Extracellular vesicles from the mycoparasitic fungus Trichoderma harzianum.

Trichoderma harzianum is a filamentous fungus that can act as a mycoparasite, saprophyte, or a plant symbiotic. It is widely used as a biological control agent against phytopathogenic fungi and can also be used for plant growth promotion and biofortification. Interaction between T. harzianum and phytopathogenic fungi involves mycoparasitism, competition, and antibiosis. Extracellular vesicles (EVs) have been described as presenting a central role in mechanisms of communication and interaction among fungus and their hosts. In this study, we characterized extracellular vesicles of T. harzianum produced during growth in the presence of glucose or S. sclerotiorum mycelia. A set of vesicular proteins was identified using proteomic approach, mainly presenting predicted signal peptides.

Overactive bladder negatively affects erectile function and promotes premature ejaculation: findings from large representative population-level study.

PURPOSE: The effect of overactive bladder (OAB) on sexual health has been evaluated extensively for women but much less for men. Therefore, the aim of this study was to evaluate the relationship between OAB and men's sexual activity and the effect of OAB on erectile dysfunction (ED) and premature ejaculation (PE) in a large representative cohort of men at the population level. METHODS: This study was based on computer-assisted web interviews that used validated questionnaires. The most recent census and the sample size estimation calculations were employed to produce a population-representative pool. RESULTS: The study included 3001 men, representative of the population in terms of age and place of residence. The frequency of sexual intercourse was higher for respondents without OAB symptoms compared with persons who had OAB (p = 0.001), but there was no association between OAB symptoms and number of sexual partners (p = 0.754). Regression models did not confirm the effect of OAB on sexual activity (odds ratio 0.993, CI 0.974-1.013, p = 0.511). Both ED and PE were more prevalent in respondents with OAB symptoms compared with persons who lacked those symptoms (p < 0.001). Importantly, the effect of OAB on ED or PE was independent of age, comorbidities, and lifestyle habits (regression coefficients of 0.13 and 0.158 for ED and PE, respectively). CONCLUSION: Overactive bladder did not significantly affect men's sexual activity, but it significantly correlated with ED and PE. Our results suggest a need in daily clinical practice to screen for OAB symptoms for persons who report ED or PE.

Detrusor Overactivity After Partial Bladder Outlet Obstruction Is Associated With High Urinary Adenosine Triphosphate Levels in Female Wistar Rats.

PURPOSE: Bladder outlet obstruction (BOO) commonly causes detrusor overactivity (DO). In this study, a post hoc analysis of previous obtained data, we investigate if DO occurring in initial phases of BOO is associated with changes in urinary adenosine triphosphate (ATP) levels. METHODS: Adult female Wistar rats were submitted to partial BOO (pBOO) or to sham obstruction. Cystometry was performed at 3 or 15 days after pBOO and saline voided was collected for ATP determination. Normality was tested using Shapiro-Wilk test. The mean frequency of voiding contractions (VCs) of the sham-operated animals at 15 days after surgery, plus or minus 3 standard deviations, was used to represent the normal range. Statistical analyses were performed using the chi-square and Mann-Whitney tests. RESULTS: DO was indicated by a VC frequency greater than or equal to 0.9 VCs/min. DO was observed in 63% of animals at 3 days and in 33% at 15 days following pBOO. ATP levels were significantly higher in rats with DO compared to those without DO. CONCLUSION: The DO phenotype, occurring in the initial phases of BOO, is associated with comparatively high urinary ATP levels.

A Peculiar Cause of Shock: Analysing Two Clinical Cases.

