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Background@#and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. @*Methods@#This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). @*Results@#Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. @*Conclusions@#Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
ABSTRACT
Background@#and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. @*Methods@#This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). @*Results@#Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. @*Conclusions@#Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
ABSTRACT
Background and Objectives@#Upon operation of the tongue base for obstructive sleep apnea syndrome (OSAS), the lingual artery and the hypoglossal nerve are put at risk of injury, resulting in fatal complications such as massive bleeding upon damage. We studied the course of lingual artery in its relation with the tongue in OSAS patients and compared it with the age-and- gender-matched normal population.Subjects and Method Korean male patients confirmed with OSAS by polysomnography, including those who had contrast-enhanced computed tomography (ceCT) of the head and neck, were defined as “OSAS group.” Patients who had their ceCT image during the same study period were defined as the “control group.” The control group was paired with the OSAS group by age and sex. By using foramen cecum (FC) as the main reference point, four reference marks were defined. For each reference point, the distance between both lingual arteries and the depth of the lingual artery from the lingual surface of the tongue were evaluated. @*Results@#The depth of the lingual artery from the lingual surface of the tongue in the OSAS group (25.1±8.6 mm) was significantly different from the control (29.5±5.9 mm) at 1 cm anterior to the FC level (p<0.014). The width of both lingual arteries was narrower in the OSAS group (20.9±2.9) than in the control (24.3±6.1) at the FC level (p<0.003). @*Conclusion@#The course of lingual artery and its spatial relation with the tongue in Korean male OSAS patients differs from the matched normal population.
ABSTRACT
Guanine nucleotide exchange factors (GEFs) play multiple functional roles in neurons. In a previous study, we reported that Arhgef4 (Rho guanine nucleotide exchange factor 4) functioned as a negative regulator of the excitatory synaptic function by sequestering postsynaptic density protein 95 (PSD-95). However, the role ofArhgef4 in behavior has not been examined. We performed comprehensive behavioral tests in knockout (KO) mice to investigate of the effects of Arhgef4 deficiency. We found that the expressed PSD-95 particle size was significantly increased in hippocampal neuronal cultures from Arhgef4 KO mice, which is consistent with the previous in vitro findings.Arhgef4 KO mice exhibited general motor activity and anxiety-like behavior comparable to those of the wild type littermates. However, spatial memory and object recognition memory were significantly enhanced in the Arhgef4 KO mice. Taken together, these data confirm the role of Arhgef4 as a negative synaptic regulator at the behavioral level.
ABSTRACT
SHP2 is an unusual protein phosphatase that functions as an activator for several signaling pathways, including the RAS pathway, while most other phosphatases suppress their downstream signaling cascades. The physiological and pathophysiological roles of SHP2 have been extensively studied in the field of cancer research. Mutations in the PTPN11 gene which encodes SHP2 are also highly associated with developmental disorders, such as Noonan syndrome (NS), and cognitive deficits including learning disabilities are common among NS patients. However, the molecular and cellular mechanism by which SHP2 is involved in cognitive functions is not well understood. Recent studies using SHP2 mutant mice or pharmacological inhibitors have shown that SHP2 plays critical role in learning and memory and synaptic plasticity. Here, we review the recent studies demonstrating that SHP2 is involved in synaptic plasticity, and learning and memory, by the regulation of the expression and/or function of glutamate receptors. We suggest that each cell type may have distinct paths connecting the dots between SHP2 and glutamate receptors, and these paths may also change with aging.
