Exploring the putative microRNAs cross-kingdom transfer in Solanum lycopersicum-Meloidogyne incognita interactions.

Introduction: Plant-pathogen interaction is an inexhaustible source of information on how to sustainably control diseases that negatively affect agricultural production. Meloidogyne incognita is a root-knot nematode (RKN), representing a pest for many crops, including tomato (Solanum lycopersicum). RKNs are a global threat to agriculture, especially under climate change, and RNA technologies offer a potential alternative to chemical nematicides. While endogenous microRNAs have been identified in both S. lycopersicum and M. incognita, and their roles have been related to the regulation of developmental changes, no study has investigated the miRNAs cross-kingdom transfer during this interaction. Methods: Here, we propose a bioinformatics pipeline to highlight potential miRNA-dependent cross-kingdom interactions between tomato and M. incognita. Results: The obtained data show that nematode miRNAs putatively targeting tomato genes are mostly related to detrimental effects on plant development and defense. Similarly, tomato miRNAs putatively targeting M. incognita biological processes have negative effects on digestion, mobility, and reproduction. To experimentally test this hypothesis, an in vitro feeding assay was carried out using sly-miRNAs selected from the bioinformatics approach. The results show that two tomato miRNAs (sly-miRNA156a, sly-miR169f) soaked by juvenile larvae (J2s) affected their ability to infect plant roots and form galls. This was also coupled with a significant downregulation of predicted target genes (Minc11367, Minc00111), as revealed by a qRT-PCR analysis. Discussions: Therefore, the current study expands the knowledge related to the cross-kingdom miRNAs involvement in host-parasite interactions and could pave the way for the application of exogenous plant miRNAs as tools to control nematode infection.

Expression of miRNA from spent pre-implantation embryos culture media.

This study examines the expression of three microRNAs (hsa-miR-661, hsa-miR-21-5p, hsa-miR-372-5p) in spent pre-implantation embryos culture media to identify possible new non-invasive biomarkers of embryo competence, predictive of development to the blastocyst stage. A preliminary analysis on 16 patients undergoing IVF cycles was performed by collecting and stored spent culture media on the fifth/sixth day of embryo culture. Expression of miRNAs was evaluated according to the embryos' fate: 1) NE/DG: non-evolved or degenerate embryos; 2) BLOK: embryos developed to the blastocyst stage. Preliminary results revealed a higher miRNAs expression in NE/DG spent media. To elucidate the roles of these miRNAs, we employed a robust bioinformatics pipeline involving: 1) in-silico miRNA Target Prediction using RNAHybrid, which identified the most-likely gene targets; 2) Construction of a Protein-Protein Interaction network via GeneMania, linking genes with significant biological correlations; 3) application of modularity-based clustering with the gLay app in Cytoscape, resulting in three size-adapted subnets for focused analysis; 4) Enrichment Analysis to discern the biological pathways influenced by the miRNAs. Our bioinformatics analysis revealed that hsa-miR-661 was closely associated with pathways regulating cell shape and morphogenesis of the epithelial sheet. These data suggest the potential use of certain miRNAs to identify embryos with a higher likelihood of developing to the blastocyst stage. Further analysis will be necessary to explore the reproducibility of these findings and to understand if miRNAs here investigated can be used as biomarkers for embryo selection before implantation into the uterus or if they may be reliable predictors of IVF outcome.

Design and Model-Driven Analysis of Synthetic Circuits with the Staphylococcus aureus Dead-Cas9 (sadCas9) as a Programmable Transcriptional Regulator in Bacteria.