Introduction: Pheochromocytoma is a rare neoplasia arising from the adrenal medulla that secretes catecholamines. Those afflicted by this condition can present a wide range of symptoms. One of the most common is paroxysmic hypertension. Interestingly, although rare, some patients present with shock. We describe two cases of pheochromocytoma in which the initial presentation was shock. Case 1. 49 year-old woman, with a history of resistant hypertension, presented to the emergency department with thoracic pain and fever. EKG, echocardiogram (ECC), and myocardial necrosis markers were compatible with Takotsubo syndrome (TS). CT demonstrated a staghorn calculus, hydronephrosis, and signs compatible with xanthogranulomatous pyelonephritis in the right kidney. Additionally, and incidentally, it revealed a 60 mm nodule on the right adrenal gland. Piperacillin/tazobactam was started immediately, and the patient was submitted to urgent upper urinary tract drainage. This procedure was complicated by a cardiorespiratory arrest that was treated with adrenaline administration. The patient was admitted to the ICU due to multifactorial shock and started alpha and, posteriorly, beta blockage. Biochemical adrenal incidentaloma endocrinologic study was negative (under hemodialysis). Multiorgan failure progressively improved. After 2 weeks, the patient was submitted to a laparoscopic transperitoneal right adrenalectomy. No complications were reported. Histological analysis revealed a pheochromocytoma. Case 2. 28-year-old woman presented to the emergency department with headaches and nausea. Vitals were compatible with shock. CT revealed an incidental 72 mm mass on the right adrenal. EKG, ECC, and myocardial necrosis markers were compatible with TS. The patient was started on alpha and, posteriorly, beta blockage. Adrenal incidentaloma endocrinological study demonstrated high urinary catecholamines. Right transperitoneal adrenalectomy was performed. No complications were noted. Histological analysis revealed a pheochromocytoma. Conclusion: Pheochromocytoma can present with complex, enigmatic, and rare clinical pictures. Clinicians should be wary of the possibility of this diagnosis when managing adrenal masses.

Sudden-Onset Disaster Mass-Casualty Incident Response: A Modified Delphi Study on Triage, Prehospital Life Support, and Processes.

The application and provision of prehospital care in disasters and mass-casualty incident response in Europe is currently being explored for opportunities to improve practice. The objective of this translational science study was to align common principles of approach and action and to identify how technology can assist and enhance response. To achieve this objective, the application of a modified Delphi methodology study based on statements derived from key findings of a scoping review was undertaken. This resulted in 18 triage, eight life support and damage control interventions, and 23 process consensus statements. These findings will be utilized in the development of evidence-based prehospital mass-casualty incident response tools and guidelines.

Gender representation at scientific congresses: focus on functional and female urology-a study from the EAU Young Academic Urologist Functional Urology Group.

PURPOSE: Female representation at scientific conferences is crucial for encouraging women pursuing an academic career. Nevertheless, gender inequity at urological conferences is common place and women are often stereotyped choosing functional urology. However, there is no evidence whether female representation is higher in functional urology. This investigations aims to analyze gender representation at functional urology sessions. METHODS: National and international urological congresses between 2019 and 2021 with a focus on functional urology and female urology sessions were evaluated. Congresses were categorized as national or international. Session type, topic, gender of chairs and speakers of the identified sessions were recorded. In addition, affiliation and medical specialty were collected for chairs. RESULTS: A total of 29 congresses were evaluated. Out of a total of 2893 chairs and speakers, 1034 (35.7%) were women and 1839 (63.6%) were men. This represents an overall gender gap of 27.9% for functional urology sessions. No significant differences in gender representation between national and international congresses could be identified (p = 0.076). When considering gender distribution of chairs, the gap was more pronounced by 35.5%. Furthermore, men were more likely to be invited to be a speaker in plenary and podiums sessions. CONCLUSIONS: Gender inequality is present in functional urology sessions. There is a need for greater efforts to achieve gender equality. An important step to remedy the situation is the inclusion of women in scientific program committees. Furthermore, support by the leadership of urological societies and academic departments is essential to herald a lasting change in gender inequality.

Incidence of urological cancers in neurological patients: a review of the literature from the EAU Young Academic Urologist Functional Group.

