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Introduction: Workplace violence (WPV) is a growing concern that constitutes a major threat to occupational health and safety, thereby comprising a priority issue for policymakers. Given the increasing prevalence of chronic diseases and comorbidities among the Lebanese population, nurses working in critical care settings encounter intense workloads and high-risk interactions, potentially increasing the risk of WPV., Objectives: This study aimed to investigate the traumatic and psychological reactions of Lebanese critical nurses who have been exposed to WPV, and the risk factors for depression and anxiety., Methods: The study utilized a cross-sectional descriptive correlational design; 112 critical care nurses from diverse departments took part in this study during the period of June to July 2021., Results: A positive, significant correlation between WPV exposure and self-reported anxiety was observed, p  = .03 with high levels of WPV, especially among patients and their families. Although verbal abuse was found to be more prevalent among critical care nurses in Lebanon compared to physical and sexual violence, the severity of the situation and its impact on the nurses' mental health and well-being cannot be ignored., Conclusions: WPV for critical care nurses is a serious issue that needs to be considered. Policy-makers should develop the politics of regulating the nursing profession, especially for critical care nurses in Lebanon., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Within the Surveillance, Epidemiology, and End Results database (2000-2019), we identified 5522 unilateral surgically treated non-metastatic chromophobe kidney cancer (chRCC) patients. This population was randomly divided into development vs. external validation cohorts. In the development cohort, the original Leibovich 2018 and GRANT categories were applied to predict 5- and 10-year cancer-specific survival (CSS). Subsequently, a novel multivariable nomogram was developed. Accuracy, calibration and decision curve analyses (DCA) tested the Cox regression-based nomogram as well as the Leibovich 2018 and GRANT risk categories in the external validation cohort. The accuracy of the Leibovich 2018 and GRANT models was 0.65 and 0.64 at ten years, respectively. The novel prognostic nomogram had an accuracy of 0.78 at ten years. All models exhibited good calibration. In DCA, Leibovich 2018 outperformed the novel nomogram within selected ranges of threshold probabilities at ten years. Conversely, the novel nomogram outperformed Leibovich 2018 for other values of threshold probabilities. In summary, Leibovich 2018 and GRANT risk categories exhibited borderline low accuracy in predicting CSS in North American non-metastatic chRCC patients. Conversely, the novel nomogram exhibited higher accuracy. However, in DCA, all examined models exhibited limitations within specific threshold probability intervals. In consequence, all three examined models provide individual predictions that might be suboptimal and be affected by limitations determined by the natural history of chRCC, where few deaths occur within ten years from surgery. Further investigations regarding established and novel predictors of CSS and relying on large sample sizes with longer follow-up are needed to better stratify CSS in chRCC.

Background and Objectives : To describe the predictors of cribriform variant status and perineural invasion (PNI) in robot-assisted radical prostatectomy (RARP) histology. To define the rates of upgrading between biopsy specimens and final histology and their possible predictive factors in prostate cancer (PCa) patients undergoing RARP. Material and Methods: Within our institutional database, 265 PCa patients who underwent prostate biopsies and consecutive RARP at our center were enrolled (2018-2022). In the overall population, two independent multivariable logistic regression models (LRMs) predicting the presence of PNI or cribriform variant status at RARP were performed. In low- and intermediate-risk PCa patients according to D'Amico risk classification, three independent multivariable LRMs were fitted to predict upgrading. Results : Of all, 30.9% were low-risk, 18.9% were intermediate-risk and 50.2% were high-risk PCa patients. In the overall population, the rates of the cribriform variant and PNI at RARP were 55.8% and 71.1%, respectively. After multivariable LRMs predicting PNI, total tumor length in biopsy cores (>24 mm [OR: 2.37, p -value = 0.03], relative to <24 mm) was an independent predictor. After multivariable LRMs predicting cribriform variant status, PIRADS (3 [OR:15.37], 4 [OR: 13.57] or 5 [OR: 16.51] relative to PIRADS 2, all p = 0.01) and total tumor length in biopsy cores (>24 mm [OR: 2.47, p = 0.01], relative to <24 mm) were independent predicting factors. In low- and intermediate-risk PCa patients, the rate of upgrading was 74.4% and 78.0%, respectively. After multivariable LRMs predicting upgrading, PIRADS (PIRADS 3 [OR: 7.01], 4 [OR: 16.98] or 5 [OR: 20.96] relative to PIRADS 2, all p = 0.01) was an independent predicting factor. Conclusions : RARP represents a tailored and risk-adapted treatment strategy for PCa patients. The indication of RP progressively migrates to high-risk PCa after a pre-operative assessment. Specifically, the PIRADS score at mpMRI should guide the decision-making process of urologists for PCa patients.

The aim of this study is to evaluate YouTube™ content in terms of the quality of information available about prostate cancer (PCa) in relation to incidence, symptomatology, and potential treatments for patients' mental health. We searched on YouTube™ for terms related to mental health combined with those relating to prostate cancer. Tools for audio-visual-content PEMAT A/V, Global Quality Score, and DISCERN score were applied for the assessment of videos' quality. A total of 67 videos were eligible. Most of the analyzed YouTube™ videos were created by physicians (52.2%) in contrast to other author categories (48.8%). According to the PEMAT A/V, the median score for Understandability was 72.7% and the overall median score for Actionability was 66.7%; the median DISCERN score was 47, which correspond to a fair quality. Only videos focusing on the topic "Psychological Effects and PCa treatment" were significantly more accurate. The General Quality Score revealed that the majority of YouTube™ videos were rated as "generally poor" (21, 31.3%) or "poor" (12, 17.9%). The results suggest that the content of YouTube™ videos is neither exhaustive nor reliable in the current state, illustrating a general underestimation of the mental health of prostate cancer patients. A multidisciplinary agreement to establish quality standards and improve communication about mental health care is needed.

Several previous studies on YouTube™ on urological field have already been published. The aim of the current study was to evaluate the quality information of YouTube TM videos on testicular pain. Using Google Trends tool, the frequency of worldwide YouTube TM and Google Search on testicular pain was examined from 2010 to 2020. The keywords "testicular pain", "testicular ache" and "scrotal pain" were used on the YouTube platform and the first 100 YouTube TM videos were analyzed for each one. The Patient Education Materials Assessment Tool (PEMAT) for Audiovisual (A/V) Materials, the DISCERN score and Misinformation tool were used to assess video quality. According to YouTube™ Search the mean relative frequency search for "testicular pain" ranged from 10.5 to 30.0%. According to Google TM Search it ranged from 73.7 to 91.0%, Of all 300 videos, 117 were eligible for the analysis. The median number of views, thumbs-up and thumbs-down was respectively: 47060 (interquartile range [IQR] = 6297.0-144188.0), 289 (IQR = 40-912) and 19 (IQR = 4-53). Of all videos, 68.4% and 31.6% were produced respectively by Medical Doctors and Other. The median PEMAT Actionability and Understandability scores were 66.7% and 66.7%, respectively. The median DISCERN score ranged from 1 to 5, with an overall median score of 3, defined from question 16. The median misinformation score ranged from 2 to 5. In conclusion, an increased interest on testicular pain was recorded on both YouTube TM and Google search during the last decade. However, according to the quality assessment tools used, YouTube™ users cannot get trustful and exhaustive information on testicular pain. Therefore, authors with/without medical background should improve the quality of information on YouTube™ videos., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

