Purpose: In contrast to the core part of the clinical interviewing and physical examination (PE) skills course, corresponding to the basic, head-to-toe, and thoracic systems, learners need structured feedback in the cluster part of the course, which includes the abdominal, neuromuscular, and musculoskeletal systems. This study evaluated the effects of using Dreyfus scale-based feedback, which has elements of continuous professional development, instead of Likert scale-based feedback in the cluster part of training in Taiwan. Methods: Instructors and final-year medical students in the 2015–2016 classes of National Yang-Ming University, Taiwan comprised the regular cohort, whereas those in the 2017–2018 classes formed the intervention cohort. In the intervention cohort, Dreyfus scale-based feedback, rather than Likert scale-based feedback, was used in the cluster part of the course. Results: In the cluster part of the course in the regular cohort, pre-trained standardized patients rated the class climate as poor, and students expressed low satisfaction with the instructors and course and low self-assessed readiness. In comparison with the regular cohort, improved end-of-course group objective structured clinical examination scores after the cluster part were noted in the intervention cohort. In other words, the implementation of Dreyfus scale-based feedback in the intervention cohort for the cluster part improved the deficit in this section of the course. Conclusion The implementation of Dreyfus scale-based feedback helped instructors to create a good class climate in the cluster part of the clinical interviewing and PE skills course. Simultaneously, this new intervention achieved the goal of promoting medical students’ readiness for interviewing, PE, and self-directed learning.

Purpose: Transarterial chemoembolization (TACE) delivers cytotoxic drugs intra-arterially and induces ischemic necrosis by arterial embolization. Embolization is achieved using a variety of agents that differ widely in particle size and range, deformation, and in vivo arterial distribution. The clinical significance of these differences has not been thoroughly characterized. The present study is to compare the efficacy of Embosphere and Embozene microspheres in TACE therapy for hepatocellular carcinoma. Materials and Methods: This retrospective study includes 108 hepatocellular carcinoma (HCC) patients who received TACE/doxorubicin with Embozene (70 patients) or Embosphere (38 patients) at a single medical center. Patient outcomes, including liver function, tumor size, tumor response, and complications after treatment, were analyzed. The change in total target lesion size and tumor response was evaluated according to embolization agent and clinical characteristics. Results: The postoperative glutamate oxaloacetate transaminase (mean, 194.5 vs. 147.5; p=0.032) and bilirubin (mean, 1.11 mg/dL vs. 0.73 mg/dL; p=0.016) were higher among patients treated with Embozene, the decrease in the number (55.86±25.55% vs. 41.81±38.51%, p=0.027) and size (56.37±25.91 mm vs. 43.44±37.89 mm, p=0.001) of liver tumors relative to baseline was greater in these patients than in those treated with Embosphere. These greater antitumor effects were achieved using lower doses of doxorubicin than for treatment with Embozene. Minor complications were more common among patients treated with Embosphere than with Embozene. Conclusion These results suggest that Embozene is more efficacious than Embosphere for HCC treatment using TACE/doxorubicin.

INTRODUCTIONPrevious studies examining brain effects of duration of illness in schizophrenia have focused on either cortical or subcortical structures. Hence this study sought to elucidate the regional grey matter changes (both cortical and subcortical) and neurocognitive correlates with increased duration of illness in a large sample of patients with schizophrenia using voxel-based morphometry.

MATERIALS AND METHODSNinety patients (72 males and 18 females) with DSM-IV diagnosis of schizophrenia were recruited and assessed using magnetic resonance imaging and a battery of neuropsychological tests.

RESULTSA longer duration of illness was associated with smaller grey matter volumes in the left superior frontal gyrus, bilateral putamen, right superior temporal gyrus, right superior occipital gyrus as well as the right thalamus. No region showed increased grey matter volume above threshold with longer duration of illness. Longer duration of illness was correlated with poorer attention.

CONCLUSIONSThe grey matter reductions in different brain regions highlighted that a distributed network of cortical and subcortical regions was associated with duration of illness. This is consistent with neural models that implicate involvement of thalamo-cortical circuitry as the disruption in these neural pathways can result in specific deficits such as poorer attention. The results have implications for the understanding of brain changes in schizophrenia, and with further studies, may guide better tailored and targeted clinical management in terms of reducing the impact of duration of illness on neural substrates in schizophrenia in the future.

Adult ; Age of Onset ; Brain ; pathology ; Cognition ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Schizophrenia ; diagnosis ; physiopathology ; Schizophrenic Psychology ; Young Adult

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1

Varus deformation in knee joint is one of the common symptoms caused by unicompartment knee osteoarthritis. Currently, several operations can be used for correcting such deformation, including high tibial osteotomy, unicondylar knee arthroplasty (UKA) and fibulectomy. UKA has been developed for over 60 years, with the advantage of normal knee kinematics restored, less incision, more bony tissue preserved and larger range of motion than total knee arthroplasty (TKA). Therefore, UKA has become a reliable method for treating unicompartment knee osteoarthritis. Fibulectomy is a new kind of surgical technique for treating varus deformation in knee joint, with the advantage of simple operation, low cost and fast recovery. At present, fibulectomy has been widely applied, but its treatment mechanism is still not clear. In this review, two clinical operations UKA and fibulectomy were summarized, and the possible mechanism of fibulectomy for treating unicompartment knee osteoarthritis was proposed from the viewpoint of biomechanics. The author hypothesized that reduction in lateral muscle force after fibulectomy would cause rebalance of the resultant joint moment, therefore, the change of joint contact position and the decrease in joint contact force might be the cause of fibulectomy to release the pain for knee osteoarthritis patients.

Background/Aims: Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without. Methods: One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation. Results: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, P<0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, P<0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, P=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (P<0.001). Conclusions The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination.

BACKGROUND AND PURPOSE: It is essential to develop a reliable predictive serum biomarker for Parkinson's disease (PD). The accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. The purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. METHODS: Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. RESULTS: The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutoff age than in the group above the cutoff age. CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.
alpha-Synuclein ; Humans ; Multiple System Atrophy ; Parkinson Disease ; ROC Curve ; Supranuclear Palsy, Progressive

BACKGROUND: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. METHODS: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. RESULTS: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-b1-stimulation in Smad2 phosphorylation and RhoA upregulation. CONCLUSION These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

BACKGROUND: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. METHODS: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. RESULTS: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-b1-stimulation in Smad2 phosphorylation and RhoA upregulation. CONCLUSION These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.