INTRODUCTION: Urological cancers can be challenging in the diagnosis and treatment of patients with neurological diseases. As a result, there are still uncertainties regarding the incidence and risk factors favouring the development of urological cancers in these patients. The aim of this study was to review the available evidence regarding the incidence for the development of urological cancers in neurological patients to provide a basis for future recommendations and research. EVIDENCE ACQUISITION: A narrative review of the literature in Medline and Scopus up to June 2019 was performed. EVIDENCE SYNTHESIS: After screening 1729 records, 30 retrospective studies were retained. For bladder cancer (BC), 21 articles were identified, including a total of 673,663 patients. Among these patients, 4744 had a diagnosis of BC (1265 females, 3214 males, gender not reported in 265). In this group, 2514 were diagnosed with BC associated with a neurological disease. For prostate cancer (PC), 14 articles were identified, including a total of 831,889 men. Among these patients, 67,543 had a diagnosis of PC and 1457 had PC and a neurological disease. Two articles reported kidney cancer (KC), one reported testicular cancer (TC) and none described penile cancer or urothelial carcinomas of the upper urinary tract in neurological patients. CONCLUSIONS: The incidence of urological cancers, especially BC and PC, in patients with neurological diseases appears comparable to the general population. However due to the paucity of studies, specific recommendations for the management are lacking in neurologically disabled patients. In this report we investigated the frequency of urinary tract cancers in patients with neurological diseases. We conclude that urological cancers, especially bladder and prostate cancer, in patients with neurological diseases occur with similar frequency as in the general population.

Revealing Corynebacterium glutamicum proteoforms through top-down proteomics.

Corynebacterium glutamicum is a bacterium widely employed in the industrial production of amino acids as well as a broad range of other biotechnological products. The present study describes the characterization of C. glutamicum proteoforms, and their post-translational modifications (PTMs) employing top-down proteomics. Despite previous evidence of PTMs having roles in the regulation of C. glutamicum metabolism, this is the first top-down proteome analysis of this organism. We identified 1125 proteoforms from 273 proteins, with 60% of proteins presenting at least one mass shift, suggesting the presence of PTMs, including several acetylated, oxidized and formylated proteoforms. Furthermore, proteins relevant to amino acid production, protein secretion, and oxidative stress were identified with mass shifts suggesting the presence of uncharacterized PTMs and proteoforms that may affect biotechnologically relevant processes in this industrial workhorse. For instance, the membrane proteins mepB and SecG were identified as a cleaved and a formylated proteoform, respectively. While in the central metabolism, OdhI was identified as two proteoforms with potential biological relevance: a cleaved proteoform and a proteoform with PTMs corresponding to a 70 Da mass shift.

Analytical tool for optimization of position sensors based on eddy currents effect.

This paper proposes an open-source tool for a fast and precise calculation of the inductance of planar coils in the presence of conductive targets. This tool, based on Grover equations, is versatile to any coil and target geometries. The performance of this tool has been validated by comparing the analytical results with experimental data and Finite Element Model (FEM) simulations. When compared with the experimental measurements, the developed analytical model and the FEM simulation retrieved similar results, with differences below 4%. The proposed tool, in addition to requiring less computing resources, is significantly faster than FEM simulations. This shows the effectiveness of the proposed approach for the analytical calculation of the inductance of planar coils in the presence of conductive plates. It combines accuracy, versatility, speed, and no need for high computational resources.

The value of surgeon's perception during transurethral resection of bladder tumors: can we trust in our eyes and experience to predict grade and staging?

Transurethral resection of newly diagnosed bladder tumors (TURBT) is a hallmark ¡n the treatment of bladder cancer. We evaluated the surgeon capacity to predict bladder tumor stage (T), grade, and presence of muscular layer based upon cystoscopic characteristics during primary TURBT. Methods: Prospective study enrolling 100 consecutive patients undergoing primary TURBT for newly diagnosed bladder cancers. Cystoscop¡c tumor characteristics at the time of TURBT was evaluated by an urology senior and a resident regarding histological grade, invasion (T stage), and presence of muscular layer in the specimen. We analyzed the surgeon's accuracy in predicting these parameters using the final histology as gold standard. In addition, the predictive capacity between seniors and residents was compared. Results: The resident's arm correctly predicted tumor invasiveness in 76% of cases, while seniors correctly predicted 87% of cases. Regarding tumor grade, high grade cancer was reported in 78% of the specimens and 75% and 77% of them were correctly predicted by residents and seniors, respectively. Finally, 80% of the TURBT specimens had muscle representativeness. In nearly 75% of the cases, both resident and senior correctly predicted the TURBT resection depth (presence of detrusor muscle in the specimen). The positive predictive value for this parameter was 79% for the resident, and 81% for the senior, and the negative predictive value was 25% and 40%, respectively. Conclusion: The surgeon's naked eye analysis showed a good, but limited predictive ability to detect non-muscle invasive and high-grade bladder tumors in TURBT specimens. Positive predictive value for muscle representativeness is around 80%, which reinforces the need of carrying out a careful and extensive TURBT, irrespective of the surgeon experience.

