Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy

Recessive mutations in chromosome 10 open reading frame 2 (C10orf2) are relevant in infantile-onset spinocerebellar ataxia (IOSCA). In this study, we investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. We investigated recessive mutations in a Korean family with two individuals affected by IOSCA. Causative mutations were investigated using whole exome sequencing. Electrophysiological analyses and muscle and nerve biopsies were performed, along with magnetic resonance imaging (MRI) of the brain and lower extremities. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. Skeletal muscle showed mitochondrial DNA (mtDNA) deletions. Both patients showed a period of normal development until 12–15 months, followed by ataxia, athetosis, hearing loss, and intellectual disability. Electrophysiological findings indicated motor and sensory polyneuropathies. Muscle biopsy revealed variations in the size and shape of myofibers with scattered, small, and angulated degenerating myofibers containing abnormal mitochondria; these observations are consistent with myopathy and may be the result of mtDNA deletions. Sural nerve biopsy revealed an axonal neuropathy. High-signal-intensity lesions in the middle cerebellar peduncles were correlated with clinical severity, and MRI of the lower legs was compatible with the hypothesis of length-dependent axonal degeneration. We identified novel compound heterozygous mutations of the C10orf2 gene as the cause of IOSCA with sensorimotor polyneuropathy and myopathy. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-014-0405-1) contains supplementary material, which is available to authorized users

Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus.

BackgroundDiabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.PurposeWe hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.MethodsRat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.ResultsQuantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.ConclusionTwo isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP

The risk of newly diagnosed cancer in patients with rheumatoid arthritis by TNF inhibitor use: a nationwide cohort study

Background : Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. Methods : Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. Results : Of the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255–0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235–0.797), breast cancer (0.146; 0.045–0.474), and genitourinary cancer (0.220; 0.059–0.820). Conclusions : The use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC17C0069

Individualized diabetes nutrition education improves compliance with diet prescription

This study was designed to evaluate the effect of individualized diabetes nutrition education. The nutrition education program was open to all type 2 diabetes patients visiting the clinic center and finally 67 patients agreed to join the program. To compare with 67 education group subjects, 34 subjects were selected by medical record review. The education program consisted of one class session for 1-2 hours long in a small group of 4~5 patients. A meal planning using the food exchange system was provided according to the diet prescription and food habits of each subject. Measurements of clinical outcomes and dietary intakes were performed at baseline and 3 months after the education session. After 3 months, subjects in education group showed improvement in dietary behavior and food exchange knowledge. In education group, intakes of protein, calcium, phosphorus, vitamin B2, and folate per 1,000 kcal/day were significantly increased and cholesterol intake was significantly decreased. They also showed significant reductions in body weight, body mass index (BMI), and fasting blood concentrations of glucose (FBS), HbA1c, total cholesterol, and triglyceride. However, no such improvements were observed in control group. To evaluate telephone consultation effect, after the nutrition education session, 34 subjects of the 67 education group received telephone follow-up consultation once a month for 3 months. The others (33 subjects) had no further contact after the nutrition education session. Subjects in the telephone follow-up group showed a decrease in BMI, FBS, and HbA1c. Moreover, the subjects who did not receive telephone follow-up also showed significant decreases in BMI and FBS. These results indicated that our individually planned education program for one session was effective in rectifying dietary behavior problems and improving food exchange knowledge, and quality of diet, leading to an improvement in the clinical outcomes. In conclusion, our individualized nutrition education was effective in adherence to diet recommendation and in improving glycemic control and lipid concentrations, while follow-up by telephone helped to encourage the adherence to diet prescription

Clinical Role of Interstitial Pneumonia in Patients with Scrub Typhus: A Possible Marker of Disease Severity

