Enzymatic Reactions using Ionic Liquids for Green Sustainable Chemical Process; Stabilization and Activation of Lipases.

The enzymatic reaction is highly respected from an environmentally-friendly point-of-view. Optimization of the reaction media and supporting materials of enzymes must be investigated in parallel with the effort to develop new enzymes. Lipases are frequently used for organic syntheses as synthetic tools even industry because of their acceptance of having a broad range of substrates, stability, and availability. We have investigated the possibility of ILs as both a solvent and activating or stabilization agent of enzymes, in particular, lipase as a model enzyme. ILs allowed recyclable use of a lipase and significant acceleration of transesterification, and also enhanced the stability and reaction activity of a lipase by immobilization through a lyophilization process. We discuss how we enhanced the enzyme capability using the IL engineering focusing on lipase-catalyzed reactions, i. e., realization of the recyclable use of an enzyme, how ILs mediated the enhanced reaction rate, and improved the stability of the enzyme.

Synthesis of Selectively gem-Difluorinated Molecules; Chiral gem-Difluorocyclopropanes via Chemo-Enzymatic Reaction and gem-Difluorinated Compounds via Radical Reaction.

The incorporation of fluorine atoms into an organic compound can alter the chemical reactivity or biological activity of the resulting compound due to the strong electron withdrawing nature of the fluorine atom. We have synthesized many original gem-difluorinated compounds and described the results in four sections. The first section describes the synthesis of optically active-gem-difluorocyclopropanes via the chemo-enzymatic reaction; we applied these compounds to liquid crystalline molecules, then further discovered a potent DNA cleavage activity for the gem-difluorocyclopropane derivatives. The second section describes the synthesis of selectively gem-difluorinated compounds via a radical reaction; we synthesized fluorinated analogues of a sex pheromone of the male African sugarcane borer, Eldana saccharina, and used the compounds as proof for investigating the origin of pheromone molecule recognition on the receptor protein. The third involves the synthesis of 2,2-difluorinated-esters by visible light-driven radical addition of 2,2-difluoroacetate with alkenes or alkynes in the presence of an organic pigment. The last section describes the synthesis of gem-difluorinated compounds via the ring-opening of gem-difluorocyclopropanes. We further developed a novel method of synthesizing gem-difluorohomoallylic alcohols via the ring-opening of gem-difluorocyclopropane and aerobic oxidation by photo-irradiation in the presence of an organic pigment. Since gem-difluorinated compounds that were prepared by the present method have two olefinic moieties with a different reactivity at the terminal position, we accomplished the synthesis of four types of gem-difluorinated cyclic alkenols via the ring-closing-metathesis (RCM) reaction.

Electrochemical synthesis of the protected cyclic (1,3;1,6)-ß-glucan dodecasaccharide.

Automated electrochemical assembly is an electrochemical method to synthesise middle-sized molecules, including linear oligosaccharides, and some linear oligosaccharides can be electrochemically converted into the corresponding cyclic oligosaccharides effectively. In this study, the target cyclic oligosaccharide is a protected cyclic (1,3;1,6)-ß-glucan dodecasaccharide, which consists of two types of glucose trisaccharides with ß-(1,3)- and ß-(1,6)-glycosidic linkages. The formation of the protected cyclic dodecasaccharide was confirmed by the electrochemical one-pot dimerisation-cyclisation of the semi-circular hexasaccharide. The yield of the protected cyclic dodecasaccharide was improved by using a stepwise synthesis via the linear dodecasaccharide.

Synthesis of gem-Difluoromethylene Containing Cycloalkenes via the Ring-Opening Reaction of gem-Difluorocyclopropanes and Subsequent RCM Reaction.

The radical-type ring-opening reaction of gem-difluorocyclopropanes and subsequent regioselective monoepoxidation of the products were demonstrated. Introduction of a vinyl or allyl group to the epoxide produced the diene derivatives that were subjected to the ring closing metathesis reaction to furnish the gem-difluoromethylene containing cyclopentene, cycloheptene, and cyclooctene derivatives in good to excellent yields.

Ionic Liquids as Tool to Improve Enzymatic Organic Synthesis.