Development of Neurogenic Detrusor Overactivity after Thoracic Spinal Cord Injury Is Accompanied by Time-Dependent Changes in Lumbosacral Expression of Axonal Growth Regulators.

Thoracic spinal cord injury (SCI) results in urinary dysfunction, which majorly affects the quality of life of SCI patients. Abnormal sprouting of lumbosacral bladder afferents plays a crucial role in this condition. Underlying mechanisms may include changes in expression of regulators of axonal growth, including chondroitin sulphate proteoglycans (CSPGs), myelin-associated inhibitors (MAIs) and repulsive guidance molecules, known to be upregulated at the injury site post SCI. Here, we confirmed lumbosacral upregulation of the growth-associated protein GAP43 in SCI animals with bladder dysfunction, indicating the occurrence of axonal sprouting. Neurocan and Phosphacan (CSPGs), as well as Nogo-A (MAI), at the same spinal segments were upregulated 7 days post injury (dpi) but returned to baseline values 28 dpi. In turn, qPCR analysis of the mRNA levels for receptors of those repulsive molecules in dorsal root ganglia (DRG) neurons showed a time-dependent decrease in receptor expression. In vitro assays with DRG neurons from SCI rats demonstrated that exposure to high levels of NGF downregulated the expression of some, but not all, receptors for those regulators of axonal growth. The present results, therefore, show significant molecular changes at the lumbosacral cord and DRGs after thoracic lesion, likely critically involved in neuroplastic events leading to urinary impairment.

Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria.

CONTEXT: The current impact of haematuria investigations on health care organisations is significant. There is currently no consensus on how to investigate patients with haematuria. OBJECTIVE: To evaluate the incidence of bladder cancer, upper tract urothelial carcinoma (UTUC), and renal cell carcinoma (RCC) among patients undergoing investigation for haematuria and identify any risk factors for bladder cancer, UTUC, and RCC (BUR). EVIDENCE ACQUISITION: Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov were searched for all relevant publications from January 1, 2000 to June 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective, retrospective, and cross-sectional studies with a minimum population of 50 patients with haematuria were considered for the review. EVIDENCE SYNTHESIS: A total of 44 studies were included. The total number of participants was 229701. The pooled incidence rate for urothelial bladder cancer was 17% (95% confidence interval [CI] 14-20%) for visible haematuria (VH) and 3.3% (95% CI 2.45-4.3%) for nonvisible haematuria (NVH). The pooled incidence rate for RCC was 2% (95% CI 1-2%) for VH and 0.58% (95% CI 0.42-0.77%) for NVH. The pooled incidence rate for UTUC was 0.75% (95% CI 0.4-1.2%) for VH and 0.17% (95% CI 0.081-0.299%) for NVH. On sensitivity analysis, the proportions of males (risk ratio [RR] 1.14, 95% CI 1.10-1.17 for VH; 1.54, 95% CI 1.34-1.78 for NVH; p < 0.00001; moderate certainty evidence) and individuals with a smoking history (RR 1.41, 95% CI 1.24-1.61 for VH; 1.53, 95% CI 1.36-1.72 for NVH; p < 0.00001; moderate certainty evidence) appeared to be higher in BUR than in non-BUR groups. CONCLUSIONS: Male gender and smoking history are risk factors for BUR cancer in haematuria, with bladder cancer being the commonest cancer. The incidence of RCC and UTUC in NVH is low. The review serves as a reference standard for future policy-making on investigation of haematuria by global organisations. PATIENT SUMMARY: Our review shows that male gender and smoking history are risk factors for cancers of the bladder, kidney, and ureter. The review also provides information on the proportion of patients who have cancer when they have blood in their urine (haematuria) and will allow policy-makers to decide on the most appropriate method for investigating haematuria in patients.

DU Is Induced by Low Levels of Urinary ATP in a Rat Model of Partial Bladder Outlet Obstruction: The Incidence of Both Events Decreases after Deobstruction.