A wide literature has studied the predictors of number comprehension and early math learning by considering both domain-general and number-specific prerequisites. However, a consensus has not been reached regarding the specific contribution of these prerequisites. This study aimed to analyze the contribution and interplay of two domain-general functions, working memory (WM) and metacognitive abilities, and number-specific prerequisites in determining number comprehension. The participants, 126 Italian first-graders, were tested on two WM capacity tasks, an early metacognition questionnaire, five number-specific prerequisites tasks (e.g., quantity and/or size comparison; placement of Arabic numeral), and the Number Knowledge Test for whole-number comprehension. We hypothesized that WM capacity would predict number comprehension both directly and indirectly via metacognition and domain-specific prerequisites. This is because both metacognition and domain-specific prerequisites might place an information load on WM to establish schemes for declarative metamemory and metacognitive monitoring and for emerging counting skills, respectively. The results confirmed these hypotheses. WM capacity was positively associated with number comprehension both directly and via increased metacognition and domain-specific prerequisites. These findings offer a model for interpreting the interplay between domain-general and number-specific predictors of whole-number comprehension, but they also underline the multiple ways in which WM capacity affects it., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: YouTube TM is an open-access source for mass information. Several previous studies of YouTube TM videos showed a high rate of misinformation in the urological field. The aim of the current study was to evaluate the quality of information on immunotherapy (IMT) for urological tumors uploaded to YouTube TM ., Methods: YouTube TM videos were searched using nine keyword combinations. The PEMAT, the DISCERN tool, and the Misinformation scale were used to assess the quality of information in YouTube TM videos about IMT for urological tumors. Descriptive statistics and Kruskal-Wallis, Chi-square, proportion, and Pearson's tests were performed., Results: According to the selection criteria, 156 YouTube TM videos were suitable for the analysis and stratified according to topic (urothelial carcinoma vs. renal cell cancer vs. prostate cancer vs. general information on IMT). According to PEMAT A/V, the overall Understandability score was 40% (Inter-Quartile Range [IQR]: 20-61.5) and the overall Actionability score was 0% (IQR: 0-25). According to the DISCERN tool, the overall DISCERN score was 44 (IQR: 39-53.2), defined as " fair ". According to the Misinformation scale, we recorded the lowest median overall score for item 4 ("IMT in multimodality approach") and item 5 ("Future perspective")., Conclusions: YouTube TM cannot be recommended as a reliable source of information on IMT for urological malignancies. In addition, YouTube TM videos contributed to the spread of misinformation by underestimating the role of IMT in a multimodality approach and missing the findings of published clinical trial results.

Introduction: Telemedicine is a most used tools in various medical and surgical scenarios. The aim of the present study was to explore attitudes and perceptions by urologic patients toward the use of telemedicine in the context of patient-physicians communication during the post-operative follow-up in a large academic tertiary urology referral department in Italy., Materials and Methods: An anonymous questionnaire consisting of 15 multiple choice questions was designed including three sections: respondents' demographics, attitudes, and perceptions towards the use of telemedicine. Invitations to participate to this anonymous questionnaire was given to outpatients attended at Urology Department, University of Naples Federico II., Results: In total 697 responses were received (participation rate 73%). The frequency of telemedicine use was described as frequently, occasional, rarely, and never by 41.6%, 30.4%, 15.1%, and 12.6% of respondents, respectively. WhatsApp messenger used by 59.5% of respondents and telephone call (34.3%) were the most common type of tools. Satisfaction in using telemedicine was reported as very satisfied, satisfied, neutral, dissatisfied, and very dissatisfied by 39.6%,41.4%,10%,7% and 2% of respondents respectively. Overall, 43.7%% of participants individuated limited interaction and risk of misdiagnosis as the major limit of telemedicine., Conclusions: Telemedicine represents the future of medical practice due to several benefits as well as convenience, increased access to care and decreased healthcare costs.

Introduction: Male infertility (MI) is one of the most important worrying topics for the fertile age population. Nowadays, several mobile health applications (MHAs) have been developed to help and assist patients suffering from male infertility (MI), but their quality and adherence to the guidelines is not solved issue yet., Materials and Methods: On 2nd July 2022, an observational cross-sectional descriptive study of all MHAs on male infertility was conducted: a search on both the iTunes App Store and Google Play Store was performed. Our group reviewed all MHAs, evaluating the quality, using Mobile Application Rating Scale (MARS), and the adherence to European Association of Urology guidelines, with a special tool created for this manuscript., Results: In the final analysis we included 10 MHAs: 20% (n = 2) from the iTunes App Store and 80% (n = 8) from the Google Play Store. Across the sample, 80% (n = 8) of the apps provided general information on MI, 60% (n = 6) focused on diagnosis and 50% (n = 5) focused on treatment options, respectively. According to MARS tool, the mean score was 2.18 (0.78), 3.78 (0.36), 3.0 (0.53), 3.19 (0.45), 2.18 (0.54) for Engagement, Functionality, Aesthetic, Information and Subjective quality, respectively. According to EAU Adherence Score, the highest score was reported by "Infertilità" with 12/15 points while the lowest score was reported by "Fertility Diet Guide", 0/15 points., Conclusions: Nowadays, MHAs present in the market are not a reliable source of information on MI. An ideal MHAs should be based on scientific evidence, user friendly, respecting privacy and security laws, making patients feel capable and confident to change personal behavior or attitudes.

Background and Objective: Blood loss represents a long-standing concern of radical prostatectomy (RP). This study aimed to assess how red line cell values changed following robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa). Materials and Methods: The blood panels of 453 consecutive PCa patients undergoing RARP at a single tertiary academic referral center, from September 2020 to April 2022, were reviewed. Data from 363 patients with the blood panel available for the following timeframe: within seven days before surgery, six hours after surgery, and the first three postoperative days, were analyzed. Specifically, hemoglobin (Hb, g/dL), red blood cells (RBCs, ×106/μL), and hematocrit (HCT, %) trends were collected. Results: Considering the Hb trend, the median values in the preoperative day, postoperative day (POD) 2, and POD 3 are 14.7 (interquartile range (IQR) = 13.9−15.4), 12.1 (IQR = 11.2−12.9), and 12.2 (IQR = 11.2−13.1), respectively. The ∆ between preoperative day and POD 2 is 2.5 (IQR = 1.8−3.2) (p < 0.001). Considering the RBCs trend, the median values in the preoperative day, POD 2, and POD 3 are 4.9 (IQR = 4.7−5.3), 4.1 (IQR = 3.8−4.4), and 4.1 (IQR = 3.8−4.5), respectively. The ∆ between preoperative day and POD 2 is 0.9 (IQR = 0.6−1.1) (p < 0.001). Considering the HCT trend, the median values in the preoperative day, POD 2, and POD 3 are 44.4 (IQR = 41.7−46.6), 36.4 (IQR = 33.8−38.9), and 36.1 (IQR = 33.5−38.7), respectively. The ∆ between preoperative day and POD 2 is 7.8 (IQR = 5.2−10.5) (p < 0.001). Conclusions: Overall, patients undergoing RARP experience a significant, but clinically limited, decline in red line cell values between the preoperative time and the second day post-surgery. These observations are important to provide physicians with knowledge of the expected postoperative course and, thus, to improve the quality of patient care.

