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1.
Front Oncol ; 13: 1308353, 2023.
Article in English | MEDLINE | ID: mdl-38162479

ABSTRACT

Background: Vascular adhesion protein-1 (VAP-1), a dual-function glycoprotein, has been reported to play a crucial role in inflammation and tumor progression. We conducted a community-based cohort study to investigate whether serum VAP-1 could be a potential biomarker for predicting incident cancers and mortality. Method: From 2006 to 2018, we enrolled 889 cancer-free subjects at baseline. Serum VAP-1 levels were measured using a time-resolved immunofluorometric assay. Cancer and vital status of the participants were obtained by linking records with the computerized cancer registry and death certificates in Taiwan. Results: During a median follow-up of 11.94 years, 69 subjects developed incident cancers and 66 subjects died, including 29 subjects who died from malignancy. Subjects in the highest tertile of serum VAP-1 had a significantly higher risk of cancer incidence (p=0.0006), cancer mortality (p=0.0001), and all-cause mortality (p=0.0002) than subjects in the other tertiles. The adjusted hazard ratios per one standard deviation increase in serum VAP-1 concentrations were 1.28 for cancer incidence (95% CI=1.01-1.62), 1.60 for cancer mortality (95% CI=1.14-2.23), and 1.38 for all-cause mortality (95% CI=1.09-1.75). The predictive performance of serum VAP-1 was better than that of gender, smoking, body mass index, hypertension, diabetes, and estimated glomerular filtration rate but lower than that of age for cancer incidence, cancer mortality, and all-cause mortality, as evidenced by higher increments in concordance statistics and area under the receiver operating characteristic curve. Conclusion: Serum VAP-1 levels are associated with a 12-year risk of incident cancer, cancer mortality, and all-cause mortality in a general population.

2.
Front Surg ; 9: 939857, 2022.
Article in English | MEDLINE | ID: mdl-36147694

ABSTRACT

Purpose: This study aims to identify the pre- and postoperative changes in the neutrophil-lymphocyte ratio (NLR) and its correlations to clinical characteristics in obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Method: Retrospectively, we included patients who has undergone LSG in our institution between January 2019 and April 2021. A total of 100 patients whose body mass index over 32.5 and received primary laparoscopic sleeve gastrectomy without infectious condition were included. Results: There was a significant decline in NLR (T0 vs. POM3 2.21 vs. 1.78, p = 0.005), neutrophil (T0 vs. POM3 5369 vs. 4050, p < 0.001) and lymphocyte count (T0 vs. POM3 2440: 2100, p < 0.001, respectively) at postoperative 3 months (POM3) compared to preoperative (T0) levels, but similar between POM3 and POM6. The declined counts (Neutrophile vs. Lymphocyte 1445.5/µl vs. 323.5/µl, p < 0.001) and percentage (Neutrophile vs. Lymphocyte 25.11% vs. 13.07%, p < 0.001) of neutrophile are higher than lymphocyte from T0 to POM3, but similar in POM3 and POM6. Preoperative NLR has a significant correlation with the preoperative body weight, preoperative insulin level, and excessive body weight loss (EBWL) at POM3. Preoperative NLR <2.36 had a sensitivity of 67.6% and a specificity of 62.5% in predicting successful weight loss (EBWL > 37.7%) at POM3 (AUC = 0.635, p = 0.032). Conclusion: There was a significant decline in NLR, neutrophil, and lymphocyte count from T0 to POM3, but similar between POM3 and POM6. The declined counts and percentage of neutrophile are higher than lymphocyte. Preoperative NLR shows the potential to be used as a prognostic biomarker for predicting successful weight loss at POM3 after LSG. Further studies could be designed to evaluate the value of prediction in successful outcome after LSG and figure out the relationship between the changes of neutrophil function and oncogenesis.

