Supplementary Material for: Low Frontal Assessment Battery Score as a Risk Factor for Falling in Patients with Hoehn-Yahr Stage III Parkinson's Disease: A 2-Year Prospective Study

<b><i>Background:</i></b> Recently, we evaluated factors responsible for falling, including walking speed evaluated with the use of originally designed, suddenly narrowed paths, in patients with Hoehn-Yahr stage III PD. We prospectively studied the same cohort of patients with PD who were followed up for 2 years, to determine predictors of future falls. <b><i>Methods:</i></b> We performed clinical assessments and evaluated balance in 26 patients. A total of 19 variables including PD-related independent variables, balance investigation-related independent variables and gait independent-related variables were evaluated. <b><i>Results:</i></b> The Frontal Assessment Battery (FAB) score (p = 0.002), Tinetti balance (p = 0.009), and gait velocity (p = 0.001) were higher in fallers than in non-fallers. On multiple logistic regression analysis, the FAB score was related to falling (odds ratio = 3.328, p = 0.033, 95% confidence interval = 1.104-10.03). On the FAB, the scores of ‘inhibitory control' and ‘sensitivity to interference' were significantly lower in fallers than in non-fallers. <b><i>Conclusions:</i></b> The use of the originally designed, suddenly narrowed path was the primary reason for demonstrating for the first time that a low FAB score is a risk factor for future falls. Calculation of the FAB score may be useful for predicting the risk of future falls

Supplementary Material for: Paradoxical Gait at a Narrowed Entrance in a Patient with Hoehn-Yahr Stage III Parkinson’s Disease

Recently, we studied fallers and non-fallers with Hoehn-Yahr stage III Parkinson’s disease (PD) using a path that suddenly narrowed, which we originally designed and produced. A risk of future falls was suggested to be related to slow gait with freezing (SGF) elicited by a fear of falling before arrival at a narrowed entrance or while walking on a narrow path, as well as to the Unified Parkinson’s Disease Rating Scale part II score, associated with SGF. In the same study, we had faller patients walk on a path that narrowed in a straight-line fashion to determine whether SGF could be improved. In one patient, who showed a unique paradoxical gait, SGF resolved. We describe this patient in the hope that our experience will provide potential clues to effective ways to prevent future falls in patients with Hoehn-Yahr stage III PD. To prevent gait instability elicited by fear of falling in patients with Hoehn-Yahr stage III PD, it might be useful to remove narrowed entrances

Supplementary Material for: Dietary fat composition affects hepatic angiogenesis and lymphangiogenesis in HCV core gene transgenic mice

Introduction: Previous research has demonstrated that an isocaloric diet rich in trans fatty acid (TFA), saturated fatty acid (SFA), and cholesterol (Chol) promoted steatosis-derived hepatic tumorigenesis in hepatitis C virus core gene transgenic (HCVcpTg) mice in different manners. Growth factor signaling and ensuing angiogenesis/lymphangiogenesis are key factors in hepatic tumorigenesis that have become recent therapeutic targets for hepatocellular carcinoma. However, the influence of dietary fat composition on these factors remains unclear. This study investigated whether the type of dietary fat would have a specific impact on hepatic angiogenesis/lymphangiogenesis in HCVcpTg mice. Methods: Male HCVcpTg mice were treated with a control diet, an isocaloric diet containing 1.5% cholesterol (Chol diet), or a diet replacing soybean oil with hydrogenated coconut oil (SFA diet) for a period of 15 months, or with shortening (TFA diet) for 5 months. The degree of angiogenesis/lymphangiogenesis and the expression of growth factors, including fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF), were evaluated in non-tumorous liver tissues using quantitative mRNA measurement, immunoblot analysis, and immunohistochemistry. Results: Long-term feeding of SFA and TFA diets to HCVcpTg mice increased the expressions of vascular endothelial cell indicators, such as CD31 and TEK tyrosine kinase, in addition to lymphatic vessel endothelial hyaluronan receptor 1, indicating that angiogenesis/lymphangiogenesis were up-regulated only by these fatty acid-enriched diets. This promoting effect correlated with elevated VEGF-C and FGF receptor 2 and 3 levels in the liver. c-Jun N-terminal kinase (JNK) and hypoxia-inducible factor (HIF) 1α, both key regulators of VEGF-C expression, were enhanced in the SFA- and TFA-rich diet groups as well. The Chol diet significantly increased the expressions of such growth factors as FGF2 and PDGF subunit B (PDGF-B), without any detectable impact on angiogenesis/lymphangiogenesis. Conclusion: This study revealed that diets rich in SFA and TFA, but not Chol, might stimulate hepatic angiogenesis/lymphangiogenesis mainly through the JNK-HIF1α-VEGF-C axis. Our observations indicate an importance of dietary fat species for preventing hepatic tumorigenesis

Supplementary Material for: Optimal Intravascular Ultrasound Criteria for Defining the Functional Significance of Intermediate Coronary Stenosis: An International Multicenter Study

<b><i>Objective:</i></b> We aimed to assess the ideal cut-off value of minimal lumen area (MLA) by intravascular ultrasound (IVUS) and its diagnostic performance to predict ischemia, using a large-scale, pooled analysis. <b><i>Methods:</i></b> Eleven centers worldwide were invited to provide their clinical, IVUS and fractional flow reserve (FFR) data. A total of 881 lesions were enrolled. <b><i>Results:</i></b> Angiographic % diameter stenosis (r = -0.373, p < 0.0001) and IVUS MLA (r = 0.289, p < 0.0001) correlated with FFR. Best cut-off value (BCV) of IVUS MLA to define the functional significance (FFR <0.8) was 2.75 mm² (AUC 0.646, 95% CI 0.609-0.684). When the diagnostic performance of IVUS MLA was tested according to the lesion location, BCV could be found only in lesions in the proximal artery and the mid-left anterior descending artery. Interestingly, Asians (n = 623) and Westerners (n = 258) showed different demographic and lesion characteristics as well as different BCVs to define ischemia. The BCV for the proximal/mid-left anterior descending artery lesions was 2.75 mm² (AUC 0.688, 95% CI 0.635-0.742) in Asians and 3.0 mm² (AUC 0.695, 95% CI 0.605-0.786) in Westerners. <b><i>Conclusion:</i></b> In this pooled analysis, an IVUS MLA of 2.75 mm² was the BCV to define the functional significance of intermediate coronary stenosis. However, when IVUS MLA is used to determine the functional significance, both the lesion and patient characteristics should be considered

Supplementary Material for: Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy

<p><b><i>Objective:</i></b> The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with muscle-invasive bladder cancer (MIBC) undergoing curative radical cystectomy (RC). <b><i>Methods:</i></b> The analysis enrolled 117 patients and the variables included age, body mass index (BMI), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), Controlling Nutritional Status score, psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables were evaluated and their prognostic values after RC were tested. <b><i>Results:</i></b> Three inflammation markers (ratios of blood cell counts) were positively correlated (<i>p</i> < 0.0001). The PNI and the BMI were positively correlated (<i>p</i> = 0.04), although they were inversely correlated with the three inflammation markers (<i>p</i> < 0.0001). Age was not significantly correlated with the inflammation markers and PMI, although older age was associated with lower PNI and lower PEF. The disease-specific survival was independently predicted by T4 tumor, positive N status, and decreased PNI. Overall survival was independently predicted by T4 tumor, mGPS, and pretreatment sarcopenia status. <b><i>Conclusions:</i></b> The inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for MIBC.</p