Background and objective: Fibrinogen and albumin are two proteins widely used, singularly and in combination, in cancer patients as biomarkers of nutritional status, inflammation and disease prognosis. The aim of our study was to investigate the preoperative fibrinogen-to-albumin ratio (FAR) as a preoperative predictor of malignancy as well as advanced grade in patients with bladder cancer. Materials and Methods: A retrospective analysis of patients who underwent TURBT at our institution between 2017 and 2021 was conducted. FAR was obtained from preoperative venous blood samples performed within 30 days from scheduled surgery and was analyzed in relation to histopathological reports, as was the presence of malignancy. Statistical analysis was performed using a Kruskal−Wallis Test, and univariate and multivariate logistic regression analysis, assuming p < 0.05 to be statistically significant. Results: A total of 510 patients were included in the study (81% male, 19% female), with a mean age of 71.66 ± 11.64 years. The mean FAR was significantly higher in patients with low-grade and high-grade bladder cancer, with values of 80.71 ± 23.15 and 84.93 ± 29.96, respectively, compared to patients without cancer (75.50 ± 24.81) (p = 0.006). Univariate regression analysis reported FAR to be irrelevant when considered as a continuous variable (OR = 1.013, 95% CI = 1.004−1.022; p = 0.004), while when considered as a categorical variable, utilizing a cut-off set at 76, OR was 2.062 (95% CI = 1.378−3.084; p < 0.0001). Nevertheless, the data were not confirmed in the multivariate analysis. Conclusions: Elevated preoperative FAR is a potential predictor of malignancy as well as advanced grade in patients with bladder cancer. Further data are required to suggest a promising role of the fibrinogen-to-albumin ratio as a diagnostic biomarker for bladder tumors.

Objectives: To assess YouTube™ videos' quality on prostate checks, especially on the digital rectal exam (DRE), and to investigate if they can inform patients correctly and eradicate their beliefs and myths., Methods: A search using as keywords "digital rectal exam for prostate cancer" was performed on the YouTubeTM platform. We selected the first 100 videos. To assess video quality content, Patient Education Materials Assessment Tool for audio-visual content (PEMAT A/V) and Misinformation tool were used., Results: Seventy-three videos were suitable for the analyses. The median PEMAT A/V Understandability score and PEMAT A/V Actionability score were 46.2% (interquartile range [IQR]: 30.8-76.9) and 50.0% (IQR: 25.0-75.0), respectively. The medi-an PEMAT A/V Understandability and Actionability scores were 69.2% (IQR: 46.2-88.5) vs 46.2% (IQR: 30.8-61.5) (p = 0.01) and 100.0% (IQR: 87.5-100.0) vs 25.0% (IQR: 25.0-68.8) (p < 0.001), for healthcare workers vs patients, respectively. According to the Misinformation tool, the median misinforma-tion score of the overall videos was 2.2 (IQR:1.7-2.8). According to the target audience, the misinformation score was 2.8 (IQR: 2.4-3.5) vs 2.0 (IQR: 1.5-2.8) (p = 0.02), for healthcare workers vs patients, respectively., Conclusions: Currently, based on our analyses, YouTubeTM videos' quality on DRE resulted unsatisfactory according to the PEMAT A/V score and the Misinformation tool. Videos targeted to healthcare workers got higher quality scores if compared to videos targeted to patients. Therefore, YouTubeTM videos' may not be considered a reliable source of information on DRE for patients.

Introduction: Several mobile health applications (MHAs) have been developed to assist and improve the quality of life of patients affected by premature ejaculation, but the scientific quality and adherence to guidelines are not yet addressed., Materials and Methods: On 25 May 2022, we conducted a search in the Apple App Store and Google Play Store. We reviewed all mobile apps from Apple App Store and Google Play Store for premature ejaculation and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines., Results: In total 9 MHA were reviewed. All MHAs are geared towards the patient and provide information about diagnoses and treatment of PE. The mean score were 2.87, 3.69, 2.77, 2.55, 2.86 for Engagement, Functionality, Aesthetics, Information, and Subjective quality respectively. MHAs reported low and medium adherence to EAU guidelines., Conclusions: MHAs provide different services in many medical fields, including male sexual dysfunction. Their development is constantly increasing, but the problems of scientific validation, content, and quality are not yet solved. Much future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps.

Objectives: The aim of this study was to investigate the role of preoperative Monocyte-to-Lymphocyte ratio (MLR) as a potential predictor of bladder cancer (BC)., Methods: Clinical data of patients who underwent TURBT at our institution between 2017 and 2021 were collected and retrospectively analysed. MLR was obtained from preoperative blood analyses performed within 1 month from hospital admission. The association of MLR with different clinic-pathological features obtained from histological reports was further analysed. Statistical analysis was performed using the Kruskal Wallis test for non-parametric variables, assuming p<0.05 as statistically significant., Results: 510 patients were included in the study (81% males, 19% females), with a mean age of 71.66 ± 11.64 years. Mean MLR was higher in patients with any-type bladder cancer, reporting an MLR of 0.41 ± 0.11 compared to 0.38 ± 0.43 in patients without bladder cancer (p=0.043). In the subsequent comparison among low-grade and high-grade bladder cancer, MLR did not report statistically significant differences, with 0.29 ± 0.12 for low-grade BC and 0.51 ± 0.81 for high-grade BC (p=0.085)., Conclusions: Our findings reported elevated preoperative MLR should be considered a potential biomarker predicting malignancy for bladder tumours. Furthermore, research are necessary to assess its role in discerning low-grade from high-grade patients., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Chemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value., Methods: Blood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels - Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC)., Results: 21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p<0.0001). Moreover, they were higher in deceased patients compared to survivors (p<0.05). Logistic univariate regression and multivariate analysis demonstrated that chemerin level at day 14 of admission was an independent risk factor for death. Accordingly, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein and tumor necrosis factor α. Finally, IHC analysis revealed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts in advanced acute respiratory distress syndrome (ARDS)., Discussion: Increased plasma chemerin levels are a marker of severity and may predict death of COVID-19 patients. However, multicentric studies are needed, before chemerin can be considered as a biomarker of severity and death used in daily clinical practice. Further studies are also necessary to identify the precise mechanisms of the chemerin/ChemR23 system in ARDS secondary to viral pneumonia., Competing Interests: BB received a financial support from Amgen and Boehringer Ingelheim. These funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article and the decision to submit for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lavis, Morra, Orte Cano, Albayrak, Corbière, Olislagers, Dauby, Del Marmol, Marchant, Decaestecker, Mascart, De Vos, Van de Borne, Salmon, Remmelink, Parmentier, Cardozo and Bondue.)

Objective: To evaluate the quality information on testicular cancer uploaded on YouTube™ videos., Methods: YouTube™ videos were searched using "Testicular cancer" as a keyword. The Patient Education Materials Assessment Tool, the Misinformation scale, and the DISCERN tool were used to assess the quality information of YouTube™ videos on testicular cancer., Results: According to the selection criteria, 121 YouTube™ videos were collected for the analysis and stratified according to uploading year (2009-2014 vs 2015-2020). According to the Patient Education Materials Assessment Tool for audio-visual content, the overall Understandability score was 60% (interquartile range 45.5-75) and the overall Actionability score was 100% (interquartile range 66.7-100). According to the Misinformation scale, the lowest median was recorded for item 6 ("Effects on fertility") and the overall median Misinformation score was 2 (interquartile range 1.3-2.8). No statistically significant differences were observed according to uploading year (all P > 0.05). Of all, only 54 (44.6%) videos mentioning treatment were subsequently analyzed. Of these videos, the overall Understandability was 71.4% (interquartile range 56.3-84.6) and the overall Actionability was 100% (interquartile range 66.7-100). The overall Misinformation score was 2.8 (interquartile range 2.2-3.5). The median DISCERN score recorded for question 16 was 5 (interquartile range 3-5)., Conclusions: YouTube™ is a fast and open-access source for mass information. The overall quality of the testicular cancer contents provided is sadly unsatisfactory, in the present likewise in the past. However, YouTube™ videos mentioning treatment options showed higher quality content, than the remaining one. Nevertheless, all the videos analyzed underestimated the testicular cancer effects on fertility. Nowadays, YouTube™ cannot be recommended as a reliable source of information on testicular cancer., (© 2022 The Japanese Urological Association.)