3.
Nutrients ; 14(4)2022 Feb 09.
Article in English | MEDLINE | ID: mdl-35215377

ABSTRACT

Growing evidence suggests that patients with Duchenne muscular dystrophy (DMD) have an increased risk of obesity and metabolic syndrome (MetS). The aim of this study was to investigate the potential risk factors for MetS and hepatic steatosis in patients with different stages of DMD. A total of 48 patients with DMD were enrolled and classified into three stages according to ambulatory status. Body mass index (BMI), serum fasting glucose, insulin, and lipid profiles including triglycerides (TG) and high-density lipoprotein were measured, and the homeostatic model assessment for insulin resistance (HOMA-IR) index was evaluated. Ultrasound examinations of the liver were performed to assess hepatic steatosis using the Nakagami parameter index (NPI). The results showed that BMI, TG, HOMA-IR, and ultrasound NPI differed significantly among DMD stages (p < 0.05). In contrast to the low rates of conventional MetS indices, including disturbed glucose metabolism (0%), dyslipidemia (14.28%), and insulin resistance (4.76%), a high proportion (40.48%) of the patients had significant hepatic steatosis. The ultrasound NPI increased with DMD progression, and two thirds of the non-ambulatory patients had moderate to severe hepatic steatosis. Steroid treatment was a risk factor for hepatic steatosis in ambulatory patients (p < 0.05). We recommend that DMD patients should undergo ultrasound evaluations for hepatic steatosis for better metabolic and nutritional management.


Subject(s)
Fatty Liver , Insulin Resistance , Muscular Dystrophy, Duchenne , Body Mass Index , Fatty Liver/diagnostic imaging , Fatty Liver/etiology , Fatty Liver/metabolism , Humans , Muscular Dystrophy, Duchenne/complications , Obesity/metabolism
4.
Comput Math Methods Med ; 2022: 7960151, 2022.
Article in English | MEDLINE | ID: mdl-35186115

ABSTRACT

During the evaluation of body surface area (BSA), precise measurement of psoriasis is crucial for assessing disease severity and modulating treatment strategies. Physicians usually evaluate patients subjectively through direct visual evaluation. However, judgment based on the naked eye is not reliable. This study is aimed at evaluating the use of machine learning methods, specifically U-net models, and developing an artificial neural network prediction model for automated psoriasis lesion segmentation and BSA measurement. The segmentation of psoriasis lesions using deep learning is adopted to measure the BSA of psoriasis so that the severity can be evaluated automatically in patients. An automated psoriasis lesion segmentation method based on the U-net architecture was used with a focus on high-resolution images and estimation of the BSA. The proposed method trained the model with the same patch size of 512 × 512 and predicted testing images with different patch sizes. We collected 255 high-resolution psoriasis images representing large anatomical sites, such as the trunk and extremities. The average residual of the ground truth image and the predicted image was approximately 0.033. The interclass correlation coefficient between the U-net and dermatologist's segmentations measured in the ratio of affected psoriasis over the body area in the test dataset was 0.966 (95% CI: 0.981-0.937), indicating strong agreement. Herein, the proposed U-net model achieved dermatologist-level performance in estimating the involved BSA for psoriasis.


Subject(s)
Body Surface Area , Machine Learning , Neural Networks, Computer , Psoriasis/diagnostic imaging , Psoriasis/pathology , Adult , Computational Biology , Computer Simulation , Humans , Image Interpretation, Computer-Assisted/methods , Image Interpretation, Computer-Assisted/statistics & numerical data , Models, Anatomic , Photography/methods , Photography/statistics & numerical data , Young Adult
5.
J Formos Med Assoc ; 121(1 Pt 1): 193-201, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33766449

ABSTRACT

BACKGROUND/PURPOSE: Hypertension is a risk factor of incident diabetes. In 2017, the ACC/AHA updated the definition of hypertension to above 130/80 mmHg, while the 2018 ESC/ESH guideline and the JNC7 criteria remained the cutoff of 140/90 mmHg. This study was aimed to investigate how different cutoffs of hypertension affect the association of hypertension to incident diabetes and the progression of insulin resistance. METHODS: A total of 1177 subjects without diabetes at baseline were followed for 4.5 years. Diabetes was diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used. RESULTS: Hypertension by both criteria was associated with incident diabetes. Change of HOMA2-IR every 5 years (ΔHOMA2-IR/5 yr) was higher in subjects with hypertension than those without (adjusted p = 0.044). Subjects with treated hypertension had the highest risk of diabetes (HR 2.98, p < 0.001) and ΔHOMA2-IR/5 yr, compared with subjects with normal blood pressure. However, the associations of hypertension, HR of incident diabetes and ΔHOMA2-IR/5 yr were attenuated by the 2017 ACC/AHA criteria, as compared with that by the JNC7 and 2018 ESC/ESH criteria. CONCLUSION: Hypertension by both criteria is associated with incident diabetes and accelerated progression of insulin resistance, and the associations are attenuated by the 2017 ACC/AHA criteria.