Ionic liquids (ILs) have now been acknowledged as reaction media for biotransformations. The first three examples were reported in this field in 2000, and since then, numerous applications have been reported for biocatalytic reactions using ILs. Two topics using ILs for enzymatic reactions have been reviewed from the standpoint of biocatalyst mediating organic synthesis; the first is "Biocatalysis in Ionic Liquids" which includes various types of biocatalytic reactions in ILs (section 2): (1) recent examples of lipase-mediated reactions using ILs as reaction media for biodiesel oil production and for sugar ester production, (2) oxidase-catalyzed reactions in ILs, (3) laccase-catalyzed reactions, (4) peroxidase-catalyzed reactions, (4) cytochrome-mediated reactions, (5) microbe-mediated hydrations, (6) protease-catalyzed reactions, (8) whole cell mediated asymmetric reduction of ketones, (10) acylase-catalyzed reactions, (11) glycosylation or cellulase-mediated hydrolysis of polysaccharides, (12) hydroxynitrile lyase-catalyzed reaction, (13) fluorinase or haloalkane dehydrogenase-catalyzed reaction, (14) luciferase-catalyzed reactions, and (15) biocatalytic promiscuity of enzymatic reactions for organic synthesis using ILs. The second is "Enzymes Activated by Ionic Liquids for Organic Synthesis", particularly describing the finding story of activation of lipases by the coating with a PEG-substituted IL (section 3). The author's opinion toward "Future Perspectives of Using ILs for Enzymatic Reactions" has also been discussed in section 4.

Synthesis of 2,2-difluoro-homoallylic alcohols via ring-opening of gem-difluorocyclopropane and aerobic oxidation by photo-irradiation in the presence of an organic pigment.

We found that aerobic oxidation took place after the visible light-mediated ring-opening reaction of gem-difluorocyclopropane in the presence of an organic dye and amine to furnish 2,2-difluoro-homoallylic alcohols in good yields.

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block.

The total synthesis of TMG-chitotriomycin using an automated electrochemical synthesizer for the assembly of carbohydrate building blocks is demonstrated. We have successfully prepared a precursor of TMG-chitotriomycin, which is a structurally-pure tetrasaccharide with typical protecting groups, through the methodology of automated electrochemical solution-phase synthesis developed by us. The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block.

Recent Progress on Nazarov Cyclizations: The Use of Iron Salts as Catalysts in Ionic Liquid Solvent Systems.

Nazarov cyclization is an important and versatile method for the synthesis of five-membered carbocycles, and extensive studies have been conducted to optimize the reaction. Among recent studies, several trends are recognized. One is the combination of different reactions with Nazarov cyclization in a one-pot reaction system which enables the preparation of unique cyclization products. The second is the use of a transition-metal catalyst, though Lewis or Brønsted acids have generally been used for the reaction. The third is the realization of the asymmetric Nazarov cyclization. The fourth is the base-catalyzed Nazarov cyclization. Furthermore, several useful protocols for realizing Nazarov cyclization have also been developed. The recent progress on Nazarov cyclizations is summarized in Section 2. Section 3 is our chronicle in this field. We focused on the use of iron as the catalyst in Nazarov cyclizations and ionic liquids as solvents: Nazarov cyclization of thiophene derivatives using FeCl3 as the catalyst was accomplished and we succeeded in demonstrating the first example of an iron-catalyzed asymmetric Nazarov reaction. We next established Nazarov cyclization of pyrrole or indole derivatives using Fe(ClO4 )3 ·Al2 O3 as the catalyst with high trans selectivities in excellent yields. Since the cyclized product was reacted with a vinyl ketone in the presence of the same iron salt, the system allowed realization of the sequential type of Nazarov/Michael reaction of pyrrole derivatives. Furthermore, we demonstrated the recyclable use of the iron catalyst and obtained the desired Nazarov/Michael reaction products in good yields for five repetitions of the reactions without any addition of the catalyst using an ionic liquid, [bmim][NTf2 ], as the solvent. We expect that the iron-catalyzed Nazarov cyclization, in particular, in an ionic liquid solvent might become a useful method to synthesize functional molecules that include cycloalkene moieties.

Development of n-Type Semiconductor Based on Cyclopentene- or Cyclohexene-Fused [C60]-Fullerene Derivatives.

