Whole genome sequence data implicate RBFOX1 in epilepsy risk in baboons

Background: Baboons exhibit a genetic generalized epilepsy (GGE) that resembles juvenile myoclonic epilepsy and may represent a suitable genetic model for human epilepsy. The genetic underpinnings of epilepsy were investigated in a baboon colony at the Southwest National Primate Research Center (San Antonio, TX) through the analysis of whole-genome sequence (WGS) data. Methods: Baboon WGS data were obtained for 38 cases and 19 healthy controls from the NCBI Sequence Read Archive and, after standard QC filtering, two subsets of variants were examined: (1) 20,881 SNPs from baboon homologs of 19 candidate GGE genes; and (2) 36,169 protein-altering SNPs. Association tests were conducted in SOLAR, and gene set enrichment analyses (GSEA) and protein-protein interaction (PPI) network construction were performed on genome-wide significant association results (Pn= 441 genes). Results: Heritability for epileptic seizure in the pedigreed baboon sample was estimated at 0.76 (SE=0.77; P=0.07). A significant association was detected for an intronic SNP in RBFOX1 (P=5.92 × 10-6; adjusted P=0.016). For protein-altering variants, GSEA revealed significant positive enrichment for genes involved in the extracellular matrix structure (ECM; FDR=0.0072) and collagen formation (FDR=0.017). Conclusions: SNP association results implicate RBFOX1 in baboon epilepsy, a gene that plays a key role in neuronal excitation and transcriptomic regulation, and has been previously linked to human epilepsy, both focal and generalized. Moreover, protein-damaging variants from across the baboon genome exhibit a wider pattern of association that links collagen-containing ECM to epilepsy risk. These findings suggest a shared genetic etiology between baboon and human forms of GGE

Whole Genome Sequence Data From Captive Baboons Implicate RBFOX1 in Epileptic Seizure Risk

In this study, we investigate the genetic determinants that underlie epilepsy in a captive baboon pedigree and evaluate the potential suitability of this non-human primate model for understanding the genetic etiology of human epilepsy. Archived whole-genome sequence data were analyzed using both a candidate gene approach that targeted variants in baboon homologs of 19 genes (n = 20,881 SNPs) previously implicated in genetic generalized epilepsy (GGE) and a more agnostic approach that examined protein-altering mutations genome-wide as assessed by snpEff (n = 36,169). Measured genotype association tests for baboon cases of epileptic seizure were performed using SOLAR, as well as gene set enrichment analyses (GSEA) and protein–protein interaction (PPI) network construction of top association hits genome-wide (p \u3c 0.01; n = 441 genes). The maximum likelihood estimate of heritability for epileptic seizure in the pedigreed baboon sample is 0.76 (SE = 0.77; p = 0.07). Among candidate genes for GGE, a significant association was detected for an intronic SNP in RBFOX1 (p = 5.92 × 10–6; adjusted p = 0.016). For protein-altering variants, no genome-wide significant results were observed for epilepsy status. However, GSEA revealed significant positive enrichment for genes involved in the extracellular matrix structure (ECM; FDR = 0.0072) and collagen formation (FDR = 0.017), which was reflected in a major PPI network cluster. This preliminary study highlights the potential role of RBFOX1 in the epileptic baboon, a protein involved in transcriptomic regulation of multiple epilepsy candidate genes in humans and itself previously implicated in human epilepsy, both focal and generalized. Moreover, protein-damaging variants from across the genome exhibit a pattern of association that links collagen-containing ECM to epilepsy risk. These findings suggest a shared genetic etiology between baboon and human forms of GGE and lay the foundation for follow-up research

Pediatric Urinary Tract Infections and Vesicoureteral Refl ux: What Have We Learned?

It has been nearly 50 years since Victor Politano and Wyland Leadbetter developed the first reliable operation for the surgical correction of vesicoureteral refl ux (VUR). It dispelled the notion of bladder outlet obstruction as the primary cause of refl ux. One might argue, however, since the operation was so reproducible that we learned too quickly how to correct VUR before truly understanding its pathophysiology and potential risk in children. There have been many controversies that have arisen lately regarding the management of refl ux. These controversies include: (1) The role of imaging in evaluating children with urinary tract infections (UTIs). More specifi cally, does every child need a voiding cystourethrogram (VCUG) and where does the DMSA scan fi t into our evaluation? (2) There is a growing concern for the use of long-term prophylactic antibiotics and we lack controlled studies that verify their usefulness. (3) Where does the endoscopic correction of reflux fi t into our armamentarium of managing children with refl ux? Is it an alternative for antibiotic prophylaxis or is it an alternative for open surgical reimplantation? (4) How do we truly establish the risk of refl ux in a given child? We have traditionally assigned risk to the grade of refl ux, however, are there other variables that may better defi ne the true risk of renal damage in a child who has refl ux and UTIs? This paper explores each of these controversial areas to stimulate us to think more deeply about this common problem that we think we know so much about Keywords: Urinary tract infection, vesicoureteral reflux, childrenAfrican Journal of Urology Vol. 13 (4) 2007: pp. 242-25

