DeFi composability as MEV non-interference

Complex DeFi services are usually constructed by composing a variety of simpler smart contracts. The permissionless nature of the blockchains where these smart contracts are executed makes DeFi services exposed to security risks, since adversaries can target any of the underlying contracts to economically damage the compound service. We introduce a new notion of secure composability of smart contracts, which ensures that adversaries cannot economically harm the compound contract by interfering with its dependencies

p16 and its putative interplay with metabolic factors in prostate cancer: An analysis based on public TCGA data

p16 is one of the most common tumour suppressor genes, mainly due to its genetic inactivation. However, the clinical significance of p16 in prostate cancer is not yet fully understood, and although p16 acts as a tumour suppressor gene, stress or oncogenic factors or alternative molecular events may overcome the role of p16 as a negative cell cycle regulator. p16 seems to be involved in the metabolic switch to glycolysis during tumorigenesis, possibly interacting with NADPH oxidase 4 (NOX4) and pyruvate kinase type M2 (PKM2), involved in energy metabolism, with differences depending on cell type. The aim of this study was to assess the putative crosstalk between p16, NOX4 and PKM2, with an involvement of miRNA-mediated regulation, in prostate cancer. Transcriptome data from a cohort of 243 patients were extracted from The Cancer Genome Atlas (TCGA) database. An elevated p16 expression level was significantly associated a high Gleason score, decreasing with the score (P<0.0001). NOX4 and PKM2 expression exhibited a similar trend as p16, with higher values in the samples with Gleason scores of 9-10 samples (P<0.0001 and P=0.02, respectively). Moreover, bioinformatics analysis by TargetScan revealed that miR-625-5p could bind to the 3'UTR of p16. A consequential pairing of the NOX4 and PKM2 target region with miR-23a-3p and miR-122-5p, respectively was also found. Of note, the miR-625-5p levels inversely correlated with p16 expression, miR-23a-3p and miR-122 with NOX4 and PKM2, respectively (data not shown). Taken together, these data suggest an interplay between p16 and metabolic factors, such as NOX4 and PKM2, and a miRNA regulation, with a potential clinical impact for the development of novel therapeutic strategies in prostate tumours

Perineal and robot-assisted vesico-urethral reconstruction for anastomotic strictures after RP

Vesico-urethral anastomotic stricture (VUAS) following radical prostatectomy is a rare clinical condition in the robot-assisted procedure era, due to the improved magnification of the surgical field and the perfect knowledge of the anatomic structures deputed to maintaining the mechanisms for urinary continence. Improvements in surgical technique such as muco-mucosal apposition, tension-free anastomosis, water-tight vesico-urethral suture, have been recognized as significant contributors to precise vesico-urethral reconstruction. Conversely, excessive intraoperative blood loss, urinary extravasation and previous history of trans-urethral prostatectomy have been commonly cited as predisposing factors for the development of postoperative scars. Terminology used in the definition of VUAS distinguishes the condition from bladder neck contracture (BNC) and identifies the exact site of the contracture/stenosis/stricture. The majority of cases involves the bladder neck and bulbo-membranous urethra mainly in patients who received radical prostatectomy plus adjuvant radiotherapy. Diagnosis of VUAS is mainly based on symptoms and retrograde urethro-cystogram imaging to identify whether or not the sphincter mechanism is involved and the length of the strictured segment, although delineation of the precise anatomy is often complex. Stricture length is a significant factor for prognosis and correlates with probability of recurrence after reparative surgeries such as urethral dilation, trans-urethral scar incision or resection and perineal urethral buccal mucosa repair. Results obtained via different surgical techniques are amply described, with the hindrance of VUAS and BNC often not being properly distinguished in the reported series of patients treated. Notwithstanding, a 0 to 69% success rate has been reported for patients with bladder neck stricture after urethral dilation and/or cold-knife incision and/or holmium laser incision and/or trans urethral resection, while a 60 to 93% success rate was obtained for patients treated via an abdominal and/or perineal approach. Repair of a long-length urethral stricture often implies the complete loss of urinary continence, whilst it does not appear to have significant impact on sexual potency if previously preserved. The risk of developing VUAS/BNC as a complication after radical prostatectomy falls from 30% of patients treated by Retropubic Radical Prostatectomy (RRP) to less than 5% of patients who received Robotic Assisted Radical Prostatectomy (RARP). Subjects with a histological diagnosis of T3 cancer, positive surgical margins and/or Gleason score >7 and treated by RARP who required early adjuvant radiotherapy, reported an overall 8.4% rate of VUAS. Lavollè et al. treated six patients with anastomotic stricture who had previously undergone radical prostatectomy by extraperitoneal robot-assisted vesico-urethral reconstruction obtaining a 50% success rate. Dinerman et al. presented a case report on a patient with long-length post prostatectomy vesico-urethral stricture by combining robotic-abdominal and open-perineal surgical procedure. The combined abdomino-perineal approach allows to provide “complete” scar removal and a new vesico-urethral anastomosis at a lower risk of developing subsequent recurrences of the stricture also in patients with long-length strictures. An extensive dissection of the bladder neck and bulbo-membranous urethra does imply the complete loss of urinary continence, that can however be recovered through subsequent or concomitant artificial sphincter implant. This novel combined technique was adopted on a series of three patients of whom two previously treated by RARP and one by RRP

