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Abstract CoQ10 (Coenzyme Q10) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ10 is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ10 and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ10 and UBIAD1 states impair ECM (extracellular matrix)-mediated oncogenic signaling and reduce ferroptosis resistance in BC settings. Analyses on human patients and mouse models reveal that UBIAD1 loss is associated with BC development and progression and UBIAD1 expression in BC limits CTCs (circulating tumor cells) survival and lung metastasis formation. Overall, this study reveals that CoQ10 and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis.

Abstract Background Malnutrition and sarcopenia significantly increase the risk of intra-hospital delirium, particularly among older adults. Given the potential correlation between calf circumference (CC) and these conditions, CC emerges as a promising predisposing factor for delirium. This study aims to investigate the independent association between delirium and anthropometric parameters, focusing on evaluating CC’s predictive capacity for intra-hospital delirium risk. Additionally, it aims to compare CC’s predictive performance with the widely used Mini Nutritional Assessment (MNA), while also considering potential gender disparities. Methods This is a retrospective study which enrolled patients aged ≥ 65 years from September 2021 to March 2022 at the Padova Hospital (Italy). Physical characteristics, intra-hospital delirium incidence, and body composition were assessed. Sarcopenia was diagnosed using the 2019 European Consensus criteria. Results Among 207 subjects, delirium affected 19% of patients. CC showed a significant association with intra-hospital delirium among the analyzed anthropometric parameters. ROC curves indicated that CC’s predictive capacity for delirium onset was comparable to MNA (p = 0.98), particularly in women. In a multivariable logistic regression model, female gender and higher cognitive and CC scores emerged as protective factors against delirium onset, with each unit increase in CC associated with a 24% reduction in the odds of delirium. Conversely, sarcopenia did not significantly influence delirium onset. Conclusions CC shows promise as a predisposing factor for intra-hospital delirium, similar to MNA, albeit with significant gender differences. CC could serve as a valuable tool for assessing delirium risk among female patients. Further validation of these findings is necessary through larger-scale studies.

Background and objective: Several novel multiport robotic systems have been developed and introduced in clinical practice after regulatory approval. The objective of this systematic review was to assess the evolution status of novel robotic platforms approved for clinical use in urological surgery according to the IDEAL framework. Methods: A systematic review was conducted using the Medline and Scopus databases according to the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (CRD42024503227). Comparative or noncomparative studies reporting on any urological procedures performed with novel robotic platforms (Hugo RAS; Versius, KangDuo, Senhance, REVO-I, Avatera, Hinotori, Dexter, or Toumai) were selected and included in the analysis. Key findings and limitations: Seventy-four eligible studies were included, of which 67 (90.5%) were noncomparative surgical series representing developmental or explorative studies according to the IDEAL criteria. Only one randomised controlled trial (comparing KangDuo vs da Vinci robot-assisted partial nephrectomy) was included. The trial showed comparable perioperative outcomes between the two robotic systems. Four studies assessed clinical outcomes for patients undergoing urological procedures using a REVO-I (1 study), Senhance (2 studies), or Hinotori (1 study) system in comparison to the same procedures performed using a da Vinci system. All studies revealed outcomes comparable to those with the da Vinci system. Limitations include the small sample size in all studies, and assessment of first-generation novel platforms versus the fourth-generation multiarm da Vinci system in most of the comparative studies. Conclusions and clinical implications: A few poor-quality studies have compared the use of novel robotic platforms to da Vinci systems in urological surgery and demonstrated comparable results. Most studies can be classified as developmental or explorative, representing the initial steps of clinical research. Large multicentre series are needed to understand whether these novel robots could offer advantages beyond cost reductions over the da Vinci systems. Patient summary: We reviewed research on new robotic systems for surgery in urology. Several studies have shown the feasibility and safety of these new robots during the most common procedures. Very few studies have assessed clinical outcomes with the new robots in comparison to the reference standard, which is a fourth-generation da Vinci robot. Large multicentre studies are needed to understand whether the new robots could offer advantages other than cost savings over the da Vinci robot.