Real-time kidney graft perfusion monitoring using infrared imaging during pediatric kidney transplantation

Q2Q2222.e1-222.e7Introduction: Ischemia times in kidney transplantation have shown to be predictive for future graft function. Preservation solutions and anticoagulation protocols have improved the management of pediatric kidney transplantation. Nonetheless, there is no current tool for intra-operative graft monitoring. The aim of this project is to present a novel technique for intra-operative real-time assessment of graft perfusion using a non-invasive infrared camera. Methods: Prospectively, the authors included 10 pediatric patients. Surgical procedure followed their institutional protocol. Infrared imaging was captured at graft preparation, vascular anastomosis, unclamping, and at 30 s, 1, 5, and 10 min after unclamping. Analyzed variables included type of transplant, ischemia and procedure times, type of anastomosis, and results of doppler/ultrasound. Postoperative variables included creatinine levels during first 72 h. Any complications were also recorded. Delta analysis was calculated to establish the variation of temperature after unclamping. Results: Average age at transplant was 9.9 years. Five cases were living donor transplants. Mean overall ischemia time was 395.6 (SD 64.4 min). Two patients had poor graft perfusion after unclamping. Of those, one had torsion of the arterial anastomosis and the other was a graft from a donor that required cardiopulmonary resuscitation for 45 min. Thermal imaging showed a correlation of 0.318 between graft temperature change and creatinine decrease. Cut-off delta for temperature for good reperfusion was above 0.2 at 1 min CONCLUSION: Real-time infrared imaging shows to be a promising option for non-invasive graft perfusion monitoring. Initial results show good correlation between intra-operative temperature changes, graft perfusion, and postoperative graft function

Historical bibliometric analysis of the top cited articles on vesicoureteral reflux 1950-2016, and incorporation of a novel impact index

Q2446.e1–446.e9Introduction and objectives Vesicoureteral reflux (VUR) has been one of the defining conditions unique to pediatric urology since its inception. The clinical implications of this disease process depend on intrinsic patient factors such as age, genetics, epigenetics, voiding habits, anatomic anomalies, and extrinsic factors such as the pathogenicity of infectious agents. Knowledge about its natural history, the implications of conservative and surgical management, and their associated outcomes have evolved dramatically over time. This study aimed to use bibliometric analyses to summarize the evolution of VUR management over time. In order to accomplish this, the most referenced articles for VUR since 1950 were identified, and a comprehensive analysis of their impact on the management and understanding of VUR was performed by creating a novel impact index. Methods A reference search was carried out for indexed citations through the portal ‘Science Citation Index’ in the subsection ‘Web of Science Core Collection’ using ‘vesicoureteral reflux’ as a MeSH term. References were analyzed and subcategorized according to various subtopics. A unique impact index was developed to adjust the number of publications for the time since publication, in order to define the impact of the paper amongst the most frequently cited papers. Articles were analyzed and data were tabulated according to the number of citations, country and institute of origin, journal of publication, impact factor, and first authorship. Results Citation counts ranged from 43 to 510, and the mean number of citations per publication was 101.43. The most discussed topic was ‘treatment’. The impact index showed that more recent publications have a higher impact. The author with the highest index impact had 271 citations in a period of 5 years. The top 150 articles were published across 23 countries, the majority being from the USA ( Summary fig. ). The most frequently cited institution had 12 publications. The journal with the highest publication referencing rate was the Journal of Urology. Conclusion The most cited articles were valuable sources of information to describe the historical evolution of the pathophysiology and management of VUR. After adjusting for time since publication, the most recent publications (i.e. those published after 1990) had a higher impact index. Combining traditional bibliometric analysis with this novel impact index may allow researchers to optimize future literature analyses, while also assisting clinicians in understanding best practices for patient management based on the available literature