Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the 17p12 region including PMP22 gene. In CMT1A patients, anticipation showing increased severity by generations has been reported in the CMT1A patients. It has also been reported that severity increases in the non-de novo cases than in the de novo cases. This study was performed to examine epigenetic differences between CMT1A cases and controls as well as between de novo cases and non-de novo cases. Methods: This study examined 40 Korean CMT1A patients and 11 controls. Methylation level was determined using the SureSelect XT Methyl-Seq reagent kit and bisulfite sequence mapping program. Results: Many differentially methylated CpG sites (DMCs) were identified in the comparisonbetween cases and controls and between de novo cases and non-de novo cases. Most DMCs were located within or nearby genes related to the nervous system, mental stress, and motor ability. Conclusions This study is the first epigenetic study to uncover the mechanism of clinical heterogeneity among CMT1A patients. We suggest that weak severity in the de novo cases than the non-de novo cases may be related to the epigenomic differences in the nerve and stress-related genes.

Objectives: The purpose of this study was to identify any difference in user experience between tablet- and augmented reality (AR) glasses-based tele-exercise programs in elderly women. Methods: Participants in the AR group (n = 14) connected Nreal glasses with smartphones to display a pre-recorded exercise program, while each member of the tablet group (n = 13) participated in the same exercise program using an all-in-one personal computer. The program included sitting or standing on a chair, bare-handed calisthenics, and muscle strengthening using an elastic band. The exercise movements were presented first for the upper and then the lower extremities, and the total exercise time was 40 minutes (5 minutes of warm-up exercises, 30 minutes of main exercises, and 5 minutes of cool-down exercises). To evaluate the user experience, a questionnaire consisting of a 7-point Likert scale was used as a measurement tool. In addition, the Wilcoxon rank-sum test was used to assess differences between the two groups. Results: Of the six user experience scales, attractiveness (p = 0.114), stimulation (p = 0.534), and novelty (p = 0.916) did not differ significantly between the groups. However, efficiency (p = 0.006), perspicuity (p = 0.008), and dependability (p = 0.049) did vary significantly between groups. Conclusions When developing an AR glasses-based exercise program for the elderly, the efficiency, clarity, and stability of the program must be considered to meet the participants’ needs.

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.

Background/Aims: Extrahepatic comorbidities and comedication are important to consider in the treatment of chronic hepatitis C (CHC) patients with direct-acting antivirals (DAAs) due to the risk of drug-drug interaction (DDI) and the effect of comorbidities on clinical outcomes. This study aimed to investigate the detailed profiles of comorbidities and comedication among Korean CHC patients. Methods: All adult patients (≥18 years old) with a primary diagnostic code of CHC in 2013 were selected from the National Health Insurance claims database. For each patient, all ICD-10 codes listed as primary or secondary diagnoses and all prescribed medications were collected. Results: Among 47,104 CHC patients (median age, 57 years; male, 49.3%), 84.8% had at least one comorbidity for a mean number of 2.4, which increased with age. The most prevalent comorbidities were hypertension, esophagitis, dyslipidemia, diabetes mellitus, and peptic ulcer. Overall, 96.8% of the patients took at least one prescribed medication, with a mean of 8.1 medications/ year, and the three most common drug types were analgesics, gastrointestinal agents, and antibacterials. Use of at least one drug with a DDI risk category of “contraindicated medication” or “required dose- reduction/additional monitoring” was observed in 97% of the overall patients. The proportion of prescribed medications that were contraindicated with DAAs varied from 2.0% to 38.9% depending on the hepatitis C virus regimen. Conclusions The majority of CHC patients had comorbidities; almost all patients took multiple prescribed medications, the number of which increased with age, and significant DDI risk was present in 97% of this Korean patient cohort. Comorbidities and comedication profiles should be considered during DAA therapy.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

ehydration, electrolyte disturbance, and acid-base imbalance are the most significant consequences of diarrhea in calves. We aimed to determine blood gas, hematological, electrolyte, and biochemical values and investigate the relationship between the physical status and blood parameters in Korean native calves (KNCs) with diarrhea. One hundred eighty KNCs with diarrhea (age < 75 days) were investigated. Blood samples were collected from the external jugular vein and analyzed using a portable clinical blood gas analyzer. The measured parameters were statistically compared according to the status of physical activity, dehydration, or prognosis. The mean values of parameters in the Calves with diarrhea showed metabolic acidosis, hyponatremia, and azotemia. The mean values of potassium, chloride, hematocrit, and hemoglobin were in the upper limit of their reference ranges. More than 75% of the calves had metabolic acidosis caused by bicarbonate loss, and 63.6% had high blood urea nitrogen (BUN) values. Moreover, BUN showed the highest correlation with the physical activity status and dehydration. pH, base excess of the extracellular fluid (BE), anion gap, potassium, hematocrit, bicarbonate, and hemoglobin were closely correlated with physical deterioration and dehydration (p < 0.001). BUN, pH, BE, and anion gap were closely correlated with physical deterioration and dehydration. These correlations between clinical symptoms and blood gas parameters can be clinically relevant in predicting the status of parameters according to clinical symptoms.

Background/Aims: The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival. Methods: Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017. Results: The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients. Conclusions The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

Background: and PurposeA cognitive intervention (CI) is thought to improve cognition and delay cognitive decline via neuronal plasticity and cognitive resilience. Subjective cognitive decline (SCD) might be the first symptomatic stage of Alzheimer's disease, but few studies have examined the beneficial effect of CIs in SCD. We aimed to determine the efficacy of a 12-week, small-group-based, multidomain CI in elderly patients with SCD. Methods: Participants diagnosed with SCD (aged 55–75 years) were consecutively allocated to three groups: group 1, which received group-based CI implementation with lifestyle modifications; group 2, which received home-based lifestyle modifications without CI; and group 3, in which no action was taken. The primary outcome variables were the scores on computerized tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The secondary outcomes included scores on tests evaluating general cognition, memory, visuospatial, and executive functions, as well as scores for the quality of life (QoL), anxiety, depression, and degree of subjective complaints. Changes in scores during the study period were compared between groups. Results: The study was completed by 56 SCD participants. The baseline characteristics did not differ among the groups. The primary outcomes (CANTAB scores) did not differ among the groups. However, the outcomes for phonemic word fluency, verbal memory, QoL, and mood were better for group 1 than for the other two groups. Improvements in verbal memory function and executive function were related to the baseline cognitive scores and group differences. Conclusions CI in SCD seems to be partially beneficial for executive function, memory, QoL, and mood, suggesting that CI is a useful nonpharmacological treatment option in this population.

Purpose: The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. Materials and Methods: Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. Results: Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. Conclusion Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.