Cortical Iron Accumulation as an Imaging Marker for Neurodegeneration in Clinical Cognitive Impairment Spectrum: A Quantitative Susceptibility Mapping Study

Objective@#Cortical iron deposition has recently been shown to occur in Alzheimer’s disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. @*Materials and Methods@#This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years;52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region.Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). @*Results@#Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (β = -216.21, P = 0.019) and insular cortex (β = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. @*Conclusion@#Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.

Relationship Between Cortical Iron and Diabetes Mellitus in Older Adults With Cognitive Complaints: A Quantitative Susceptibility Map Study

Purpose@#Diabetes mellitus (DM) is implicated in the pathogenesis of iron dysregulation and Alzheimer’s disease. We aimed to evaluate whether the presence of DM and status of cognitive impairment affect cortical iron accumulation in older adults, as quantified by the susceptibility measurements using the deep neural network QSMnet+. @*Materials and Methods@#In this retrospective analysis of a prospective cohort, 50 patients with normal cognition with or without subjective memory impairment (controls), 49 with early mild cognitive impairment (MCI), and 43 with late MCI were evaluated. We employed QSMnet+ to compute a quantitative susceptibility map and FreeSurfer 6.0 to obtain anatomical labels. The effects of MCI and DM on cortical susceptibility and volume were evaluated using a two-way analysis of covariance. @*Results@#Whole-cortex susceptibility differed according to MCI (p < 0.001) but not according to DM (p = 0.554), with higher values in the early and late MCI groups than in the control group. MCI and the DM status showed a significant interaction in the whole cortex (p = 0.023). Among the patients with early MCI, those with DM exhibited higher cortical susceptibility than those without DM, whereas those with late MCI showed no such difference. Cortical susceptibility did not correlate with the cortical volume in patients with DM and inversely correlated with the cortical volume in patients without DM. Only disease status (p = 0.008) and DM (p = 0.023) were independent predictors of whole-cortex susceptibility, after correcting for covariates. @*Conclusion@#Our findings demonstrated that cognitive impairment and DM are linked to alterations in cortical susceptibility in older adults. This observation suggests that cortical iron accumulation results from the combined effects of DM and neurodegenerative processes related to the cognitive status.

The relationship between miRNA-26b and connective tissue growth factor in rat models of aortic banding and debanding

Background/Aims@#Connective tissue growth factor (CTGF) is a profibrotic factor implicated in pressure overload-mediated myocardial fibrosis. In this study, we determined the role of predicted CTGF-targeting microRNAs (miRNAs) in rat models of aortic stenosis and reverse cardiac remodeling. @*Methods@#Minimally invasive ascending aortic banding was performed in 24 7-week-old male Sprague-Dawley rats, which were divided into three groups. The banding group consisted of eight rats that were sacrificed immediately after 6 weeks of aortic constriction. The debanding group underwent aortic constriction for 4 weeks and was sacrificed 2 weeks after band removal. The third group underwent sham surgery. We investigated the expression of CTGF, transforming growth factor-β1 (TGFβ1), and matrix metalloproteinase-2 using ELISA and examined miRNA-26b, miRNA-133a, and miRNA-19b as predicted CTGF-targeting miRNAs based on miRNA databases in 24-hour TGFβ-stimulated and TGFβ- washed fibroblasts and myocardial tissues from all subjects. @*Results@#CTGF was elevated in 24-hour TGFβ-stimulated fibroblasts and decreased in 24-hour TGFβ-washed fibroblasts. miRNA-26b was significantly increased in TGFβ-washed fibroblasts compared with control and TGFβ-stimulated fibroblasts (p < 0.05). CTGF expression was significantly higher in the banding group than that in the sham and debanding groups. The relative expression levels of miRNA-26b were higher in the debanding group than in the banding group. @*Conclusions@#The results of our study using models of aortic banding and debanding suggested that miRNA-26b was significantly increased after aortic debanding. The in vitro model yielded the same results: miRNA-26b was upregulated after removal of TGFβ from fibroblasts.