Synthetic circuit design is crucial for engineering microbes that process environmental cues and provide biologically relevant outputs. To reliably scale-up circuit complexity, the availability of parts toolkits is central. Streptococcus pyogenes (sp)-derived CRISPR interference/dead-Cas9 (CRISPRi/spdCas9) is widely adopted for implementing programmable regulations in synthetic circuits, and alternative CRISPRi systems will further expand our toolkits of orthogonal components. Here, we showcase the potential of CRISPRi using the engineered dCas9 from Staphylococcus aureus (sadCas9), not previously used in bacterial circuits, that is attractive for its low size and high specificity. We designed a collection of ∼20 increasingly complex circuits and variants in Escherichia coli, including circuits with static function like one-/two-input logic gates (NOT, NAND), circuits with dynamic behavior like incoherent feedforward loops (iFFLs), and applied sadCas9 to fix a T7 polymerase-based cascade. Data demonstrated specific and efficient target repression (100-fold) and qualitatively successful functioning for all circuits. Other advantageous features included low sadCas9-borne cell load and orthogonality with spdCas9. However, different circuit variants showed quantitatively unexpected and previously unreported steady-state responses: the dynamic range, switch point, and slope of NOT/NAND gates changed for different output promoters, and a multiphasic behavior was observed in iFFLs, differing from the expected bell-shaped or sigmoidal curves. Model analysis explained the observed curves by complex interplays among components, due to reporter gene-borne cell load and regulator competition. Overall, CRISPRi/sadCas9 successfully expanded the available toolkit for bacterial engineering. Analysis of our circuit collection depicted the impact of generally neglected effects modulating the shape of component dose-response curves, to avoid drawing wrong conclusions on circuit functioning.

The Role of Checkpoint Inhibitor Expression Directly on Exfoliated Cells from Bladder Cancer: A Narrative Review.

Bladder cancer (BCa) is a common type of cancer that affects the urinary bladder. The early detection and management of BCa is critical for successful treatment and patient outcomes. In recent years, researchers have been exploring the use of biomarkers as a non-invasive and effective tool for the detection and monitoring of BCa. One such biomarker is programmed death-ligand 1 (PD-L1), which is expressed on the surface of cancer cells and plays a crucial role in the evasion of the immune system. Studies have shown that the PD-L1 expression is higher in BCa tumors than in healthy bladder tissue. Additionally, PD-L1 expression might even be detected in urine samples in BCa patients, in addition to the examination of a histological sample. The technique is being standardized and optimized. We reported how BCa patients had higher urinary PD-L1 levels than controls by considering BCa tumors expressing PD-L1 in the tissue specimen. The expression of PD-L1 in urinary BCa cells might represent both a diagnostic and a prognostic tool, with the perspective that the PD-L1 expression of exfoliate urinary cells might reveal and anticipate eventual BCa recurrence or progression. Further prospective and longitudinal studies are needed to assess the expression of PD-L1 as a biomarker for the monitoring of BCa patients. The use of PD-L1 as a biomarker for the detection and monitoring of BCa has the potential to significantly improve patient outcomes by allowing for earlier detection and more effective management of the disease.

Design of a stable ethanologenic bacterial strain without heterologous plasmids and antibiotic resistance genes for efficient ethanol production from concentrated dairy waste.

Engineering sustainable bioprocesses that convert abundant waste into fuels is pivotal for efficient production of renewable energy. We previously engineered an Escherichia coli strain for optimized bioethanol production from lactose-rich wastewater like concentrated whey permeate (CWP), a dairy effluent obtained from whey valorization processes. Although attractive fermentation performances were reached, significant improvements are required to eliminate recombinant plasmids, antibiotic resistances and inducible promoters, and increase ethanol tolerance. Here, we report a new strain with chromosomally integrated ethanologenic pathway under the control of a constitutive promoter, without recombinant plasmids and resistance genes. The strain showed extreme stability in 1-month subculturing, with CWP fermentation performances similar to the ethanologenic plasmid-bearing strain. We then investigated conditions enabling efficient ethanol production and sugar consumption by changing inoculum size and CWP concentration, revealing toxicity- and nutritional-related bottlenecks. The joint increase of ethanol tolerance, via adaptive evolution, and supplementation of small ammonium sulphate amounts (0.05% w/v) enabled a fermentation boost with 6.6% v/v ethanol titer, 1.2 g/L/h rate, 82.5% yield, and cell viability increased by three orders of magnitude. Our strain has attractive features for industrial settings and represents a relevant improvement in the existing ethanol production biotechnologies.

Reporting ChAracteristics of cadaver training and sUrgical studies: The CACTUS guidelines.