Properties of cyclopentene- or cyclohexene-fused [C60]-fullerene derivatives as the acceptor in photovoltaic cells have been investigated by use of poly(3-hexylthiophene) (P3HT) as the model donor polymer. Several cyclopentene- or cyclohexene-fused [C60]-fullerene derivatives show high power conversion efficiency (PCE). The highest PCE was obtained for 3',6'-dihydro-4'-phenoxycarbonyl-6'-methylbenzo[1,9][5,6](C60-Ih)fullerene (3.2%); this is superior to that of [C60]-PCBM with the P3HT polymer under the same experimental conditions. PCE of the OPV devices with alkyl-substituted cyclohexene-fused [C60]-fullerenes depended on the alkyl substituent on the cyclohexene ring; compounds with substituents of odd-number alkyl groups showed better PCE than those compounds possessing even-number alkyl groups.

Visceral Abdominal Obesity Measured by Computed Tomography is Associated With Increased Risk of Colonic Diverticulosis.

GOALS: To investigate whether visceral obesity measured by computed tomography (CT) is a risk factor for colonic diverticulosis. BACKGROUND: The association between colonoscopy-proven diverticulosis and visceral obesity has not been studied. STUDY: A cohort of 1445 participants (1117 nondiverticulosis and 328 diverticulosis) undergoing colonoscopy and CT was prospectively analyzed. Diverticulosis was diagnosed by high-resolution colonoscopy. The associations between body mass index (BMI), visceral adipose tissue (VAT) area, subcutaneous adipose tissue (SAT) area, and diverticulosis were estimated using odds ratios (ORs) adjusted for age, sex, alcohol, smoking, medications, and comorbidities. RESULTS: In multivariate analysis, diverticulosis was significantly associated with VAT area and SAT area for both categorical data and trend (P for trend <0.001), but not BMI.Diverticulosis had a positive association with VAT area and SAT area for both categorical data and trend (P for trend <0.001) in men, but none of these associations were noted in women. In the subanalysis of normal-weight patients (BMI<25), diverticulosis was independently associated with VAT area and SAT area (P for trend <0.001). The adjusted ORs for VAT area ≥100 cm² was significantly increased in right-sided (OR, 1.8), left-sided (OR, 2.3), and bilateral (OR, 3.0) diverticula (P for trend <0.001). CONCLUSIONS: Abdominal obesity measured by CT, not BMI, is associated with colonic diverticulosis, even when body weight was normal. These findings suggest an important role for visceral fat accumulation in diverticulosis development. A high visceral fat was positively associated with the distribution of diverticula.

Visceral abdominal fat measured by computed tomography is associated with an increased risk of colorectal adenoma.

We investigated whether visceral adipose tissue (VAT) measured by computed tomography (CT) is a risk factor for colorectal adenoma. For a total of 1,328 patients (857 without adenoma, 471 with colorectal adenoma) undergoing colonoscopy and CT, associations between colorectal adenoma and body mass index (BMI), VAT area and subcutaneous adipose tissue (SAT) were assessed using odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for age, sex, family history, smoking, alcohol intake, diabetes mellitus, aspirin use and nonsteroidal anti-inflammatory drug use. Multivariate analysis showed that colorectal adenoma was marginally associated (p=0.06) with BMI, but not with SAT, while it was significantly associated with VAT and the VAT to SAT ratio (VAT/SAT) for both categorical data and trend (p<0.05). When the obesity indices were considered simultaneously, colorectal adenoma remained significantly associated with VAT and VAT/SAT (p<0.05), but not BMI and SAT. In patients with colorectal adenoma, the adjusted OR for the highest quartiles of VAT and VAT/SAT was 1.90 (95% CI 1.16-3.13) and 2.25 (95% CI 1.49-3.41), respectively, compared to the lowest quartiles. Only VAT area was significantly associated with colorectal adenoma in both men and women (p<0.05). Proximal, multiple and advanced adenomas had significantly higher VAT areas (p<0.05) than distal, solitary and nonadvanced adenomas. Our findings implicate abdominal VAT in the development and progression of colorectal adenoma, and it was better obesity index for colorectal adenoma than BMI in both sexes.

Increase in colonic diverticulosis and diverticular hemorrhage in an aging society: lessons from a 9-year colonoscopic study of 28,192 patients in Japan.