ABSTRACT
SHP2 is an unusual protein phosphatase that functions as an activator for several signaling pathways, including the RAS pathway, while most other phosphatases suppress their downstream signaling cascades. The physiological and pathophysiological roles of SHP2 have been extensively studied in the field of cancer research. Mutations in the PTPN11 gene which encodes SHP2 are also highly associated with developmental disorders, such as Noonan syndrome (NS), and cognitive deficits including learning disabilities are common among NS patients. However, the molecular and cellular mechanism by which SHP2 is involved in cognitive functions is not well understood. Recent studies using SHP2 mutant mice or pharmacological inhibitors have shown that SHP2 plays critical role in learning and memory and synaptic plasticity. Here, we review the recent studies demonstrating that SHP2 is involved in synaptic plasticity, and learning and memory, by the regulation of the expression and/or function of glutamate receptors. We suggest that each cell type may have distinct paths connecting the dots between SHP2 and glutamate receptors, and these paths may also change with aging.
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BACKGROUND AND PURPOSE: Thrombectomy within 24 hours can improve outcomes in selected patients with a clinical-infarct mismatch. We devised an easy-to-use visual estimation tool that allows infarct volume estimation in centers with limited resources. METHODS: We identified 1,031 patients with cardioembolic or large-artery atherosclerosis infarction on diffusion-weighted images (DWIs) obtained before recanalization therapy and within 24 hours of onset, and occlusion of the internal carotid or middle cerebral artery. Acute DWIs were mapped onto a standard template and used to create visual reference maps with known lesion volumes, which were then used in a validation study (with 130 cases) against software estimates of infarct volume. RESULTS: The DWI reference map chart comprises 144 maps corresponding to 12 different infarct volumes (0.5, 1, 2, 3, 5, 7, 9, 11, 13, 15, 17, and 19 mL) in each of 12 template slices (Montreal Neurological Institute z-axis –15 to 51 mm). Infarct volume in a patient is estimated by selecting a slice with a similar infarct size at the corresponding z-axis level on the reference maps and then adding up over all slices. The method yielded good correlations to software volumetrics and was easily learned by both experienced and junior physicians, with approximately 1 to 2 minutes spent per case. The sensitivity, specificity, and accuracy for detecting threshold infarct volumes ( 90%). CONCLUSIONS: We developed easy-to-use reference maps that allow prompt and reliable visual estimation of infarct volumes for triaging patients to thrombectomy in acute stroke.
Subject(s)
Humans , Atherosclerosis , Cerebral Infarction , Decision Making , Diffusion Magnetic Resonance Imaging , Infarction , Medical Staff, Hospital , Methods , Middle Cerebral Artery , Sensitivity and Specificity , Stroke , ThrombectomyABSTRACT
Vacuolar protein sorting-associated protein 13B (VPS13B), also known as COH1, is one of the VPS13 family members which is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Mutations in the VPS13B gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the patho-physiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a Vps13b exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that Vps13b mutant mice showed reduced activity in open field test and significantly shorter latency to fall in the rotarod test, suggesting that the mutants have motor deficits. In addition, we found that Vps13b mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The Vps13b mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that Vps13b mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. Vps13b mutant mice may serve as a useful model to investigate the pathophysiology of VPS13B-associated disorders.
Subject(s)
Animals , Humans , Mice , Autism Spectrum Disorder , Cognition Disorders , Exons , Intellectual Disability , Learning Disabilities , Memory, Short-Term , Models, Animal , Muscle Hypotonia , Phenotype , Rotarod Performance Test , Social Behavior , Spatial Learning , WaterABSTRACT
OBJECTIVE: This study aimed to determine the factors affecting pathologic discrepancy and final diagnosis between colposcopic biopsy and pathology by loop electrosurgical excision procedure (LEEP). METHODS: Between 2004 and 2016, 1,200 patients who underwent LEEP were enrolled for this study. 667 underwent cervical cytology, human papillomavirus (HPV) test, colposcopic biopsy, and LEEP. We analyzed patient's age, menopausal status, number of delivery, abortion times, cervical cytology, number of punch biopsies, HPV type, LEEP, and interval between colposcopic biopsy and LEEP. RESULTS: Logistic regression analysis of the final diagnosis showed that age 30–39 years and other high HPV group types were associated with cancer diagnosis, whereas atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), high-grade squamous intraepithelial lesion (HSIL), and HPV type 16 affected the diagnosis of cervical intraepithelial neoplasia (CIN) 2. The overall concordance rate of histopathology between punch biopsy and LEEP was 43.3%. The rates of detecting a more severe lesion by LEEP than those by biopsy were 23.1%. The rates of a less severe lesion detected by LEEP than those by biopsy were 33.6%. Factors related with biopsy underestimation were as follows: < 1 vaginal delivery, HSIL, number of punch biopsies and HPV type. Punch biopsy number is a unique factor of biopsy overestimation. CONCLUSION: Patients with ASC-H, HSIL, and HPV type 16 may undergo conization immediately without colposcopic biopsy. We suggest that colposcopically directed 3 to 5 punch biopsies may be used to determine the need for conization.
