of acidic conditions on decomposition of methylene blue in aqueous solution by air microbubbles.

Methylene blue (MB) has recently been proposed as a new chemical probe to colorimetrically verify the presence of hydroxyl radicals and was applied to the microbubble technique in this report. The degradation of MB in water was observed by air microbubbles under acidic condition or adding H2O2. The discoloration of MB induced by air microbubbles supports that hydroxyl radicals are generated by the collapse of microbubbles in water. The decomposition rate of MB increases with increasing the concentration of acids (HCl, HNO3, H2SO4) and H2O2 up to ab. 2 mM, and becomes almost constant above ab. 2 mM. Note that the decomposition rate of MB mainly depends on pH, not the kind of acid and that adding salt slightly enhanced the decomposition of MB. The fact that the blue-shift of the absorbance band of MB was observed for not H2O2 but acids proposed that the methyl groups of MB are preferentially dissociated under acidic conditions due to the protonation of dimethylamino group.

Current Medical and Social Issues for Hospitalized Heart Failure Patients in Japan and Factors for Improving Their Outcomes　- Insights From the REAL-HF Registry.

Background: We investigated the current medical and social conditions and outcomes of heart failure (HF) patients in Hiroshima Prefecture, a local district in Japan. Methods and Results: From March 2017 to February 2018 we enrolled all adult patients with hospitalized HF in 8 regional core hospitals that provided an interprofessional team approach for HF patients. We collected patients' clinical characteristics and information regarding living circumstances, cognitive function, quality of life, and interprofessional team approach. For patients discharged home, we followed up the primary endpoint (all-cause death and all-cause unscheduled readmission), conditions of outpatient cardiac rehabilitation, and home nursing-care services over a 1-year period after discharge. Of the registered patients (n=1,218), 39.2% were super-elderly (≥85 years old); more than half of these patients had preserved ejection fraction (≥50%). In the follow-up cohort (n=632), 140 patients (22.2%) were readmitted with HF exacerbation as the primary endpoint, and almost half (n=295, 46.7%) experienced any primary endpoint. The multivariate analysis adjusted for medical and social factors showed that completion of outpatient cardiac rehabilitation (5-month program) remained a strong negative predictor of the primary endpoint (hazard ratio: 0.15; 95% confidence interval: 0.05-0.48; P=0.0013). Conclusions: Our cohort study highlighted the super-aging of current HF patients in Japan. Cardiac rehabilitation through continuous team approach appears to be associated with favorable overall outcomes in this population.

Impregnation of poly(L-lactide-ran-δ-valerolactone) with essential bark oil using supercritical carbon dioxide.

This work studied the incorporation of essential bark oil from Thujopsis dolabrata var. hondae, which is known to repel various insects, in poly(L-lactide-ran-δ-valerolactone) [poly(L-LA-ran-VL)] using supercritical carbon dioxide (scCO2). The poly(L-LA-ran-VL) was synthesized by first purifying the monomers by azeotropic distillation with benzene, followed by polymerization with Sn(oct)2 using the same equipment, representing an efficient one-pot process. The copolymerization of L-LA with VL using this technique at a feed ratio of 90/10 mol/mol gave poly(L-LA-ran-VL) (91/9) with a molecular weight of 6.48 × 104 g/mol and a high yield of 74.9%. Products with molecular weights over 5.0 × 104 g/mol were obtained at L-LA feed proportions of 70 to 90%. Impregnation trials were conducted between 40 and 120 °C at 14 MPa for 3 h. The oil content of a 73/27 specimen was found to increase significantly during processing at 100 or 120 °C. During enzymatic degradation with proteinase K, the 91/9 specimen showed the fastest degradation rate. Although the 71/29 sample was slowly hydrolyzed in a phosphate buffer at pH 7.0, the release of oil vapor from this material was slightly higher than that from the 91/9 specimen, and the vapor release rate continuously increased throughout the hydrolysis process.

