Phosphoproteomics of retinoblastoma:A pilot study identifies aberrant kinases

Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation in cancer provides clues about the affected signalling cascades in cancer. Phosphoproteomics is an ideal tool for the study of phosphorylation changes in proteins. Hence, global phosphoproteomics of retinoblastoma (RB) was carried out to identify signalling events associated with this cancer. Over 350 proteins showed differential phosphorylation in RB compared to control retina. Our study identified stress response proteins to be hyperphosphorylated in RB which included H2A histone family member X (H2AFX) and sirtuin 1. In particular, Ser140 of H2AFX also known as gamma-H2AX was found to be hyperphosphorylated in retinoblastoma, which indicated the activation of DNA damage response pathways. We also observed the activation of anti-apoptosis in retinoblastoma compared to control. These observations showed the activation of survival pathways in retinoblastoma. The identification of hyperphosphorylated protein kinases including Bromodomain containing 4 (BRD4), Lysine deficient protein kinase 1 (WNK1), and Cyclin-dependent kinase 1 (CDK1) in RB opens new avenues for the treatment of RB. These kinases can be considered as probable therapeutic targets for RB, as small-molecule inhibitors for some of these kinases are already in clinical trials for the treatment other cancers

Integrating transcriptomic and proteomic data for accurate assembly and annotation of genomes

© 2017 Wong et al.; Published by Cold Spring Harbor Laboratory Press. Complementing genome sequence with deep transcriptome and proteome data could enable more accurate assembly and annotation of newly sequenced genomes. Here, we provide a proof-of-concept of an integrated approach for analysis of the genome and proteome of Anopheles stephensi, which is one of the most important vectors of the malaria parasite. To achieve broad coverage of genes, we carried out transcriptome sequencing and deep proteome profiling of multiple anatomically distinct sites. Based on transcriptomic data alone, we identified and corrected 535 events of incomplete genome assembly involving 1196 scaffolds and 868 protein-coding gene models. This proteogenomic approach enabled us to add 365 genes that were missed during genome annotation and identify 917 gene correction events through discovery of 151 novel exons, 297 protein extensions, 231 exon extensions, 192 novel protein start sites, 19 novel translational frames, 28 events of joining of exons, and 76 events of joining of adjacent genes as a single gene. Incorporation of proteomic evidence allowed us to change the designation of more than 87 predicted noncoding RNAs to conventional mRNAs coded by protein-coding genes. Importantly, extension of the newly corrected genome assemblies and gene models to 15 other newly assembled Anopheline genomes led to the discovery of a large number of apparent discrepancies in assembly and annotation of these genomes. Our data provide a framework for how future genome sequencing efforts should incorporate transcriptomic and proteomic analysis in combination with simultaneous manual curation to achieve near complete assembly and accurate annotation of genomes

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Single-port laparoscopic right colonic resection

Background: The laparoscopic approach is a recognized treatment option for colonic resection. We present the first single-port operation for colonic resection using standard laparoscopic equipment and techniques. Methods: A single-port laparoscopic right colonic resection was successfully performed using GelPort (Applied Medical, Orange County, CA, USA) and a standard laparoscopic approach. Results: The procedure was completed in 105 min through a single periumbilical incision. There was minimal blood loss and no post-operative problems. Conclusion: Single-port laparoscopic techniques can be applied to colonic surgery. It negates morbidity associated with trochar insertion and port sites. It should be performed by surgeons familiar with laparoscopic colorectal techniques.3 page(s