The Role of a Multidisciplinary Approach in Gender Affirmation Surgery: What to Expect and Where Are We Currently?

Gender Affirmation Surgeries (GASs), erstwhile called Sex Reassignment Surgeries (SRSs), may be necessary for transgender individuals to change their bodily sexual characteristics and thereby affirm their gender identity. GASs encompass all medically necessary interventions to relieve gender dysphoria and should be available to patients who wish to, and who meet the surgical criteria of the World Professional Association for Transgender Health (WPATH) and Standards of Care (SOC). The comprehensive clinical assessment involves many health specialists, including general practitioners, psychologists, psychiatrists, speech therapists, endocrinologists, surgeons, anesthesiologists, nurses, and other healthcare professionals. To define the patients’ complex care needs and their objectives, high-volume specialized centers, accredited training programs, skilled surgeons and health professionals specializing in transgender care within a multidisciplinary team are essential. Currently, the most prominent challenges are related to ethical issues such as the treatment of underage individuals, fertility, parenting and the potential for regret after GAS. Finally, although GAS has been practiced for more than half a century, data on long-term follow-up represents a further topic for investigation

Role of Chlamydia Trachomatis infection in young men : what we need to know?

Chlamydia Trachomatis infections are the most common sexually transmitted bacterial infections worldwide: Because Chlamydia Trachomatis infections are asymptomatic in approximately 50% of infected men and 70% of infected women, there is a high risk for reproductive tract sequelae and high diffusion of the disease. Recently some studies improved the comprehension of this infection and its natural history highlighting the fact that severe complications can be avoided only by a proper early diagnosis and appropriate treatment. We reviewed the literature related to the new findings in the treatment of Chlamydia Trachomatis infection in sexually active young men. Articles from 1960-2014 were identified through a Medline search using the keywords "Chlamydia Trachomatis" combined with "urethritis", "epididymitis", "prostatitis" "treatment" or "management". Several studies highlighted that Chlamidia are only metabolically active in the host cell and therefore only targeted intracellularly by antibiotics. However, even if the standard therapy includes intracellularly-accumulated antibiotics such as tetracyclines or macrolides, recent evidences highlight the role of quinolones. In particular recent studies hilight the role of prulifloxacin in the treatment of chronic prostatitis patients for improving patient's quality of life and decreasing the IL-8 level. However, there is a need for future studies and to diffuse the knowledge about Chlamydia Trachomatis especially in urological clinical practice, in order to reduce the risk of diagnosis failure

Loss of heterozygosis on chromosome 18q21-23 and muscle-invasive bladder cancer natural history

Loss of heterozygosis (LOH) on chromosome (Chr) 18q21-23 was reported to be one of the most common genetic alterations identified in bladder cancer. The current study aimed to determine the prognostic role of LOH on Chr 18q21-23 in patients diagnosed with muscle-invasive urothelial bladder carcinoma (MIBC). A total of 34 consecutive patients were enrolled in the present prospective study. LOH on Chr 18 was assessed by performing multiplex polymerase chain reaction on paired blood and tumour tissue samples from each patient. The following primers were used in the present study: D18S51, MBP LW and MBP H. These data were then compared with follow-up information. The main outcome measure was patient status at the end of the follow-up. Cox regression was used to evaluate the impact of each parameter on cancer-specific survival and the Kaplan Meier test for disease-free survival was plotted in order to estimate survival. Out of 34 patients, 18 (52.9%) exhibited ≥1 alteration in one of the loci analysed on chromosome 18, while 16 (47.1%) revealed no alterations. No correlation was identified with stage (P=0.18) or grade (P=0.06); however, LOH on Chr 18q21-23 was significantly associated with a lower recurrence-free probability (P<0.0001). Kaplan-Meier curves demonstrated a significant association between patient status at follow-up and LOH on Chr 18 (P<0.001). In addition, multivariate analysis identified LOH on Chr 18 (P<0.001) and stage (P=0.01) as independent survival predictors. Furthermore, artificial neural network analysis was consistent with the results of the multivariate analysis. In conclusion, the present study highlighted the role of LOH on Chr 18q21-23 in predicting the clinical outcome of patients with MIBC

