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Abstract A growing body of evidence suggests the role of male hypogonadism as a possible harbinger for poor clinical outcomes across hospitalized Covid-19 patients. Accordingly, we sought to investigate the impact of dysregulated hypothalamic-pituitary–gonadal axis on the severity of the clinical manifestations for hospitalized Covid-19 patients matched with healthy controls through a systematic review and meta-analysis. Databases were searched from inception to March 2022. A standardized mean difference (SMD) meta-analysis focused on hospitalized Covid-19 patients and healthy controls was developed for studies who reported total testosterone (TT) and luteinizing hormone (LH) levels at hospital admission. Overall, n = 18 series with n = 1575 patients between 2020 and 2022 were reviewed. A significant decrease in SMD of TT levels in Covid-19 patients compared to paired controls was observed (− 3.25 nmol/L, 95%CI − 0.57 and − 5.93). This reduction was even more consistent when matching severe Covid-19 patients with controls (− 5.04 nmol/L, 95%CI − 1.26 and − 8.82) but similar for Covid-19 survivors and non-survivors (− 3.04 nmol/L, 95%CI − 2.04 and − 4.05). No significant variation was observed for serum LH levels across studies. Patient related comorbidities, year of the pandemic, and total lymphocyte count were associated with the observed estimates. TT levels may be a useful serum marker of poor outcomes among Covid-19 patients. These findings may support the development of ad-hoc clinical trials in the Covid-19 risk-group classification and subsequent disease monitoring. The interplay between TT and immune response should be evaluated in future researches.

Background: Contrast-enhanced ultrasound (CEUS) is a diagnostic tool that is gaining popularity for its ability to improve overall diagnostic accuracy in bladder cancer (BC) staging. Our aim is to determine the cumulative diagnostic performance of CEUS in predicting preoperative muscle invasiveness using a comprehensive systematic review and pooled meta-analysis. Methods: A systematic review until October 2023 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patients with BC suspicion were offered CEUS before the transurethral resection of the bladder tumor (TURBT). The diagnostic performance of CEUS was evaluated based on non-muscle-invasive bladder cancer (NMIBC) vs. muscle-invasive bladder cancer (MIBC) confirmed at the final histopathological examination after TURBT. The outcomes were determined through pooled sensitivity, specificity, pooled positive likelihood ratio (PLR+), negative likelihood ratio (PLR−), and area under the summary receiver operating characteristic (SROC) along with their respective 95% confidence intervals (CI). Results: Overall, five studies were included. In these studies, a total of 362 patients underwent CEUS prior to TURBT. The pooled sensitivity and specificity were 0.88 (95% CI: 0.81–0.93) and 0.88 (95% CI: 0.82–0.92), respectively. SROC curve depicted a diagnostic accuracy of 0.94 (95% CI: 0.81–0.98). The pooled PLR+ and PLR− were 7.3 (95% CI: 4.8–11.2) and 0.14 (95% CI: 0.08–0.23), respectively. Conclusions: Our meta-analysis indicates that CEUS is highly accurate in the diagnosis and staging for BC. Beyond its accuracy, CEUS offers the advantage of being a cost-effective, safe, and versatile imaging tool.

Contrast-enhanced ultrasound (CEUS) is an advanced imaging technique that integrates conventional US with the intravenous injection of specific US contrast agents (UCAs), combining the non-invasiveness of US with the higher accuracy of contrast-enhanced imaging. In contrast with magnetic resonance imaging (MRI), computed tomography (CT) and cystoscopy, CEUS has few contraindications, and UCAs are non-nephrotoxic agents that can be safely used in patients with kidney failure. CEUS is a well-established method for the detection of liver lesions and for echocardiography, and its indications are expanding. The updated 2018 WFUMB-EFSUMB guidelines have added the urinary bladder under non-hepatic applications of CEUS. The technique is able to distinguish between benign tissue, such as clots or hematoma, and malignant lesions by perfusing the mass with contrast agent. Thanks to the different perfusion rates of the various layers of the bladder wall, CEUS is also able to predict tumor invasion depth and stage. Despite that, current urological guidelines do not include CEUS as a plausible imaging technique for bladder urothelial carcinoma. The main reason for this omission might be the presence of scarce randomized evidence and the absence of large validated series. In this review, we describe the rationale behind the use of CEUS in bladder cancer and the added value of this imaging technique in the detection and staging of bladder lesions. In addition, we researched the available literature on the topic and then described the results of randomized clinical trials and a meta-analysis investigating the accuracy of CEUS in bladder cancer diagnosis and staging. The reported studies show that CEUS is a highly accurate diagnostic and staging tool for BC, reaching levels of specificity and sensitivity in differentiating between Ta-T1, or low-grade BC, and T2, or high-grade BC, that are comparable to those shown by the reference standard methods. Nonetheless, several limitations were found and are highlighted in this review. The aim of this study is to further validate and promote the use of CEUS as a quick, economic and effective diagnostic tool for this high-impact disease.