The relationship between miRNA-26b and connective tissue growth factor in rat models of aortic banding and debanding

Background/Aims@#Connective tissue growth factor (CTGF) is a profibrotic factor implicated in pressure overload-mediated myocardial fibrosis. In this study, we determined the role of predicted CTGF-targeting microRNAs (miRNAs) in rat models of aortic stenosis and reverse cardiac remodeling. @*Methods@#Minimally invasive ascending aortic banding was performed in 24 7-week-old male Sprague-Dawley rats, which were divided into three groups. The banding group consisted of eight rats that were sacrificed immediately after 6 weeks of aortic constriction. The debanding group underwent aortic constriction for 4 weeks and was sacrificed 2 weeks after band removal. The third group underwent sham surgery. We investigated the expression of CTGF, transforming growth factor-β1 (TGFβ1), and matrix metalloproteinase-2 using ELISA and examined miRNA-26b, miRNA-133a, and miRNA-19b as predicted CTGF-targeting miRNAs based on miRNA databases in 24-hour TGFβ-stimulated and TGFβ- washed fibroblasts and myocardial tissues from all subjects. @*Results@#CTGF was elevated in 24-hour TGFβ-stimulated fibroblasts and decreased in 24-hour TGFβ-washed fibroblasts. miRNA-26b was significantly increased in TGFβ-washed fibroblasts compared with control and TGFβ-stimulated fibroblasts (p < 0.05). CTGF expression was significantly higher in the banding group than that in the sham and debanding groups. The relative expression levels of miRNA-26b were higher in the debanding group than in the banding group. @*Conclusions@#The results of our study using models of aortic banding and debanding suggested that miRNA-26b was significantly increased after aortic debanding. The in vitro model yielded the same results: miRNA-26b was upregulated after removal of TGFβ from fibroblasts.

Exploring Generalization Capacity of Artificial Neural Network for Myelin Water Imaging

Purpose@#To understand the effects of datasets with various parameters on pretrained network performance, the generalization capacity of the artificial neural network for myelin water imaging (ANN-MWI) is explored by testing datasets with various scan protocols (i.e., resolution and refocusing RF pulse shape) and types of disorders (i.e., neuromyelitis optica and edema). @*Materials and Methods@#ANN-MWI was trained to generate a T2 distribution, from which the myelin water fraction value was measured. The training and test datasets were acquired from healthy controls and multiple sclerosis patients using a multiecho gradient and spin-echo sequence with the same scan protocols. To test the generalization capacity of ANN-MWI, datasets with different settings were utilized.The datasets were acquired or generated with different resolutions, refocusing pulse shape, and types of disorders. For all datasets, the evaluation was performed in a white matter mask by calculating the normalized root-mean-squared error (NRMSE) between the results from the conventional method and ANN-MWI. Additionally, for the patient datasets, the NRMSE was calculated in each lesion mask. @*Results@#The results of ANN-MWI showed high reliability in generating myelin water fraction maps from the datasets with different resolutions. However, the increased errors were reported for the datasets with different refocusing pulse shapes and disorder types. Specifically, the region of lesions in edema patients reported high NRMSEs. These increased errors indicate the dependency of ANN-MWI on refocusing pulse flip angles and T 2 characteristics. @*Conclusion@#This study proposes information about the generalization accuracy of a trained network when applying deep learning to processing myelin water imaging.

Exploring Generalization Capacity of Artificial Neural Network for Myelin Water Imaging

Purpose@#To understand the effects of datasets with various parameters on pretrained network performance, the generalization capacity of the artificial neural network for myelin water imaging (ANN-MWI) is explored by testing datasets with various scan protocols (i.e., resolution and refocusing RF pulse shape) and types of disorders (i.e., neuromyelitis optica and edema). @*Materials and Methods@#ANN-MWI was trained to generate a T2 distribution, from which the myelin water fraction value was measured. The training and test datasets were acquired from healthy controls and multiple sclerosis patients using a multiecho gradient and spin-echo sequence with the same scan protocols. To test the generalization capacity of ANN-MWI, datasets with different settings were utilized.The datasets were acquired or generated with different resolutions, refocusing pulse shape, and types of disorders. For all datasets, the evaluation was performed in a white matter mask by calculating the normalized root-mean-squared error (NRMSE) between the results from the conventional method and ANN-MWI. Additionally, for the patient datasets, the NRMSE was calculated in each lesion mask. @*Results@#The results of ANN-MWI showed high reliability in generating myelin water fraction maps from the datasets with different resolutions. However, the increased errors were reported for the datasets with different refocusing pulse shapes and disorder types. Specifically, the region of lesions in edema patients reported high NRMSEs. These increased errors indicate the dependency of ANN-MWI on refocusing pulse flip angles and T 2 characteristics. @*Conclusion@#This study proposes information about the generalization accuracy of a trained network when applying deep learning to processing myelin water imaging.