INTRODUCTION: Recent systematic reviews highlighted increasing use of cadaveric models in the surgical training, but reports on the characteristics of the models and their impact on training are lacking, as well as standardized recommendations on how to ensure the quality of surgical studies. The aim of our survey was to provide an easy guideline that would improve the quality of the studies involving cadavers for surgical training and research. METHODS: After accurate literature review regarding surgical training on cadaveric models, a draft of the CACTUS guidelines involving 10 different items was drawn. Afterwards, the items were improved by questionnaire uploaded and spread to the experts in the field via Google form. The guideline was then reviewed following participants feedback, ergo, items that scored between 7 and 9 on nine-score Likert scale by 70% of respondents, and between 1 and 3 by fewer than 15% of respondents, were included in the proposed guideline, while items that scored between 1 and 3 by 70% of respondents, and between 7 and 9 by 15% or more of respondents were not. The process proceeded with Delphi rounds until the agreement for all items was unanimous. RESULTS: In total, 42 participants agreed to participate and 30 (71.4%) of them completed the Delphi survey. Unanimous agreement was almost always immediate concerning approval and ethical use of cadaver and providing brief outcome statement in terms of satisfaction in the use of the cadaver model through a short questionnaire. Other items were subjected to the minor adjustments. CONCLUSION: 'CACTUS' is a consensus-based guideline in the area of surgical training, simulation and anatomical studies and we believe that it will provide a useful guide to those writing manuscripts involving human cadavers.

Intravesical Therapy for Non-Muscle-Invasive Bladder Cancer: What Is the Real Impact of Squamous Cell Carcinoma Variant on Oncological Outcomes?

Background and Objectives: To evaluate the oncological impact of squamous cell carcinoma (SCC) variant in patients submitted to intravesical therapy for non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: Between January 2015 and January 2020, patients with conventional urothelial NMIBC (TCC) or urothelial NMIBC with SCC variant (TCC + SCC) and submitted to adjuvant intravesical therapies were collected. Kaplan-Meier analyses targeted disease recurrence and progression. Uni- and multivariable Cox regression analyses were used to test the role of SCC on disease recurrence and/or progression. Results: A total of 32 patients out of 353 had SCC at diagnosis. Recurrence was observed in 42% of TCC and 44% of TCC + SCC patients (p = 0.88), while progression was observed in 12% of both TCC and TCC + SCC patients (p = 0.78). At multivariable Cox regression analyses, the presence of SCC variant was not associated with higher rates of neither recurrence (p = 0.663) nor progression (p = 0.582). Conclusions: We presented data from the largest series on patients with TCC and concomitant SCC histological variant managed with intravesical therapy (BCG or MMC). No significant differences were found in term of recurrence and progression between TCC and TCC + SCC. Despite the limited sample size, this study paves the way for a possible implementation of the use of intravesical BCG and MMC in NMIBC with histological variants.

Prostate cancer testicular metastasis: Are they underestimated? Case report and analysis of the literature.

INTRODUCTION: We aim to present a rare case of a patient who developed a late testicular metastasis of PCa after radical prostatectomy. CASE DESCRIPTION: A 78 years old man presenting for left testicular swelling slowly increasing of size over the last 2 months. He underwent a retropubic radical prostatectomy and extended bilateral lymphadenectomy in 2007 for prostatic adenocarcinoma. At the time of the presentation the last PSA was 0.91 ng/mL. The patient underwent a standard left orchifunicolectomy in April 2019 without intra- or perioperative complications. The pathological analysis showed a testicular metastasis of acinar adenocarcinoma. CONCLUSIONS: In conclusion, testicular metastasis from PCa are uncommon conditions. PSA evaluation and physical examination of all sites of metastasis and accurate evaluation of all signs/symptoms during the clinical visit remains crucial to the diagnosis of recurrence.

Ectopic adrenal tissue in the kidney: A systematic review.