Subject(s)
Diabetes Mellitus , Hypertension , Insulin Resistance , Diabetes Mellitus/epidemiology , Humans , Hypertension/epidemiology , Prospective Studies
6.
J Clin Med ; 10(19)2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34640449

ABSTRACT

BACKGROUND: The performance of chest radiography-based age and sex prediction has not been well validated. We used a deep learning model to predict the age and sex of healthy adults based on chest radiographs (CXRs). METHODS: In this retrospective study, 66,643 CXRs of 47,060 healthy adults were used for model training and testing. In total, 47,060 individuals (mean age ± standard deviation, 38.7 ± 11.9 years; 22,144 males) were included. By using chronological ages as references, mean absolute error (MAE), root mean square error (RMSE), and Pearson's correlation coefficient were used to assess the model performance. Summarized class activation maps were used to highlight the activated anatomical regions. The area under the curve (AUC) was used to examine the validity for sex prediction. RESULTS: When model predictions were compared with the chronological ages, the MAE was 2.1 years, RMSE was 2.8 years, and Pearson's correlation coefficient was 0.97 (p < 0.001). Cervical, thoracic spines, first ribs, aortic arch, heart, rib cage, and soft tissue of thorax and flank seemed to be the most crucial activated regions in the age prediction model. The sex prediction model demonstrated an AUC of >0.99. CONCLUSION: Deep learning can accurately estimate age and sex based on CXRs.

7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1274-1277, 2020 07.
Article in English | MEDLINE | ID: mdl-33018220

ABSTRACT

Multiphase computed tomographic angiography (CTA) have been demonstrated to be a reliable imaging tool for evaluating cerebral collateral circulation that can be used to select acute ischemic patients for recanalization therapy. We proposed using bone subtraction techniques to visualize multiphase CTA for clinicians to make fast and consistent decisions in the imaging triage of acute stroke patients. A total of 40 multiphase brain CTA datasets were collected and processed by two bone subtraction methods. The reference method used pre-contrast (phase 0) scans to create ground truth bone masks by thresholding. The tested method used only contrast enhanced (phases 1, 2, and 3) scans to extract bone masks with two versions (U-net and atrous) of 3D multichannel convolution neural networks (CNNs) in a supervised deep learning paradigm for semantic segmentation. Half (n = 20) of the datasets were used to train and half (n = 20) were used to test the conventional 3D U-net and a patch-based 3D multichannel atrous CNN. The tested U-net and atrous CNNs achieved a mean intersection over union (IoU) scores of 90.0% +/- 2.2 and 93.9% +/- 1.2 respectively.Clinical Relevance-This bone subtraction technique helps to visualize CTA volumetric datasets in the form of full brain angiogram-like images to assist the clinicians in the emergency department for evaluating acute ischemic stroke patients.


Subject(s)
Brain Ischemia , Stroke , Angiography , Computed Tomography Angiography , Humans , Neural Networks, Computer , Stroke/diagnostic imaging
8.
Article in English | MEDLINE | ID: mdl-32713841

ABSTRACT

INTRODUCTION: Primary aldosteronism (PA) is a common form of secondary hypertension that has significant cardiovascular events and increased prevalence of metabolic syndrome and diabetics. Although plasma aldosterone concentration is positively correlated with visceral fat area (VFA) in non-PA individuals, the role of visceral adiposity associated with clinical success after surgery is not known. RESEARCH DESIGN AND METHODS: We analyzed patients who underwent adrenalectomy for aldosterone-producing adenoma (APA) at the Taiwan PA Investigator group. VFA was calculated from the abdominal CT scan at APA diagnosis, and all patients received adrenalectomy. RESULTS: The study involved 100 consecutive patients with APA (42 males; mean age 49.3 years) matched with 41 essential hypertension (EH) patients. Patients with APA had smaller VFA (p=0.010) than their EH counterparts. Multiple linear regression analysis revealed that the duration of hypertension (p=0.007), but not plasma aldosterone, was negatively correlated with VFA in patients with APA. Logistic regression analysis showed that log VFA (OR=0.065, p<0.001) and duration of hypertension before PA diagnosis (OR=0.919, p=0.011) can predict complete clinical success after adrenalectomy. Multifactor-adjusted generalized additive model demonstrated that log VFA <9.2 was associated with complete cure of hypertension. Furthermore, VFA was increased at 6 months after adrenalectomy (p=0.045). CONCLUSIONS: Patients with APA had smaller VFA than their EH counterparts, and VFA increased after adrenalectomy. Clinical complete cure of hypertension after surgery was associated with smaller VFA and shorter duration of hypertension at PA diagnosis, suggesting a potential interplay of visceral adiposity and aldosterone of the patients with APA.