This study investigated the effect of clove essential oil used prior to stunning by cranial percussion and hypothermia on Nile tilapia (Oreochromis niloticus) welfare and fillet quality. A total of 100 tilapias were divided into four groups in a 2 × 2 factorial design, exploring two stunning methods with and without clove essential oil. Behavioral responses, glucose, lactate, pH, water holding capacity, color parameters, lipid and protein oxidation, and oxidative stress were analyzed. The application of clove essential oil resulted in 100% numbing in swimming and stimulus response behaviors, and 96% in balance and eye vestibule reflex variables. Significant reductions in glucose (12.12 mg dL−1) for hypothermia group (p = 0.001) and lactate (3.36 mmol L−1) for cranial percussion (p = 0.004), 0.028 nmol lipid oxidation in hypothermia treatment (p = 0.009), and 0.134 nmol carbonyls/mg protein (p = 0.001) were observed. There was a reduction in luminosity (p = 0.010) and red intensity (p = 0.001) in the group of fish fillet that received cranial percussion, however, there was no difference in the group stunned by hypothermia. Clove essential oil demonstrates effectiveness in pre-slaughter stress mitigation, influencing the antioxidant system positively. Its usage in pre-slaughter protocols could contribute to improved fillet quality, presenting a promising alternative for enhancing tilapia welfare during slaughter.

The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the “Achilles’ heel” of the EVLP due to a more fluid accumulation than in the supine standard position.

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Improving well-being, allowing for sustainable lifestyles, and enhancing waste control are aims of the United Nations in the 2030 Agenda for Sustainable Development [...]

Objective: To assess the effectiveness of Platelet Concentrates (PCs) in the contest of Hemorrhagic, Actinic, and Radiation Cystitis, plus Urethral Obstruction or Stenosis. Eligibility criteria: Open article in English or Italian regarding in situ applications of PCs for the selected pathologies. Information sources: MEDLINE, Cochrane Library, and ELSEVIER. Risk of bias: High (and discussed). Methods for synthesis of results: Selection of relevant contents, resumed by digital tools, checked by authors and used throughout the manuscript. Included studies: 13 screened articles + 7 personal sources + 37 “extra” articles. Synthesis of results: Pre-clinical and clinical studies demonstrated substantial symptom relief, mucosal restoration, and improved growth factor levels, reducing recurrence rates and complications. However, preparation protocols and results varied among studies. Limitations of evidence: Frequent low-quality studies with mall sample size, plus heterogeneous experimental setups and nomenclature/preparations. Interpretation: PCs demonstrate promise due to their bioactive components, enhancing tissue repair and reducing inflammation with no significant adverse events. Despite positive outcomes in pre-clinical and clinical studies, variability in preparation protocols and small sample sizes, together with inconsistent results, highlight the need for high-quality research to validate PCs’ clinical efficacy and cost-effectiveness.

Objective: Prostate cancer, the second most diagnosed cancer among men, requires precise diagnostic techniques to ensure effective treatment. This review explores the technological advancements, optimal application conditions, and benefits of targeted prostate biopsies facilitated by multiparametric magnetic resonance imaging (mpMRI). Methods: A systematic literature review was conducted to compare traditional 12-core systematic biopsies guided by transrectal ultrasound with targeted biopsy techniques using mpMRI. We searched electronic databases including PubMed, Scopus, and Web of Science from January 2015 to December 2024 using keywords such as “targeted prostate biopsy”, “fusion prostate biopsy”, “cognitive prostate biopsy”, “MRI-guided biopsy”, and “transrectal ultrasound prostate biopsy”. Studies comparing various biopsy methods were included, and data extraction focused on study characteristics, patient demographics, biopsy techniques, diagnostic outcomes, and complications. Conclusion: mpMRI-guided targeted biopsies enhance the detection of clinically significant prostate cancer while reducing unnecessary biopsies and the detection of insignificant cancers. These targeted approaches preserve or improve diagnostic accuracy and patient outcomes, minimizing the risks associated with overdiagnosis and overtreatment. By utilizing mpMRI, targeted biopsies allow for precise targeting of suspicious regions within the prostate, providing a cost-effective method that reduces the number of biopsies performed. This review highlights the importance of integrating advanced imaging techniques into prostate cancer diagnosis to improve patient outcomes and quality of life.

