A wearable soft robot that can alleviate the pain and fear of the wearer.

Social soft robotics may provide a new solution for alleviating human pain and fear. Here, we introduce a hand-held soft robot that can be clenched by the wearer. The robot comprises small airbags that can be inflated to provide the wearer with a feeling of being clenched. We then conducted an in-depth study of 66 adults who participated in a pain research protocol using thermal stimulation to investigate the effect of wearing the robot on pain perception and fear of injections. Pain assessment scale scores for perceived pain decreased significantly [Formula: see text] when participants wore the robot compared with the baseline condition in which the robot was not worn. In addition, the saliva test results showed a downward trend in oxytocin level when the robot provided the wearer with haptic feedback via the inflation of the internal airbags in response to the wearer's clench. Furthermore, the negative psychological state of participants, as measured using the positive and negative affect scale, improved significantly when wearing the robot. We also revealed that the salivary cortisol level, an indicator of stress, decreased significantly across all participants at the end of the experiment. In addition, participants' fear of injections was significantly improved after participation in the experiment. These results suggest that the wearable soft robot may alleviate the human perception of pain and fear in during medical treatments, such as vaccinations.

Visceral disseminated varicella-zoster virus infection in an immunocompetent host.

Varicella-zoster virus (VZV) can cause visceral disseminated VZV infection in immunocompromised patients. We experienced visceral disseminated VZV infection in an immunocompetent host. A 78-year-old woman visited our hospital complaining of abdominal pain that had persisted for 7 days. On day 3 after admission, a skin rash with blisters appeared mainly on her head and trunk that was diagnosed as generalized zoster via rapid skin VZV diagnostic kit. Esophagogastroduodenoscopy showed gastric erosions, and VZV was detected by real-time polymerase chain reaction testing of the gastric mucosal biopsy specimen. Computed tomography imaging also revealed pancreatitis and colitis, and she was diagnosed as having visceral disseminated VZV infection involving multiple organs. She was treated with acyclovir intravenously, after which her skin rash and abdominal pain disappeared. Because visceral disseminated VZV infection can occur in immunocompetent patients, this disease should be considered in patients with unexplained inflammatory lesions of the gastrointestinal tract or pancreas.

Weight Shift Movements of a Social Mediator Robot Make It Being Recognized as Serious and Suppress Anger, Revenge and Avoidance Motivation of the User.

Humans can become aggressive during text messaging. To maintain a healthy interpersonal relationship through text messaging, our negative mental states, such as anger, have to be well-controlled. This paper discusses the use of a handheld social robot deployed as a mediator in text messaging between humans. The robot is equipped with a movable weight inside its body. By controlling the movement of the internal weight during the time when the robot speaks out messages received from a human sender, we hypothesize that the psychological state of a receiver who holds the robot can be affected (for example, he/she will listen to the messages more seriously). In a controlled study (n = 94), in which participants were manipulated to be frustrated by using a context scenario, we studied the effect of three dialogue scripts with/without weight shifts. Results showed that introducing weight shifts together with the robot speech suppressed on average 23% of the user's anger. However, only 3.5% of the anger was suppressed when the weight shifts were not applied. Additionally, in cases where the robot showed empathy to the user in words with weight shifts, the user's revenge urge was successfully reduced by 22%. There was almost no effect confirmed when the weight shifts were not applied. A similar effect was also found in avoidance motivation: 15% of the avoidance motivation was reduced if weight shifts were applied. The reductions in revenge and avoidance motivation are considered important factors for human forgiveness. Therefore, our findings provide experimental evidence that weight shifts can be an effective expression modality for mediator robots, from the perspective of not only suppressing the user's anger but also by inducing forgiveness during messaging.

Daclatasvir and asunaprevir improves health-related quality of life in Japanese patients infected with hepatitis C virus.

AIMS: Interferon-free direct-acting antiviral agent (DAA) regimens for chronic hepatitis C virus (HCV) patients have improved their health-related quality of life (HRQOL). Currently, there are no published data assessing the impact of DAAs regimens without sofosbuvir on HRQOL. The aim of this study was to investigate the improvement of HRQOL in Japanese HCV patients treated with a protease inhibitor and a nonstructural protein 5A inhibitor. METHODS AND RESULTS: A total of 123 Japanese genotype 1b HCV patients receiving daclatasvir (DCV) and asunaprevir (ASV) for 24 weeks were enrolled. HRQOL was assessed using the Japanese version of the Chronic Liver Disease Questionnaire (CLDQ) at baseline; weeks 4, 12, and 24; and post-24 weeks. Changes in CLDQ scores were calculated by subtracting the CLDQ score at each time point from the baseline value. Improvement in the mean change of the Japanese version of the CLDQ score became statistically significant as early as week 4 after the initiation of treatment (+9.3%; P < 0.0001) and was sustained during and after DCV/ASV treatment. The changes of CLDQ at posttreatment week 24 in patients with sustained virological responses (SVR) were significantly higher than those in patients without SVR (0.4% and -4.1%, respectively; P < 0.05). CONCLUSIONS: This study of DCV/ASV treatment for Japanese HCV patients in a clinical setting demonstrated that HRQOL can improve as early as at the initiation of treatment and can continue during and after treatment, regardless of the classes of DAAs regimens and race. Moreover, SVR are needed to continue HRQOL improvement.