INTRODUCTION: Ectopic adrenal tissue in the kidney, including "Ectopic adrenal tissue" and "Adrenal-renal fusion", is a rare event with a specific behavior which may be difficult to distinguish clinically from renal neoplasms. We performed a systematic review on ectopic adrenal tissue variants reported in the literature underlining its clinical aspects. METHODS: Manuscripts which presented a case report or case series of ectopic adrenal tissue in the kidney were included even if published in original articles, reviews, or letters to the editor. A specific search on SCOPUS®, PubMed®, and Web of Science® database was performed. Only English language papers published in a period ranging between August 1991 and April 2020 were considered. Additionally, a case we had at our institution is described, and its characteristics are included. Data on clinical presentation, type of adrenal anomaly, location, anatomopathological and immune-histotype characteristics were collected. RESULTS: We identified 888 manuscripts. Among these 29 were included in this systematic review. Overall, 39 patients with renal adrenal fusion or adrenal ectopia were considered. In most cases, the diagnosis was made incidentally, or following investigation for flank pain, abdominal pain, or endocrinological disorders. CT scan frequently identified a solid vascularized lesion that was difficult to distinguish from renal neoplasm. Adrenal fusion was mostly located at the level of the upper pole. Adrenal rest was found in the renal parenchyma, renal hilum, or retroperitoneum in close proximity to the renal peduncle. Often these ectopic adrenal tissue lesions follow a benign behavior and can be classified as functioning or non-functioning adenomas. Rarely, they may experience neoplastic degeneration. The most frequently positive markers were inhibin, vimentin, melan-A, synaptophysin and anti-p450 scc. CONCLUSIONS: Ectopic adrenal tissue in the kidney is a rare event with specific clinical characteristics that need to be identified in order to arrive at a correct diagnosis and carry out appropriate treatment management.

The role of the multi-disciplinary team and multi-disciplinary therapeutic protocol in the management of the chronic pelvic pain: There is strenght in numbers!

INTRODUCTION: The aim of the study is to evaluate the effectiveness of a Multi-disciplinary team (MDT) and multi-disciplinary approach in the treatment of Chronic Pelvic Pain (CPP). METHODS: The data of all consecutive patients referred for a CPP from 11/2016 to 2/2019 has been prospectively collected. The sample was divided in two groups: Group A, made by patients managed after the institution of our MDT, and Group B, made of patients managed before this date. The MDT is composed by three urogynecologists, a psychologist and a physiotherapist. All Group A patients underwent a weekly bladder instillation with dimethyl sulfoxide (DMSO), kinesiotherapy for trigger points and Percutaneous Tibial Nerve Stimulation for 10 consecutive weeks. Patients were asked to perform a self-treatment following the Stanford Protocol and to adhere to a specific diet. All Group B patients were managed only with DMSO instillations and a strict diet. RESULTS: The Group A was made of 41 females and 6 males while the Group B was made of 38 females and 5 males. The Group A patients showed a statistically significant improvement in the Pelvic Pain Urgency Frequency, in the frequency times reported at the 6 months voiding diary, and a better Patient Global Impression of Improvement. CONCLUSIONS: Our data support the efficacy of the MDT in the management of CPP. The multimodal approach might represent an effective and reproducible non-invasive option to manage successfully CPP.

CRISPR Interference Modules as Low-Burden Logic Inverters in Synthetic Circuits.

CRISPR and CRISPRi systems have revolutionized our biological engineering capabilities by enabling the editing and regulation of virtually any gene, via customization of single guide RNA (sgRNA) sequences. CRISPRi modules can work as programmable logic inverters, in which the dCas9-sgRNA complex represses a target transcriptional unit. They have been successfully used in bacterial synthetic biology to engineer information processing tasks, as an alternative to the traditionally adopted transcriptional regulators. In this work, we investigated and modulated the transfer function of several model systems with specific focus on the cell load caused by the CRISPRi logic inverters. First, an optimal expression cassette for dCas9 was rationally designed to meet the low-burden high-repression trade-off. Then, a circuit collection was studied at varying levels of dCas9 and sgRNAs targeting three different promoters from the popular tet, lac and lux systems, placed at different DNA copy numbers. The CRISPRi NOT gates showed low-burden properties that were exploited to fix a high resource-consuming circuit previously exhibiting a non-functional input-output characteristic, and were also adopted to upgrade a transcriptional regulator-based NOT gate into a 2-input NOR gate. The obtained data demonstrate that CRISPRi-based modules can effectively act as low-burden components in different synthetic circuits for information processing.

Hospital care in Departments defined as COVID-free: A proposal for a safe hospitalization protecting healthcare professionals and patients not affected by COVID-19.