Patients with epilepsy are prone to cognitive decline, depression, anxiety and other behavioral disorders. Cognitive comorbidities are particularly common and well-characterized in people with temporal lobe epilepsy, while inconsistently addressed in epileptic animals. Therefore, the aim of this study was to ascertain whether there is good evidence of cognitive comorbidities in animal models of epilepsy, in particular in the rat pilocarpine model of temporal lobe epilepsy. We searched the literature published between 1990 and 2023. The association of spontaneous recurrent seizures induced by pilocarpine with cognitive alterations has been evaluated by using various tests: contextual fear conditioning (CFC), novel object recognition (NOR), radial and T-maze, Morris water maze (MWM) and their variants. Combination of results was difficult because of differences in methodological standards, in number of animals employed, and in outcome measures. Taken together, however, the analysis confirmed that pilocarpine-induced epilepsy has an effect on cognition in rats, and supports the notion that this is a valid model for assessment of cognitive temporal lobe epilepsy comorbidities in preclinical research.

Background: Coronavirus Disease-2019 (COVID-19), driven by the SARS-CoV-2 virus, has disproportionately affected the elderly, with comorbidities like sarcopenia worsening prognosis. Considering the significant impact of RNA vaccines on survival rates in this population, our objective is to investigate the impact of vaccination on the survival of hospitalized elderly patients with COVID-19, considering the presence or absence of sarcopenia. Methods: Prospective study conducted on 159 patients aged>65 years from September 2021 to March 2022. Data about clinical and body composition, and mortality at 12-months after discharge were recorded. Sarcopenia was diagnosed according to the 2019 European Consensus criteria. Results: At the twelfth month post-discharge, vaccinated sarcopenic individuals exhibited a mortality risk similar to vaccinated non-sarcopenic individuals, and lower than unvaccinated non-sarcopenic patients. Cox regression analysis, adjusted for age, gender, comorbidity, functional and vaccinal status, showed that the presence of sarcopenia did not significantly impact the risk of death within 12-months post-discharge. Discussion: Vaccination emerges as a protective measure for sarcopenic patients, countering the potential adverse effects of sarcopenia on COVID-19 outcomes, underscoring the importance of immunization in the frail elderly with a call for meticulous monitoring of its benefits. Conclusions: Our study represents the first attempt to analyze the vaccine's effect on survival in sarcopenic hospitalized older adults with COVID-19. The administration of vaccination to sarcopenic patients proves pivotal, as its omission could lead to notably unfavorable outcomes within this specific population.

Abstract Objectives The aim of this study is to assess the aetiology, perioperative outcomes and treatment failure of contemporary patients undergoing open or robot‐assisted ureteral reconstruction for iatrogenic injuries. Patients and methods We retrospectively analysed consecutive patients who underwent ureteral reconstruction for iatrogenic injuries at two academic centres 07/2013 and 06/2022. A variety of open or robot‐assisted procedures were performed, including uretero‐cystoneostomy, Boari bladder flap, uretero‐ureterostomy, ileal replacement and pyelo‐ureteroplasty. All procedures were performed by a single surgeon with extensive experience in open and robot‐assisted surgery and preference‐based management. Outcome measures were aetiology, estimated blood loss, length of stay, postoperative complications and treatment failure, defined as upper tract obstruction requiring permanent urinary drainage. We also planned a subgroup analysis comparing the outcomes between open and robot‐assisted procedures. Results Fifty‐nine patients were included. Most injuries were consequent to endourological procedures (44%). The most frequently performed procedures were uretero‐cystoneostomy (49.2%) and Boari bladder flap (32.2%). Forty (67.8%) were open, and 19 (32.2%) were robot‐assisted procedures. Major postoperative complications were recorded in seven (11.9%) patients. After a median follow‐up of 42 months (interquartile range 12–24), treatment failure was observed in seven (11.9%) cases. Robot‐assisted versus open procedures were associated with decreased estimated blood loss (p = 0.01), length of stay (p