Subject(s)
Adenoma , Hyperaldosteronism , Adenoma/complications , Adenoma/surgery , Adiposity , Aldosterone , Humans , Hyperaldosteronism/complications , Hyperaldosteronism/diagnosis , Hyperaldosteronism/epidemiology , Male , Middle Aged , Taiwan
9.
Diabetes Res Clin Pract ; 161: 108050, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32035116

ABSTRACT

AIMS: Insulin resistance (IR) changes over time during the development of type 2 diabetes. Some reports showed that obesity was associated with progression of IR. However, no study has explored if change of IR predicts incident diabetes, and no study has investigated other factors associated with the change. METHODS: In this study, 1184 subjects without diabetes at baseline were enrolled in 2006-2016 with a median follow-up period of 4.5 years. Diabetes was diagnosed by oral glucose tolerance test and hemoglobin A1c, or if anti-diabetic agents were used. HOMA2-IR and ISI0,120 were used to estimate IR. RESULTS: The annual changes of HOMA2-IR(ΔHOMA2-IR/year) and ISI0,120(ΔISI0,120/year) were associated with BMI, waist circumference(WC), glucose, HbA1c, triglyceride and HDL-cholesterol. Subjects with pre-diabetes or metabolic syndrome were associated with a more rapid increase of IR. ΔHOMA2-IR/year and ΔISI0,120/year were correlated with annual changes of BMI and WC. The hazard ratios for ΔHOMA2-IR/year and ΔISI0,120/year to predict incident diabetes were 1.39 (95% CI 1.22-1.59, p < 0.001) and 0.13 (95% CI 0.09-0.19, p < 0.001) in adjusted models, respectively. CONCLUSIONS: Change of IR can be used as a surrogate marker of incident diabetes. The progression of IR is an important pathophysiologic link between risk factors and the incidence of diabetes.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/etiology , Insulin Resistance/physiology , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Female , Humans , Incidence , Male , Middle Aged , Risk Factors
10.
Magn Reson Med ; 82(2): 763-774, 2019 08.
Article in English | MEDLINE | ID: mdl-30957300

ABSTRACT

PURPOSE: The purpose of this study was to investigate the feasibility of in vivo imaging of human pancreatic ductal cells by OATP1B3 reporter gene under MRI. METHODS: A human cell line (PANC-1) derived from the pancreatic ductal epithelium was used in this study. After transduction of OATP1B3, the cellular physiological functions and the ability of intracellular uptake of the MRI contrast medium (Gd-EOB-DTPA) were examined. Induced differentiation of the PANC-1 cells into hormone-secreting cells were performed to simulate pancreatic ß-like cells. The hormone-secreting cells were implanted into rats and in vivo MRI was evaluated. RESULTS: The mRNA and proteins of OATP1B3 were highly expressed. No significant change of cellular physiological functions was found after the expression. After induced differentiation, the hormone secretion capacities of the OATP1B3-expressing PANC-1 cells were confirmed. Intra-cellular uptake of Gd-EOB-DTPA was determined in vitro by inductively coupled plasma mass spectrometry and MRI. In vivo MRI of the OATP1B3-expressing xenograft revealed an increased signal intensity after contrast enhancement. CONCLUSION: OATP1B3 can be used as a safe and feasible in vivo MRI gene reporter for human pancreatic ductal cells.


Subject(s)
Genes, Reporter/genetics , Insulin-Secreting Cells/metabolism , Insulin/metabolism , Magnetic Resonance Imaging/methods , Animals , Cell Line , Contrast Media , Feasibility Studies , Female , Gadolinium DTPA , Heterografts/chemistry , Heterografts/diagnostic imaging , Heterografts/metabolism , Humans , Insulin-Secreting Cells/chemistry , Mice , Mice, SCID , Molecular Imaging , Rats , Solute Carrier Organic Anion Transporter Family Member 1B3/chemistry , Solute Carrier Organic Anion Transporter Family Member 1B3/genetics , Solute Carrier Organic Anion Transporter Family Member 1B3/metabolism
11.
Int J Obes (Lond) ; 43(3): 512-522, 2019 03.
Article in English | MEDLINE | ID: mdl-30022055