Curative Effects for B-Cell Lymphoma Accomplished by Direct-Acting Antiviral Agents of Hepatitis C.

Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus with the capabilities of tumorigenesis. We present an HCV-infected patient affected with B-cell lymphomas after suffering from hepatocellular carcinoma. The patient exhibited curative effects for lymphomas after treatment with sofosbuvir and ledipasvir, which is shown clearly with a positron emission tomography scanner.

Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

Can the Abbott RealTime hepatitis C virus assay be used to predict therapeutic outcomes in hepatitis C virus-infected patients undergoing triple therapy?

BACKGROUND/AIMS: We compared the predictive abilities of the Abbott Real Time hepatitis C virus (HCV) assay (ART) with those of standard serum HCV ribonucleic acid (RNA) detection methods in patients undergoing triple therapy, which involves treatment with a protease inhibitor combined with pegylated interferon and ribavirin. MATERIALS AND METHODS: In this study, 28 patients underwent triple therapy. The hepatitis C virus ribonucleic acid (HCV RNA) level of each patient was measured at weeks 0, 4, 8, and 12 after the initiation of therapy using the Roche COBAS AmpliPrep/COBAS TaqMan HCV assay version 1.0 (CAP/CTM v1.0) and ART. RESULTS: At week 8 after the initiation of therapy, the sustained virological response (SVR) rate among patients who tested negative and positive for HCV RNA using CAP/CTM v1.0, was 80.0% (20/25) and 33.3% (1/3), and using ART, it was 91.3% (21/23) and 0.0% (0/5), respectively. Although at week 8, the predictive capability of CAP/CTM v1.0 was 78.5%, ART was found to be a more accurate predictor of future SVR status with a rate of 92.9%. CONCLUSION: These results indicate that the presence or absence of serum HCV RNA, evaluated using ART at week 8 after the initiation of therapy, may be useful for predicting therapeutic outcomes in patients receiving triple therapy.

Hemoglobin Decrease with Iron Deficiency Induced by Daclatasvir plus Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b.

BACKGROUND: Decreased hemoglobin (Hb) level has been supposed to be a relatively rare side effect of a combination therapy against hepatitis C virus that consists of the NS5A inhibitor daclatasvir (DCV) and the NS3/4A protease inhibitor asunaprevir (ASV). METHODS: The study was conducted in 75 patients with genotype 1b chronic hepatitis C virus infection who had started combination therapy with DCV and ASV at St. Marianna University School of Medicine Hospital between September 2014 and December 2014. RESULTS: Among the patients examined, decreased Hb level by ≥1.5 g/dL from the values at treatment initiation was observed in 11 individuals. This was accompanied by decreased mean corpuscular volume, and iron and ferritin levels. CONCLUSIONS: These findings suggest that the mechanism of the phenomenon is caused by iron deficiency. The underlying mechanism and clinical impacts will need to be further examined.

Thrombomodulin in the management of acute cholangitis-induced disseminated intravascular coagulation.

AIM: To evaluate the need for thrombomodulin (rTM) therapy for disseminated intravascular coagulation (DIC) in patients with acute cholangitis (AC)-induced DIC. METHODS: Sixty-six patients who were diagnosed with AC-induced DIC and who were treated at our hospital were enrolled in this study. The diagnoses of AC and DIC were made based on the 2013 Tokyo Guidelines and the DIC diagnostic criteria as defined by the Japanese Association for Acute Medicine, respectively. Thirty consecutive patients who were treated with rTM between April 2010 and September 2013 (rTM group) were compared to 36 patients who were treated without rTM (before the introduction of rTM therapy at our hospital) between January 2005 and January 2010 (control group). The two groups were compared in terms of patient characteristics at the time of DIC diagnosis (including age, sex, primary disease, severity of cholangitis, DIC score, biliary drainage, and anti-DIC drugs), the DIC resolution rate, DIC score, the systemic inflammatory response syndrome (SIRS) score, hematological values, and outcomes. Using logistic regression analysis based on multivariate analyses, we also examined factors that contributed to persistent DIC. RESULTS: There were no differences between the rTM group and the control group in terms of the patients' backgrounds other than administration. DIC resolution rates on day 9 were higher in the rTM group than in the control group (83.3% vs 52.8%, P < 0.01). The mean DIC scores on day 7 were lower in the rTM group than in the control group (2.1 ± 2.1 vs 3.5 ± 2.3, P = 0.02). The mean SIRS scores on day 3 were significantly lower in the rTM group than in the control group (1.1 ± 1.1 vs 1.8 ± 1.1, P = 0.03). Mortality on day 28 was 13.3% in the rTM group and 27.8% in the control group; these rates were not significantly different (P = 0.26). Multivariate analysis identified only the absence of biliary drainage as significantly associated with persistent DIC (P < 0.01, OR = 12, 95%CI: 2.3-60). Although the difference did not reach statistical significance, primary diseases (malignancies) (P = 0.055, OR = 3.9, 95%CI: 0.97-16) and the non-use of rTM had a tendency to be associated with persistent DIC (P = 0.08, OR = 4.3, 95%CI: 0.84-22). CONCLUSION: The add-on effects of rTM are anticipated in the treatment of AC-induced DIC, although biliary drainage for AC remains crucial.