Serenoa repens associated with selenium and lycopene extract and bromelain and methylsulfonylmethane extract are able to improve the efficacy of levofloxacin in chronic bacterial prostatitis patients

Objective: To date, the management of patients with chronic bacterial prostatitis (CBP) is not satisfactory, especially in terms of symptoms relief. Here, we evaluated the efficacy and the safety of a combination of serenoa repens, selenium and lycopene extract + bromelain and methylsulfonylmethane extract associated with levofloxacin in patients with CBP. Materials and methods: All patients with clinical and instrumental diagnosis of CBP, admitted to a single Urological Institution from March to June 2015 were enrolled in this phase III study. All enrolled patients were randomized into two groups: Group A received levofloxacin 500 mg o.d. for 14 days associated with lycopene and methylsulfonylmethane; Group B received levofloxacin (500 mg o.d. for 14 days) only. Clinical and microbiological analyses were carried out at the time of admission (T0) and during the followups at 1 month (T1) and 6 months (T2) from the end of the treatment. NIH Chronic Prostatitis Symptom Index (CPSI), International Prostatic Symptom Score (IPSS) and Quality of Well-Being (QoL) questionnaires were used. The main outcome measures were the rate of microbiological cure and the improvement in questionnaire results from baseline at the end of the follow-ups period. Results: Forty patients were enrolled in Group A and 39 in Group B. During the follow-up (T1), we recorded a significant changes in terms of NIH-CPSI and IPSS in Group A (mean difference: 17.6 ± 2.65; 12.2 ± 2.33; p &lt; 0.01; p &lt; 0.05, respectively) and versus Group B at the intergroup analysis (mean difference: -9 ± 1.82; -8.33 ± 1.71; p &lt; 0.05; p &lt; 0.05, respectively). No differences were reported in terms of microbiological findings between the two groups. At the second follow-up visit (T2), questionnaire results demonstrated statistically significant differences between groups (p &lt; 0.001). One patient in Group A (2.5%) and 7 patients (17.9%) in Group B showed a symptomatic and microbiological recurrence (p = 0.02). Conclusions: The combination of serenoa repens, selenium, lycopene + bromelain and methylsulfonylmethane extracts improved the clinical efficacy of levofloxacin in patients affected by CBP without the development of side effects

Clinical use of hyaluronic acid in andrology: A review

Hyaluronic acid is a glycosaminoglycan widely used in the fields of orthopedics, ophthalmology, and aesthetic medicine due to its significant ability to reduce the synthesis of pro-inflammatory proteins and its activity against oxidative stress, a feature of many degenerative illnesses

16 years follow-up evaluation of immediate vs delayed vs. combined hormonal therapy on fertility of patients with cryptorchidism: results of a longitudinal cohort study

To investigate in a longitudinal cohort study, the best treatment to preserve fertility in cryptorchid subjects. Patients treated with immediate hormonal vs. delayed vs. combined (hormone plus surgery) therapy consecutively enrolled during the period 1987-1997, were evaluated

Human papillomavirus infection is not related with prostatitis-related symptoms: results from a casecontrol study.

PurposeTo investigate the relationship between human papillomavirus (HPV) infection and prostatitis-related symptoms.Materials and MethodsAll young heterosexual patients with prostatitis-related symptoms attending the same Center from January 2005 to December 2010 were eligible for this case-control study. Sexually active asymptomatic men were considered as the control group. All subjects underwent clinical examination, Meares-Stamey test and DNA-HPV test. Patients with prostatitis-related symptoms and asymptomatic men were compared in terms of HPV prevalence. Moreover, multivariable Cox proportional hazards regression analysis was performed to determine the association between HPV infection and prostatitis-related symptoms.ResultsOverall, 814 out of 2,938 patients (27.7%) and 292 out of 1,081 controls (27.0%) proved positive to HPV. The HPV genotype distribution was as follows: HR-HPV 478 (43.3%), PHR-HPV 77 (6.9%), LR-HPV 187 (16.9%) and PNG-HPV 364 (32.9%). The most common HPV genotypes were: 6, 11, 16, 26, 51, 53 and 81. No difference was found between the two groups in terms of HPV infection (OR 1.03; 95% CI 0.88-1.22; p = 0.66). We noted a statistically significant increase in HPV infection over the period 2005 to 2010 (p < 0.001) in both groups. Moreover, we found a statistically significant increase in HPV 16 frequency from 2005 to 2010 (p = 0.002).ConclusionsThis study highlights that prostatitis-like symptoms are unrelated to HPV infection. Secondary, we highlight the high prevalence of asymptomatic HPV infection among young heterosexual men