ABSTRACT

BACKGROUND/OBJECTIVES: Vascular adhesion protein-1 (VAP-1) can enhance tissue glucose uptake in cell studies and normalize hyperglycemia in animal studies. However, serum VAP-1 concentration (sVAP-1) is higher in subjects with diabetes in cross-sectional studies. In this cohort study, we test our hypothesis that sVAP-1 is increased in prediabetes to counteract hyperglycemia and is associated with incident diabetes negatively. SUBJECTS/METHODS: From 2006 to 2012, 600 subjects without diabetes from Taiwan Lifestyle Study were included and followed regularly. Diabetes was diagnosed if FPG ≥ 126 mg/dL (7 mmol/L), 2-h plasma glucose (2hPG) during an oral glucose tolerance test (OGTT) ≥ 200 mg/dL (11.1 mmol/L), or hemoglobin A1c (HbA1c) ≥ 6.5%, or if the subject received anti-diabetic medications. Abdominal fat areas were measured by abdominal computed tomography and sVAP-1 was analyzed by ELISA. RESULTS: sVAP-1 was higher in subjects with prediabetes (p < 0.05) and increased during an OGTT (p < 0.001). Fasting sVAP-1 was associated with the response of sVAP-1 during an OGTT (p < 0.001). Besides, sVAP-1 was associated negatively with body mass index (BMI, r = -0.1449, p = 0.003), waist circumference (r = -0.1425, p = 0.004), abdominal visceral (r = -0.1457, p = 0.003), and subcutaneous (r = -0.1025, p = 0.035) fat areas, and serum high-sensitivity C-reactive protein (hsCRP) concentration (r = -0.2035, p < 0.0001), and positively with plasma adiponectin concentration (r = 0.2086, p < 0.0001), adjusted for age and gender. After 4.7 ± 2.6 years, 73 subjects (12.2%) developed incident diabetes. High sVAP-1 predicted a lower incidence of diabetes, adjusted for age, gender, BMI, family history of diabetes, HbA1c, HOMA2-%B and HOMA2-IR (HR = 0.66, 95% CI = 0.50-0.88, p < 0.01). CONCLUSIONS: sVAP-1 is increased in response to hyperglycemia. It is associated with obesity and serum hsCRP concentration negatively, and plasma adiponectin concentration positively. Besides, a high sVAP-1 is associated with a lower incidence of diabetes in human.


Subject(s)
Amine Oxidase (Copper-Containing)/blood , Cell Adhesion Molecules/blood , Hyperglycemia , Prediabetic State , Adiponectin/blood , Adult , C-Reactive Protein/analysis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Female , Humans , Hyperglycemia/blood , Hyperglycemia/epidemiology , Hyperglycemia/metabolism , Longitudinal Studies , Male , Middle Aged , Obesity , Prediabetic State/blood , Prediabetic State/epidemiology , Prediabetic State/metabolism , Taiwan , Up-Regulation
12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 1035-1038, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31946070

ABSTRACT

Inspired by the outstanding performance of deep convolutional neural networks (CNNs), nowadays modern computer-aided detection (CAD) systems for CT lung nodules generally delve into 2D or 3D CNNs directly without considering traditional image preprocessing techniques. However, detection of large pulmonary nodules and masses are computationally challenging, especially for 3D CNNs. In this paper, we examine the possibility of using volume visualized CT thin-slab images with 2D CNNs to reduce computation complexity and improve CAD performance. We tested 4 types of images: original 2D CT, 2D projection of thin slabs, mixture by arranging original and projection in different color channels, and mixture by the pixelwise maximum intensity of original CT and projection. We evaluated these images on a dataset of 30 CT scans with 30 different-sized nodules and masses on GoogLeNet via a transfer learning and cross validation paradigm. We found that projection visualization alone had a better or equal area-under curve score for all the different-sized nodules and masses. However, mixture by the maximum of CT and projection demonstrated a preferred performance with a true positive rate of 0.8 and a false positive rate of 0.046 in detecting large nodules and masses.


Subject(s)
Tomography, X-Ray Computed , Humans , Lung Neoplasms , Neural Networks, Computer , Radiographic Image Interpretation, Computer-Assisted
13.
Clin Neurophysiol ; 129(9): 1899-1906, 2018 09.
Article in English | MEDLINE | ID: mdl-30005217

ABSTRACT

OBJECTIVE: This study aimed to investigate the association between mismatch negativity (MMN) and volumes of several brain regions measured using a semi-automated method in patients with schizophrenia and healthy controls. METHODS: MMN in response to duration deviants and magnetic resonance imaging were acquired from 36 schizophrenia patients and 14 healthy controls. FreeSurfer was used for volumetric analysis. MMN amplitudes, brain volumes and their association were compared between schizophrenia and controls. Correlation analysis and multiple linear regression analysis were used to examine the correlated variables of MMN. RESULTS: MMN amplitude was significantly lower in the schizophrenia group. In schizophrenia, MMN was positively correlated with age and negatively correlated with left hippocampal and right pars opercularis volumes. The association between left hippocampal volume and MMN in schizophrenia remained significant after controlling for potential confounders. CONCLUSIONS: Smaller hippocampal volume may play a role in the abnormal manifestation of MMN in schizophrenia. SIGNIFICANCE: The significant association between MMN and left hippocampal volume may suggest unique neurobiological contribution of hippocampus in auditory processing in schizophrenia.