Subject(s)
Female , Humans , Atypical Squamous Cells of the Cervix , Biopsy , Uterine Cervical Dysplasia , Cervix Uteri , Conization , Diagnosis , Logistic Models , Papanicolaou Test , Pathology , Squamous Intraepithelial Lesions of the CervixABSTRACT
Benign multicystic peritoneal mesothelioma (BMPM) is rare and difficult to diagnose before surgery. We report a case of BMPM incidentally discovered during laparoendoscopic single site surgery (LESS) for treatment of a pelvic mass. A 47-year-old Korean menopaused woman presented to our outpatient clinic with a pelvic mass. She had a history of right ovary cystectomy with adhesiolysis at a local hospital in 2010. Imaging study of the pelvis revealed a multilocular cystic mass. LESS was performed and multiple grapelike clusters of cysts were seen in the uterus, cul-de-sac, both adnexa, pelvic wall, and omentum. The appendix was grossly free. Frozen biopsy confirmed BMPM. Excision of multiple cyst clusters of cysts, resection of the uterus with both adnexa, appendectomy, omentectomy, and adhesiolysis were performed with LESS. She is well for 2 years with no recurrence. BMPM should be included in the differential diagnosis when small multichamber cystic mass is found on ultrasonography.
Subject(s)
Female , Humans , Middle Aged , Ambulatory Care Facilities , Appendectomy , Appendix , Biopsy , Cystectomy , Diagnosis, Differential , Mesothelioma , Omentum , Ovary , Pelvis , Recurrence , Ultrasonography , UterusABSTRACT
What is memory? How does the brain process the sensory information and modify an organism's behavior? Many neuroscientists have focused on the activity- and experience-dependent modifications of synaptic functions in order to solve these fundamental questions in neuroscience. Recently, the plasticity of intrinsic excitability (called intrinsic plasticity) has emerged as an important element for information processing and storage in the brain. As the cerebellar Purkinje cells are the sole output neurons in the cerebellar cortex and the information is conveyed from a neuron to its relay neurons by forms of action potential firing, the modulation of the intrinsic firing activity may play a critical role in the cerebellar learning. Many voltage-gated and/or Ca²⁺-activated ion channels are involved in shaping the spiking output as well as integrating synaptic inputs to finely tune the cerebellar output. Recent studies suggested that the modulation of the intrinsic excitability and its plasticity in the cerebellar Purkinje cells might function as an integrator for information processing and memory formation. Moreover, the intrinsic plasticity might also determine the strength of connectivity to the sub-cortical areas such as deep cerebellar nuclei and vestibular nuclei to trigger the consolidation of the cerebellar-dependent memory by transferring the information.
Subject(s)
Action Potentials , Electronic Data Processing , Brain , Cerebellar Cortex , Cerebellar Nuclei , Cerebellum , Fires , Ion Channels , Learning , Memory , Neuronal Plasticity , Neurons , Neurosciences , Plastics , Purkinje Cells , Vestibular NucleiABSTRACT
Travel-acquired dengue cases have been increasing as the overall global dengue burden has expanded. In Korea, imported dengue cases have been reported since 2000 when it first became a notifiable disease. During the first four months of 2016, three times more dengue cases were reported in Korea than during the same period the previous year. A safe and efficacious vaccine for travelers would be beneficial to prevent dengue disease in individual travelers and potentially decrease the risk of virus spread to non-endemic areas. Here, we summarize the characteristics of dengue vaccines for travelers and review dengue vaccines currently licensed or in clinical development.