Bread, a staple food consumed worldwide, plays a pivotal role in nutrition. Nevertheless, it is to be underlined that white bread is classified as a high glycemic index food, and its frequent consumption can lead to rapid increases in blood glucose, potentially causing metabolic stress and contributing to insulin resistance and type 2 diabetes. So, there is a growing interest in bread formulations with ingredients that can lower its GI. With this view, bread was formulated, substituting wheat with chickpea flour, red chicory powder, and three distinct types of resistant starch. The results showed the different resistant starches’ impacts on the glycemic index reduction. Specifically, chemically modified tapioca RS IV produced a bread formulation with a low predicted glycemic index (pGI < 55). Retrograded starch from tapioca (RS III) allows the bread to reach a pGI value of 55, the upper value for classifying a food as low pGI. The retrograded starch from corn (RS III) allows a decrease in the bread’s glycemic index, but the product is still classified as ‘high pGI’ (>70). Moreover, the addition of by-products rich in polyphenols contributes to a lowering of the pGI. Concerning the technological parameters, the outcome revealed an increase in the moisture content across all the newly formulated samples compared to the control. At the same time, the volume and specific volume showed a decrease. The newly formulated samples exhibited a higher baking loss, particularly when incorporating resistant starch, which increased the hardness and chewiness with decreased cohesiveness. In conclusion, incorporating chickpea flour, red chicory powder, and tapioca-resistant starch (RS III and IV) offers a promising strategy for producing high-fiber bread with a low glycemic index, catering to health-conscious consumers.

This study evaluates the fermentation performances of non-Saccharomyces strains in fermenting cherry must from Italian cherries unsuitable for selling and not intended to be consumed fresh, and their effects on the chemical composition of the resulting wine. Fermentation trials in 100 and 500 mL of must were carried out to select 21 strains belonging to 11 non-Saccharomyces species. Cherry wines obtained by six select strains were chemically analyzed for fixed and volatile compounds. Quantitative data were statistically analyzed by agglomerative hierarchical clustering, partial least squared discriminant analysis, and principal component analysis. Wines revealed significant differences in their composition. Lactic acid and phenylethyl acetate levels were very high in wines produced by Lachancea and Hanseniaspora, respectively. Compared to S. cerevisiae wine, non-Saccharomyces wines had a lower content of fatty acid ethyl esters 4-vinyl guaiacol and 4-vinyl phenol. The multivariate analysis discriminated between wines, demonstrating the different contributions of each strain to aroma components. Specifically, all wines from non-Saccharomyces strains were kept strictly separate from the control wine. This study provided comprehensive characterization traits for non-conventional strains that enhance the aroma complexity of cherry-based wine. The use of these yeasts in cherry wine production appears promising. Further investigation is required to ascertain their suitability for larger-scale fermentation.

Context: Rectal injury (RI) is a dreaded complication after radical prostatectomy (RP), increasing the risk of early postoperative complications, such as bleeding and severe infection/sepsis, and late sequelae, such as a rectourethral fistula (RUF). Considering its traditionally low incidence, uncertainty remains as to predisposing risk factors and management. Objective: To examine the incidence of RI after RP in contemporary series and to propose a pragmatic algorithm for its management. Evidence acquisition: A systematic literature search was performed using the Medline and Scopus databases. Studies reporting data on RI incidence were selected. Subgroup analyses were conducted to assess the differential incidence by age, surgical approach, salvage RP after radiation therapy, and previous benign prostatic hyperplasia (BPH)-related surgery. Evidence synthesis: Eighty-eight, mostly retrospective noncomparative, studies were selected. The meta-analysis obtained a pooled RI incidence of 0.58% (95% confidence interval [CI] 0.46–0.73) in contemporary series with significant across-study heterogeneity (I2 = 100%, p