Electromyography-signal-based muscle fatigue assessment for knee rehabilitation monitoring systems

This study suggested a new EMG-signal-based evaluation method for knee rehabilitation that provides not only fragmentary information like muscle power but also in-depth information like muscle fatigue in the field of rehabilitation which it has not been applied to. In our experiment, nine healthy subjects performed straight leg raise exercises which are widely performed for knee rehabilitation. During the exercises, we recorded the joint angle of the leg andEMGsignals from four prime movers of the leg: rectus femoris (RFM), vastus lateralis, vastus medialis, and biceps femoris (BFLH). We extracted two parameters to estimate muscle fatigue from the EMG signals, the zero-crossing rate (ZCR) and amplitude of muscle tension (AMT) that can quantitatively assess muscle fatigue from EMG signals. We found a decrease in the ZCR for the RFM and the BFLH in the muscle fatigue condition for most of the subjects. Also, we found increases in theAMT for the RFM and the BFLH. Based on the results, we quantitatively confirmed that in the state of muscle fatigue, the ZCR shows a decreasing trend whereas theAMT shows an increasing trend. Our results show that both the ZCR and AMT are useful parameters for characterizing the EMG signals in the muscle fatigue condition. In addition, our proposed methods are expected to be useful for developing a navigation system for knee rehabilitation exercises by evaluating the two parameters in two-dimensional parameter space.

The Clinical Usefulness of Thermo-Sensitive Hydrogel-Type Allogeneic Keratinocytes for Treatment of Deep Second-Degree Burn

PURPOSE: Aim of this study was to assess the safety and effectiveness of Keraheal-Allo® (Biosolution Co., Ltd., Korea) in patients with deep second-degree burn as a part of post marketing surveillance. METHODS: Seventy-five patients with deep second-degree burn were enrolled from April 2017 to October 2017. Keraheal-Allo, a thermos-sensitive hydrogel-type allogeneic keratinocytes, was applied to 90 deep second-degree burn sites of 75 patients. After application of Keraheal-Allo, the efficacy was assessed as the period of 100% re-epithelialization that was evaluated every time dressing was changed. RESULTS: The mean re-epithelialization period in the treated sites with KeraHeal-allo was 13.67±5.11 days. There was no severe adverse event. CONCLUSION: In conclusion, this thermo-sensitive hydrogel-type allogeneic keratinocytes have the clinical usefulness in terms of the safety, efficacy and ease of use.

Myelin Water Fraction MRI in a Case of Clinically Probable Amyotrophic Lateral Sclerosis / 대한임상신경생리학회지

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that clinically manifests both upper and lower motor neuron signs. However, it is unknown where and how the motor neuron degeneration begins, and conflicting hypotheses have been suggested. Recent advanced radiological techniques enable us to look into ALS neuropathology in vivo. Herein, we report a case with upper motor neuron-predominant ALS in whom the results of brain magnetic resonance imaging (MRI) and myelin water fraction MRI suggest axonal degeneration.

Basaloid Squamous Cell Carcinoma on the Skin of the Hand

No abstract available.

Lymphoepithelioma-like Carcinoma of the Skin in the Cheek with a Malignant Metastatic Cervical Lymph Node

No abstract available.

A Phase III, Randomized, Double-Blind, Matched-Pairs, Active-Controlled Clinical Trial and Preclinical Animal Study to Compare the Durability, Efficacy and Safety between Polynucleotide Filler and Hyaluronic Acid Filler in the Correction of Crow's Feet: A

The Rejuran(R) is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran(R) on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire(R); and Group 3 were treated with Rejuran(R). The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran(R) treatment for crow's feet on one side and Yvoire-Hydro(R) on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran(R) group showed similar durability and inflammatory response to the Yvoire(R) group. Upon efficacy assessment, the Rejuran(R) group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran(R), as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.