Subject(s)
Dengue Vaccines , Dengue , KoreaABSTRACT
Percutaneous transhepatic biliary drainage (PTBD) is a modality that is used to decompress obstructive jaundice due to impacted stones, benign stricture or cancer. The PTBD catheter is removed percutaneously after the restoration of internal biliary drainage. We experienced a case of a 62-year-old man with peritonitis due to the migration of the PTBD catheter into the peritoneal cavity; we successfully removed it using peroral endoscopy. Although rare, the PTBD catheter may migrate into the peritoneal cavity during the removal of it. In these cases, clinicians should consider the peroral endoscopic removal of the PTBD catheter.
Subject(s)
Humans , Middle Aged , Catheters , Cholestasis , Constriction, Pathologic , Drainage , Endoscopes , Endoscopy , Jaundice, Obstructive , Peritoneal Cavity , PeritonitisABSTRACT
No abstract available.
Subject(s)
Arteries , Ataxia , Infarction , Spinal Cord Vascular DiseasesABSTRACT
Intracranial lesions may show contrast enhancement through various mechanisms that are closely associated with the disease process. The preferred magnetic resonance sequence in contrast imaging is T1-weighted imaging (T1WI) at most institutions. However, lesion enhancement is occasionally inconspicuous on T1WI. Although fluid-attenuated inversion recovery (FLAIR) sequences are commonly considered as T2-weighted imaging with dark cerebrospinal fluid, they also show mild T1-weighted contrast, which is responsible for the contrast enhancement. For several years, FLAIR imaging has been successfully incorporated as a routine sequence at our institution for contrast-enhanced (CE) brain imaging in detecting various intracranial diseases. In this pictorial essay, we describe and illustrate the diagnostic importance of CE-FLAIR imaging in various intracranial pathologic conditions.
Subject(s)
Humans , Arachnoid Cysts/diagnosis , Brain/pathology , Brain Neoplasms/diagnosis , Contrast Media , Magnetic Resonance Imaging/methodsABSTRACT
OBJECTIVE: To investigate the relationship of somatization and depression with the degree of lower urinary tract symptoms suggestive of benign prostate hyperplasia (LUTS/BPH) and changes in psychometric profiles including somatization and depression after treatment of LUTS/BPH. METHODS: Subjects were evaluated at baseline and at week 12 following routine treatment for LUTS/BPH using the International Prostate Symptom Score (IPSS) to measure the severity of LUTS/BPH, the Overactive Bladder Symptom Score (OABSS) to measure the severity of OAB, the Patient Health Questionnaire-9 (PHQ-9) to assess depression, and the Patient Health Questionnaire-15 (PHQ-15) to evaluate somatization. The correlation of somatization and depression with the degree of LUTS/BPH symptoms at baseline and changes in somatization and depression after LUTS/BPH treatment were assessed using relevant statistical analyses. RESULTS: One hundred and twenty patients agreed to participate in this study, and 101 (84.2%) completed the 12-week trial and responded to the study questionnaires. At baseline, total IPSS score was correlated with PHQ-9 (r=0.475, p=0.005) and PHQ-15 (r=0.596, p<0.001) scores. The results after the 12-week treatment clearly show significant improvement in both PHQ-9 (p <0.001) and PHQ-15 (p=0.019) scores, and the PHQ-9 (r=0.509, p=0.048) and PHQ-15 (r=0.541, p=0.016) scores were positively correlated with total IPSS. CONCLUSION: Our preliminary results indicated that severity of LUTS is correlated with severity of somatization and depression. Further, the improvement of LUTS after treatment may have positive impacts on somatization and depression.