Snake envenoming is a major, but neglected, tropical disease. Among venomous snakes, those inducing neurotoxicity such as kraits (Bungarus genus) cause a potentially lethal peripheral neuroparalysis with respiratory deficit in a large number of people each year. In order to prevent the development of a deadly respiratory paralysis, hospitalization with pulmonary ventilation and use of antivenoms are the primary therapies currently employed. However, hospitals are frequently out of reach for envenomated patients and there is a general consensus that additional, non-expensive treatments, deliverable even long after the snake bite, are needed. Traumatic or toxic degenerations of peripheral motor neurons cause a neuroparalysis that activates a pro-regenerative intercellular signaling program taking place at the neuromuscular junction (NMJ). We recently reported that the intercellular signaling axis melatonin-melatonin receptor 1 (MT1) plays a major role in the recovery of function of the NMJs after degeneration of motor axon terminals caused by massive Ca2+ influx. Here we show that the small chemical MT1 agonists: Ramelteon and Agomelatine, already licensed for the treatment of insomnia and depression, respectively, are strong promoters of the neuroregeneration after paralysis induced by krait venoms in mice, which is also Ca2+ mediated. The venom from a Bungarus species representative of the large class of neurotoxic snakes (including taipans, coral snakes, some Alpine vipers in addition to other kraits) was chosen. The functional recovery of the NMJ was demonstrated using electrophysiological, imaging and lung ventilation detection methods. According to the present results, we propose that Ramelteon and Agomelatine should be tested in human patients bitten by neurotoxic snakes acting presynaptically to promote their recovery of health. Noticeably, these drugs are commercially available, safe, non-expensive, have a long bench life and can be administered long after a snakebite even in places far away from health facilities.

Introduction Eosinophilic cystitis is a rare condition which causes common symptoms and may mimic other conditions. Eosinophilic cystitis has several causes such as hypereosinophilic syndrome, inflammatory diseases, neoplasia, parasites or fungal infection, IgE‐related diseases, Drug Reaction and Eosinophilia and Systemic Symptoms (DRESS) syndrome, or Churg‐Strauss syndrome. Therefore, differential diagnosis is difficult. Case presentation We report the case of a middle‐aged man affected by eosinophilic cystitis with persistent hematuria and other peculiar symptoms that may be brought back to hypereosinophilic crisis. Conclusion Conservative approach is preferred, avoiding radical cystectomy rather than corticosteroid, antihistaminic and second line therapy. Hyperbaric therapy is an innovative approach for severe relapsing gross hematuria without specific literature and should be studied for further indications.

Objective: Prostate cancer, the second most diagnosed cancer among men, requires precise diagnostic techniques to ensure effective treatment. This review explores the technological advancements, optimal application conditions, and benefits of targeted prostate biopsies facilitated by multiparametric magnetic resonance imaging (mpMRI). Methods: A systematic literature review was conducted to compare traditional 12-core systematic biopsies guided by transrectal ultrasound with targeted biopsy techniques using mpMRI. We searched electronic databases including PubMed, Scopus, and Web of Science from January 2015 to December 2024 using keywords such as "targeted prostate biopsy", "fusion prostate biopsy", "cognitive prostate biopsy", "MRI-guided biopsy", and "transrectal ultrasound prostate biopsy". Studies comparing various biopsy methods were included, and data extraction focused on study characteristics, patient demographics, biopsy techniques, diagnostic outcomes, and complications. Conclusion: mpMRI-guided targeted biopsies enhance the detection of clinically significant prostate cancer while reducing unnecessary biopsies and the detection of insignificant cancers. These targeted approaches preserve or improve diagnostic accuracy and patient outcomes, minimizing the risks associated with overdiagnosis and overtreatment. By utilizing mpMRI, targeted biopsies allow for precise targeting of suspicious regions within the prostate, providing a cost-effective method that reduces the number of biopsies performed. This review highlights the importance of integrating advanced imaging techniques into prostate cancer diagnosis to improve patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

In the wake of the United Nations’ Agenda 2030, a global commitment to advancing well-being, sustainable living, and waste reduction, the spotlight on cereal-based food products with high added value has intensified [...]