Evaluation of hepatic tissue blood flow using xenon computed tomography with fibrosis progression in nonalcoholic fatty liver disease: comparison with chronic hepatitis C.

AIMS: The present study evaluated the utility of xenon computed tomography (Xe-CT) as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF) in patients with nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (CH-C). METHODS: Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined. RESULTS: In group 1, portal venous TBF (PVTBF), hepatic arterial (HATBF), and total hepatic TBF (THTBF) were significantly lower in patients with in nonalcoholic steatohepatitis (NASH) than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively). In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively). In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C. CONCLUSIONS: PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.

A novel endoscopic papillectomy after a pancreatic stent placement above the pancreatic duct orifice: inside pancreatic stenting papillectomy.

BACKGROUND: Although pancreatic stenting is recommended for the prevention of postprocedure pancreatitis during endoscopic papillectomy (EP), in some patients it is technically difficult to perform postprocedure insertion of a pancreatic stent after endoscopic resection. GOALS: This study assessed the feasibility of a novel EP for the purpose of reliable post-EP pancreatic stenting. STUDY: We conducted a prospective pilot study involving 10 consecutive patients with tumor of the major duodenal papilla. We developed a novel pancreatic stent, which is attached to a suture, and devised a method by which the stent is first placed at an upstream migration into the major pancreatic duct above the orifice before resection and then placed at an appropriate location after endoscopic resection by pulling the suture attached to the stent [inside pancreatic stenting papillectomy (IPSP)]. RESULTS: The pancreatic stent was successfully placed at an upstream migration into the pancreatic duct above the orifice in 9 of the 10 patients. For the 9 patients with successful pancreatic stent placement, IPSP was performed. Although the suture was cut in 1 patient, pancreatic stents could be placed appropriately across the orifice by pulling the suture in all patients. Although bleeding occurred in 3 patients, there was no pos-procedure pancreatitis. CONCLUSIONS: IPSP is a practicable method allowing reliable post-EP pancreatic stenting and can contribute to pancreatitis prevention. However, larger studies need to be performed before its use can be recommended.

Xenon computed tomography can evaluate the improvement of hepatic hemodynamics before and after endoscopic injection sclerotherapy.

BACKGROUND: Xenon computed tomography (Xe-CT) provides quantitative information on tissue blood flow (TBF). In the present study, Xe-CT was performed in patients with esophagogastric varices (EGV) before and after endoscopic injection sclerotherapy (EIS) to evaluate hepatic blood flow (HBF), hepatic arterial TBF (HATBF) and portal venous TBF (PVTBF). METHODS: Subjects comprised of 88 patients with EGV (49 men, 39 women, average age 65.8 ± 11.5 years, median age 68 years, 30-86 years) and liver cirrhosis related to either hepatitis C virus (C) (n = 33), hepatitis B virus (B) (n = 3), alcohol (AL) (n = 22), AL + C (n = 7), AL + B (n = 1), B + C + AL (n = 1), nonalcoholic steatohepatitis (NASH) (n = 4), autoimmune hepatitis (AIH) (n = 5), primary biliary cirrhosis (PBC) (n = 2), or cryptogenic (n = 10) were enrolled. All patients, who were enrolled in this study, were performed EIS for prophylaxis. Xe-CT and measurement of the retention rate of indocyanine green 15 min after administration (ICG R15) were performed before and after EIS. Total hepatic TBF (THTBF) and PVTBF/HATBF ratio (P/A) were also calculated. RESULTS: PVTBF, HATBF, THTBF, P/A and ICG R15 before EIS were 28.3 ± 8.91, 22.5 ± 14.4 and 50.8 ± 17.6 ml/100 ml/min, 1.62 ± 0.71 and 28.8 ± 12.7 %, respectively and those after EIS were 31.9 ± 10.0, 19.3 ± 11.6, and 51.2 ± 17.0 ml/100 ml/min, 1.92 ± 0.84 and 23.6 ± 11.3 %, respectively. PVTBF and P/A after EIS were significantly higher than those before EIS (p = 0.00444, p = 0.0179, respectively), and HATBF and ICG R15 after EIS were significantly lower than those before EIS (p = 0.00129, p < 0.001, respectively). CONCLUSIONS: Xenon computed tomography showed that PVTBF increased after EIS for EGV and HATBF decreased in response to an increase in PVTBF.