Myocardial Mechanics in a Rat Model with Banding and Debanding of the Ascending Aorta

BACKGROUND: Aortic banding and debanding models have provided useful information on the development and regression of left ventricular hypertrophy (LVH). In this animal study, we aimed to evaluate left ventricular (LV) deformation related to the development and regression of LVH. METHODS: Minimally invasive ascending aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats underwent a sham operation. Thirty-five days later, the band was removed. Echocardiographic and histopathologic analysis was assessed at pre-banding, 35 days of banding and 14 days of debanding. RESULTS: Banding of the ascending aorta created an expected increase in the aortic velocity and gradient, which normalized with the debanding procedure. Pressure overload resulted in a robust hypertrophic response as assessed by gross and microscopic histology, transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 +/- 0.8 vs. 33.2 +/- 2.0 vs. 26.6 +/- 2.8, p < 0.001]. The circumferential (CS) and radial strains were not different between the groups. However, there were significant differences in the degree of fibrosis according to the banding status (fibrosis; 0.10 +/- 0.20% vs. 5.26 +/- 3.12% vs. 4.03 +/- 3.93%, p = 0.003), and global CS showed a significant correlation with the degree of myocardial fibrosis in this animal model (r = 0.688, p = 0.028). CONCLUSION: In this animal study, simulating a severe LV pressure overload state, a significant increase in the LV mass index did not result in a significant reduction in the LV mechanical parameters. The degree of LV fibrosis, which developed with pressure overload, was significantly related to the magnitude of left ventricular mechanics.

Endovascular treatment of ruptured infected aortic aneurysm with sepsis / 대한외과학회지

The generally accepted treatment for infected aortic aneurysms involves open surgical resection and debridement, with in situ or extra-anatomical bypass. Occasionally, endovascular management can be substituted for the standard operation dependent on the patient's condition. We report the case of an 81-year-old female with a ruptured infected aortic aneurysm and sepsis, successfully treated endovascularly. She had been on oral antibiotics for one year and is doing well 2 years after discharge.

Therapeutic Potential of Human Adipose Stem Cells in a Rat Myocardial Infarction Model

PURPOSE: Stem cell transplantation is expected to have good effects in the treatment of myocardial infarction (MI). We tested the effect of the transplantation of human adipose-derived cells (ASCs) in Sprague-Dawley (SD) rats with myocardial infarctions. MATERIALS AND METHODS: ASCs were isolated from the waste of elective abdominal surgery. The MI model was set up in SD rats by permanent ligation of the left anterior descending coronary artery. One week after MI, either 1 x 10(6) ASCs or an equal volume of phosphate-buffered saline (PBS) was injected into the infarct zone. Cardiac function was assessed by echocardiography, 1 day, 1 week, 2 weeks, and 4 weeks after treatment. Four weeks after transplantation, immunohistochemistry was performed. RESULTS: Left ventricular function, including fractional shortening (FS), and ejection fraction (EF) showed a significant improvement in the ASCs transplantation group compared to the PBS group 4 weeks after treatment (p < 0.05). The anterior wall thickness of the left ventricle was significantly thicker in the ASCs transplantation group compared to the PBS group (p < 0.01). Multiple troponin T staining, and irregular, small amounts of connexin 43 expression also was observed in the ASCs transplantation group. Infarcted myocardium showed higher capillary density in the ASCs transplantation group than in the PBS injected group (p < 0.01). CONCLUSION: This study provides encouraging evidence that transplantation of ASCs can improve cardiac function of infarct myocardium in rat models with a limitation of cardiac remodeling, improved wall thickness, and increased neovascularization.

Erythromycin Inhibits Interleukin-6 and Interleukin-8 Expression and Promotes Apoptosis of Activated Human Neutrophils in Vitro

Diffuse panbronchiolitis (DPB) is a pulmonary disease characterized by chronic inflammation of the bronchioles and chronic infiltration of inflammatory cells in the lungs. Macrolides are effective therapeutic agents for chronic respiratory tract diseases, such as DPB. However, the mechanisms by which macrolides modulate the immune responses in patients with DPB remain unclear. To understand clinical efficacy for the treatment of DPB by macrolides, the effects of erythromycin (EM) on the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8) by human neutrophils were examined. Pre-treatment with EM significantly decreased the expression of IL-6 and IL-8 transcripts by lipopolysaccharide (LPS)-stimulated human neutrophils. EM also reversed the enhanced survival of human neutrophils by LPS. These data indicate that EM has achieved therapeutic effect for patients with DPB, in part, through decreasing the expression of pro-inflammatory cytokines and the survival of neutrophils.

Alpha-Calcitonin Gene-Related Peptide-Null Mice Shows Normal Responses to Various Noxious Stimuli

Despite the wealth of data concerning the roles of alpha-CGRP in nociceptive behaviors, alpha-CGRP-null mice showed no obvious phenotypic differences in nociceptive behaviors from wild type. The present studies specifically demonstrate that alpha-CGRP null mice showed no CGRP immunoreactivity from the spinal cord, implying that CGRPs in the mice spinal cord are mainly a-isoforms. However, the nociceptive behaviors of the null mice are not significantly different from the wild type mice in thermal nociceptive behaviors on hotplate, chemical nociception tests to intraplantar capsaicin or formalin injection, and visceral pain behaviors to intraperitoneal acetic acid or magnesium sulfate injections. These data suggest that alpha-CGRP is dispensable for nociceptive behaviors or that compensatory mechanisms may exist to overcome the absence of this peptide.

