This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases.This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guide‑ lines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to pre‑ sent recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.

Background: Ischemic stroke is a serious neurological disorder caused by blockages in cerebral artery. Protein phosphatase 2A (PP2A) is a phosphatase that performs a critical role in cell signaling and growth. PP2A subunit B acts as a neuroprotective agent in the nerve system. Chlorogenic acid, which is mainly found in roasted coffee, has antioxi‑ dant, anti-inflammatory, and anti-apoptotic effects. We hypothesized that chlorogenic acid modulates PP2A subunit B expression in ischemic stroke models and glutamate-mediated neurons. Middle artery occlusion (MCAO) surgery was operated and chlorogenic acid (30 mg/kg) or phosphate buffer saline was treated 2 h after MCAO. The cerebral cortex was collected 24 h after surgery and the change of PP2A subunit B expression was analyzed. Glutamate and/ or chlorogenic acid were treated in cultured neurons, further study was performed. Results: A decrease in PP2A subunit B expression in MCAO animals was identified. Chlorogenic acid alleviated this decrease due to ischemic injury. Moreover, the number of PP2A subunit B-positive cells in the ischemic cerebral cortex was significantly decreased, chlorogenic acid alleviated this decrease. We also found protective effects of chlo‑ rogenic acid in neurons exposed to glutamate. Glutamate decreased the expression of PP2A subunit B and chloro‑ genic acid mitigated this decrease. Our results elucidated that chlorogenic acid performs neuroprotective functions and attenuates the reduction of PP2A subunit B by brain damage and glutamate-mediated excitotoxicity. Conclusions We showed that chlorogenic acid attenuated the decrease of PP2A subunit B in ischemic injury and neurons exposed to glutamate. Since PP2A subunit B contributes to the protection of brain tissue, we can sug‑ gest that chlorogenic acid preserves neurons by modulating PP2A subunit B during ischemic damage.

Background/Aims: The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout. Methods: We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment. Results: The study included 232 patients. ‘Gout concern overall’ scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and ‘well-being during attack’ scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the ‘well-being during attack’ and ‘gout concern during attack’ scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the ‘gout concern overall’ and ‘gout concern during attack’ scores (p = 0.04 and p = 0.002, respectively). Conclusions Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.

Purpose: Obesity has emerged as a critical global public health concern as it is associated with and increases susceptibility to various diseases. This condition is characterized by the excessive enlargement of adipose tissue, primarily stemming from an inequity between energy intake and expenditure. The purpose of this study was to investigate the potential of sweet pumpkin powder in mitigating obesity and metabolic disorders in leptin-deficient obese (ob/ob) mice and to compare the effects of raw sweet pumpkin powder (HNSP01) and heat-treated sweet pumpkin powder (HNSP02). Methods: Leptin-deficient obese mice were fed a diet containing 10% HNSP01 and another containing 10% HNSP02 for 6 weeks. Results: The supplementation of ob/ob mice with HNSP01 and HNSP02 resulted in decreased body weight gain, reduced adipose tissue weight, and a smaller size of lipid droplets in the adipose tissue and liver. Furthermore, the ob/ob-HNSP01 and ob/ob-HNSP02 supplemented groups exhibited lower levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and insulin, as well as a reduced atherogenic index in comparison with the control group. Molecular analysis also demonstrated that the intake of HNSP01 and HNSP02 resulted in a diminished activation of factors associated with fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase, while concurrently enhancing factors associated with lipolysis, including adipose triglyceride lipase and hormone-sensitive lipase, in the adipose tissue. Conclusion Taken together, these findings collectively demonstrate the potential of sweet pumpkin powder as a functional food ingredient with therapeutic properties against obesity and its associated metabolic disorders, such as insulin resistance and dyslipidemia.

Background: There are several differences in the clinical course of hypertension due to the biological and social differences between men and women. Resistant hypertension is an advanced disease state, and significant gender difference could be expected, but much has not been revealed yet. The purpose of this study was to compare gender differences on the current status of blood pressure (BP) control and clinical prognosis in patients with resistant hypertension. Methods: This is a multicenter, retrospective cohort study using common data model databases of 3 tertiary hospitals in Korea. Total 4,926 patients with resistant hypertension were selected from January 2017 to December 2018. Occurrence of dialysis, heart failure (HF) hospitalization, myocardial infarction, stroke, dementia or all-cause mortality was followed up for 3 years. Results: Male patients with resistant hypertension were younger but had a higher cardiovascular risk than female patients. Prevalence of left ventricular hypertrophy and proteinuria was higher in men than in women. On-treatment diastolic BP was lower in women than in men and target BP achievement rate was higher in women than in men.During 3 years, the incidence of dialysis and myocardial infarction was higher in men, and the incidence of stroke and dementia was higher in women. After adjustment, male sex was an independent risk factor for HF hospitalization, myocardial infarction, and all-cause death. Conclusion In resistant hypertension, men were younger than women, but end-organ damage was more common and the risk of cardiovascular event was higher. More intensive cardiovascular prevention strategies may be required in male patients with resistant hypertension.