The Prostate Imaging Reporting and Data System (PI-RADS) classification is based on a scale of values from 1 to 5. The value is assigned according to the probability that a finding is a malignant tumor (prostate carcinoma) and is calculated by evaluating the signal behavior in morphological, diffusion, and post-contrastographic sequences. A PI-RADS score of 3 is recognized as the equivocal likelihood of clinically significant prostate cancer, making its diagnosis very challenging. While PI-RADS values of 4 and 5 make biopsy necessary, it is very hard to establish whether to perform a biopsy or not in patients with a PI-RADS score 3. In recent years, machine learning algorithms have been proposed for a wide range of applications in medical fields, thanks to their ability to extract hidden information and to learn from a set of data without previous specific programming. In this paper, we evaluate machine learning approaches in detecting prostate cancer in patients with PI-RADS score 3 lesions via considering clinical-radiological characteristics. A total of 109 patients were included in this study. We collected data on body mass index (BMI), location of suspicious PI-RADS 3 lesions, serum prostate-specific antigen (PSA) level, prostate volume, PSA density, and histopathology results. The implemented classifiers exploit a patient's clinical and radiological information to generate a probability of malignancy that could help the physicians in diagnostic decisions, including the need for a biopsy.

The management of patients with prostate cancer (PCa) and previous or synchronous colorectal cancer (CRC) represents a challenging issue. A systematic review was performed in May 2022 to summarize available evidence about the diagnosis, management, and outcomes of these patients. Twenty-seven studies involving 252 patients were identified. Overall, 163 (64.7%) and 89 (35.3%) patients had synchronous and metachronous PCa and CRC, respectively. In patients with synchronous diseases, PCa treatment involved active surveillance in 1 patient, radical prostatectomy (RP) in 36 patients, radiotherapy (RT) in 60 patients, RP plus RT in 1 patient, proton beam therapy in 1 patient, and cryoablation in 1 patient. In patients with previous CRC treatment, prostate biopsy was mostly performed by transrectal approach ( n = 24). The trans-perineal and suprapubic approaches were adopted in 12 and 6 cases, respectively. Surgical PCa treatment in these cases involved endoscopic extraperitoneal RP, robot-assisted RP, and not otherwise specified RP in 30, 15, and 2 cases, respectively. Biochemical recurrence rates ranged from 20% to 28%. Non-surgical PCa treatment options included brachytherapy, RT plus androgen deprivation therapy, and RT alone in 23, 2 and 4 patients, respectively. PCa specific survival was reported by one study and was 100%.

Spinal cord injury (SCI) is a relevant medical and social problem. According to the World Health Organization, the commonly estimated worldwide annual incidence of SCI is 40 to 80 cases per million population. After the SCI experience, most men present with sexual dysfunction (erectile dysfunction (ED) and ejaculatory dysfunction), fertility problems (such as impaired spermatogenesis, abnormalities in sperm viability, motility, and morphology), and systemic disorders such as genitourinary infection and endocrine imbalances. The best options available for managing the ejaculatory disorders in patients suffering from SCI are penile vibratory stimulation (PVS) and electroejaculation (EEJ). Furthermore, the treatment of ED in SCI patients consists of medical therapies including phosphodiesterase 5 inhibitors (PDE5i), intracavernosal injections (ICI), vacuum erection devices (VEDs), and surgical as penile prosthesis (PP). This review provides a snapshot of the current evidence for the mechanisms of sexual dysfunction and infertility in SCI patients, discusses the best management strategies for these conditions, and offers our perspective on the direction of future research.

The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients ( n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes ( n = 61, 52.1%) followed by the lungs ( n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC.

Objective: To evaluate the quality of YouTube™ videos on placenta accreta and to investigate if they can be used as a reliable source of information., Methods: We queried YouTube™ with terms related to placenta accreta. Patient Education Materials Assessment Tool for audio-visual content (PEMAT A/V), Global Quality Score (GQS), DISCERN score and Misinformation tool were used to assess videos' quality content., Results: Sixty-four videos were suitable for the analyses. Of those, 42 (65.6%) and 22 (34.4%) were produces by healthcare works and others, respectively. The median PEMAT A/V Understandability and Actionability score was 75 and 66.7%, respectively. According to GQS, 31.2 and 45.3% videos were excellent or good and generally poor or poor, respectively. The median DISCERN score of section 1 was 27 (out of 40), of section 2 was 16 (out of 35) and of section 3 was 2 (out of 5). According to Misinformation tool, the worst described aspect was the one regarding the possible risk factor associated to placenta accreta. Performing the quality assessment according to video authoring entity, videos produced by healthcare workers harbored a higher quality content, relative to the others., Conclusions: Currently, the overall consideration of YouTube™ video content on placenta accreta is low. Societies should invest new sources in producing higher quality videos to provide a helpful tool for physician during the counselling with patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The Internet is an important and easily accessible source of information. The aim of the current study was to investigate the quality of YouTube videos on cystoscopy and to establish if they can be used as a reliable information tool for internet users., Materials and Methods: The search term "cystoscopy" was used on YouTube platform and the first 120 YouTube videos were analyzed. To assess the video quality Patient Education Materials Assessment Tool (PEMAT) for Audiovisual (A/V) Materials (Understandability and Actionability sections), Misinformation score and Global Quality Score (GQS) were used., Results: Of all 120 videos, 72 were included in the analyses. Of all videos, 59.7% (n = 43), and 40.3% (n = 29) were targeted to General Public and Healthcare Workers. Moreover, "technical aspects" was the main topic addressed (n = 29, 40.3%). The median PEMAT A/V Understandability and Actionability scores were 50.0% (IQR: 39.1-70.0) and 66.7% (IQR: 33.3- 100.0), respectively. The median Misinformation score ranged from 1.0 to 3.0. According to GQS, 22 (30.6%), 26 (36.1%), 16 (22.2%), 8 (11.1%) videos were poor, generally poor, moderate, and good, respectively. No video was evaluated as excellent., Conclusions: Today, YouTube videos on cystoscopy are more frequently uploaded by healthcare workers, who share information about specific aspects of this procedure. However, the quality of YouTube contents on cystoscopy is still poor. Therefore, currently users interested in cystoscopy cannot rely on YouTube to get good informative material on this topic. In consequence, future authors should focus on improving the quality of video contents on cystoscopy.

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

[FeFe]-hydrogenases are complex metalloenzymes, key to microbial energy metabolism in numerous organisms. During anaerobic metabolism, they dissipate excess reducing equivalents by using protons from water as terminal electron acceptors, leading to hydrogen production. This reaction is coupled to reoxidation of specific redox partners [ferredoxins, NAD(P)H or cytochrome c 3 ], that can be used either individually or simultaneously ( via flavin-based electron bifurcation). [FeFe]-hydrogenases also serve additional physiological functions such as H 2 uptake (oxidation), H 2 sensing, and CO 2 fixation. This broad functional spectrum is enabled by a modular architecture and vast genetic diversity, which is not fully explored and understood. This Mini Review summarises recent advancements in identifying and characterising novel [FeFe]-hydrogenases, which has led to expanding our understanding of their multiple roles in metabolism and functional mechanisms. For example, while numerous well-known [FeFe]-hydrogenases are irreversibly damaged by oxygen, some newly discovered enzymes display intrinsic tolerance. These findings demonstrate that oxygen sensitivity varies between different [FeFe]-hydrogenases: in some cases, protection requires the presence of exogenous compounds such as carbon monoxide or sulphide, while in other cases it is a spontaneous built-in mechanism that relies on a reversible conformational change. Overall, it emerges that additional research is needed to characterise new [FeFe]-hydrogenases as this will reveal further details on the physiology and mechanisms of these enzymes that will enable potential impactful applications., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morra.)