The COVID-19 pandemic influenced the normal course of clinical practice leading to significant delays in the delivery of healthcare services for patients non affected by COVID-19. In the near future, it will be crucial to identify facilities capable of providing health care in compliance with the safety of healthcare professionals, administrative staff and patients. All the staff involved in the project of a Covid-free hospital should be subjected to a diagnostic swab for COVID-19 before the beginning of healthcare activity and then periodically in order to avoid the risk of contamination of patients during the process of care. The modifications of various activities involved in the process of care are described: outpatient care, reception of inpatients, inpatient ward and operating room. For outpatient care, modality of appointment procedure, characteristics of waiting room and personal protective equipment (PPE) for healthcare professionals and administrative staff are presented. Reception of inpatients shall be conditional on a negative swab for COVID-19 obtained with a drive-in procedure. The management of the operating room represents the most crucial step of the patient's care process. The surgical team should be restricted and monitored with periodic swabs; surgical procedures should be performed by experienced surgeons according to standard procedures; surgical training experimental treatments and research protocols should be suspended. Adequate personal protective equipment and measures to reduce aerosolization in the operating room (closed circuits, continuous cycle insufflators, fume extraction) should be adopted. Prevention of possible transmission of the virus during procedures in open, laparoscopic and endoscopic surgery is to use a multi-tactic approach, which includes correct filtration and ventilation of the operating room, the use of appropriate PPE (FFP3 plus surgical mask and protective visor for all the staff working in the operating room) and smoke evacuation devices with a suction and filter system.   on behalf of the UrOP Executive Committee Giuseppe Ludovico, Angelo Cafarelli, Ottavio De Cobelli, Ferdinando De Marco, Giovanni Ferrari, Stefano Pecoraro, Angelo Porreca, Domenico Tuzzolo.

Intensive simulation training on urological mini-invasive procedures using Thiel-embalmed cadavers: The IAMSurgery experience.

INTRODUCTION: The objective of the study was to evaluate the benefits perceived by the use of cadaver models by IAMSurgery attendees and to define indications to standardize future similar training camps. MATERIALS AND METHODS: A 25-item survey was distributed via e-mail to all the participants of previous training courses named as "Urological Advanced Course on Laparoscopic Cadaver Lab" held at the anatomy department of the University of Malta, for anonymous reply. Participants were asked to rate the training course, the Thiel's cadaveric model, and make comparison with other previously experienced simulation tools. RESULTS: The survey link was sent to 84 attendees, with a response rate of 47.6% (40 replies). There was improvement in the median self-rating of the laparoscopic skills before and after the training camp with a mean difference of 0.55/5 points in the post-training skills compared to the basal (p < 0.0001). The 72.2% of the urologists interviewed considered Thiel's HCM better than other training methods previously tried, while five urologists (27.8%) considered it equal (p = 0.00077). Globally, 77.5% (31) of attendees found the training course useful, and 82.5% (33) would advise it to colleagues. CONCLUSIONS: Thiel's fixed human cadaveric models seem to be ideal for training purposes, and their use within properly structured training camps could significantly improve the surgical skills of the trainees. An important future step could be standardization of the training courses using cadavers, and their introduction into the standardized European curriculum.

Engineering endogenous fermentative routes in ethanologenic Escherichia coli W for bioethanol production from concentrated whey permeate.

Whey permeate (WP) is a lactose-rich waste effluent, generated during cheese manufacturing and further valorization steps, such as protein extraction. The production of ethanol by WP fermentation has been proposed to increase cost-competitiveness of dairy waste processing. In previous work, the Escherichia coli W strain was selected for its efficient growth in dairy waste and it was engineered to convert lactose into ethanol as the main fermentation product from WP and concentrated WP (CWP). To improve its performance, here the lactate dehydrogenase, fumarate reductase and pyruvate formate lyase fermentative routes were disrupted, obtaining new deletion strains. In test tubes, growth and fermentation profiles obtained in standard laboratory media and CWP showed large differences, and were affected by oxygen, medium and ethanologenic gene expression level. Among the tested strains, the one with triple deletion was superior in both high-oxygen and low-oxygen test tube fermentations, in terms of ethanol titer, rate and yield. The improved performance was due to a lower inhibition by medium acidification rather than an improved ethanol flux. The parent and triple deletion strains showed similar performance indexes in pH-controlled bioreactor experiments. However, the deletion strain showed lower base consumption and residual waste, in terms of both dry matter and chemical oxygen demand after distillation. It thus represents a step towards sustainable dairy wastewater valorization for bioenergy production by decreasing process operation costs.