Serum peptides, represented by complement 3f des-arginine, are useful for prediction of the response to pegylated interferon-α plus ribavirin in patients with chronic hepatitis C.

AIM: Biomarkers predicting sustained virological response (SVR) to pegylated interferon-α plus ribavirin (PEG IFN-α/RBV) were investigated. METHODS: Peptides in pretreatment sera from 107 patients with hepatitis C virus (HCV) genotype 1 were comprehensively analyzed by mass spectrometry. Ion intensity of the peptides was used to generate discriminant models between the responders who achieved SVR (R) and the non-responders (NR) to PEG IFN-α/RBV. RESULTS: In total, 107 peptides were detected in a training set (n = 23). A discriminant model using a peptide, complement 3f des-arginine (C3f-dR), showed sensitivity of 35% and specificity of 94% for SVR prediction in a testing set (n = 68). In all the R and NR (n = 96), an area under the receiver-operator curve (AUROC) of 0.64 in the C3f-dR model was increased to 0.78 by addition of platelet (PLT) counts (C3f-dR/PLT model). Another model using the 107 peptides (AUROC, 0.77) also showed higher AUROC (0.79) by addition of hemoglobin (Hb), body mass index (BMI) and age (107P/Hb/BMI/Age model). The sensitivity and specificity of the C3f-dR/PLT model were 59% and 88%, and those of the 107P/Hb/BMI/Age model were 70% and 92%, respectively. The C3f-dR/PLT model showed high AUROC (0.82), similar to that of interleukin-28B rs8099917 genotype analysis (0.86) in the 45 tested patients. Prediction by the combination of the C3f-dR/PLT model, the 107P/Hb/BMI/Age model and the rs8099917 genotype analysis was accurate in 44 out of the 45 patients (AUROC, 0.95). CONCLUSION: Serum peptides, especially C3f-dR, would be useful predictors for SVR to PEG IFN-α/RBV. The complements may be involved in the HCV elimination.

[Gemcitabine therapy for unresectable pancreatic cancer in elderly patients].

We evaluated the therapeutic effect of gemcitabine (GEM) therapy in 153 unresectable pancreatic cancer (UPC) patients, divided into younger patients (under 65), early-stage elderly patients (age 65-74) and advanced-stage elderly patients (age 75 and over). Among those patients who received only best supportive care (BSC), the most common reasons to be selected for BSC were family requests in the advanced-stage elderly patients, and poor general condition in the rest. Among the patients who received GEM therapy, there were no significant differences in response rate, or adverse events including the rate of dose reduction, postponement or cessation of GEM administration due to toxicity. Multivariate analysis using patient backgrounds and response to GEM therapy showed that CA 19-9 response and performance status did not change with age. GEM therapy for both early-stage and advanced-stage elderly UPC patients was as safe and useful as in younger patients.

Lysophosphatidic acid cooperates with EGF in inducing branching morphogenesis of embryonic mouse salivary epithelium.

Epithelial morphogenesis is supported by diffusible growth factors and by nondiffusible cell substrata, such as laminin and fibronectin. When embedded in a laminin-rich basement-membrane substratum, embryonic mouse submandibular epithelium undergoes cell proliferation and branching morphogenesis in response to epidermal growth factor (EGF) in mesenchyme-free culture but not in serum-free medium. In this study, we sought to identify the biologically active factor in serum. As this factor was heat-stable and trypsin-resistant, the lipid fraction was analyzed. Horse serum was fractionated by ethanol extraction, Folch partition with chloroform-methanol-water, and high-performance liquid chromatography, and we tested the branch-inducing activity of each fraction. We also analyzed the partially purified fraction with a mass spectrometer, indicating that the active fraction largely consisted of lysophosphatidyl-hexose. Finally we identified the molecule as lysophosphatidic acid (LPA), because, whereas lysophosphatidyl-inositol had only a slight branch-inducing activity, its relevant LPA fully substituted for serum and induced branching morphogenesis in cooperation with EGF. LPA receptor genes were expressed in submandibular epithelial cells. DNA-synthesizing cells were abundant only when cultured in the presence of both EGF and LPA, but not either singly.