OKseqHMM: a genome-wide replication fork directionality analysis toolkit

Motivation: During each cell division, tens of thousands of DNA replication origins are coordinately activated to ensure the complete duplication of the entire human genome. However, the progression of replication forks can be challenged by numerous factors. One such factor is transcription-replication conflicts (TRC), which can either be co-directional or head-on with the latter being revealed as more dangerous for genome integrity. Results: In order to study the direction of replication fork movement and TRC, we developed a bioinformatics tool, called OKseqHMM, to directly measure the genome-wide replication fork directionality (RFD) as well as replication initiation and termination from data obtained by Okazaki fragment sequencing (OK-Seq) and related techniques. Availability and Implementation: We have gathered and analyzed OK-seq data from a large number of organisms including yeast, mouse and human, to generate high-quality RFD profiles and determine initiation zones and termination zones by using Hidden Markov Model (HMM) algorithm (all tools and data are available at https://github.com/CL-CHEN-Lab/OK-Seq). In addition, we have extended our analysis to data obtained by related techniques, such as eSPAN and TrAEL-seq, which also contain RFD information. Our works, therefore, provide an important tool and resource for the community to further study TRC and genome instability, in a wide range of cell line models and growth conditions, which is of prime importance for human health.

Complete diphallia associated with unusual multiple congenital anomalies: case report and review of literatures

Background Diphallus (duplication of phallus) is rarely encountered in surgical practice with only 100 cases reported in literature. Some cases may be isolated but mostly associated with other anomalies, without clear data about its etiology. Case presentation We reported a 1-day-old newborn baby who was presented with complete duplication of the phallus, one of them being hypospadic associated with a high type imperforate anus, omphalocele, congenital pouch colon, sacral meningocele, and other congenital anomalies not reported before in such combinations. Multiple stages surgical corrective procedures were performed over a period of 4 years with 4–6 months interval between each stage, starting with the management of omphalocele and colostomy, ended by excision of the abnormal phallus with abdominoplasty and closure of colostomy. The outcome was evaluated, and literatures were reviewed in relation to types, presentations, and options for surgical correction with optimal outcomes. Conclusion A combination of diphallia and other abnormalities in our patient are not reported previously in such manner and were very difficult to be corrected. Only expert pediatric surgeons should treat such conditions as every case is unique in nature. In all conditions, the abnormal phallus should be excised, and the final aim is to achieve a continent child with cosmetically acceptable genitalia.

Complete duplication of the urethra in a boy with epispadias

Duplication of the urethra is a rare abnormality that can occur with other urogenital tract congenital pathologies. Ischemia at embryogenesis, urogenital sinus defect, Muller`s duct anomaly and incomplete mesodermal fusion are the pathophysiological mechanisms of the pathology onset. Duplication of the urethra diagnostics is based on clinical examination, disease anamnesis, urethrography and magnetic resonance imaging. It is nessessary to consider Effmann and Leibowitz classification, urethras and prostate location and urethral orifice distance on operation of additional urethra removing. Clinical case. Presenting a clinical case of a boy with grade I epispadias and complete duplication of the urethra. Urination was maintained and was performed from the dorsal-epispadic urethra, the ventral urethra was obliterated in the distal region. According to the data of magnetic resonance imaging: double urethra is traced, dorsal – comes out from the anterior parts of the bladder wall, continues along the dorsal surface under the dorsal neurovascular bundle, above the cavernous bodies. The urethra opening is traced at the level of the upper surface of the head of the penis. The distal / ventral urethra comes out from the posterior parts of the lower bladder wall, typically continues down through the prostate embryo, rotated forward between of the corporas cavernosas stipes, and had a typical location with except for the level of the penis head, where it bends and merges with the dorsal urethra, which opens with a single opening. The surgery of excision of an additional urethra on child was performed. During the examination of the child of 6 months after surgery: urination with one stream from the ventral urethra at the apex of the head of the penis, stream freely passes the Nelaton catheter No. 10, child holds urine, there was no complaints. Performing of the next stage of the operation (penis plastic surgery) is planned after 1 year of the previous stage. Conclusions. In cases of epispadias is possible a congenital defect – a complete douplication of the urethra with the ventral urethra obliteration at the top of the head, which may not be determined in epispadias surgery preparation. Doubling of the urethra in boys requires magnetic resonance imaging for a better orientation in the defect anatomy and to determine the tactics of further surgical treatment. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: complete duplication of the urethra, surgical treatment, children.

A Case of Renal Pelvic Cancer with a Complete Duplication of the Renal Pelvis and Ureter

This paper describes a case of renal pelvic cancer with a complete duplication of the renal pelvis and ureter, which is substantially rare. A 76-year-old man was referred to the hospital because of gross hematuria for 2 years. A tumor was detected in the upper right kidney using enhanced computed tomography and magnetic resonance imaging scan, and the downstream ureter was suspected to open into the prostate. Retrograde ureteroscopy via the ectopic ureter orifice showed a hemorrhagic papillary tumor consistent with imaging findings. Laparoscopic radical nephroureterectomy was performed and the prostate was preserved because the tumor was only in the renal pelvis. Histopathological examination showed the tumor as a high-grade urothelial carcinoma. There was no sign of recurrence at one and a half years after operation. Ureteroscopy was effective in detecting an upper urinary tract tumor, even via ectopic ureter orifice, and preserving the prostate was possible.

Double Trouble! Rare Complete Duplication of the Entire Urinary Tract With Dual Neurogenic Bladders Necessitating Dual Intermittent Catheterization

We report a striking duplication of the entire urinary collecting system in an 18-year-old male with 2 renal pelves and 2 ureters on either side, along with a complete duplication of the bladder and urethra.

Caudal duplication syndrome in an adolescent: Rare concoction of duplication anomalies

Caudal duplication syndrome is a rare and interesting entity with a reported prevalence of <1/100,000 births. Caudal duplication syndrome encompasses a diverse spectrum of anomalies primarily involving partial or complete duplication of organs comprising the gastrointestinal, genitourinary and distal neural tube systems. The term ‘caudal duplication syndrome’ was coined by Dominguez et al. in 1993, in a case series of six patients presenting with findings pertaining to duplication anomalies of genitourinary system, hindgut, lumbosacral spine and cord. We here report a unique case of caudal duplication presenting in late adolescence and briefly review the available literature on this rare abnormality.

Dismembered extravesical reimplantation of ectopic ureter in duplex kidney with incontinence

Ectopic ureter is a rare but pertinent cause of incontinence in young women. We report a 12-year-old girl who presented with reports of incontinence since birth. She was evaluated and found to have complete duplication of the left ureter, with the upper moiety ureter opening into the vestibule of the vagina just below the external urethra meatus. She was managed surgically by dismembered extravesical reimplantation of the upper moiety ureter instead of the conventional method of common sheath reimplantation, sparing the patient a wide cystostomy and intravesical dissection. One year postsurgery, the patient is asymptomatic and dry. Dismembered reimplantation of the ectopic ureter is a simple and reproducible technique which avoids manipulation of the normal lower moiety ureter and its associated potential complications. At the same time, it ensures that the patient is dry without any adverse effect on the lower moiety or its ureter.