Port-site metastasis and atypical recurrences after robotic-assisted radical cystectomy (RARC): an updated comprehensive and systematic review of current evidences.

The objective of this systematic review is to evaluate the current evidence regarding atypical metastases in patients undergoing robotic-assisted radical cystectomy (RARC). A review of the current literature was conducted through the Medline and NCBI PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases in October 2019. From the literature search using the cited keys and after a careful evaluation of the full texts, we included 31 articles in the study. Fourteen studies (45.2%) reported at least an atypical recurrence during the follow-up period with a rate between 4 and 40% of all the recurrences. Overall, 105 (1.63%) of the 6720 patients who have been evaluated in the included studies developed an atypical recurrence. Sixty-three (60%) of these atypical metastases were peritoneal carcinomatosis, 16 (15.2%) extrapelvic lymph nodes metastases, 11 (10.5%) port-site metastases, 10 (9.5%) retroperitoneal nodal metastases, while 5 (3.8%) patients developed more than one type of atypical recurrence. In literature, there is a low but not negligible incidence of atypical recurrences after RARC. However, publication bias and retrospective design of most studies could influence the evidences. Further prospective randomized studies are needed to clarify the real risk of patients undergoing RARC to develop atypical metastases.

Prostate-specific antigen levels and proportion of biopsy positive cores are independent predictors of upgrading patterns in low-risk prostate cancer.

BACKGROUND: The aim of this study is to evaluate clinical factors associated with the risk of tumor upgrading patterns in low risk prostate cancer (PCA) patients undergoing radical prostatectomy. METHODS: In a period running from January 2013 to December 2016, 245 low risk patients underwent RP. Patients were classified into three groups, which included case with pathology grade group one (no upgrading pattern), two-three (intermediate upgrading pattern), and four-five (high upgrading pattern). The association of factors with the upgrading risk was evaluated by the multinomial logistic regression model. It was used a receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis to assess the efficacy of predictors. RESULTS: Overall, tumor upgrading was detected in 158 patients (67.3%). Tumor upgrading patterns were absent in 80 patients (32.7%), intermediate in 152 cases (62%) and high in 13 subjects (5.3%). Median prostate specific (PSA) levels and proportion of biopsy positive core (BPC) were higher in patients with intermediate (PSA=6 ng/mL; BPC=0.28) and high (PSA=8.9 ng/mL; BPC=0.33) than those without (PSA=5.7 ng/mL; BPC=0.17) and the difference was significant (PSA: P=0.002; BPC: P=0.001). When compared to not upgraded cases, higher BPC proportions were independent predictors of intermediate upgrading patterns (odds ratio, OR=36.711; P<0.0001; AUC=0.613) while higher PSA values were independent predictors of high upgrading patterns (OR=2.033, P<0.0001; AUC=0.779). CONCLUSIONS: PSA and BPC were both independent predictors of tumor upgrading in low risk PCA. BPC associated with the risk of intermediate tumor upgrading patterns, but showed a low discrimination power. PSA associated with high upgrading patterns and showed a fair discrimination power in the model. Tumor upgrading risk patterns should be evaluated in low risk PCA patients before treatment.

A Bioinformatics Approach to Explore MicroRNAs as Tools to Bridge Pathways Between Plants and Animals. Is DNA Damage Response (DDR) a Potential Target Process?

MicroRNAs, highly-conserved small RNAs, act as key regulators of many biological functions in both plants and animals by post-transcriptionally regulating gene expression through interactions with their target mRNAs. The microRNA research is a dynamic field, in which new and unconventional aspects are emerging alongside well-established roles in development and stress adaptation. A recent hypothesis states that miRNAs can be transferred from one species to another and potentially target genes across distant species. Here, we propose to look into the trans-kingdom potential of miRNAs as a tool to bridge conserved pathways between plant and human cells. To this aim, a novel multi-faceted bioinformatic analysis pipeline was developed, enabling the investigation of common biological processes and genes targeted in plant and human transcriptome by a set of publicly available Medicago truncatula miRNAs. Multiple datasets, including miRNA, gene, transcript and protein sequences, expression profiles and genetic interactions, were used. Three different strategies were employed, namely a network-based pipeline, an alignment-based pipeline, and a M. truncatula network reconstruction approach, to study functional modules and to evaluate gene/protein similarities among miRNA targets. The results were compared in order to find common features, e.g., microRNAs targeting similar processes. Biological processes like exocytosis and response to viruses were common denominators in the investigated species. Since the involvement of miRNAs in the regulation of DNA damage response (DDR)-associated pathways is barely explored, especially in the plant kingdom, a special attention is given to this aspect. Hereby, miRNAs predicted to target genes involved in DNA repair, recombination and replication, chromatin remodeling, cell cycle and cell death were identified in both plants and humans, paving the way for future interdisciplinary advancements.