Neuroinflammation is associated with several neurological disorders including temporal lobe epilepsy. Seizures themselves can induce neuroinflammation. In an in vivo model of epilepsy, the supplementation of brain-derived neurotropic factor (BDNF) and fibroblast growth factor-2 (FGF-2) using a Herpes-based vector reduced epileptogenesis-associated neuroinflammation. The aim of this study was to test whether the attenuation of the neuroinflammation obtained in vivo with BDNF and FGF-2 was direct or secondary to other effects, for example, the reduction in the severity and frequency of spontaneous recurrent seizures. An in vitro model of neuroinflammation induced by lipopolysaccharide (LPS, 100 ng/mL) in a mouse primary mixed glial culture was used. The releases of cytokines and NO were analyzed via ELISA and Griess assay, respectively. The effects of LPS and neurotrophic factors on cell viability were determined by performing an MTT assay. BDNF and FGF-2 were tested alone and co-administered. LPS induced a significant increase in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and NO. BDNF, FGF-2, and their co-administration did not counteract these LPS effects. Our study suggests that the anti-inflammatory effect of BDNF and FGF-2 in vivo in the epilepsy model was indirect and likely due to a reduction in seizure frequency and severity.

Bladder cancer (BCa) is one of the most diagnosed urological malignancies. A timely and accurate diagnosis is crucial at the first assessment as well as at the follow up after curative treatments. Moreover, in the era of precision medicine, proper molecular characterization and pathological evaluation are key drivers of a patient-tailored management. However, currently available diagnostic tools still suffer from significant operator-dependent variability. To fill this gap, physicians have shown a constantly increasing interest towards new resources able to enhance diagnostic performances. In this regard, several reports have highlighted how artificial intelligence (AI) can produce promising results in the BCa field. In this narrative review, we aimed to analyze the most recent literature exploring current experiences and future perspectives on the role of AI in the BCa scenario. We summarized the most recently investigated applications of AI in BCa management, focusing on how this technology could impact physicians’ accuracy in three widespread diagnostic areas: cystoscopy, clinical tumor (cT) staging, and pathological diagnosis. Our results showed the wide potential of AI in BCa, although larger prospective and well-designed trials are pending to draw definitive conclusions allowing AI to be routinely applied to everyday clinical practice.

Abstract Hepatozoon spp. is the causative agent of a vector-borne parasitic disease in many animal species. In felids, Hepatozoon felis, Hepatozoon canis and Hepatozoon silvestris have been molecularly isolated. Hepatozoonosis usually causes asymptomatic infections in domestic cats, but clinical cases have recently been reported in Europe. We describe the first Italian case of hepatozoonosis in a cat with an unusual presentation. An 11-year-old neutered European shorthair cat was urgently hospitalized for intestinal intussusception. Hematology, biochemistry, FIV-FeLV tests, blood smears and molecular investigation targeting the 18S rRNA gene of Hepatozoon spp. were performed on blood samples; in addition, histological and molecular investigations were performed to analyze surgical samples to identify Hepatozoon infection. Hepatozoon gamonts were detected in granulocytes in the blood smear, and Hepatozoon spp. DNA was confirmed by PCR on blood. The intussusception was caused by a sessile endoluminal nodule that was surgically removed. Histologically, many elements referring to parasitic tissue forms were identified in the intestinal cells, and then the specimens were molecularly confirmed to harbor H. silvestris. This is the first description of symptomatic hepatozoonosis in a domestic cat in Italy. Hepatozoon silvestris has been described in wild felids, which are usually resilient to the infection, whereas the domestic cat seems to be more susceptible. Indeed, H. silvestris in cats usually presents tropism for skeletal muscle and myocardium with subsequent clinical manifestations. This is the first description of a domestic cat with H. silvestris localized in the intestinal epithelium and associated with intussusception. Graphical abstract

