Robot-assisted laparoscopy and sentinel node biopsy in high risk endometrial cancer

Surgery is standard treatment for early stage endometrial cancer (EC), the most common gynaecological malignancy in developed countries. Traditionally, surgery has been performed by laparotomy (LT). Comprehensive surgical staging, including pelvic (PLND) and paraaortic (PALND) lymph node dissection, is associated with morbidity and possible reduction in quality of life. Minimally invasive surgery (MIS) is associated with less morbidity, albeit newer MIS techniques, i.e. robot-assisted laparoscopic surgery (RALS), has not been compared with LT in a randomised setting. The sentinel lymph node technique is well established in other malignancies, however, the experience in EC is limited. The aim of this thesis was to evaluate if RALS for PLND and infrarenal PALND (IRPALND) in women with high risk EC is noninferior to LT in harvesting lymph nodes, to investigate short- and long-term morbidity as well as quality of life. We also wanted to evaluate the sentinel lymph node biopsy concept as a diagnostic tool for detecting lymph node metastases (LNM). In the RASHEC trial, we randomised 120 women with stage I-II EC with high-risk tumour features to hysterectomy, bilateral salpingo-oophorectomy, PLND and IRPALND by either RALS or LT between 2013 and 2016. Primary endpoint was paraaortic lymph node count. Patient-reported outcome (EORTC QLQ-C30 and the endometrial cancer module EN-24, EQ- 5D for generic health status) was assessed before surgery and 12 months after surgery. Computed tomography (CT) was performed at baseline, 3 and 12 months after surgery. Patient characteristics were evenly distributed between the two groups. In the per protocol analysis of 96 patients, difference of means with a 95% confidence interval was within the noninferiority margin for infrarenal paraaortic lymph node count (-1.6, 95% CI -5.78 - 2.57). No difference in perioperative complications (Clavien-Dindo classification) or readmissions to hospital within 30 days after surgery was found. RALS was associated with longer operation time (p<0.001) but less total blood loss (p<0.001), shorter hospital stay (p<0.001) and lower health care cost (p<0.05) compared to LT. We found no difference in self-reported lower limb lymphoedema, occurrence of lymphocysts, serious adverse events or admission to hospital for any reason between the two groups 12 months after surgery. Moreover, there was no difference in health-related quality of life. The Sentinel node in High Risk Endometrial Cancer (SHREC- study) is a prospective nonrandomised trial recruiting consecutive patients from two tertiary referral centres in Sweden (Lund and Stockholm) between 2014 and 2018 where each woman served as her own control. In total 261 patients underwent pelvic sentinel node biopsy followed by completion lymphadenectomy of which 257 were analysed. The sentinel lymph node biopsy algorithm applied in the SHREC-trial demonstrated a sensitivity for detection of LNM of 100% (95% CI 92-100) and a negative predictive value of 100% (95% CI 98-100). This thesis demonstrates that RALS is non-inferior to LT in harvesting infrarenal paraaortic lymph nodes. RALS was associated with shorter hospital stay and lower health care cost and there were no evident differences in morbidity or quality of life. Consequently, we find RALS to be a valid option for comprehensive surgical staging including IRPALND in high risk endometrial cancer. The choice of surgical modality should be made based on surgeons’ and patient preference. The sentinel lymph node biopsy algorithm has a satisfactory bilateral mapping rate and complete detection of LNM, corroborating previous reports. Gold standard diagnostic lymphadenectomy in women EC should therefore be replaced by the less invasive sentinel lymph node biopsy

The study of Kufic inscriptional elements (Surah Yasin) in Shoushtar Congregational Mosque