Subject(s)
Brain/physiopathology , Evoked Potentials/physiology , Schizophrenia/physiopathology , Acoustic Stimulation , Adult , Brain/diagnostic imaging , Electroencephalography , Evoked Potentials, Auditory/physiology , Female , Hippocampus/diagnostic imaging , Hippocampus/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Organ Size/physiology , Schizophrenia/diagnostic imaging , Young Adult
14.
Sci Rep ; 8(1): 9249, 2018 06 18.
Article in English | MEDLINE | ID: mdl-29915377

ABSTRACT

Inflammation, oxidative stress, and the formation of advanced glycated end-products (AGEs) are important components of atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation. Its enzymatic activity, semicarbazide-sensitive amine oxidase (SSAO), can catalyze oxidative deamination reactions to produce hydrogen peroxide and aldehydes, leading to the subsequent generation of AGEs. This study aimed to investigate the effect of VAP-1/SSAO inhibition on atherosclerosis. In our study, immunohistochemical staining showed that atherosclerotic plaques displayed higher VAP-1 expression than normal arterial walls in apolipoprotein E-deficient mice, cholesterol-fed New Zealand White rabbits and humans. In cholesterol-fed rabbits, VAP-1 was expressed on endothelial cells and smooth muscle cells in the thickened intima of the aorta. Treatment with PXS-4728A, a selective VAP-1/SSAO inhibitor, in cholesterol-fed rabbits significantly decreased SSAO-specific hydrogen peroxide generation in the aorta and reduced atherosclerotic plaques. VAP-1/SSAO inhibition also lowered blood low-density lipoprotein cholesterol, reduced the expression of adhesion molecules and inflammatory cytokines, suppressed recruitment and activation of macrophages, and decreased migration and proliferation of SMC. In conclusion, VAP-1/SSAO inhibition reduces atherosclerosis and may act through suppression of several important mechanisms for atherosclerosis.


Subject(s)
Amine Oxidase (Copper-Containing)/antagonists & inhibitors , Atherosclerosis/drug therapy , Enzyme Inhibitors/therapeutic use , Feeding Behavior , Allylamine/analogs & derivatives , Allylamine/pharmacology , Allylamine/therapeutic use , Amine Oxidase (Copper-Containing)/metabolism , Animals , Aorta/metabolism , Apolipoproteins E/deficiency , Atherosclerosis/blood , Atherosclerosis/pathology , Benzamides/pharmacology , Benzamides/therapeutic use , Body Weight , Cell Adhesion Molecules/metabolism , Cholesterol , Cytokines/metabolism , Enzyme Inhibitors/pharmacology , Fasting/blood , Humans , Hydrogen Peroxide/metabolism , Inflammation Mediators/metabolism , Macrophage Activation , Male , Matrix Metalloproteinase 9/metabolism , Mice , Myocytes, Smooth Muscle/metabolism , Plaque, Atherosclerotic/pathology , Proliferating Cell Nuclear Antigen/metabolism , Rabbits
15.
Med Oncol ; 34(8): 143, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28726044

ABSTRACT

Although current staging workups could differentiate most patients with operable from inoperable advanced gastric cancers, there are still some patients with low-volume peritoneal carcinomatosis, defined as only metastasis with multiple subcentimeter lesions in peritoneum, receiving unnecessary open-close procedures. The computed tomography (CT) of the patients with unresectable advanced gastric cancer harboring low-volume peritoneal carcinomatosis was retrospectively identified and then thoroughly reviewed by two independent radiologists unaware of the peritoneal carcinomatosis status. Of the 798 patients with newly diagnosed gastric cancer between January 2007 and December 2010, 52 patients harboring advanced gastric cancer with low-volume peritoneal carcinomatosis receiving surgery with curative intent were identified. Descriptive statistic was used for the radiologic characteristics. The most common radiologic characteristic of CT was omental fat stranding (57.7%), followed by omental clustered subcentimeter nodules (53.8%), distant enlarged lymph node (40.4%), distant grouping of small lymph nodes (36.5%), peritoneal nodules or thickening (34.6%), minimal loculated ascites (21.2%), intestinal wall thickening or irregularity (9.6%), and hydronephrosis or hydroureter without stone or urothelial lesion (5.8%). Comprehensively reviewing the radiologic characteristics of CT may identify the patients harboring advanced gastric cancer with low-volume peritoneal carcinomatosis.