Guglielmo Mantica,1 Francesco Chierigo,1,2 Farzana Cassim,3 Francesca Ambrosini,1,2 Stefano Tappero,1,2 Rafaela Malinaric,1,2 Stefano Parodi,1,2 Andrea Benelli,4 Federico Dotta,4 Marco Ennas,4 Martina Beverini,1,2 Chiara Vaccaro,5 Salvatore Smelzo,6 Giovanni Guano,1,2 Federico Mariano,1,2 Calogero Paola,1,2 Giorgia Granelli,1,2 Virginia Varca,5 Carlo Introini,4 Salvatore Dioguardi,7 Alchiede Simonato,7 Andrea Gregori,8 Franco Gaboardi,6 Carlo Terrone,1,2 André Van der Merwe3 1IRCCS Ospedale Policlinico San Martino, U.O. Urologia, Genova, Italy; 2Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy; 3Department of Urology, Tygerberg Academic Hospital, Stellenbosch University, Cape Town, South Africa; 4Department of Urology, Galliera Hospital, Genoa, Italy; 5Department of Urology, ASST Rhodense, G. Salvini Hospital, Milan, Italy; 6Department of Urology, San Raffaele Turro Hospital, Milan, Italy; 7Department of Surgical, Oncological, and Oral Sciences, Section of Urology, University of Palermo, Palermo, Italy; 8Urology Unit, Ospedale Sacco, Milan, ItalyCorrespondence: Guglielmo Mantica, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Genoa, 16132, Italy, Tel +390105552815, Email guglielmo.mantica@gmail.comPurpose: To evaluate the prostate cancer (PCa) detection rate in men with chronic use of Aspirin and to compare it with the detection rate of non-users.Patients and Methods: Prospectively maintained database regarding patients undergoing prostate biopsy over the last 10 years in five institutions. Patients were divided into two groups according to their exposure to Aspirin. We relied on multivariable linear and logistic regression models to test whether Aspirin administration was associated with lower PSA values at prostate biopsy, higher PCa diagnosis, and higher Gleason Grade Grouping (GGG) at biopsy.Results: Were identified 1059 patients, of whom 803 (76%) did not take Aspirin vs 256 (24%) were taking it. In multivariable log-linear regression analysis, Aspirin administration was associated with lower PSA levels (OR 0.83, 95% CI 0.71– 0.97, p = 0.01), after controlling for age, prostate volume, smoking history, associated inflammation at prostate biopsy, presence of PCa at biopsy, and GGG. In multivariable logistic regression analysis, Aspirin administration was not found to be a predictor of PCa at prostate biopsy (OR 1.40, 95% CI 0.82– 2.40, p = 0.21) after controlling for age, PSA, smoking history, prostate volume, findings at digital rectal examination and the number of biopsy cores. In patients with PCa at prostate biopsy (n = 516), Aspirin administration was found to predict higher GGG (OR 2.24, 95% CI 1.01– 4.87, p = 0.04).Conclusion: Aspirin administration was found to be a predictor of more aggressive GGG. These findings suggest that a lower PSA threshold should be considered in patients taking Aspirin, as, despite low PSA levels, they might harbour aggressive PCa.Keywords: prostate-specific antigen, aspirin, inflammation, prostate cancer, prostate biopsy

Introdução: O aumento do número de casos de síndrome respiratória aguda grave (SRAG) associado ao SARS-CoV-2 originou uma das maiores emergências mundiais de saúde pública. Objetivo: Avaliar o perfil epidemiológico da SRAG no estado de Minas Gerais, durante 2020 e 2021. Método: Realizou-se pesquisa transversal, descritiva, retrospectiva e qualiquantitativa. Os dados foram coletados do sistema SIVEP-Gripe e do Painel de Monitoramento dos Casos de COVID-19, dos anos de 2020 e 2021. As variáveis analisadas foram: total de casos de COVID-19, total de SRAG e SRAG por COVID-19, idade, sexo, raça, classificação final e evolução final. Resultados: O estado apresentou 315.726 casos de SRAG e, destes, 58,6% foram causados pelo SARS-CoV-2. A maioria dos indivíduos que apresentou SRAG eram do sexo masculino, faixa etária de acima dos 60 anos e raça parda. Dentre os casos de SRAG, 23,3% evoluíram para óbito, e destes 77,6% tinham como causa a COVID-19. As regionais de Uberlândia, Belo Horizonte, Coronel Fabriciano, Patos de Minas, Uberaba, Ituiutaba, Leopoldina, Governador Valadares e Juiz de Fora apresentaram as maiores ocorrências de SRAG/habitantes. As regionais São João del-Rei, Teófilo Otoni, Passos e Uberaba destacaram-se por apresentar elevada taxa de letalidade dos pacientes que apresentaram SRAG por COVID-19. Conclusões: A distribuição dos casos e óbitos notificados de SRAG em Minas Gerais foi heterogênea, com número maior de casos em municípios com maior densidade demográfica. As questões elencadas nesta pesquisa apontaram as deficiências e fragilidades nas capacidades de resposta ao enfrentamento da pandemia, o que indica a necessidade de descentralização e reestruturação do sistema de saúde de diversos municípios do estado.