Background: Surfactant protein D (SP-D) and pulmonary club cell protein 16 (CC-16) are called "pneumoproteins" and are involved in host defense against oxidative stress, inflammation, and viral outbreak. This study aimed to determine the predictive value of these pneumoproteins on the incidence of acute respiratory distress syndrome (ARDS) or death in patients with coronavirus disease-2019 (COVID-19)., Methods: This retrospective study included 87 patients admitted to an emergency department. Blood samples were collected on three time points (days 1, 5, and 14 from hospital admission). SP-D and CC-16 serum levels were determined, and univariate and multivariate analyses considering confounding variables (age, body mass index, tobacco use, dyspnea, hypertension, diabetes mellitus, neutrophil-to-lymphocyte ratio) were performed., Results: Based on the multivariate analysis, SP-D level on D1 was positively and slightly correlated with subsequent development of ARDS, independent of body mass index, dyspnea, and diabetes mellitus. CC-16 level on D1 was modestly and positively correlated with fatal outcome. A rise in SP-D between D1 and D5 and D1 and D14 had a strong negative association with incidence of ARDS. These associations were independent of tobacco use and neutrophil-to-lymphocyte ratio., Conclusions: Overall, our data reveal that increase in SP-D levels is a good prognostic factor for patients with COVID-19, and that initial CC-16 levels correlated with slightly higher risk of death. SP-D and CC-16 may prove useful to predict outcomes in patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tiezzi, Morra, Seminerio, Van Muylem, Godefroid, Law-Weng-Sam, Van Praet, Corbière, Orte Cano, Karimi, Del Marmol, Bondue, Benjelloun, Lavis, Mascart, van de Borne and Cardozo.)

This study aims at investigating the relationship between working memory updating and working memory capacity in preschool children. A sample of 176 preschoolers (36-74 months) was administered a working memory updating task (Magic House) along with three working memory capacity tests that specifically measure their core attentional component (M capacity, as defined in the theory of constructive operators): Backward Word Span, Mr. Cucumber, and Direction Following Task. Correlational analyses and cross-classification prediction analyses were performed. Updating and capacity were significantly correlated, although the correlations were not high when age was partialled out. Capacity increased with age, and mediated the relation between age and updating. More importantly, cross-classification prediction analysis revealed that high updating scores with low M capacity, and low updating scores with relatively high M capacity, are possible events; the only combination ruled out was a low updating score with precocious development of M capacity. These facts demonstrate that updating skills in preschoolers depends on M capacity but does not coincide with it. Therefore, in cognitive developmental theories, the constructs of working memory updating and capacity should be distinguished, and on practical grounds, different tests should be used to measure them.

Aim: To evaluate the quality of YouTube™ videos on bladder pain syndrome (BPS) and to investigate whether they can be used as a reliable source of information., Methods: The search term "bladder pain syndrome" was used on YouTube TM platform. The first 100 videos were selected. Patient Education Materials Assessment Tool for audio-visual content (PEMAT A/V), Global Quality Score (GQS), Misinformation tool, and DISCERN score were used to assess videos' quality content. Pearson's test was used to assess potential correlations between variables., Results: Seventy-nine videos were suitable for the analyses. The median PEMAT A/V Understandability score and PEMAT A/V Actionability score were 66.7% (interquartile range [IQR]: 46.2-100.0) and 75.0% (IQR: 37.5-100.0), respectively. According to GQS, 26 (32.9%), 32 (40.5%), 3 (3.8%), 15 (19.0%), and 3 (3.8%) videos were excellent, good, moderate, generally poor, and poor, respectively. According to Misinformation tool, of all videos, 81% (n = 64), 6.3% (n = 5), 5.1% (n = 4), 5.1% (n = 4), 2.5% (n = 2) had respectively no, very little, moderate, high, and extreme misinformation. The overall median DISCERN score ranged from 5.0 (IQR: 2.0-5.0) to 5.0 (IQR: 5.0-5.0). A positive statistically significant correlation was found between video length and PEMAT A/V Understandability (r = 0.27, p = 0.01), video length and PEMAT A/V Actionability (r = .26, p = 0.02), and video length and DISCERN Question 16 (r = 0.28, p = 0.01)., Conclusions: Nowaday, the overall quality of YouTube TM videos on BPS have been evaluated good according to PEMAT A/V, GQS, Misinformation tool, and DISCERN score. It is possible to assume that YouTube TM may be considered as a reliable source of information on BPS., (© 2021 Wiley Periodicals LLC.)

The purpose of this mini review is to provide data about pre-clinical and clinical evidence exploring the impact of circadian desynchrony on spermatogenesis. Several lines of evidence exist demonstrating that disruption of circadian rhythms may interfere with male fertility. Experimental knock-out or knock-down of clock genes, physiologically involved in the regulation of circadian rhythms, are associated with impairments of fertility pathways in both animal and human models. Moreover, disruption of circadian rhythms, due to reduction of sleep duration and/or alteration of its architecture can negatively interfere in humans with circulating levels of male sexual hormones as well as with semen parameters. Unfortunately, current evidence remains low due to study heterogeneity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fusco, Longo, De Sio, Arcaniolo, Celentano, Capece, La Rocca, Mangiapia, Califano, Morra, Turco, Spena, Spirito, Fusco, Cirillo, De Luca, Napolitano, Mirone and Creta.)

Elucidating the distribution of intermediates at the active site of redox metalloenzymes is vital to understanding their highly efficient catalysis. Here we demonstrate that it is possible to generate, and detect, the key catalytic redox states of an [FeFe]-hydrogenase in a protein crystal. Individual crystals of the prototypical [FeFe]-hydrogenase I from Clostridium pasteurianum (CpI) are maintained under electrochemical control, allowing for precise tuning of the redox potential, while the crystal is simultaneously probed via Fourier Transform Infrared (FTIR) microspectroscopy. The high signal/noise spectra reveal potential-dependent variation in the distribution of redox states at the active site (H-cluster) according to state-specific vibrational bands from the endogeneous CO and CN - ligands. CpI crystals are shown to populate the same H-cluster states as those detected in solution, including the oxidised species Hox, the reduced species Hred/HredH + , the super-reduced HsredH + and the hydride species Hhyd. The high sensitivity and precise redox control offered by this approach also facilitates the detection and characterisation of low abundance species that only accumulate within a narrow window of conditions, revealing new redox intermediates.

Recently, the marketable value of ω-3 fatty acid, particularly eicosapentaenoic acid (EPA), increased considering their health effects for human consumption. Microalgae are considered a valuable and "green" source of EPA alternative to fish oils, but considerable efforts are necessary for their exploitation at an industrial level. Due to the high operation costs of photoautotrophic microalgae cultivation, heterotrophic growth represents a promising economic solution. Marine diatoms are the major ecological producers of ω-3 fatty acids. Few species of diatoms are capable to grow in the dark using organic carbon sources. The marine diatom Cyclotella cryptica was cultivated for 14 days under photoautotrophic and heterotrophic conditions to define the effects on growth parameters, lipid production, total fatty acids and EPA content. Photoautotrophic conditions led to a total EPA production of 1.6% of dry weight, 12.2 mg L -1 culture and productivity of 0.9 mg L -1 day -1 . The heterotrophy cultures reported a total EPA production of 2.7% of dry cell weight, 18 mg L -1 culture, a productivity of 1.3 mg L -1 day -1 , which are promising values in the prospective of improving culture parameters for the biotechnological exploitation of dark cultivation. C. cryptica could be a potential candidate for the heterotrophic production of EPA, also considering its robustness, capacity to resist to bacterial contaminations and plasticity of lipid metabolism.

