End-Stage Kidney Failure in Oman: An Analysis of Registry Data with an Emphasis on Congenital and Inherited Renal Diseases

\ua9 2017 Intisar Al Alawi et al. Globally, end-stage kidney disease (ESKD) is a huge burden on health care systems. The aims of this study were to perform a comprehensive epidemiological and etiological report of ESKD patients commencing RRT in Oman with an emphasis on genetic causes and inherited kidney disease. All newly registered Omani patients with ESKD commencing RRT from 2001 until 2015 (n=2,922) were analysed using the RRT register in Oman. All potentially genetic or inherited causes of ESKD were reviewed. In Oman, ESKD is more prevalent in males (57.1%) than females (42.9%) with a median age of incident ESKD of 53 years. Diabetic nephropathy was the most prevalent cause of ESKD (46%), followed by hypertensive nephropathy (19%), glomerulonephritis (15%), and inherited kidney disease (5%). For patients less than 20 years of age inherited kidney disease accounted for 32.5% of cases. Of this cohort with inherited renal disease, 40.3% had autosomal dominant polycystic kidney disease, 11.5% had congenital anomalies of the kidney and urinary tract, 9.4% had Alport syndrome, and 7.2% had autosomal recessive polycystic kidney disease. This study represents a comprehensive population-based epidemiological and etiological report of ESKD patients in Oman commencing RRT. Inherited kidney disease was the leading cause of paediatric ESKD

Parents\u27 perceptions and concerns about their children\u27s weight

Background: For parents to address overweight or obesity in their children, they first need to perceive their child to be overweight and to show some level of concern. We aimed to: (1) measure the level of misclassification between children&rsquo;s actual and parent-perceived weight status, and (2) determine the level of parent concern about their child&rsquo;s (actual) weight and whether concern varied according to the accuracy of parents&rsquo; perceptions.Methods: Participants were 1711 primary school children aged 5&ndash;12 years from the Barwon-South West region of Victoria, Australia. Height and weight were measured and weight status determined using international standards. Parents completed a Computer Assisted Telephone Interview (CATI) that included questions relating to their child&rsquo;s weight.Results: 448 children (26.2% of sample) were overweight or obese. Of these, weight status for almost half (48%) was underestimated by parents. This &lsquo;bias&rsquo; did not vary according to the child&rsquo;s gender, parent&rsquo;s education, or household socio-economic status but did for child&rsquo;s age and parent-respondent gender. More than half (57%) of the parents of overweight-obese children expressed no concern about their child&rsquo;s weight. Parents who underestimated the weight status of their overweight child were significantly less concerned (P &lt; 0.001) about their child&rsquo;s weight than those who correctly perceived their child as overweight.Conclusions: Parents were relatively poor judges of overweight or obesity in their own child and consequently there was a lack of appropriately directed concern. Education to help parents correctly classify their child&rsquo;s weight status should be part of efforts to prevent unhealthy weight gain.<br /

Hospitalization and mortality following non-attendance for hemodialysis according to dialysis day of the week : a European cohort study

Background The extension of the interdialytic interval due to due to dialysis session non-attendance varies according to which session of the week the patient misses. The impact of this on subsequent hospitalization and mortality is unknown. Methods The ARO cohort study prospectively collected data from hemodialysis patients across 15 European countries on demography, comorbidity, laboratory, hospitalisation, mortality and individual hemodialysis sessions from 2007 to 2014. Event rates for death and hospitalisation according to dialysis day of the week were calculated for patients who attended the three previous scheduled hemodialysis sessions, who then on the next scheduled dialysis day either attended or did not attend. The hazard ratio for these events following non-attendance for the first compared to the second dialysis session of the week was estimated using Cox proportional hazards model adjusted for patient demographics. Results 3.8 million hemodialysis sessions in 9397 patients were analysed. The non-attendance rates for Monday/Wednesday/Friday sessions were 0.8, 0.9% & 1.4% respectively, and for Tuesday/Thursday/Saturday sessions were 0.6, 1.0% & 1.2% respectively. Compared to those who attended, for the 48–72 h between non-attendance and the next scheduled haemodialysis session, mortality significantly increased from 4.86 to 51.9/100 pt-yrs and hospitalisation increased from 0.58 to 2.1/yr. As time from the two-day break increased, the risk associated with non-attendance lessened: compared to missing the second hemodialysis session, missing the first session had a hazard ratio for mortality of 2.04 (95% CI 1.27–3.29), and for hospitalisation 1.78 (95% CI 1.29–2.47). In patients who attended their scheduled dialysis session and the three preceding, after the two-day break there were absolute increases in mortality (8.3 vs. 4.9/100 pt-yrs) and hospitalisation (1.0 vs. 0.6/yr for the rest of the week) comparable to previous studies. Conclusions In addition to hospitalisation and mortality increases seen after the two-day break, additional harm may be manifested in the greater increases in mortality and hospitalisation observed after non-attendance for the first hemodialysis session after the two-day break compared to missing other sessions