Positive Association between Preoperative Total Testosterone and Lymph Node Invasion in Intermediate Risk Prostate Cancer.

INTRODUCTION: Prostate cancer (PCa) patients who are classified into the intermediate risk category represent a heterogeneous population needing further preoperative risk assessment. OBJECTIVES: To evaluate clinical total testosterone (TT) associations with lymph node invasion (LNI) in intermediate risk PCa. MATERIAL AND METHODS: Between November 2014 and July 2016, intermediate risk PCa was assessed in 154 patients who underwent extended pelvic lymph node dissection if the risk of LNI was higher than 5%. Clinical factors associated with the risk LNI were investigated by the multinomial logistic regression model. RESULTS: The risk of LNI was assessed higher than 5% in 40.9% of cases of whom 15.5% had LNI. In the multivariate model, the risk of LNI was independently increased by prostate specific antigen (OR = 1.185; p = 0.021) and TT (OR = 1.004; p = 0.036). As a result, TT was an independent factor that associated with LNI because it increased the risk of LNI by 4% for each increment unit of TT. CONCLUSION: Preoperative TT independently increased the risk of LNI in the intermediate risk class of PCa patients elected to radical prostatectomy and extended pelvic lymph node dissection. TT might be a useful preoperative factor for stratifying intermediate risk patients because of the positive association of TT with high grade tumors.

Robotic surgery in patients with achondroplastic dwarfism: evaluation of risks and issues in an anatomical challenging bilateral partial nephrectomy.

The reports on the performance of robotic surgery in patients with dwarfism are anecdotal; anesthesiological issues and a challenging anatomy are the main factors that lead most of surgeons to prefer a more traditional approach. We present a case of bilateral robotic partial nephrectomy in a patient affected by achondroplastic dwarfism and aim to evaluate risks and issues in this type of surgery.

Quality of life following urinary diversion: Orthotopic ileal neobladder versus ileal conduit. A multicentre study among long-term, female bladder cancer survivors.

INTRODUCTION: Women undergoing radical cystectomy (RC) followed by urinary diversion (UD) for bladder cancer experience a substantial reduction in health-related quality of life (HRQOL). At present, studies comparing long-term QOL outcomes for different UD methods, needed to inform evidence-based choices of bladder reconstruction for female patients, are sparse. Our objective was to compare two common UD methods in terms of their HRQOL outcomes in women. MATERIALS AND METHODS: We retrospectively analysed HRQOL in 73 consecutive female bladder cancer patients having undergone orthotopic ileal neobladder (IONB, N = 24) or ileal conduit (IC, N = 49) following RC between 2007 and 2013 in six Italian academic urological centres. Patients had no evidence of tumour recurrence and were actively followed up. Validated Italian versions of the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder-cancer-specific (QLQ-BLM30) questionnaires were used to evaluate HRQOL. RESULTS: Patients in the IONB group were significantly younger than those in the IC group (median age: 67 and 73 years, respectively, p = 0.02). Barring that, the two groups did not present statistically significant differences in median length of follow-up (43 vs 54 months), pathological stage, grading of the neoplasm, or adjuvant chemo - or radiotherapy. No significant differences in QOL were found between the groups, with the exception of financial difficulties, affecting IONB patients significantly more than IC patients (mean score on a scale of 0-100: 33.3 ±â€¯29.5 vs 18.4 ±â€¯19.3, respectively; p = 0.05). CONCLUSION: Financial difficulties was the only HRQOL item to differ between the two UD groups.