Tick-transmitted apicomplexans of the genera Cytauxzoon and Hepatozoon affect a wide range of felids worldwide, but little is known about them. Recently, several studies addressed the species circulating in Europe, their distribution, and their hosts. Molecular assays are the method of choice for their detection. Unfortunately, conventional PCRs already described are time- and cost-consuming and specific for either Hepatozoon or Cytauxzoon detection. This study was developed to evaluate (i) the occurrence of Cytauxzoon and Hepatozoon in felids using a fast and cost-saving real-time PCR capable of detecting both protozoa simultaneously, (ii) the distribution of Cytauxzoon and Hepatozoon species in north-eastern Italy, and (iii) the involvement of other susceptible felid hosts in the same area. An SYBR® Green-based real-time PCR with primers targeting the 18S-rRNA was validated and applied to 237 felid samples, i.e., whole blood from 206 domestic cats and 12 captive exotic felids, and tissues from 19 wildcats. Positive results were obtained by melting temperature curve analysis due to the specific melting peak (i.e., 81°C Cytauxzoon spp.; 78–78.5°C Hepatozoon spp.). Positive samples were subjected to conventional PCR, followed by sequencing for species identification. Phylogenetic analyses were performed to assess relatedness among European isolates. Data on domestic cats (age class, sex, origin, management, and lifestyle) were recorded, and statistical analyses were performed to identify potential risk factors. A total of 31 (15%) domestic cats were positive for Hepatozoon spp. (i.e., 12 for H. felis, 19 for H. silvestris), while six (2.9%) for C. europaeus. The prevalence of Hepatozoon felis was significantly (p

Fluorescence confocal microscopy (FCM) represents a novel diagnostic technique able to provide real-time histological images from non-fixed specimens. As a consequence of its recent developments, FCM is gaining growing popularity in urological practice. Nevertheless, evidence is still sparse, and, at the moment, its applications are heterogeneous. We performed a narrative review of the current literature on this topic. Papers were selected from the Pubmed, Embase, and Medline archives. We focused on FCM applications in prostate cancer (PCa), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Articles investigating both office and intraoperative settings were included. The review of the literature showed that FCM displays promising accuracy as compared to conventional histopathology. These results represent significant steps along the path of FCM’s formal validation as an innovative ready-to-use diagnostic support in urological practice. Instant access to a reliable histological evaluation may indeed significantly influence physicians’ decision-making process. In this regard, FCM addresses this still unmet clinical need and introduces intriguing perspectives into future diagnostic pathways. Further studies are required to thoroughly assess the whole potential of this technique.

Fibrous particles interact with cells and organisms in complex ways that can lead to cellular dysfunction, cell death, inflammation, and disease. The development of conductive transparent networks (CTNs) composed of metallic silver nanowires (AgNWs) for flexible touchscreen displays raises new possibilities for the intimate contact between novel fibers and human skin. Here, we report that a material property, nanowire-bending stiffness that is a function of diameter, controls the cytotoxicity of AgNWs to nonimmune cells from humans, mice, and fish without deterioration of critical CTN performance parameters: electrical conductivity and optical transparency. Both 30- and 90-nm-diameter AgNWs are readily internalized by cells, but thinner NWs are mechanically crumpled by the forces imposed during or after endocytosis, while thicker nanowires puncture the enclosing membrane and release silver ions and lysosomal contents to the cytoplasm, thereby initiating oxidative stress. This finding extends the fiber pathology paradigm and will enable the manufacture of safer products incorporating AgNWs.

ObjectivesThis study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.Materials and methodsWe pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.ResultsFor oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.ConclusionReferring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.