Controlled formation of catalytically-relevant states within crystals of complex metalloenzymes represents a significant challenge to structure-function studies. Here we show how electrochemical control over single crystals of [NiFe] hydrogenase 1 (Hyd1) from Escherichia coli makes it possible to navigate through the full array of active site states previously observed in solution. Electrochemical control is combined with synchrotron infrared microspectroscopy, which enables us to measure high signal-to-noise IR spectra in situ from a small area of crystal. The output reports on active site speciation via the vibrational stretching band positions of the endogenous CO and CN - ligands at the hydrogenase active site. Variation of pH further demonstrates how equilibria between catalytically-relevant protonation states can be deliberately perturbed in the crystals, generating a map of electrochemical potential and pH conditions which lead to enrichment of specific states. Comparison of in crystallo redox titrations with measurements in solution or of electrode-immobilised Hyd1 confirms the integrity of the proton transfer and redox environment around the active site of the enzyme in crystals. Slowed proton-transfer equilibria in the hydrogenase in crystallo reveals transitions which are only usually observable by ultrafast methods in solution. This study therefore demonstrates the possibilities of electrochemical control over single metalloenzyme crystals in stabilising specific states for further study, and extends mechanistic understanding of proton transfer during the [NiFe] hydrogenase catalytic cycle., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Working memory capacity and executive functions play important roles in the early development of drawing and language, but we lack models that specify the relationships among these representational systems and cognitive functions in toddlers. To respond to this need, the present study investigated the relations between drawing and language in very young children, and the role of working memory capacity, inhibition, and shifting in the association between these two representational systems. The participants were 80 children, 25-37 months old. The results revealed that in toddlers (a) all the measures of working memory, inhibition, and shifting loaded on a single factor of general executive functioning; (b) language and drawing are two distinct, but substantially correlated, representational systems; and (c) the development of executive function has a strong impact on language development, which in turn influences the development of drawing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Panesi and Morra.)

This study presents a new working memory measure for toddlers, inspired by the Spin-the-Pots (Hughes & Ensor, 2005), which we modified structuring it as a memory span task. As in the original task, we required toddlers to retrieve objects hidden in little boxes; however, in our Memory Span Spin-the-Pots (MSSP) we used smaller numbers of targets, and we systematically manipulated memory load, covering or not the display, and rotating it or not. Two experiments involved participants between 18 months and three years. In Experiment 1 we examined the effects of covering and rotation on toddlers' memory. Either covering or rotating the stimuli hindered their performance, and combining both transformations yielded an under-additive interaction. Moreover, the effect of covering decreased in the second half of the procedure. In Experiment 2 we validated the MSSP as a working memory measure by comparing it with the Imitation Sorting Task (IST; Alp, 1994). We found that the MSSP correlated with the IST, also with age partialled out, although the IST was easier. In both experiments, the scores increased with age. Overall, this research sheds light on some variables that affect toddlers' performance on the MSSP, and shows that it can be used as a valid working memory measure for toddlers. The results are discussed considering the attentional processes presumably involved., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Seismocardiography (SCG) records cardiac and blood-induced motions transmitted to the chest surface as vibratory phenomena. Evidences demonstrate that acute myocardial ischemia (AMI) profoundly affects the SCG signals. Multidimensional SCG records cardiac vibrations in linear and rotational dimensions, and scalar parameters of kinetic energy can be computed. We speculate that AMI and revascularization profoundly modify cardiac kinetic energy as recorded by SCG. Methods: Under general anesthesia, 21 swine underwent 90 min of myocardial ischemia induced by percutaneous sub-occlusion of the proximal left anterior descending (LAD) coronary artery and subsequent revascularization. Invasive hemodynamic parameters were continuously recorded. SCG was recorded during baseline, immediately and 80 min after LAD sub-occlusion, and immediately and 60 min after LAD reperfusion. i K was automatically computed for each cardiac cycle ( iK CC ) in linear ( iK Lin ) and rotational ( iK Rot ) dimensions. i K was calculated as well during systole and diastole ( iK < 0.0001). Regional LV wall abnormalities were observed as follows: anterior MI, 17.6% (three out of 17); septal MI, 5.8% (one out of 17); antero-septal MI, 47.1% (eight out of 17); and infero-septal MI, 29.4% (five out of 17). In the linear dimension, i K L i n C C , i K L i n S y s , and i K L i n D i a dropped by 43, 52, and 53%, respectively ( Sys and iK Dia = 0.03, respectively) from baseline to the end of reperfusion. In the rotational dimension, i K R o t C C and i K R o t S y s dropped by 30 and 36%, respectively ( Results: Upon LAD sub-occlusion, 77% of STEMI and 24% of NSTEMI were observed. Compared to baseline, troponins increased from 13.0 (6.5; 21.3) ng/dl to 170.5 (102.5; 475.0) ng/dl, and LVEF dropped from 65.0 ± 0.0 to 30.6 ± 5.7% at the end of revascularization (both p < 0.0001). Regional LV wall abnormalities were observed as follows: anterior MI, 17.6% (three out of 17); septal MI, 5.8% (one out of 17); antero-septal MI, 47.1% (eight out of 17); and infero-septal MI, 29.4% (five out of 17). In the linear dimension, i K L i n C C , i K L i n S y s , and i K L i n D i a dropped by 43, 52, and 53%, respectively ( p < 0.0001, p < 0.0001, and p = 0.03, respectively) from baseline to the end of reperfusion. In the rotational dimension, i K R o t C C and i K R o t S y s dropped by 30 and 36%, respectively ( p = 0.0006 and p < 0.0001, respectively), but i K R o t D i a did not change ( p = 0.41). All the hemodynamic parameters, except the pulmonary artery pulse pressure, were significantly correlated with the parameters of iK , except for the diastolic component. Conclusions: In this very context of experimental AMI with acute LV regional dysfunction and no concomitant AMI-related heart valve disease, linear and rotational i K parameters, in particular, systolic ones, provide reliable information on LV contractile dysfunction and its effects on the downstream circulation. Multidimensional SCG may provide information on the cardiac contractile status expressed in terms of i K during AMI and reperfusion. This automatic system may empower health care providers and patients to remotely monitor cardiovascular status in the near future., Competing Interests: P-FM, DG, and AHo declare having direct ownership of shares in Healthcare Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morra, Pitisci, Su, Hossein, Rabineau, Racape, Gorlier, Herpain, Migeotte, Creteur and van de Borne.)

Bladder cancer (BCa) is an endocrine-related tumour and the activation of androgen signalling pathways may promote bladder tumorigenesis. We summarized the available preclinical and clinical evidence on the implications of the manipulation of androgen signalling pathways on the outcomes of BCa therapies. A systematic review was performed in December 2020. We included papers that met the following criteria: original preclinical and clinical research; evaluating the impact of androgen signalling modulation on the outcomes of BCa therapies. Six preclinical and eight clinical studies were identified. The preclinical evidence demonstrates that the modulation of androgen receptor-related pathways has the potential to interfere with the activity of the Bacillus Calmette Guerin, doxorubicin, cisplatin, gemcitabine, and radiotherapy. The relative risk of BCa recurrence after transurethral resection of the bladder tumour (TURBT) is significantly lower in patients undergoing therapy with 5 alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT) (Relative risk: 0.50, 95% CI: 0.30-0.82; p = 0.006). Subgroup analysis in patients receiving 5-ARIs revealed a relative risk of BCa recurrence of 0.46 (95% CI: 0.22-0.95; p = 0.040). A significant negative association between the ratio of T1 BCa patients in treated/control groups and the relative risk of BCa recurrence was observed. Therapy with 5-ARIs may represent a potential strategy aimed at reducing BCa recurrence rate, mainly in patients with low stage disease. Further studies are needed to confirm these preliminary data.

Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical manifestations are reported, such as short stature, cognitive and behavioral disability, temperature instability, hypotonia, hypersomnia, hyperphagia, and multiple endocrine abnormalities, including growth hormone deficiency and hypogonadism. The hypogonadism in PWS is due to central and peripheral mechanisms involving the hypothalamus-pituitary-gonadal axis. The early diagnosis and management of hypogonadism in PWS are both important for physicians in order to reach a better quality of life for these patients. The aim of this study is to summarize and investigate causes and possible therapies for hypogonadism in PWS. Additional studies are further needed to clarify the role of different genes related to hypogonadism and to establish a common and evidence-based therapy.

Ballistocardiography (BCG) and Seismocardiography (SCG) assess the vibrations produced by cardiac contraction and blood flow, respectively, by means of micro-accelerometers and micro-gyroscopes. From the BCG and SCG signals, maximal velocities (V Max ), integral of kinetic energy (iK), and maximal power (P Max ) can be computed as scalar parameters, both in linear and rotational dimensions. Standard echocardiography and 2-dimensional speckle tracking imaging echocardiography were performed on 34 healthy volunteers who were infused with increasing doses of dobutamine (5-10-20 μg/kg/min). Linear V Max of BCG predicts the rates of left ventricular (LV) twisting and untwisting (both p < 0.0001). The linear P Max of both SCG and BCG and the linear iK of BCG are the best predictors of the LV ejection fraction (LVEF) (p < 0.0001). This result is further confirmed by mathematical models combining the metrics from SCG and BCG signals with heart rate, in which both linear P Max and iK strongly correlate with LVEF (R = 0.7, p < 0.0001). In this setting of enhanced inotropism, the linear V Max of BCG, rather than the V Max of SCG, is the metric which best explains the LV twist mechanics, in particular the rates of twisting and untwisting. P Max and iK metrics are strongly associated with the LVEF and account for 50% of the variance of the LVEF.

Introduction: Auricular low-level transcutaneous vagus nerve stimulation (aLL-tVNS) has emerged as a promising technology for cardiac arrhythmia management but is still experimental. In this physiological study, we hypothesized that aLL-tVNS modulated the autonomic nervous balance through a reduction of sympathetic tone and an increase in heart rate variability (HRV). We investigated the muscle sympathetic nerve activity (MSNA) recorded by microneurography during vagally mediated aLL-tVNS and active control on healthy volunteers., Methods: In this crossover, double-blind controlled study, healthy men ( N = 28; 27 ± 4 years old) were assigned to aLL-tVNS applied to cymba and lobe (active control) of the right ear. Each participant was randomly allocated to the three sequences (5 Hz, 20 Hz, and active control-5 Hz) during one session. MSNA signal was recorded at rest, during voluntarily apnea and aLL-tVNS. Sympathetic activity was expressed as: 1) number of bursts per minute (burst frequency, BF) and 2) MSNA activity calculated as BF x mean burst amplitude and expressed as changes from baseline (%). RR intervals, HRV parameters and sympathetic activity were analyzed during 5 min-baseline, 10 min-stimulation, and 10 min-recovery periods. Mixed regression models were performed to evaluate cymba-(5-20 Hz) effects on the parameters with stimulation., Results: During apnea and compared to baseline, BF and MSNA activity increased ( p = 0.002, p = 0.001, respectively). No stimulation effect on RR intervals and HRV parameters were showed excepted a slightly increase of the LF/HF ratio with stimulation in the cymba-5Hz sequence (coef. ± SE: 0.76 ± 0.32%; p = 0.02). During stimulation, reductions from baseline in BF (Coef. ± SE: -4.8 ± 1.1, p < 0.001) was observed but was not statistically different from that one in the active control. Reduction of MSNA activity was not significantly different between sequences., Conclusion: Acute right cymba aLL-tVNS did not induce any overall effects neither on heart rate, HRV nor MSNA variables on healthy subjects when compared to active control. Interestingly, these findings questioned the role of active controls in medical device clinical trials that implied subjective endpoints., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Gauthey, Morra, van de Borne, Deriaz, Maes and le Polain de Waroux.)

Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. BCG and SCG kinetic energies (KE) and their temporal integrals ( i K) during a single heartbeat are computed in linear and rotational dimensions. Our aim was to test the hypothesis that i K from BCG and SCG are related to sympathetic activation during maximal voluntary end-expiratory apnea. Multiunit muscle sympathetic nerve traffic [burst frequency (BF), total muscular sympathetic nerve activity (tMSNA)] was measured by microneurography during normal breathing and apnea ( n = 28, healthy men). i K of BCG and SCG were simultaneously recorded in the linear and rotational dimension, along with oxygen saturation ([Formula: see text]) and systolic blood pressure (SBP). The mean duration of apneas was 25.4 ± 9.4 s. SBP, BF, and tMSNA increased during the apnea compared with baseline ( P = 0.01, P = 0.002,and P = 0.001, respectively), whereas [Formula: see text] decreased ( P = 0.02). At the end of the apnea compared with normal breathing, changes in i K computed from BCG were related to changes of tMSNA and BF only in the linear dimension ( r  = 0.85, P < 0.0001; and r = 0.72, P = 0.002, respectively), whereas changes in linear i K of SCG were related only to changes of tMSNA ( r = 0.62, P = 0.01). We conclude that maximal end expiratory apnea increases cardiac kinetic energy computed from BCG and SCG, along with sympathetic activity. The novelty of the present investigation is that linear i K of BCG is directly and more strongly related to the rise in sympathetic activity than the SCG, mainly at the end of a sustained apnea, likely because the BCG is more affected by the sympathetic and hemodynamic effects of breathing cessation. BCG and SCG may prove useful to assess sympathetic nerve changes in patients with sleep disturbances. NEW & NOTEWORTHY Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. Kinetic energies (KE) and their temporal integrals ( i K) during a single heartbeat are computed from the BCG and SCG waveforms in a linear and a rotational dimension. When compared with normal breathing, during an end-expiratory voluntary apnea, i K increased and was positively related to sympathetic nerve traffic rise assessed by microneurography. Further studies are needed to determine whether BCG and SCG can probe sympathetic nerve changes in patients with sleep disturbances.

Objective: To investigate if modern seismocardiography (SCG) and ballistocardiography (BCG) are useful in the detection of hemodynamic changes occurring during simulated obstructive apneic events., Methods: Forty-seven healthy volunteers performed a voluntary maximum Mueller maneuver (MM) for 10 s, and SCG and BCG signals were simultaneously taken. The kinetic energy of a set of cardiac cycles before and during the apneic episode was automatically computed from the rotational and linear channels of the SCG and BCG waveforms and its temporal integral (i K) was derived (unit of measure: microjoules per second (µJ·s)). The estimated transmural pressure (eP TM ) was assessed as the difference between systemic blood pressure and maximal inspiratory pressure (MIP). The Wilcoxon sign-rank test was used to evaluate differences in energy measurements between normal respiration and the loaded inspiration maneuver. Cardiac kinetic energies and the MIP produced during the MM were compared by linear regression analysis following log transformation in order to assess the correlation between variables., Main Results: The [Formula: see text] during normal breathing increased from 1.1(0.8; 1.4) to 1.9(1.4; 4.3) µJ·s during MM (p < 0.001). Meanwhile, [Formula: see text] increased from 54 (31; 92) to 84 (44; 153) µJ·s, (p < 0.001). The [Formula: see text] and [Formula: see text] of a set of cardiac cycles during the MM were negatively associated with the MIP (r: -0.59, p < 0.001 and r: -0.53, p = 0.001 for [Formula: see text] and [Formula: see text], respectively). When eP TM was considered, this association became positive (r: +0.58, p < 0.001 and r:+0.60, p < 0.001, for [Formula: see text] and [Formula: see text], respectively). When the i K LIN was considered as the comparative factor, correlations with the MIP and eP TM were weak and insignificant. Men had higher values of i K than women., Significance: Simulated obstructive apnea elicits large rotational i K swings, which are related to the intensity of the inspiratory effort and, as such, to the intensity of the left ventricular afterload. Computation of cardiac kinetic energy through BCG and SCG may shed further light on the impact of obstructive respiratory events on the cardiovascular system.