A Colonic Perineurioma.

Perineurioma is a mesenchymal neoplasm best known in soft-tissue pathology. A colonic perineurioma is a relatively recently described entity and sometimes encountered in specimens from the large intestine, especially distal colon. Without its recognition, a perineurioma can be misdiagnosed as other more common gastrointestinal spindle cell neoplasms. Here, we describe a case of colonic perineurioma with polypoid growth extruding into the intestinal lumen. Case. A woman in her seventh decade of life underwent a follow-up colonoscopy after an uneventful resection of a benign colonic polyp. A previously undetected 6-mm polyp was found in the sigmoid colon and was resected endoscopically. Microscopic examination of the lesion revealed a proliferation of bland spindle cells in the lamina propria mucosae, which were immunohistochemically positive for epithelial membrane antigen, claudin 1, and glucose transporter-1. A colonic perineurioma was diagnosed.

Hospitalization and medical cost of patients with elevated serum N-terminal pro-brain natriuretic peptide levels.

BACKGROUND: Patients with heart failure (HF) are reportedly at high risk for 'all-cause' re-hospitalization. A biomarker for HF, N-terminal pro-brain natriuretic peptide (NT-proBNP), enables to simply detect patients with possible HF (pHF). We examined the hospitalization and medical cost of Japanese patients detected by an elevated serum NT-proBNP, and also evaluated the effects of institutional team approaches for HF on their all-cause hospitalizations. METHODS: We retrospectively extracted all adult patients with serum NT-proBNP ≥400 pg/ml measured between January and March 2012 in Hiroshima University Hospital as pHF-positive patients. We studied their all-cause hospitalization records during the past 3-year period. We also extracted all pHF-negative patients with NT-proBNP <400 pg/ml and studied as well. In the pHF-positive patients followed for 3 years after starting interprofessional team approaches to prevent the onset and exacerbation of HF in the hospital, we compared the hospitalization and medical cost between the 3-year periods before and after the start of the team approaches. RESULTS: We enrolled 432 pHF-positive and 485 pHF-negative patients with one or more hospitalization records. Compared to the pHF-negative patients, the pHF-positive patients had longer total hospitalization days (median [interquartile range], 30 [13-58] versus. 18 [8-39], p <0.0001) and higher total medical cost for hospitalizations (2.42 [1.07-5.08] versus. 1.80 [0.79-3.65] million yen, p <0.0001). A subset of 303 pHF-positive patients was followed for 3 years after starting the team approaches, and we found that both total hospitalization days (30 [13-57] to 8 [0-31]) and medical cost for hospitalizations (2.59 [1.37-5.05] to 0.76 [0-2.38] million yen) showed marked reduction in them. CONCLUSIONS: Patients with an elevated serum NT-proBNP have longer hospitalizations and higher costs for all-cause hospitalizations than those without. Institutional team approaches for HF may reduce them.

A CLCN1 mutation in dominant myotonia congenita impairs the increment of chloride conductance during repetitive depolarization.

Myotonia congenita is caused by mutation of the CLCN1 gene, which encodes the human skeletal muscle chloride channel (ClC-1). The ClC-1 protein is a dimer comprised of two identical subunits each incorporating its own separate pore. However, the precise pathophysiological mechanism underlying the abnormal ClC-1 channel gating in some mutants is not fully understood. We characterized a ClC-1 mutation, Pro-480-Thr (P480T) identified in dominant myotonia congenita, by using whole-cell recording. P480T ClC-1 revealed significantly slowed activation kinetics and a slight depolarizing shift in the voltage-dependence of the channel gating. Wild-type/mutant heterodimers exhibited similar kinetic properties and voltage-dependency to mutant homodimers. Simulating myotonic discharge with the voltage clamp protocol of a 50 Hz train pulse, the increment of chloride conductance was impaired in both wild-type/mutant heterodimers and mutant homodimers, clearly indicating a dominant-negative effect. Our data showed that slow activation gating of P480T ClC-1 impaired the increment of chloride conductance during repetitive depolarization, thereby accentuating the chloride conductance reduction caused by a slight depolarizing shift in the voltage-dependence of the channel gating. This pathophysiology may explain the clinical features of myotonia congenita.