PURPOSES: Colonoscopic evidence of epidemiological trends in diverticulosis and diverticular bleeding is scarce. We evaluated trends in diverticular disease and associated factors over 9 years. METHODS: Twenty-eight thousand one hundred ninety-two patients who underwent colonoscopy at an emergency hospital were reviewed from an electronic endoscopy database. Diverticula were classified as right-sided, left-sided, and bilateral types, and time trends in the proportion in diverticulosis, type, and diverticular bleeding were determined. Associations of age (≤39, 40-59, and ≥60 years), sex, and year increase with disease and odds ratios were estimated using logistic regression. RESULTS: Diverticulosis was identified in 6,150 patients (20.3 %; mean age, 67.6 years) and was predominantly right-sided (48.0 %). Diverticular bleeding was found in 427 (1.5 %; mean age, 69.7 years) and was predominantly bilateral (47.0 %). Proportion of colonic diverticulosis increased significantly (P < 0.01 for trend) from 66.0 % (1,424/2,157) in 2003 to 70.1 % (2,914/4,159) in 2011 and was associated (P < 0.01) with an increased number of patients aged ≥60 years. Proportion of diverticular bleeding increased significantly (P < 0.01 for trend) from 1.02 % (22/2,157) in 2003 to 1.67 % (69/4,159) in 2011 and was associated (P = 0.04) with an increased number of patients aged 40-59 years. Diverticulosis, right and bilateral type, and diverticular bleeding were independently associated with the 9-year trend after adjustment by age and sex. CONCLUSIONS: Colonic diverticulosis and diverticular bleeding are prevalent and increasing in Japan. Given the significant association of age with this trend, both diseases can be expected to increase for decades to come.

Antimicrobial photodynamic therapy suppresses dental plaque formation in healthy adults: a randomized controlled clinical trial.

BACKGROUND: Oral care is important for oral and systemic health, especially for elderly institutionalized individuals and compromised patients. However, conventional mechanical plaque control is often difficult for these patients because of the pain or the risk of aspiration. Although antimicrobial photodynamic therapy (aPDT), which is considered an alternative or adjunct to mechanical approaches, has potential application as a less stressful method of daily plaque control, no clinical application of this technique has been reported. METHODS: We investigated the inhibitory effect of a combination of toluidine blue O (TBO), and a red light-emitting diode (LED) on dental plaque formation in healthy volunteers. The optimal concentration of TBO was determined in preliminary in vitro experiments to evaluate the bactericidal effect of aPDT on Streptococcus oralis and to clarify its safety in fibroblast cells. To survey the mechanism of TBO-mediated aPDT, the quality and quantity of reactive oxygen species (ROS) generated during aPDT were also examined using electron spin resonance (ESR) spectroscopy. Subsequently, the inhibitory effect of aPDT on dental plaque formation was investigated in eleven subjects as a clinical pilot study. The right or left mandibular premolars were randomly assigned to the treatment (with aPDT) or control (without aPDT) groups. In total, aPDT was applied six times (twice per day) to the teeth in the test group over a period of four days. On the fourth day, the study concluded and the analyses were performed. RESULTS: A combination of 500 or 1000 µg/ml TBO and LED irradiation for 20 s significantly decreased the number of colony forming units of Streptococcus oralis. The cytotoxicity of aPDT was comparable to that of standard antiseptics used in the oral cavity. Hydroxyl radicals were detected by ESR analysis, but singlet oxygen was not. A randomized controlled trial demonstrated that aPDT with 1000 µg/ml TBO and red LED irradiation significantly suppressed dental plaque formation without harming teeth or the surrounding tissues. CONCLUSIONS: aPDT has the potential to be a promising novel technical modality for dental plaque control. TRIAL REGISTRATION: This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (number UMIN000012504).

On the Moisture Absorption Capability of Ionic Liquids.

