Long-term outcomes for Asian patients with X-linked hypophosphataemia : rationale and design of the SUNFLOWER longitudinal, observational cohort study

Introduction X-linked hypophosphataemic rickets/osteomalacia (XLH) is a chronic, debilitating genetic disease characterised by skeletal abnormalities and growth disorder. The burden of XLH begins in childhood and continues throughout life. Conventional medical therapy with phosphate, active vitamin D and surgery do not address the underlying pathophysiology of the disease. While treatment during childhood may improve bone deformity and growth retardation, a large proportion of adult patients still fail to reach normal stature. Furthermore, adult patients with XLH report comorbidities associated with unresolved childhood disease, as well as newly developed disease-related complications and significantly impaired quality of life (QOL). Despite the multiple negative aspects of XLH, Asian consensus statements for diagnosis and management are lacking. Methods and analysis The Study of longitUdinal observatioN For patients with X-Linked hypOphosphataemic rickets/osteomalacia in collaboration With Asian partnERs study is a longitudinal observational cohort study of patients with XLH, designed to determine the medical characteristics and burdens (physical, emotional and financial) of this progressive disease and to evaluate the impact of treatment (including the use of burosumab) on clinical outcomes. The study was initiated in April 2018, and registration will remain open until 30 April 2022. The sample size planned for analyses is 160 patients, consisting of 100 patients in Japan and 60 patients in Korea. Up to 5 years of observation are planned per patient, from enrolment through to April 2023. Prospective and retrospective data will be collected to evaluate variables, including height/growth, rickets severity score, QOL, motor function and biomarkers for phosphate metabolism and bone turnover. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Osaka University, the Ethics Committee of Kyowa Kirin Co and by the Ethics Committee of each participating medical institution. Two interim analyses and associated publications are planned using retrospective and enrolment data at year 1 and results at year 3

A single nucleotide polymorphism in CAPN1 associated with marbling score in Korean cattle

<p>Abstract</p> <p>Background</p> <p>Marbling score (MS) is the major quantitative trait that affects carcass quality in beef cattle. In this study, we examined the association between genetic polymorphisms of the micromolar calcium-activated neutral protease gene (micro-calpain, <it>CAPN1</it>) and carcass traits in Korean cattle (also known as Hanwoo).</p> <p>Results</p> <p>By direct DNA sequencing in 24 unrelated Korean cattle, we identified 39 sequence variants within exons and their flanking regions in <it>CAPN1</it>. Among them, 12 common polymorphic sites were selected for genotyping in the beef cattle (<it>n </it>= 421). Statistical analysis revealed that a polymorphism in the 3'UTR (<it>c.2151*479C>T</it>) showed significant association with MS (<it>P</it>^{<it>cor</it>.}= 0.02).</p> <p>Conclusion</p> <p>Our findings suggest that polymorphisms in <it>CAPN1 </it>might be one of the important genetic factors involved in carcass quality in beef cattle, although it could be false positive association.</p

Growth hormone-releasing hormone (GHRH) polymorphisms associated with carcass traits of meat in Korean cattle

BACKGROUND: Cold carcass weight (CW) and longissimus muscle area (EMA) are the major quantitative traits in beef cattle. In this study, we found several polymorphisms of growth hormone-releasing hormone (GHRH) gene and examined the association of polymorphisms with carcass traits (CW and EMA) in Korean native cattle (Hanwoo). RESULTS: By direct DNA sequencing in 24 unrelated Korean cattle, we identified 12 single nucleotide polymorphisms within the 9 kb full gene region, including the 1.5 kb promoter region. Among them, six polymorphic sites were selected for genotyping in our beef cattle (n = 428) and five marker haplotypes (frequency > 0.1) were identified. Statistical analysis revealed that -4241A>T showed significant associations with CW and EMA. CONCLUSION: Our findings suggest that polymorphisms in GHRH might be one of the important genetic factors that influence carcass yield in beef cattle. Sequence variation/haplotype information identified in this study would provide valuable information for the production of a commercial line of beef cattle

The Pathogenetic Role of Reactive Oxygen Species in Aminonucleoside Nephrosis

We studied the pathogenetic role of reactive oxygen species (ROS) in rats with puromycin aminonucleoside nephrosis (PAN). Heavy albuminuria with markedly decreased density of the anionic sites (AS) on glomerular basement membrane (GBM) (2. 6 ± O. 98 compared to 20. 0 ± 1. 61 AS/l,OOOnm GBM in control) developed 7 days after PA injection. The malondialdehyde (MDA) levels in kidney homogenates increased gradually (1. 16 ± O. 18 at day -1 to 1. 97 ± O. 23/g protein at day 5). While catalase or dimethyl sulfoxide, administered with PA, did not affect the course of PAN. superoxide dismutase and allopurinol reduced proteinuria and decreased loss of the AS (11. 7 ± 2. 80 and 13, 7 ± 1. 27 AS/l.000nm GBM, reo spectively) at day 7. These findings suggest that proteinuria in PAN results from the loss of GBM AS. in which ROS generated by xanthine oxidase system plays an import. ant role