Interstitial pneumonia (IP) frequently occurs in patients with scrub typhus, but its clinical significance is not well known. This study was designed to evaluate interstitial pneumonia as a marker of severity of the disease for patients with scrub typhus. We investigated clinical parameters representing the severity of the disease, and the chest radiographic findings for 101 patients with scrub typhus. We then compared these clinical factors between patients with and without IP. We also studied the relationship between IP and other chest radiographic findings. The chest radiography showed IP (51.4%), pleural effusion (42.6%), cardiomegaly (14.9%), pulmonary alveolar edema (20.8%), hilar lymphadenopathy (13.8%) and focal atelectasis (11.8%), respectively. The patients with IP (n=52) had higher incidences in episode of hypoxia (p=0.030), hypotension (p=0.024), severe thrombocytopenia (p=0.036) and hypoalbuminemia (p=0.013) than the patients without IP (n=49). The patients with IP also had higher incidences of pleural effusion (p<0.001), focal atelectasis (p=0.019), cardiomegaly (p<0.001), pulmonary alveolar edema (p=0.011) and hilar lymphadenopathy (p<0.001) than the patients without IP. Our data suggest that IP frequently occurs for patients with scrub typhus and its presence is closely associated with the disease severity of scrub typhus

Corrected QTc interval combined with troponin value and mortality in acute ischemic stroke

Background and PurposeCardiac biomarkers including, elevated troponin (ET) and prolonged heart rate-corrected QT (PQTc) interval on electrocardiography are known to frequent and have a prognostic significance in patients with acute ischemic stroke (AIS). However, it is still challenging to practically apply the results for appropriate risk stratification. This study evaluate whether combining ET and PQTc interval can better assess the long-term prognosis in AIS patients.MethodsIn this prospectively registered observational study between May 2007 and December 2011, ET was defined as serum troponin-I ≥ 0.04 ng/ml and PQTc interval was defined as the highest tertile of sex-specific QTc interval (men ≥ 469 ms or women ≥ 487 ms).ResultsAmong the 1,668 patients [1018 (61.0%) men; mean age 66.0 ± 12.4 years], patients were stratified into four groups according to the combination of ET and PQTc intervals. During a median follow-up of 33 months, ET (hazard ratio [HR]: 4.38, 95% confidence interval [CI]: 2.94–6.53) or PQTc interval (HR: 1.53, 95% CI: 1.16–2.01) alone or both (HR: 1.77, 95% CI: 1.16–2.71) was associated with increased all-cause mortality. Furthermore, ET, PQTc interval alone or both was associated with vascular death, whereas only ET alone was associated with non-vascular death. Comorbidity burden, especially atrial fibrillation and congestive heart failure, and stroke severity gradually increased both with troponin value and QTc-interval.ConclusionsIn patients with AIS, combining ET and PQTc interval on ECG enhances risk stratification for long-term mortality while facilitating the discerning ability for the burden of comorbidities and stroke severity

Balloon Dilatation for Corrosive Esophageal Strictures in Children: Radiologic and Clinical Outcomes