Due to their many attractive physicochemical properties, ionic liquids (ILs) have received extensive attention with numerous applications proposed in various fields of science and technology. Despite this, the molecular origins of many of their properties, such as the moisture absorption capability, are still not well understood. For insight into this, we systematically synthesized 24 types of ILs by the combination of the dimethyl phosphate anion with various types of alkyl group-substituted cyclic cations─imidazolium, pyrazolium, 1,2,3-triazolium, and 1,2,4-triazolium cations─and performed a detailed analysis of the dehumidification properties of these ILs and their aqueous solutions. It was found that these IL systems have a high dehumidification capability (DC). Among the monocationic ILs, the best performance was obtained with 1-cyclohexylmethyl-4-methyl-1,2,4-triazolium dimethyl phosphate, whose DC (per mol) value is 14 times higher than that of popular solid desiccants like CaCl2 and silica gel. Dicationic ILs, such as 1,1'-(propane-1,3-diyl)bis(4-methyl-1,2,4-triazolium) bis(dimethyl phosphate), showed an even better moisture absorption, with a DC (per mol) value about 20 times higher than that of CaCl2. Small- and wide-angle X-ray scattering measurements of eight types of 1,2,4-triazolium dimethyl phosphate ILs were performed and revealed that the majority of these ILs form nanostructures. Such nanostructures, which vary with the identity of the IL and the water content, fall into three main categories: bicontinuous microemulsions, hexagonal cylinders, and micelle-like structures. Water in the solutions exists primarily in polar regions in the nanostructures; these spaces function as water pockets at relatively low water concentrations. Since the structure and stability of the aggregated forms of the ILs are mainly governed by the interactions of nonpolar groups, the alkyl side chains of the cations play an important role in the DC and temperature-dependent equilibrium water vapor pressure of the IL solutions. Our experimental findings and molecular dynamics simulation results shed light on the moisture absorption mechanism of the IL aqueous solutions from a molecular perspective.

Characterization of Information-Transmitting Materials Produced in Ionic Liquid-based Neuromorphic Electrochemical Devices for Physical Reservoir Computing.

Device implementation of reservoir computing, which is expected to enable high-performance data processing in simple neural networks at a low computational cost, is an important technology to accelerate the use of artificial intelligence in the real-world edge computing domain. Here, we propose an ionic liquid-based physical reservoir device (IL-PRD), in which copper cations dissolved in an IL induce diverse electrochemical current responses. The origin of the electrochemical current from the IL-PRD was investigated spectroscopically in detail. After operating the device under various operating conditions, X-ray photoelectron spectroscopy of the IL-PRD revealed that electrochemical reactions involving Cu, Cu2O, Cu(OH)2, CuSx, and H2O occur at the Pt electrode/IL interface. These products are considered information transmission materials in IL-PRD similar to neurotransmitters in biological neurons. By introducing the Faradaic current components due to the electrochemical reactions of these materials into the output signal of IL-PRD, we succeeded in improving the time-series data processing performance of the nonlinear autoregressive moving average task. In addition, the information processing efficiency in machine learning to classify electrocardiogram signal waveforms was successfully improved by using the output current from IL-PRD. Optimizing the electrochemical reaction products of IL-PRD is expected to advance data processing technology in society.

Location in the ascending colon is a predictor of refractory colonic diverticular hemorrhage after endoscopic clipping.

BACKGROUND: Predictors of refractory colonic diverticular hemorrhage after endoscopic clipping (EC) remain unclear. OBJECTIVE: To elucidate the predictors of uncontrolled bleeding after EC. DESIGN: Retrospective study. SETTING: Two tertiary referral centers. PATIENTS: Eighty-nine patients with colonic diverticular hemorrhage who underwent EC as a first-line treatment were included. INTERVENTIONS: If bleeding remained uncontrolled after 1 or 2 EC sessions, other interventions (transcatheter arterial embolization, endoscopic band ligation, or surgery) were performed. Patients were divided into EC-controlled and EC-uncontrolled groups; the characteristics of each group were compared. MAIN OUTCOME MEASUREMENTS: Comorbidities, location of bleeding diverticula, and EC technique (direct vs indirect placement). RESULTS: Initial treatment with EC was successful in 87 patients. Early rebleeding (primary failure) occurred in 30 of 87 patients (34%). Secondary failure occurred in 6 of 22 patients treated with reclipping (27%). Cumulatively, 78 patients were successfully managed with EC. Non-EC treatments were required in 11 patients. Location in the right side of the colon, particularly in the ascending colon, was significantly more common in the EC-uncontrolled group than in the EC-controlled group (P = .017 and P = .0029, respectively). Although the difference was not significant, bleeding was successfully managed in all 13 patients treated with direct placement. Bleeding remained uncontrolled after EC in 11 of 52 ascending cases (21%) treated with indirect placement. Diverticular hemorrhage in other locations was managed regardless of EC technique. LIMITATIONS: Retrospective study. CONCLUSIONS: Location in the ascending colon is a significant predictor of refractory colonic diverticular hemorrhage after EC. Indirect placement of hemoclips in ascending lesions is ineffective.