Objectives: To investigate, in initial phases of bladder outlet obstruction (BOO), the urinary ATP levels, the incidence of detrusor underactivity (DU), and if they change after deobstruction. Methods: Adult female Wistar rats submitted to partial BOO (pBOO) and sham-obstruction were used. Cystometry was performed 3 or 15 days after pBOO and fluid was collected from the urethra for ATP determination. Bladders were harvested for morphological evaluation of the urothelium. DU was defined as the average of voiding contractions (VC) of sham-operated animals, with 3 SD at 15 days after the sham surgery. In another group of animals in which pBOO was relieved at 15 days and bladders were let to recover for 15 days, the incidence of DU and ATP levels were also accessed. The Kruskal-Wallis test was followed by Dunn's multiple comparisons test, and Spearman's correlation test was used. Results: DU was present in 13% and 67% of the bladders at 3 and 15 days after pBOO, respectively, and in 20% of the bladders at 15 days after deobstruction. ATP levels were significantly lower in DU/pBOO versus sham and non-DU/pBOO rats. A strong positive correlation between ATP levels and VC/min was obtained (r = 0.63). DU bladders had extensive areas in which umbrella cells appeared stretched, the width exceeding that presented by sham animals. Conclusions: Low urothelial ATP parallels with a high incidence of DU early after pBOO.

Treatment of idiopathic overactive bladder with botulinum toxin: real-life results and patients' expectations.

Background: Overactive bladder (OAB) is a prevalent syndrome affecting 11% to 16% of the adult population. When first-line pharmacological therapy is not effective, intradetrusorial injections of onabotulinumtoxinA (BTX-A) might have an important role in controlling symptoms. The main aim of this study was to access both the efficacy and safety of intradetrusor injections of 100U BTX-A in real clinical practice, among women with idiopathic OAB (iOAB). Methods: Retrospective study, based on clinical diaries in 136 iOAB female patients, with or without urinary incontinence, submitted to BTX-A injections, between 2005 and 2018 in a tertiary university hospital. Positive response was considered only when the patient mentioned she had great improvement after the injection, otherwise, it was considered negative. Results: A positive response was obtained in 90 patients (66%) after the first injection. Women with a positive response after the first treatment had 7.5 times more chances to improve with the second (P = .01). Discontinuation of the therapy after the first injection was neither dependent on the presence of incontinence at baseline (P = .73) nor it was related to age (P = .6). On univariate analyses, none of the parameters evaluated was useful of predicting successful response, although there was a trend in women who had had a previous midurethral sling surgery for stress urinary incontinence, to have a lower chance of having a positive response after the first injection (P = .06).Thirty-nine women (29%) had at least 1 adverse event, urinary tract infection, and straining to void were the most frequent. Women above 65 years old had less risk of developing a urinary tract infection (P = .04). Conclusion: In real clinical practice, BTX-A injection is an effective (66%) and safe treatment, capable of improving quality of life. Moreover, responding to the first injection seems to predict good clinical outcomes in the second treatment. This procedure can be done with minimal restrictions.

Prognostic Factors in Penile Cancer: Should We Avoid Inguinal Lymph Node Staging?

INTRODUCTION: Penile cancer (PC) is a rare neoplasm, mostly in developed countries. Herewith, we evaluate the main prognostic factors of patients with PC undergoing surgery. METHODS: This is a retrospective analysis of prognostic factors of overall survival in 65 patients with PC treated at a tertiary referral center over the last 15 years (2004-2018). RESULTS: Almost half (48%) of the patients were diagnosed at an advanced local stage pT3/4. Thirty-eight (58%) patients underwent inguinal lymphadenectomy, and 25 (66%) were negative for lymph node (LN) invasion. Overall survival was 80% at a median follow-up of 31 months. In the multivariate analysis, the main factors of poor prognosis were nodal staging (pN) (p = 0.008) and perineural invasion (p = 0.023). The presence of LN metastasis and perineural invasion in the primary tumor increased the risk of death by 29 (hazard ratio 29.0, 95% confidence interval 2.4-354.2) and 13 (hazard ratio 12.7, 95% confidence interval 1.4-112.0) times, respectively. DISCUSSION/CONCLUSION: Late diagnosis of PC has a negative impact on overall survival, as nodal invasion correlates with survival. Despite the high number of negative inguinal lymphadenectomy, we continue to advocate aggressive surgical treatment of this disease due to the poor prognosis associated with LN metastasis.