The increasing diffusion of genetic analysis regarding the pathogenetic variants (PVs) of genes involved in DNA Damage Repair (DDR) mechanisms and the development of Poly ADP ribose polymerase (PARP) inhibitors (PARPis) led to the first valid precision medicine option tailored toward metastatic prostate cancer (mPC). The concept of anticipation in the systemic treatment of mPC was initially adopted for androgen receptor signaling inhibitors (ARSIs) to describe the expansion of their indications, from the setting of the late-stage second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) to first-line therapy in selected cases. There is already mounting evidence in favor of the anticipation of PARPis in the first line of mCRPC therapy, and further evidence in favor of mHSPC is emerging. Many studies have demonstrated the synergism between ARSIs and PARP inhibitors. Recent discoveries regarding the crosstalk between the androgen receptor (AR) and DNA repair mechanisms are disconnecting the use of PARPis from genetic analysis. The new message emerging is that the combination of PARPis with ARSIs may work independently of DDR mutational status. As a matter of fact, most of the recent trials analyzing the combination of PARPis with abiraterone or enzalutamide as a first-line therapy enrolled mCRPC patients irrespective of their mutational status. The PROPEL trial concluded that the advantage of the combination was independent of PV status, despite a higher advantage being reported in the BRCA1/2 mutated subgroup. The MAGNITUDE trial, however, showed a significant advantage only in the DDR mutated subgroup, and the DDR non-mutated cohort was closed for further enrollment. The combination of PARPis with ARSIs represents a significant strategy with a view to the anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR genes.

Exosomes are extracellular nanovesicles (EV), that is, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in cases of tumorigenesis open up different scenarios on their possible application to research into new biomarkers. The first purpose of the present review was to specifically analyze and compare different methodologies available for the use of exosomes in prostate cancer (PC). The most widely applied methodologies include ultracentrifugation techniques, size-based techniques, immunoaffinity capture-based techniques (mainly ELISA), and precipitation. To optimize the acquisition of exosomes from the reference sample, more techniques can be applied in sequence for a single extraction, thereby determining an increase in labor time and costs. The second purpose was to describe clinical results obtained with the analysis of PSA-expressing exosomes in PC; this provides an incredibly accurate method of discriminating between healthy patients and those with prostate disease. Specifically, the IC-ELISA alone method achieved 98.57% sensitivity and 80.28% specificity in discriminating prostate cancer (PC) from benign prostatic hyperplasia (BPH). An immunocapture-based ELISA assay was performed to quantify and characterize carbonic anhydrase (CA) IX expression in exosomes. The results revealed that CA IX positive exosomes were 25-fold higher in plasma samples from PC patients than in those from healthy controls. The analysis of PC-linked exosomes represents a promising diagnostic model that can effectively distinguish patients with PC from those with non-malignant prostatic disease. However, the use of exosome analysis in clinical practice is currently limited by several issues, including a lack of standardization in the analytical process and high costs, which are still too high for large-scale use.