A study of Nutritional Improvement in the Patients with Neurologic Disorders by Changing Enteral Feeding Methods

Protein-calories malnutrition is common among patients in the hospital. In particular, elderly patients with neurologic disorders has more risk of nutritional deficiency due to swallowing difficulty. Enteral tube feeding is more economical, physiological and immunological than parenteral nutrition for patients who have adequate gastrointestinal function. This study was conducted patients with neurologic disorders who received enteral nutrition at Asan Medical Center from February 1 to October 10, 2002. The control group (48 patients) were given traditional feeding methods 4 times a day while the treatment group (45 patients) were given improved feeding methods 3 times a day. We assessed nutritional status of patients and compared to both groups. We investigated body weight, serum albumin, hemoglobin, total lymphocyte count by means of nutrition markers. The objectives of this study is to reduce the time needed for nutritional requirement of patients without an increase in gastrointestinal intolerances. The results of this study are as follows: 1. Nutritional status of many patients in both groups were either malnourished or at risk for malnutrition. 2. The time to arrive to the nutritional requirements were 6.21 +/- 0.35 days for the control group and 4.24 +/- 0.52 days for the treatment group. The treatment group showed a significantly shorter amount of time. 3. The changes of the nutritional marker in the control group showed a significant drop in body weight, serum albumin and serum hemoglobin while the treatment group experienced a significant increase in body weight, serum albumin and total lymphocyte count. 4. Feeding intolerane such as diarrhea, high residual volume, ileus, nausea and vomiting were investigated. Diarrhea found in 25.1% (12 patients) of the control group and 22.2% (10 patients) of the treatment group and these findings are not significant.

Impact of Laser in Situ Keratomileusis (LASIK) Treatment on Quality of Life in Myopia Patients

PURPOSE: To evaluate the impact of LASIK on vision-related quality of life (QOL) in myopia patients METHODS: This study included 288 patients who received laser in situ keratomileusis (LASIK) between July and December 2001 from two eye clinics located in Seoul and Pusan. Myopia-specific Quality of Life Questionnaire (MQLQ) was developed. MQLQ contained 34 questions in 4 domains that assess the effect of LASIK on visual function, visual symptoms, social and role function, and psychological well-being. Baseline QOL for the condition that refractive error was corrected by glasses or contact lenses before undergoing LASIK were evaluated by means of self-administered questionnaire. The evaluation was repeated at 4 days, 1 month, 3 months, and 6 months after LASIK. All question items were rated on a scale ranging from 1 (maximal dysfuntion) to 5 (no dysfunction). RESULTS: Average score for the MQLQ changed from 3.20 preoperatively to 3.76, 3.99, 4.07, and 4.11 at 4 days, 1 month, 3 months, and 6 months after surgery, indicating a continuous improvement of overall QOL following LASIK. Among the 4 dimensions, social and role function showed the biggest improvement (changes in score: 1.48, p=0.001), followed by psychological well-being(0.98, p=0.001), visual function(0.67. p=0.001), and visual symptoms (0.49, p=0.001). CONCLUSIONS: LASIK has a significant contribution to improve QOL in myopia patients.

Normal Anxiety, Fear and Depression-related Behaviors in Mice Lacking alpha-Calcitonin Gene-Related Peptide

Calcitonin gene-related peptide (CGRP) expressing neurons are distributed widely throughout the central and peripheral nervous systems. Due to its distribution and pharmacological studies, CGRP has been implicated to be involved in anxiety, fear and depression. In this study, alphaCGRP-knockout mice were used to assess the consequences of removing this neuropeptide to the mice behaviors. alphaCGRP-knockout mice performed equally as well as wild type mice in the light-dark transition test and in the elevated plus maze test of anxiety. alphaCGRP-null mice behaved similarly as wild-type mice in the Porsolt swim test of depression. They also exhibited normal learning and memory in the fear conditioning tasks. It is concluded that alphaCGRP is not essential for mice to be able to perform these tests, despite the presence of alphaCGRP in the relevant regions of the brain.