Subject(s)
Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/secondary , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
16.
J Physiol ; 595(2): 505-521, 2017 01 15.
Article in English | MEDLINE | ID: mdl-27121603

ABSTRACT

KEY POINTS: Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria-derived septic complications. Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive. A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes. Pyruvate suppressed epithelial cell death in an ATP-independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut. Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti-necroptotic role of glycolytic pyruvate under ischaemic stress. ABSTRACT: Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor-interacting protein kinase (RIP)-dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium-glucose transporter 1 ameliorated ischaemia/reperfusion-induced epithelial injury, partly via anti-apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1-dependent epithelial necroptosis and villus destruction accompanied by a reduction in crypt proliferation. Enteral glucose uptake decreased epithelial cell death and increased crypt proliferation, and ameliorated mucosal histological damage. Instillation of cell-permeable pyruvate suppressed epithelial cell death in an ATP-independent manner and improved the villus morphology but failed to maintain crypt function. Conversely, the administration of liposomal ATP partly restored crypt proliferation but did not reduce epithelial necroptosis and histopathological injury. Lastly, glucose and pyruvate attenuated mucosal-to-serosal macromolecular flux and prevented enteric bacterial translocation upon blood reperfusion. In conclusion, glucose metabolites protect against ischaemic injury through distinct modes and sites, including inhibition of epithelial necroptosis by pyruvate and the promotion of crypt proliferation by ATP.


Subject(s)
Adenosine Triphosphate/metabolism , Enterocytes/metabolism , Enterocytes/pathology , Glucose/metabolism , Pyruvic Acid/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Animals , Apoptosis , Enterocytes/ultrastructure , Jejunum/metabolism , Jejunum/pathology , Jejunum/ultrastructure , Liver/microbiology , Male , Microscopy, Electron, Transmission , Necrosis , Protein Serine-Threonine Kinases/metabolism , Rats, Wistar , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Spleen/microbiology
17.
Asian J Surg ; 40(1): 61-65, 2017 Jan.
Article in English | MEDLINE | ID: mdl-23978432

ABSTRACT

Extracranial and meningeal seeding of glioblastoma multiforme is rare. We report herein a case of glioblastoma in a 41-year-old man who underwent surgical resection, concomitant chemoradiotherapy (CCRT) and seven courses of adjuvant chemotherapy with temozolomide. The patient then complained of intermittent severe lower back pain and gait disturbance. Imaging studies demonstrated that although the intracranial residual tumors were well-controlled by the treatment, meningeal seeding involving the brainstem and spinal cord was present. The patient died 2 months after the diagnosis of spinal seeding. This case illustrates the need for consideration of extracranial metastasis if a patient is symptomatic, even if the intracranial tumor appears responsive to treatment. We suggested that the prophylactic craniospinal irradiation may be considered in patients at high risk of meningeal seeding immediately after surgery.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/pathology , Chemoradiotherapy, Adjuvant , Dacarbazine/analogs & derivatives , Glioblastoma/secondary , Meningeal Neoplasms/secondary , Neoplasm Seeding , Adult , Brain Neoplasms/therapy , Dacarbazine/therapeutic use , Fatal Outcome , Glioblastoma/therapy , Humans , Male , Temozolomide
18.
PLoS One ; 11(1): e0146913, 2016.
Article in English | MEDLINE | ID: mdl-26812647

ABSTRACT

PURPOSE: To assess the inter session reproducibility of automatic segmented MRI-derived measures by FreeSurfer in a group of subjects with normal-appearing MR images. MATERIALS AND METHODS: After retrospectively reviewing a brain MRI database from our institute consisting of 14,758 adults, those subjects who had repeat scans and had no history of neurodegenerative disorders were selected for morphometry analysis using FreeSurfer. A total of 34 subjects were grouped by MRI scanner model. After automatic segmentation using FreeSurfer, label-wise comparison (involving area, thickness, and volume) was performed on all segmented results. An intraclass correlation coefficient was used to estimate the agreement between sessions. Wilcoxon signed rank test was used to assess the population mean rank differences across sessions. Mean-difference analysis was used to evaluate the difference intervals across scanners. Absolute percent difference was used to estimate the reproducibility errors across the MRI models. Kruskal-Wallis test was used to determine the across-scanner effect. RESULTS: The agreement in segmentation results for area, volume, and thickness measurements of all segmented anatomical labels was generally higher in Signa Excite and Verio models when compared with Sonata and TrioTim models. There were significant rank differences found across sessions in some labels of different measures. Smaller difference intervals in global volume measurements were noted on images acquired by Signa Excite and Verio models. For some brain regions, significant MRI model effects were observed on certain segmentation results. CONCLUSIONS: Short-term scan-rescan reliability of automatic brain MRI morphometry is feasible in the clinical setting. However, since repeatability of software performance is contingent on the reproducibility of the scanner performance, the scanner performance must be calibrated before conducting such studies or before using such software for retrospective reviewing.