A multicenter survey of the management after gastric endoscopic submucosal dissection related to postoperative bleeding.

BACKGROUND AND AIMS: Bleeding is a major complication after gastric endoscopic submucosal dissection (ESD). An evidence-based strategy for postoperative care related to delayed bleeding is required. We conducted a multicenter survey to assess the current status of management after gastric ESD. METHODS: A total of 1,814 gastric epithelial neoplasms in 2009 at ten tertiary referral centers were enrolled. The current status of the management after gastric ESD (use of an antisecretory drug, food intake, and second-look endoscopy) at participating hospitals was assessed. Furthermore, the rate of post-ESD bleeding and the differences in each parameter were retrospectively analyzed. RESULTS: Postoperative bleeding occurred in 100 cases (5.5%), which included 62 cases of bleeding within 24 h after ESD. In all of the hospitals, proton pump inhibitors (PPIs) were used. The median administration period was 56 days (range 14-60 days). Food intake was resumed from postoperative day (POD) 1 in 4 hospitals and from POD 2 in 6 hospitals. Second-look endoscopy was performed for almost all cases, fewer cases, and rarely or none in 6, 2, and 2 hospitals, respectively. The day of second-look endoscopy varied among hospitals. There was no statistical relationship between the postoperative bleeding rate and the differences in these three parameters. CONCLUSIONS: Post-ESD management (duration of PPI use, resumption of food intake, and performance of second-look endoscopy) varied among the medical centers; thus, randomized controlled trials are required for an optimal strategy after gastric ESD.

Effects of carbon dioxide insufflation in esophageal endoscopic submucosal dissection.

BACKGROUND/AIMS: Although carbon dioxide (CO2) insufflation has successfully replaced air insufflation in a variety of procedures, the effects of CO2-insufflation in esophageal endoscopic submucosal dissection (ESD) have not been adequately investigated. This study was designed to evaluate the effects of CO2 insufflation in esophageal ESD. METHODOLOGY: From January 2009 to January 2011, 57 superficial esophageal neoplasias in 54 patients (51 men and 3 women) were treated under conscious sedation with midazolam and pethidine hydrochloride, using ESD technique with a combination of small-caliber-tip transparent hood and flex knife. They were divided into air-insufflation (39 lesions, 37 patients) and CO2-insufflation (18 lesions, 17 patients) groups and therapeutic efficacy and complications were retrospectively evaluated in each group. RESULTS: The rate of en bloc resection was 100% and there were no complications in each group. No significant differences were seen in procedural time, the amount of pethidine hydrochloride required, body temperature and white blood cell count on post-procedure day 1, and length of hospital stay after ESD. A difference in the amount of midazolam required between the air-insufflation group and the CO2-insufflation group was noted (6mg vs. 4mg, p=0.0017). CONCLUSIONS: CO2-insufflation could be considered useful for reducing patients' discomfort in esophageal ESD.

Diagnostic utility of lung echography for congestive heart failure performed by junior resident doctors.

Background: Dyspnea is a high priority symptom in the emergency department, with heart failure (HF) as one of its leading causes. Recently, the "comet tail sign (CTS)," a pulmonary ultrasonographic sign, has been proposed as an efficacious tool for detecting pulmonary edema. However, to the best of our knowledge, there have been no published data regarding its utility when performed by non-experts, including junior residents. Methods: Between September 2017 and December 2018, patients with dyspnea, who were admitted to the ER, were enrolled. CTS was evaluated by junior residents at the ER. All patients were evaluated by cardiologists independently, and clinical HF was defined as requiring pharmacological intervention by a cardiologist. At the end of this study, we investigated the results of CTS, laboratory data, and available radiological images. Results: A total of 95 patients were enrolled in the current study, wherein 42 patients were treated by cardiologists as those with clinical HF. Our results showed that CTS could identify clinical HF with a sensitivity of 71.4% and a specificity of 81.1%. The sensitivity of CTS against brain natriuretic peptide (BNP) (cut-off value, 100 pg/ml) was calculated at 92.5%. Furthermore, when evaluated together with peripheral edema, CTS identified clinical HF with a sensitivity of 96%. False positives for CTS included bilateral pneumonia, hypoalbuminemia, and interstitial pneumonitis. Conclusions: Our results indicate that CTS is a simple and effective tool for the use of non-experts, including junior residents.