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.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare neoplasm that is frequently located in the distal extremities. Emerging evidence suggests that MIFS can also affect the proximal limbs, trunk, and scalp, and aggressive clinical courses have been noted. We report a case of MIFS that occurred suddenly in the patient’s forearm and grew rapidly within 2 weeks. A level of Ki-67 was observed in the patient’s lesion, which constitutes a considerable finding compared with most MIFS cases. The patient underwent surgical tumor removal, and no evidence of recurrence was noted. We highlight this case in view of its sudden occurrence and rapid local progression, which contradicts the usual features of this disease, suggesting that this clinical course might be attributable to the high Ki-67 value.

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.

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.

No abstract available.
Epilepsy ; Humans ; Ophthalmoplegia

PURPOSE: Thrombosis of the portal vein, known as pylephlebitis, is a rare and fatal complication caused by intraperitoneal infections. The disease progression of superior mesenteric venous thrombosis (SMVT) is not severe. This study aimed to determine the clinical features, etiology, and prognosis of SMVT. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 41 patients with SMVT from March 2000 to February 2017. We obtained a list of 305 patients through the International Classification of Disease-9 code system and selected 41 patients with SMVT with computed tomography. Data from the medical records included patient demographics, comorbidities, review of system, laboratory results, clinical courses, and treatment modalities. RESULTS: The causes of SMVT were found to be intraperitoneal inflammation in 27 patients (65.9%), malignancy in 7 patients (17.1%), and unknown in 7 patients (17.1%). Among the patients with intraperitoneal inflammation, 14 presented with appendicitis (51.9%), 7 with diverticulitis (25.9%), and 2 with ileus (7.4%). When comparing patients with and without small bowel resection, the differences in symptom duration, bowel enhancement and blood culture were significant (P=0.010, P=0.039, and P=0.028, respectively). CONCLUSION: SMVT, caused by intraperitoneal inflammation, unlike portal vein thrombosis including pylephlebitis, shows mild prognosis. In addition, rapid symptom progression and positive blood culture can be the prognostic factors related to extensive bowel resection. Use of appropriate antibiotics and understanding of disease progression can help improve the outcomes of patients with SMVT.
Anti-Bacterial Agents ; Appendicitis ; Classification ; Comorbidity ; Demography ; Disease Progression ; Diverticulitis ; Humans ; Ileus ; Inflammation ; Medical Records ; Mesenteric Ischemia ; Portal Vein ; Prognosis ; Retrospective Studies ; Thrombosis ; Venous Thrombosis

The Editorial Office of Obstet Gynecol Sci would like to correct the author list.