A Pediatric Case of Long-term Untreated Distal Renal Tubular Acidosis

Distal renal tubular acidosis (dRTA) is a rare renal tubular disorder characterized by normal anion gap metabolic acidosis, hypokalemia, and high urine pH. It can be inherited or acquired. In untreated pediatric patients with dRTA, rickets and growth retardation are common. We report the case of a 12-year-old Lao girl who presented with typical clinical features of dRTA with severe bone deformities that developed after a bed-ridden state due to a bicycle accident at the age of 8 years. Initial laboratory tests revealed metabolic acidosis with a normal anion gap, hypokalemia, and alkali urine. Renal ultrasonography revealed bilateral medullary nephrocalcinosis. Whole exome sequencing revealed no pathogenic mutations. After treatment with oral alkali, potassium, and vitamin D, she could walk and run. Later, she underwent corrective orthopedic surgeries for bony deformities. Thus, in pediatric dRTA patients, despite severe symptoms remaining untreated, accurate diagnosis and proper management can improve quality of life

KNOW-Ped CKD (KoreaN cohort study for outcomes in patients with pediatric CKD): Design and methods

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background The global prevalence of chronic kidney disease (CKD) is increasing. In children, CKD exhibits unique etiologies and can have serious impacts on childrens growth and development. Therefore, an aggressive approach to preventing the progression of CKD and its complications is imperative. To improve the understanding and management of Asian pediatric patients with CKD, we designed and launched KNOW-Ped CKD (KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease), a nationwide, prospective, and observational cohort study of pediatric CKD with funding from the Korean government. Methods/design From seven major centers, 450 patients <20 years of age with CKD stages I to V are recruited for the comprehensive assessment of clinical findings, structured follow-up, and bio-specimen collection. The primary endpoints include CKD progression, defined as a decline of estimated glomerular filtration rate by 50 %, and a requirement for renal replacement therapy or death. The secondary outcomes include the development of left ventricular hypertrophy or hypertension, impairment of growth, neuropsychological status, behavioral status, kidney growth, and quality of life. Discussion With this study, we expect to obtain more information on pediatric CKD, which can be translated to better management for the patients. Trial registration NCT02165878(ClinicalTrials.gov), submitted on June 11, 2014

Abnormal Motion of the Interventricular Septum after Coronary Artery Bypass Graft Surgery: Comprehensive Evaluation with MR Imaging

OBJECTIVE: To define the mechanism associated with abnormal septal motion (ASM) after coronary artery bypass graft surgery (CABG) using comprehensive MR imaging techniques. MATERIALS AND METHODS: Eighteen patients (mean age, 58 +/- 12 years; 15 males) were studied with comprehensive MR imaging using rest/stress perfusion, rest cine, and delayed enhancement (DE)-MR techniques before and after CABG. Myocardial tagging was also performed following CABG. Septal wall motion was compared in the ASM and non-ASM groups. Preoperative and postoperative results with regard to septal wall motion in the ASM group were also compared. We then analyzed circumferential strain after CABG in both the septal and lateral walls in the ASM group. RESULTS: All patients had normal septal wall motion and perfusion without evidence of non-viable myocardium prior to surgery. Postoperatively, ASM at rest and/or stress state was documented in 10 patients (56%). However, all of these had normal rest/stress perfusion and DE findings at the septum. Septal wall motion after CABG in the ASM group was significantly lower than that in the non-ASM group (2.1+/-5.3 mm vs. 14.9+/-4.7 mm in the non-ASM group; p < 0.001). In the ASM group, the degree of septal wall motion showed a significant decrease after CABG (preoperative vs. postoperative = 15.8+/-4.5 mm vs. 2.1+/-5.3 mm; p = 0.007). In the ASM group after CABG, circumferential shortening of the septum was even larger than that of the lateral wall (-20.89+/-5.41 vs. -15.41+/-3.7, p < 0.05) CONCLUSION: Abnormal septal motion might not be caused by ischemic insult. We suggest that ASM might occur due to an increase in anterior cardiac mobility after incision of the pericardiumope