Rab40 proteins are an atypical subgroup of Rab GTPases containing a unique suppressor of the cytokine signaling (SOCS) domain that is recruited to assemble the CRL5 E3 ligase complex for proteolytic regulation in various biological processes. A nonsense mutation deleting the C-terminal SOCS box in the RAB40B gene was identified in a family with axonal peripheral neuropathy (Charcot-Marie-Tooth disease type 2), and pathogenicity of the mutation was assessed in model organisms of zebrafish and Drosophila. Compared to control fish, zebrafish larvae transformed by the human mutant hRAB40B-Y83X showed a defective swimming pattern of stalling with restricted localization and slower motility. We were consistently able to observe reduced labeling of synaptic markers along neuromuscular junctions of the transformed larvae. In addition to the neurodevelopmental phenotypes, compared to normal hRAB40B expression, we further examined ectopic expression of hRAB40B-Y83X in Drosophila to show a progressive decline of locomotion ability. Decreased ability of locomotion by ubiquitous expression of the human mutation was reproduced not with GAL4 drivers for neuron-specific expression but only when a pan-glial GAL4 driver was applied. Using the ectopic expression model of Drosophila, we identified a genetic interaction in which Cul5 down regulation exacerbated the defective motor performance, showing a consistent loss of SOCS box of the pathogenic RAB40B. Taken together, we could assess the possible gain-of-function of the human RAB40B mutation by comparing behavioral phenotypes in animal models; our results suggest that the mutant phenotypes may be associated with CRL5-mediated proteolytic regulation.

The accuracy and convenience of continuous glucose monitoring (CGM), which efficiently evaluates glycemic variability and hypoglycemia, are improving. There are two types of CGM: professional CGM and personal CGM. Personal CGM is subdivided into real-time CGM (rt-CGM) and intermittently scanned CGM (isCGM). CGM is being emphasized in both domestic and foreign diabetes management guidelines. Regardless of age or type of diabetes, CGM is useful for diabetic patients undergoing multiple insulin injection therapy or using an insulin pump. rt-CGM is recommended for all adults with type 1 diabetes (T1D), and can also be used in type 2 diabetes (T2D) treatments using multiple insulin injections. In some cases, short-term or intermittent use of CGM may be helpful for patients with T2D who use insulin therapy other than multiple insulin injections and/or oral hypoglycemic agents. CGM can help to achieve A1C targets in diabetes patients during pregnancy. CGM is a safe and cost-effective alternative to self-monitoring blood glucose in T1D and some T2D patients. CGM used in diabetes management works optimally with proper education, training, and follow up. To achieve the activation of CGM and its associated benefits, it is necessary to secure sufficient repetitive training and time for data analysis, management, and education. Various supports such as compensation, insurance coverage expansion, and reimbursement are required to increase the effectiveness of CGM while considering the scale of benefit recipients, policy priorities, and financial requirements.

The World Health Organization 2016 edition assigned anaplastic lymphoma kinase (ALK) rearrangement-associated renal cell carcinoma (ALK-RCC) as an emerging renal tumor entity. Identifying ALK-RCC is important because ALK inhibitors have been shown to be effective in treatment. Here, we report the case of a 14-year-old young man with ALK-RCC. Computed tomography revealed a well-demarcated 5.3-cm enhancing mass at the upper pole of the left kidney. There was no further history or symptoms of the sickle-cell trait. The patient underwent left radical nephrectomy. Pathologically, the mass was diagnosed as an unclassified RCC. Targeted next-generation sequencing identified a TPM3-ALK fusion gene. The present report and literature review demonstrate that TPM3-ALK RCC may be associated with distinct clinicopathological features. Microscopically, the tumors showed diffuse growth and tubulocystic changes with inflammatory cell infiltration. Tumor cells were dis-cohesive and epithelioid with abundant eosinophilic cytoplasm and cytoplasmic vacuoles. If morphological features and TFE3 expression are present in adolescent and young patients, molecular tests for ALK translocation should be performed. This awareness is critically important, because ALK rearrangement confers sensitivity to ALK inhibitors.
Adolescent ; Carcinoma, Renal Cell ; Cytoplasm ; Eosinophils ; Gene Rearrangement ; Humans ; Kidney ; Lymphoma ; Nephrectomy ; Phosphotransferases ; Vacuoles ; World Health Organization

Glutamate induces neurotoxicity during brain development, causing nerve damage. Protein phosphatase 2A (PP2A) is a type of serine/threonine phosphatase that regulates various biological functions. Among the PP2A subunit types, subunit B is abundant in brain tissue and plays an essential role in the nervous system. This study investigated changes in PP2A subunit B expression through glutamate exposure in the cerebral cortex of newborn rats. Sprague-Dawley rat pups (7 days after birth) were injected intraperitoneally with vehicle or glutamate (10 mg/kg). After 4 h of drug treatment, the brain tissue was isolated and fixed for morphological study. In addition, the cerebral cortex was collected for RNA and protein works. We observed severe histopathological changes including swollen neuron and atrophied dendrite in the glutamate exposed cerebral cortex. Glutamate exposure leads to a decrease in PP2A subunit B. Reverse-transcription PCR and Western blot analyses confirmed that glutamate induces a decrease of PP2A subunit B in the cerebral cortex of newborn rats. Moreover, immunohistochemical study showed a decrease in PP2A subunit B positive cells. The reduction of PP2A subunit B expression is considered an indicator of neurodegenerative damage. These results suggest that glutamate exposure causes neuronal damage in the cerebral cortex of new born rats through a decrease in PP2A subunit B.