Subject(s)
Brain/anatomy & histology , Magnetic Resonance Imaging/standards , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies
19.
PLoS One ; 9(11): e112355, 2014.
Article in English | MEDLINE | ID: mdl-25401949

ABSTRACT

OBJECTIVE: Whether retroperitoneal fat should be included in the measurement of visceral fat remains controversial. We compared the relationships of fat areas in peritoneal, retroperitoneal, and subcutaneous compartments to metabolic syndrome, adipokines, and incident hypertension and diabetes. METHODS: We enrolled 432 adult participants (153 men and 279 women) in a community-based cohort study. Computed tomography at the umbilicus level was used to measure the fat areas. RESULTS: Retroperitoneal fat correlated significantly with metabolic syndrome (adjusted odds ratio (OR), 5.651, p<0.05) and the number of metabolic abnormalities (p<0.05). Retroperitoneal fat area was significantly associated with blood pressure, plasma glycemic indices, lipid profile, C-reactive protein, adiponectin (r =  -0.244, P<0.05), and leptin (r = 0.323, p<0.05), but not plasma renin or aldosterone concentrations. During the 2.94 ± 0.84 years of follow-up, 32 participants developed incident hypertension. Retroperitoneal fat area (hazard ration (HR) 1.62, p = 0.003) and peritoneal fat area (HR 1.62, p = 0.009), but not subcutaneous fat area (p = 0.14) were associated with incident hypertension. Neither retroperitoneal fat area, peritoneal fat area, nor subcutaneous fat areas was associated with incident diabetes after adjustment. CONCLUSIONS: Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in terms of its relationship with metabolic syndrome and incident hypertension. Retroperitoneal fat area should be included in the measurement of visceral fat for cardio-metabolic studies in human.


Subject(s)
Abdominal Fat/anatomy & histology , Body Weights and Measures , Abdominal Fat/metabolism , Abdominal Fat/pathology , Adipokines/metabolism , Adult , Aged , Comorbidity , Female , Humans , Hypertension/epidemiology , Hypertension/etiology , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Middle Aged , Organ Size , Public Health Surveillance , Risk Factors , Tomography, X-Ray Computed
20.
PLoS One ; 8(11): e76212, 2013.
Article in English | MEDLINE | ID: mdl-24223698

ABSTRACT

BACKGROUND: Computer-aided diagnosis (CADx) software that provides a second opinion has been widely used to assist physicians with various tasks. In dermatology, however, CADx has been mostly limited to melanoma or melanocytic skin cancer diagnosis. The frequency of non-melanocytic skin cancers and the accessibility of regular digital macrographs have raised interest in developing CADx for broader applications. OBJECTIVES: To investigate the feasibility of using CADx to diagnose both melanocytic and non-melanocytic skin lesions based on conventional digital photographic images. METHODS: This study was approved by an institutional review board, and the requirement to obtain informed consent was waived. In total, 769 conventional photographs of melanocytic and non-melanocytic skin lesions were retrospectively reviewed and used to develop a CADx system. Conventional and new color-related image features were developed to classify the lesions as benign or malignant using support vector machines (SVMs). The performance of CADx was compared with that of dermatologists. RESULTS: The clinicians' overall sensitivity, specificity, and accuracy were 83.33%, 85.88%, and 85.31%, respectively. New color correlation and principal component analysis (PCA) features improved the classification ability of the baseline CADx (p = 0.001). The estimated area under the receiver operating characteristic (ROC) curve (Az) of the proposed CADx system was 0.949, with a sensitivity and specificity of 85.63% and 87.65%, respectively, and a maximum accuracy of 90.64%. CONCLUSIONS: We have developed an effective CADx system to classify both melanocytic and non-melanocytic skin lesions using conventional digital macrographs. The system's performance was similar to that of dermatologists at our institute. Through improved feature extraction and SVM analysis, we found that conventional digital macrographs were feasible for providing useful information for CADx applications. The new color-related features significantly improved CADx applications for skin cancer.


Subject(s)
Image Interpretation, Computer-Assisted , Skin Neoplasms/diagnosis , Software , Adult , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Photography , Principal Component Analysis , ROC Curve , Reproducibility of Results , Support Vector Machine
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