Metabolic evaluation in urolithiasis - study of the prevalence of metabolic abnormalities in a tertiary centre.

INTRODUCTION: Metabolic abnormalities are one of the most important risk factors for urinary stone disease. Our objective was to determine the prevalence of metabolic abnormalities in patients referred to the urolithiasis outpatient clinic of a tertiary centre. MATERIAL AND METHODS: We performed a cross-sectional study evaluating 67 patients referred to the urolithiasis outpatient clinic. Metabolic evaluation was performed, including one 24-hour urine sample. RESULTS: Metabolic abnormalities could be identified in 92.5% patients. Almost a quarter of the patients had only one metabolic abnormality and 67.6% had more than one abnormality. The most prevalent metabolic abnormalities were hypercalciuria (54.5%), hyperoxaluria (34.7%) and hyperuricosuria (32.3%). Patients with hypercalciuria were older (54.7 vs. 47.8 years, p = 0.018) and family history of stone disease was significantly more frequent among patients with hyperoxaluria (71.4% vs. 28.6%, p = 0.013). There was a positive linear relationship between body mass index (BMI) and urinary calcium (r = 0.247, p = 0.048) and a negative linear relationship between BMI and urinary pH (r = -0.254, p = 0.046). CONCLUSIONS: Given the high prevalence of metabolic abnormalities, metabolic evaluation should be performed in every patient with urolithiasis evaluated in a tertiary setting.

Improving Intraoperative Communication in Trauma: The Educational Effect of the Joint DSTC™-DATC™ Courses.

BACKGROUND: Operative management of severe trauma requires excellent communication among team members. The surgeon and anesthesiologist need to interact efficiently, exchanging vital information. The Definitive Surgical Trauma Care (DSTC) and Definitive Anesthesia Trauma Care (DATC) courses provide an excellent opportunity for teamwork training. Our goal was to study the impact of the joint DSTC-DATC courses in candidates' self-reported assessment in communication skills and techniques in a simulated intraoperative trauma scenario. METHODS: Study population consists of 93 candidates (67 surgeons and 26 anesthesiologists) participating in four consecutive joint DSTC-DATC courses in May and June 2019 in Brazil (3) and in Portugal (1). Median age was 30 years; 53 (60%) of subjects were male (46 senior residents and 47 specialists). All participants attended joint lectures, case discussions and surgical skills session, emphasizing intraoperative communication. Post-course survey on several aspects of perioperative communication (responses on a Likert scale) was conducted with participants being asked which aspects of intraoperative communication they valued the most. RESULTS: All participants responded to the survey. Results displayed an increase in the self-assessed importance of team briefing and intraoperative communication, particularly routine periodic communication, rather than only at critical moments. Postoperative team debriefing was also valued as highly relevant. Closed-loop and direct, by-name communication were highly rated. Self-reported communication skills improved significantly during the course. CONCLUSIONS: Joint training in the DSTC-DATC courses improved candidates' perception and skills on proficient intraoperative communication. Further studies should address both the durability of these changes and the potential impact on patient care.

In the Beginning ... It was Already the End.

Sometimes, the presentation of some diseases can be fulminating. The authors present the case of a 51-year- old male brought to the emergency department visibly drunk and complaining of abdominal pain. Immediately, the diagnosis of hemorrhagic shock due to an accentuated drop of the hemoglobin level was made. After stabilization, he underwent a computed tomography of the abdomen, revealing a hepatocellular carcinoma with rupture of the Glisson capsule and massive intraperitoneal hemorrhage. With this case, the authors want to bring attention to a rare first presentation of hepatocellular carcinoma with a catastrophic result.

Por vezes a apresentação de algumas patologias pode ser fulminante. Os autores apresentam o caso de um doente de 51 anos que foi trazido ao Serviço de Urgência em etilismo agudo com dor abdominal mas rapidamente foi constatado choque com queda acentuada da hemoglobina confirmando-se choque hemorrágico. Após estabilização realizou Tomografia Computadorizada abdominal constatando-se carcinoma hepatocelular com rotura da cápsula de gleason e hemorragia intra-peritoneal maciça. Com este caso os autores pretendem chamar a atenção para uma apresentação inicial rara de carcinoma hepatocelular mas cujo resultado é catastrófico.