Propylene glycol and glycerol are e-cigarette constituents that facilitate liquid vaporization and nicotine transport. As these small hydrophilic molecules quickly cross the lung epithelium, we hypothesized that short-term cessation of vaping in regular users would completely clear aerosol deposit from the lungs and reverse vaping-induced cardiorespiratory toxicity. We aimed to assess the acute effects of vaping and their reversibility on biological/clinical cardiorespiratory parameters [serum/urine pneumoproteins, hemodynamic parameters, lung-function test and diffusing capacities, transcutaneous gas tensions (primary outcome), and skin microcirculatory blood flow]. Regular e-cigarette users were enrolled in this randomized, investigator-blinded, three-period crossover study. The periods consisted of nicotine-vaping (nicotine-session), nicotine-free vaping (nicotine-free-session), and complete cessation of vaping (stop-session), all maintained for 5 days before the session began. Multiparametric metabolomic analyses were used to verify subjects' protocol compliance. Biological/clinical cardiorespiratory parameters were assessed at the beginning of each session (baseline) and after acute vaping exposure. Compared with the nicotine- and nicotine-free-sessions, a specific metabolomic signature characterized the stop-session. Baseline serum club cell protein-16 was higher during the stop-session than the other sessions ( P < 0.01), and heart rate was higher in the nicotine-session ( P < 0.001). Compared with acute sham-vaping in the stop-session, acute nicotine-vaping (nicotine-session) and acute nicotine-free vaping (nicotine-free-session) slightly decreased skin oxygen tension ( P < 0.05). In regular e-cigarette-users, short-term vaping cessation seemed to shift baseline urine metabolome and increased serum club cell protein-16 concentration, suggesting a decrease in lung inflammation. Additionally, acute vaping with and without nicotine decreased slightly transcutaneous oxygen tension, likely as a result of lung gas exchanges disturbances.

Background: Cytochrome P450 enzymes (CYPs) are monooxygenases present in every domain of life. In fungi CYPs are involved in virulence. Fusarium wilt of lettuce, caused by F. oxysporum f. sp. lactucae, is the most serious disease of lettuce. F. oxysporum f.sp. lactucae MSA35 is an antagonistic fungus. Pathogenic formae specialis of F. oxysporum possess a CYP belonging to the new family CYP505. This enzyme hydroxylates saturated fatty acids that play a role in plant defence., Methods: Molecular tools were adopted to search for cyp505 gene in MSA35 genome. cyp505 gene expression analysis in pathogenic and antagonistic Fusarium was performed. The enzyme was expressed in its recombinant form and used for catalytic reactions with fatty acids, the products of which were characterized by mass spectrometry analysis., Results: A novel MSA35 self-sufficient CYP505 is differentially expressed in antagonistic and pathogenic F. oxysporum. Its expression is induced by the host plant lettuce in both pathogenesis and antagonism during the early phase of the interaction, while it is silenced during the late phase only in antagonistic Fusarium. Mass-spectrometry investigations proved that CYP505A1 mono-hydroxylates lauric, palmitic and stearic acids., Conclusions: The ability of CYP505A1 to oxidize fatty acids present in the cortical cell membranes together with its differential expression in its Fusarium antagonistic form point out to the possibility that this enzyme is associated with Fusarium pathogenicity in lettuce., General Significance: The CYP505 clan is present in pathogenic fungal phyla, making CYP505A1 enzyme a putative candidate as a new target for the development of novel antifungal molecules., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To assess if micro-accelerometers and gyroscopes may provide useful information for the detection of breathing disturbances in further studies., Approach: Forty-three healthy volunteers performed a 10 s end-expiratory breath-hold, while ballistocardiograph (BCG) and seismocardiograph (SCG) determined changes in kinetic energy and its integral over time (iK, J · s). BCG measures overall body accelerations in response to blood mass ejection into the main vasculature at each cardiac cycle, while SCG records local chest wall vibrations generated beat-by-beat by myocardial activity. This minimally intrusive technology assesses linear accelerations and angular velocities in 12 degrees of freedom to calculate iK during the whole cardiac cycle. iK produced during systole and diastole were also computed., Main Results: The iK during normal breathing was 87.1 [63.3; 132.8] µJ · s for the SCG and 4.5 [3.3; 6.2] µJ · s for the BCG. Both increased to 107.1 [69.0; 162.0] µJ · s and 6.1 [4.4; 9.0] µJ · s, respectively, during breath-holding (p   =  0.003 and p   <  0.0001, respectively). The iK of the SCG further increased during spontaneous respiration following apnea (from 107.1 [69.0; 162.0] µJ · s to 160.0 [96.3; 207.3] µJ · s, p   <  0.0001). The ratio between the iK of diastole and systole increased from 0.35 [0.24; 0.45] during apnea to 0.49 [0.31; 0.80] (p   <  0.0001) during the restoration of respiration., Significance: A brief voluntary apnea generates large and distinct increases in SCG and BCG waveforms. iK monitoring during sleep may prove useful for the detection of respiratory disturbances. ClinicalTrials.gov number: NCT03760159.

Studying the role of individual differences in team sports performance is a challenge. The main problem is having an available measure of individual performance of each member of the team. In particular, in youth sports, where the level of specialization is reactively low, it appears appropriate that this measure takes the entire performance of the athlete into consideration (i.e., that it assesses all of the athlete's gestures), while maintaining an ecological validity criterion. Therefore, we devised and calculated an individual assessment measure in volleyball following the subsequent steps: Firstly, we video-recorded at least three volleyball games for each of the 114 youth volleyball players who participated in the study. Then, two independent expert observers evaluated each individual performance by attributing a score to every single gesture performed by the athletes during the games. The derived individual score was adjusted and controlled for the team performance measure, namely the result of each Set the athlete participated in (and for the amount of participation of the athlete to each game). The final measure of individual performance in volleyball proved to be reliable, showing a high level of interrater agreement ( r = .841, p < .001) and a significant correlation with the amount of experience in volleyball ( r = .173, p < .05).

Non-invasive remote detection of cardiac and blood displacements is an important topic in cardiac telemedicine. Here we propose kino-cardiography (KCG), a non-invasive technique based on measurement of body vibrations produced by myocardial contraction and blood flow through the cardiac chambers and major vessels. KCG is based on ballistocardiography and measures 12 degrees-of-freedom (DOF) of body motion. We tested the hypothesis that KCG reliably assesses dobutamine-induced haemodynamic changes in healthy subjects. Using a randomized double-blinded placebo-controlled crossover study design, dobutamine and placebo were infused to 34 volunteers (25 ± 2 years, BMI 22 ± 2 kg/m², 18 females). Baseline recordings were followed by 3 sessions of increasing doses of dobutamine (5, 10, 20 μg/kg.min) or saline solution. During each session, stroke volume (SV) and cardiac output (CO) were determined by echocardiography and followed by a 90 s KCG recording. Measured linear accelerations and angular velocities were used to compute total Kinetic energy (iK) and power (Pmax). KCG sorted dobutamine infusion vs. placebo with 96.9% accuracy. Increases in SV and CO were correlated to iK (r = +0.71 and r = +0.8, respectively, p < 0.0001). Kino-cardiography, with 12-DOF, allows detecting dobutamine-induced haemodynamic changes with a high accuracy and present a major improvement over single axis ballistocardiography or seismocardiography.