Shoushtar Congregational Mosque is one of the oldest mosques in Iran. Al-Motazebollah, the 13th Abbasid caliph, order the construction of this monument in 254 AH, and it was completed during the reign of 23rd Caliph, al-Mostarshedobellah (512-529 AH). The mosque was later renovated. This mosque has several inscriptions written in Kufic script. One of these inscriptions is mounted on the wall of the mosque. The inscription is 32 meters in length, with some of the verses of Surah Yasin being rendered in Kufic script. The current study aimed to investigate the elements of this inscription and its rules of calligraphy and visual quality.  The current study aimed to find out the details of this valuable inscription, thereby revealing the specific feature of these inscriptional elements and their quantitative diversity. Concerning this issue, "Abdollah Quchani and Mahnaz Rahimiifar" (2003) have addressed some of the existing inscriptions in a book entitled "Inscriptions of Mosques in Shooshtar Congregational Mosque and Imamzadeh Abdullah”.Seyyed Vahid Mousavi Jazayeri" (2016) in a book entitled "Kufic Stone Inscriptions 1” studied Kufic scripts of Shushtar Congregational Mosque. In 2015, the same author explored the conceptual meaning of the inscription and the reason behind the type of script in another book, "The Kufic Inscriptions of Shushtar Congregational Mosque 2. In addition, Ibrahim Delavaran (2016) investigated these inscriptions from the third century to the late Qajar Period in his thesis "The Aesthetic Study of Shushtar Islamic Inscriptions" Sara Omidbakhsh (2018) did an article entitled “A comparative study of mosques with an emphasis on Shushtar Congregational Mosque as Islamic-Iranian architecture”. The difference between the mentioned study and the literature lies in the investigation of Kufic script elements of Surah Yassin in Shooshtar Congregational Mosque

4D Biofabrication of fibrous artificial nerve graft for neuron regeneration

In this paper, we describe the application of the 4D biofabrication approach for the fabrication of artificial nerve graft. Bilayer scaffolds consisting of uniaxially aligned polycaprolactone-poly(glycerol sebacate) (PCL-PGS) and randomly aligned methacrylated hyaluronic acid (HA-MA) fibers were fabricated using electrospinning and further used for the culture of PC-12 neuron cells. Tubular structures form instantly after immersion of fibrous bilayer in an aqueous buffer and the diameter of obtained tubes can be controlled by changing bilayer parameters such as the thickness of each layer, overall bilayer thickness, and medium counterion concentration. Designed scaffolds showed a self-folded scroll-like structure with high stability after four weeks of real-time degradation. The significance of this research is in the fabrication of tuneable tubular nerve guide conduits that can simplify the current existing clinical treatment of neural injuries. © 2020 The Author(s). Published by IOP Publishing Ltd

Bioinformatics design of CRISPR guide RNA for genomic knockout of ABCB1 gene

Abstract Background: Over-expression of P-Glycoprotein (Pgp) induces acquired drug resistance. Therefore, targeting Pgp as a dominant efflux transporter involved in emergence of multidrug resistance (MDR) has become a major strategy for reversibility of sensitivity to chemotherapy. Objectives: The aim of this study was to design sgRNAs targeting ABCB1 in order to knockout and inhibit the expression of Pgp in Adriamycin resistant (A2780/ADR) ovarian cancer cell line. Methods: This study was performed as a bioinformatics and computational research in Qazvin University of Medical Sciences in collaboration with the Isfahan University of Medical Sciences during 2015-2016. All the 28 exons of the ABCB1 gene were separately investigated in terms of single guide RNA (sgRNA) target sites with regards to the highest on-target and lowest off-target activities, using www.deskgen.com website. Three sgRNA sequences were chosen and synthesized by the GeneCopoeia company. All the plasmids were validated after extraction using BamH1 and EcoR1 restriction enzymes. Results: Sequences of the three sgRNAs were selected close to the start codon (ATG) in order to maximize the possibility of exons 4 and 5 knockout. Digested pCRISPR-CG01, using BamH1 and EcoR1, was electrophorized on 1.5% agarose gel. Detection of the two 330bp and 10100bp fragments on the gel confirmed the integrity of the plasmid and success of the restriction enzyme digestion. Conclusions: The vectors containing the designed sgRNA sequences and CRISPR associated protein (Cas9) can inhibit Pgp gene expression in cell lines over-expressing this gene, including A2780/ADR. Keywords: Drug Resistance, P-Glycoprotein, Ovarian Cancer, CRISP