A Nonsurgical means of fecal diversion : the Zassi Bowel Management System

PURPOSE: Patients with perineal burns and immobile hospitalized patients with severe excoriation from incontinence caused by excessive diarrhea pose difficult management problems, frequently requiring stoma formation. The Zassi Bowel Management System (Zassi Medical Evolutions, Fernandina Beach, Florida) multichannel intrarectal catheter was evaluated for its safety and its ability to divert feces away from perineal skin to allow wound and skin healing. METHODS: A prospective cohort study was conducted on inpatients from the Burns and Geriatric Units. Patients with previous rectal disease were excluded. Perineal skin and wound healing was measured before and after tube insertion by using the perianal disease activity index score. Data regarding patient comfort, wound contamination, dressing changes, bed linen changes, and adverse events were collected. Proctoscopy was performed before and after tube insertion. RESULTS: Twenty-two tubes were inserted in 20 patients (7 perineal burns, 13 severe perineal excoriations). Mean perianal disease activity index scores reduced from 14 to 6.4 (P < 0.0001) after tube insertion. Mean dressing changes reduced from 3.3 to 1.5 times per day (P < 0.01), and mean bed linen changes in the incontinent patients reduced from 9.3 to 1.2 times per day (P < 0.0001). Mean duration of rectal intubation was 14 days. Proctoscopy after tube removal was normal in all cases. One patient developed a superficial ulcer on the buttock from retention strapping. CONCLUSIONS: The Zassi Bowel Management System tube allows diversion of feces away from the perineum for wound healing. It is safe, effective, and may help avoid stoma formation.6 page(s

Nosocomial Clostridium difficile infection : possible cause of anastomotic leakage after anterior resection of the rectum [1]

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Cell- and gene- based therapeutics for periodontal regeneration

Periodontitis is a disease of the periodontium, characterized by loss of connective tissue attachment and supporting the alveolar bone. Therefore, to regenerate these lost tissues of the periodontium researchers have included a variety of surgical procedures including grafting materials growth factors and the use of barrier membranes, ultimately resulting into regeneration that is biologically possible but clinically unpredictable. Recently a newer approach of delivering DNA plasmids as therapeutic agents is gaining special attention and is called gene delivery method. Gene therapy being considered a novel approach have a potential to channel their signals in a very systematic and controlled manner thereby providing encoded proteins at all stages of tissue regeneration. The aim of this review was to enlighten a view on the application involving gene delivery and tissue engineering in periodontal regeneration

Laparoscopic repair of internal hernia following laparoscopic anterior resection

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Karydakis flap repair for sacrococcygeal pilonidal sinus disease : how important is technique?

Numerous operative and conservative treatments have been described in the published work for the management of sacrococcygeal pilonidal sinus; yet there remains considerable debate over its ideal treatment. This report is an audit of our results using the Karydakis flap repair in the management of this condition. We analysed prospective data on 70 patients who had had a Karydakis procedure. The length of follow up ranged from 1 to 79 months (median 36 months). Seventy-one operations were carried out in 70 patients. This included 12 patients (17%) who had previously undergone between one and four procedures (median 2) for recurrent disease. Superficial wound breakdown occurred in 27 patients (38%) and complete wound breakdown occurred in six patients (8.4%). These wounds were allowed to heal by secondary intent. The median time to complete healing for superficial and complete wound breakdown was 80 and 84 days, respectively. Disease recurrence occurred in three patients (4.2%) - two of whom had recurrent disease at the time of this presentation. Of the three patients who had a recurrence after our surgery, two had a superficial breakdown and one had a complete wound breakdown. Sacrococcygeal pilonidal disease has a low recurrence rate when treated by the Karydakis operation involving flattening of the midline cleft. This procedure avoids the need for more complicated flap repairs.3 page(s

Plugs unplugged. Anal fistula plug : the Concord experience

Purpose: The purpose of this study was to analyse preliminary experience and outcomes with the Cook Surgisis AFP™ anal fistula plug (Cook Medical, Bloomington, IN, USA) with respect to the treatment of complex anal fistulae in a specialist colorectal unit. Methods: Data on all patients who were treated with the Surgisis AFP™ between October 2006 and January 2009 were retrospectively reviewed. The plug was placed in accordance with the Cook guidelines. Successful closure of the anal fistula was defined as absence of drainage at final follow-up with no subsequent abscess formation or further intervention required. Results: Thirty-two patients underwent a total of 35 anal fistula plug insertion procedures. No patients were lost to follow-up. The median follow-up was 15 months (2-29 months). The overall success rate was 13 out of 35 (37%). For those in the subgroups of Crohn's disease and cryptoglandular disease, the success rate was 1 out of 3 (33%) and 11 out of 31 (35%), respectively. Conclusion: This series demonstrates a success rate for the Cook Surgisis AFP™ of 37%. These results in patients managed in a specialist unit confirm that the Surgisis AFP™ is a useful option in the management of complex fistulae.3 page(s