Amelioration effect of 18β-Glycyrrhetinic acid on methylation inhibitors in hepatocarcinogenesis -induced by diethylnitrosamine

Aimsuppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid.MethodIn the current work, we investigated the effect of sole GA combined with different agents such as doxorubicin (DOX) or probiotic bacteria (Lactobacillus rhamanosus) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats’ liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats’ liver tissue.ResultsOur results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively.ConclusionGA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes

PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation

Consequences of perinatal treatment with l-arginine and antioxidants for the renal transcriptome in spontaneously hypertensive rats

Treating spontaneously hypertensive rats (SHR) with l-arginine, taurine, and vitamins C and E (ATCE) during nephrogenesis (2 weeks before to 4 weeks after birth) persistently lowers blood pressure. Hypothetically, differential gene expression in kidney of SHR vs. normotensive Wistar–Kyoto rats (WKY) is partially corrected by maternal ATCE in SHR. Differential gene expression in 2-days, 2-weeks, and 48-week-old rats was studied using oligonucleotide chips. Transcription factor binding sites (TFBS) of differentially expressed genes were analyzed in silico. Differential gene expression varied between SHR+ATCE and SHR, suggesting both direct and indirect effects; but, few genes were modulated toward WKY level and there was little overlap between ages. TFBS analysis suggests less Elk-1-driven gene transcription in both WKY and SHR+ATCE vs. SHR at 2 days and 2 weeks. Concluding, in SHR, persistent antihypertensive effects of maternal ATCE are not primarily due to persistent corrective transcription. Less Elk-1-driven transcription at 2 days and 2 weeks may be involved

Lymphocyte recruitment and homing to the liver in primary biliary cirrhosis and primary sclerosing cholangitis

The mechanisms operating in lymphocyte recruitment and homing to liver are reviewed. A literature review was performed on primary biliary cirrhosis (PBC), progressive sclerosing cholangitis (PSC), and homing mechanisms; a total of 130 papers were selected for discussion. Available data suggest that in addition to a specific role for CCL25 in PSC, the CC chemokines CCL21 and CCL28 and the CXC chemokines CXCL9 and CXCL10 are involved in the recruitment of T lymphocytes into the portal tract in PBC and PSC. Once entering the liver, lymphocytes localize to bile duct and retain by the combinatorial or sequential action of CXCL12, CXCL16, CX3CL1, and CCL28 and possibly CXCL9 and CXCL10. The relative importance of these chemokines in the recruitment or the retention of lymphocytes around the bile ducts remains unclear. The available data remain limited but underscore the importance of recruitment and homing

Sparse Representation of Brain Aging: Extracting Covariance Patterns from Structural MRI

An enhanced understanding of how normal aging alters brain structure is urgently needed for the early diagnosis and treatment of age-related mental diseases. Structural magnetic resonance imaging (MRI) is a reliable technique used to detect age-related changes in the human brain. Currently, multivariate pattern analysis (MVPA) enables the exploration of subtle and distributed changes of data obtained from structural MRI images. In this study, a new MVPA approach based on sparse representation has been employed to investigate the anatomical covariance patterns of normal aging. Two groups of participants (group 1∶290 participants; group 2∶56 participants) were evaluated in this study. These two groups were scanned with two 1.5 T MRI machines. In the first group, we obtained the discriminative patterns using a t-test filter and sparse representation step. We were able to distinguish the young from old cohort with a very high accuracy using only a few voxels of the discriminative patterns (group 1∶98.4%; group 2∶96.4%). The experimental results showed that the selected voxels may be categorized into two components according to the two steps in the proposed method. The first component focuses on the precentral and postcentral gyri, and the caudate nucleus, which play an important role in sensorimotor tasks. The strongest volume reduction with age was observed in these clusters. The second component is mainly distributed over the cerebellum, thalamus, and right inferior frontal gyrus. These regions are not only critical nodes of the sensorimotor circuitry but also the cognitive circuitry although their volume shows a relative resilience against aging. Considering the voxels selection procedure, we suggest that the aging of the sensorimotor and cognitive brain regions identified in this study has a covarying relationship with each other

Geolocation with respect to persona privacy for the Allergy Diary app - a MASK study

Background: Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel network: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission's Article 29 Working Party stated that geolocation information is personal data. To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method. Methods: Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization). Results: Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54,500 (58. 5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users' life privacy. Discussion: k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases.Peer reviewe