Objective: We retrospectively evaluated the effectiveness of the esophageal balloon dilatation (EBD) in children with a corrosive esophageal stricture. Materials and Methods: The study subjects included 14 patients (M:F = 8:6, age range: 17-85 months) who underwent an EBD due to a corrosive esophageal stricture. The causative agents for the condition were glacial acetic acid (n = 9) and lye (n = 5). Results: A total of 52 EBD sessions were performed in 14 patients (range 1-8 sessions). During the mean 15-month follow-up period (range 1-79 months), 12 patients (86%) underwent additional EBD due to recurrent esophageal stricture. Dysphagia improved after each EBD session and oral feeding was possible between EBD sessions. Long-term success (defined as dysphagia relief for at least 12 months after the last EBD) was achieved in two patients (14%). Temporary success of EBD (defined as dysphagia relief for at least one month after the EBD session) was achieved in 17 out of 52 sessions (33%). A submucosal tear of the esophagus was observed in two (4%) sessions of EBD. Conclusion: Only a limited number of children with corrosive esophageal strictures were considered cured by EBD. However, the outcome of repeated EBD was sufficient to allow the children to eat per os prior to surgical management.Doo EY, 2009, CLIN RADIOL, V64, P265, DOI 10.1016/j.crad.2008.10.001PARK JY, 2009, KOREAN J PEDIAT, V52, P446Hyoung J, 2008, J VASC INTERV RADIOL, V19, P736, DOI 10.1016/j.jvir.2008.01.015Ko HK, 2006, J VASC INTERV RADIOL, V17, P1327, DOI 10.1097/01.RVI.0000232686.29864.0AWeintraub JL, 2006, J VASC INTERV RADIOL, V17, P831, DOI 10.1097/01.RVI.0000217964.55623.19Wilkinson AG, 2004, PEDIATR RADIOL, V34, P414, DOI 10.1007/s00247-004-1164-1Huang YC, 2004, PEDIATR SURG INT, V20, P207, DOI 10.1007/s00383-004-1153-3Lan LCL, 2003, J PEDIATR SURG, V38, P1712, DOI 10.1016/S0022-3468(03)00638-9Fasulakis S, 2003, PEDIATR RADIOL, V33, P682, DOI 10.1007/s00247-003-1011-9Hamza AF, 2003, J PEDIATR SURG, V38, P828Kukkady A, 2002, PEDIATR SURG INT, V18, P486, DOI 10.1007/s00383-002-0798-zYEMING W, 2002, J PEDIATR SURG, V37, P398Jayakrishnan VK, 2001, PEDIATR RADIOL, V31, P98Lisy J, 1998, ACAD RADIOL, V5, P832Yararbai O, 1998, HEPATO-GASTROENTEROL, V45, P59KIM IO, 1993, RADIOLOGY, V189, P741HAN HY, 1993, J KOREAN RADIOL SOC, V29, P1181SONG HY, 1992, RADIOLOGY, V184, P373GUNDOGDU HZ, 1992, J PEDIATR SURG, V27, P767LOVEJOY FH, 1990, NEW ENGL J MED, V323, P668MAYNAR M, 1988, RADIOLOGY, V167, P703DELANGE EE, 1988, RADIOLOGY, V167, P45SATO Y, 1988, AM J ROENTGENOL, V150, P639MCLEAN GK, 1987, RADIOLOGY, V165, P35GOLDTHORN JF, 1984, RADIOLOGY, V153, P655LONDON RL, 1981, GASTROENTEROLOGY, V80, P173MUHLETALER CA, 1980, AM J ROENTGENOL, V134, P1137RAGHEB MI, 1976, SURGERY, V79, P494

Effect of Chongkukjang on histamine-induced skin wheal response: A randomized, double-blind, placebo-controlled trial

AbstractBackgroundStudies in animals have demonstrated the antiallergenic properties of Chongkukjang (CKJ), a traditional Korean food made by fermentation of soybean with Bacillus subtilis. CKJ might therefore be used as an ingredient in a functional food designed to suppress allergies. The purpose of this study was to investigate the effect of CKJ on histamine-induced skin wheal response in healthy participants.MethodsA randomized, double-blind, placebo-controlled trial was conducted. Sixty participants (48 women and 12 men) were randomly assigned to one of two groups: One group received 35 g CKJ daily for 12 weeks, and the other received a placebo at the same dosing frequency. A skin prick test with histamine (10 mg/mL) was conducted on the ventral forearm 10 cm from the elbow, and assessed 15 minutes later. Outcomes included measurement of efficacy [skin wheal response, immunoglobulin E (IgE), histamine, interferon-gamma, interleukin-4, eosinophil, and eosinophil cationic protein (ECP)], and safety (adverse events, laboratory test results, electrocardiogram, anthropometric values, and vital signs).ResultsFifty-five participants (28 in the CKJ group and 27 in the placebo group) completed the study. After 12 weeks of supplementation, participants in the CKJ group showed a significant reduction in histamine-induced skin wheal areas compared with placebo group (p < 0.05). At 12 weeks, the CKJ group showed a significant improvement in percentage change from baseline in histamine-induced wheal area, compared with the placebo group (p < 0.05). CKJ did not influence blood levels of IgE, histamine, interferon-gamma, interleukin-4, eosinophil, or ECP.ConclusionOral administration of CKJ for 12 weeks resulted in a reduction of the skin wheal response to histamine, with no apparent adverse effects. Trial registration: ClinicalTrials.gov: NCT01402141