The conformational alteration of the mutated extracellular domain of Fas in an adult T cell leukemia cell line.

Fas (APO-1/CD95) is a cell surface receptor involved in apoptosis. Almost all adult T cell leukemia (ATL) cells express abundant Fas antigen and show apoptosis induced by IgM anti-Fas monoclonal antibody (mAb). We established the ATL cell line, RSO4, which was obtained from Fas-sensitive ATL cell line SO4 and showed resistance to apoptosis induced by the mAb. By sequencing analysis of Fas gene, we found the mutation with the transition of A-G at nucleotide 373 at exon 2 among the extracellular domain (ECD), resulting in substitution of arginine for histidine. The molecular modeling suggested the definitive conformational alteration around residues 52-58 among the cysteine-rich domain (CRD) 1. It was suggested that the polymerization of Fas antigen, which was the essential process for the efficient induction of apoptosis, was interfered by the alteration of CRD1, and that this portion, named the "histidine-rich region," played a critical role in Fas assembly.

Resveratrol induces downregulation in survivin expression and apoptosis in HTLV-1-infected cell lines: a prospective agent for adult T cell leukemia chemotherapy.

Resveratrol, a phytoalexin found in grapes and wine, has been shown to exhibit a wide range of pharmacological properties and is believed to play a role in the chemoprevention of human cancer. Resveratrol has also been shown to induce antiproliferation and apoptosis of several leukemia cell lines. In the present study, we investigated the effect of resveratrol in adult T cell leukemia. Our present observations showed that resveratrol induced growth inhibition in all five human T cell lymphotrophic virus-1-infected cell lines examined, with 50% effective dose of 10.4-85.6 mM. In the resveratrol-treated cells, induction of apoptosis was confirmed by annexin V-based analyses and morphological changes. The most surprising observation was that resveratrol treatment resulted in a gradual decrease in the expression of survivin, an antiapoptotic protein, during cell apoptosis. These findings indicate that resveratrol inhibits the growth of human T cell lymphotrophic virus-1-infected cell lines, at least in part, by inducing apoptosis mediated by downregulation in survivin expression. In view of the accumulating evidence that survivin may be an important determinant of a clinical response in adult T cell leukemia, our present findings have led to the suggestion that resveratrol, a common constituent of the human diet, merits further investigation as a potential therapeutic agent for this incurable disease.

Matrix metalloproteinase-9 and vascular endothelial growth factor: a possible link in adult T-cell leukaemia cell invasion.

Plasma from a total of 57 patients with adult T-cell leukaemia (ATL) (acute ATL, 39 patients; lymphoma ATL, one patient; chronic ATL, 15 patients; smouldering ATL, two patients) and 20 healthy controls was analysed for the presence of type IV gelatinase activity with clinical features. A significant elevation of plasma matrix metalloproteinase-9 (MMP-9) was observed in some ATL patients, particularly in the patients with malignant cell infiltration. MMP-9 was found to be secreted into the conditioned medium from all ATL cell lines examined. Moreover, the corresponding mRNA was detectable both in all ATL cell lines examined and in the majority of primary acute ATL cells, indicating that ATL cells are capable of synthesizing and secreting MMP-9. We previously demonstrated that a high incidence of ATL cell infiltration was closely related to a high plasma level of vascular endothelial growth factor (VEGF) produced by ATL cells themselves. This present study showed that the presence of increased plasma MMP-9 was closely associated with elevated plasma VEGF in ATL patients. Furthermore, we showed that both increased plasma MMP-9 and VEGF were significantly related to high ATL cell infiltration. All these findings strongly suggest that MMP-9 and VEGF act co-operatively in the process of ATL cell invasion.