Clinical Application of Liver MR Imaging in Wilson's Disease

Objective: To determine whether there is a correlation between liver MR findings and the clinical manifestations and severity of liver dysfunction in patients with Wilson`s disease. Materials and Methods: Two radiologists retrospectively evaluated MR images of the liver in 50 patients with Wilson`s disease. The Institutional Review Board approved this retrospective study and informed consent was waived. MR images were evaluated with a focus on hepatic contour abnormalities and the presence of intrahepatic nodules. By using Fisher`s exact test, MR findings were compared with clinical presentations (neurological and non-neurological) and hepatic dysfunction, which was categorized by the Child-Pugh classification system (A, B and C). Follow-up MR images were available for 17 patients. Results: Contour abnormalities of the liver and intrahepatic nodules were observed in 31 patients (62%) and 25 patients (50%), respectively. Each MR finding showed a statistically significant difference (p < 0.05) among the three groups of Child-Pugh classifications (A, n = 36; B, n = 5; C, n = 9), except for splenomegaly (p = 0.243). The mean age of the patients with positive MR findings was higher than that of patients with negative MR findings. For patients with Child-Pugh class A (n = 36) with neurological presentation, intrahepatic nodules, surface nodularity, and gallbladder fossa widening were more common. Intrahepatic nodules were improved (n = 8, 47%), stationary (n = 5, 29%), or aggravated (n = 4, 24%) on follow-up MR images. Conclusion: MR imaging demonstrates the contour abnormalities and parenchymal nodules of the liver in more than half of the patients with Wilson`s disease, which correlates with the severity of hepatic dysfunction and clinical manifestations.Cope-Yokoyama S, 2010, WORLD J GASTROENTERO, V16, P1487, DOI 10.3748/wjg.v16.i12.1487Akhan O, 2009, EUR J RADIOL, V69, P147, DOI 10.1016/j.ejrad.2007.09.029Taly AB, 2007, MEDICINE, V86, P112, DOI 10.1097/MD.0b013e318045a00eMerle U, 2007, GUT, V56, P115, DOI 10.1136/gut.2005.087262Akpinar E, 2007, EUR J RADIOL, V61, P25, DOI 10.1016/j.ejrad.2006.11.006Kozic D, 2006, ACTA RADIOL, V47, P624, DOI 10.1080/02841850600702176Kim TJ, 2006, AM J NEURORADIOL, V27, P1373SEO JK, 2006, KOREAN J HEPATOL, V12, P333Panagiotakaki E, 2004, AM J MED GENET A, V131A, P168, DOI 10.1002/ajmg.a.30345Chu WCW, 2004, AM J ROENTGENOL, V183, P1339ALA A, 2004, CLIN LIVER DIS, V8, P787Gitlin JD, 2003, GASTROENTEROLOGY, V125, P1868, DOI 10.1053/S0016-5085(03)01512-9Ferenci P, 2003, LIVER INT, V23, P139Akhan O, 2002, EUR RADIOL, V12, pS66, DOI 10.1007/s00330-002-1589-6Awaya H, 2002, RADIOLOGY, V224, P769, DOI 10.1148/radiol.2243011495Ito K, 1999, RADIOLOGY, V211, P723Ko SF, 1998, ABDOM IMAGING, V23, P56MERGO PJ, 1994, RADIOGRAPHICS, V14, P1291BULL PC, 1993, NAT GENET, V5, P327TANZI RE, 1993, NAT GENET, V5, P344DAVIES SE, 1989, HISTOPATHOLOGY, V15, P385CANCADO EL, 1987, ARQ NEURO-PSIQUIAT, V45, P131CHILD CG, 1964, LIVER PORTAL HYPERTE, P50

High Prevalence of Opisthorchis viverrini Infection in a Riparian Population in Takeo Province, Cambodia

Opisthorchis viverrini infection was found to be highly prevalent in 3 riverside villages (Ang Svay Chek A, B, and C) of the Prey Kabas District, Takeo Province. This area is located in the southern part of Cambodia, where the recovery of adult O. viverrini worms was recently reported. From May 2006 until May 2010, fecal examinations were performed on a total of 1,799 villagers using the Kato-Katz thick smear technique. In the 3 villages, the overall positive rate for helminth eggs ranged from 51.7 to 59.0% (av. 57.4%), and the percentage positive for O. viverrini was 46.4-50.6% (47.5%). Other helminths detected included hookworms (13.2%), echinostomes (2.9%), Trichuris trichiura (1.3%), Ascaris lumbricoides (0.6%), and Taenia spp. (0.06%). The prevalence of O. viverrini eggs appeared to reflect a lower infection in younger individuals (<20 years) than in the adult population (>20 years). Men (50.4%) revealed a significantly higher (P=0.02) prevalence than women (44.3%). The Ang Svay Chek villages of the Prey Kabas District, Takeo Province, Cambodia have been confirmed to be a highly endemic area for human O. viverrini infection