Background: Cyclothymia seems to be often associated with coexisting ADHD symptoms, although this comorbidity is understudied. Emotional dysregulation is a core symptom of both conditions. Methods: Adult subjects with cyclothymia were consecutively enrolled at the outpatient service of the Second Psychiatry Unit of the Pisa University Hospital (Italy). Screening for ADHD was performed using the Adult ADHD Self-Report Scale (ASRS). We analyzed differences in sociodemographic and clinical characteristics between subjects with and without ADHD symptomatology. Results: Of the total sample of 107 subjects, 43 % screened positive for ADHD. ADHD+ subjects were significantly younger than ADHD- subjects, had a lower level of education, a higher prevalence of psychiatric comorbidity, and a more frequent family history for ADHD and alcohol use disorder. In addition, ADHD+ subjects scored higher than ADHD- subjects on the affective instability, negative emotionality, and emotional impulsivity subscales of the RIPoSt-40 questionnaire, as well as on the 40‐item version of Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-40) total score. They also showed a stronger association with the cyclothymic and depressive subscales of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-M) scale. Limitations: the small sample size, the cross-sectional nature of the study, the use of self-report questionnaires, and the use of a screening test to assess comorbidity with ADHD symptomatology. Conclusions: ADHD symptomatology is very common in cyclothymic individuals, and emotional dysregulation blurs the diagnostic boundaries between the two disorders. Several clinical features suggest the need for systematic evaluation of ADHD in patients with cyclothymic disorder.

Several events in an animal’s life are considered stressful. Among them, the most studied and significant are transportation, weaning, and adaptation to climate change. Moreover, other events, such as the separation from the dam, moving from the original farm to another, management practices, such as regrouping with other animals, and new hierarchical conditions, represent routine conditions in the bovine’s life, which can influence the animal’s homeostasis. The purpose of this study is to evaluate the changes in blood parameters of 45 calves introduced into a new environment from their original farms. Blood samples were collected upon arrival at a genetic center (T1), 7 (T2), 30 (T3), and 120 (T4) days after arrival. Blood count, protein electrophoresis, clinical chemistry, and innate immunity parameters were performed on the samples. Significant alterations in some clinical chemistry parameters were related to liver function in the serum protein and the values of IL-6 and TNF-α; the main cytokines mediating the stress response emerged from the results. The evidence indicates the mild response to adaptation stress by calves raised in close association with people after their introduction into a new environment.

Transportation is a recurring event in a farm animal’s life, and it is considered one of the main stressors with possible negative repercussions for both the health and welfare of farm animals. The objective of the present study was to examine the effect of transportation on some blood variables of 45 young bulls moved from their original farms to a livestock collection centre. Transportation took no more than 8 h and was carried out between January and March 2021. Blood samples were taken before transportation (T0), upon arrival at the collection centre (T1), and 7 days after arrival (T2). Samples were processed for blood cell count, clinical chemistry analyses, serum protein electrophoresis, and the evaluation of innate immunity parameters. The results showed a typical stress leukogram with neutrophilia and changes in the neutrophil:lymphocyte ratio. No significant alterations were observed in either serum proteins or pro-inflammatory cytokines. Significant, albeit transient, alterations were observed in some clinical chemistry parameters after transportation, which could be accounted for by stressful conditions such as the transportation itself and handling and mixing with other animals. Our results indicated that the adopted transportation conditions only slightly affected the blood variables under study with no significant impact on animal welfare.

The spotted fever group of Rickettsiae is a heterogeneous group of Rickettsiae transmitted by ticks, causing similar diseases in humans (spotted fever). Until recently, it was supposed that a single pathogenic tick-borne SFG Rickettsia circulated in each different geographic area and that R. conorii subsp. conorii was the SFG Rickettsiae circulating in Italy, but in the last decade, thanks to molecular diagnostic, several different Rickettsia species, previously not considered pathogenic for decades, have been isolated from ticks and definitively associated to human disease, also in Italy. The present survey was carried out with the aim of investigating the presence of different SFG Rickettsia species in a geographic area where no information was available. Ticks collected from animals submitted to necropsy, removed from humans in local hospitals and collected from the environment were identified and tested by PCR for Rickettsia spp. based on the gltA gene, and positive PCR products were sequenced. A total of 3286 ticks were collected. Fifteen tick species were recognized, the most represented (79.52%) species in the collection was Ixodes ricinus, followed by Rhipicephalus sanguineus (9.13%). The overall prevalence of Rickettsia infection was 7.58%. Eight species of Rickettsia were identified, the most frequent was R. monacensis (56%), followed by R. helvetica (25.50%). Noteworthy, is the detection in the present study of Rrhipicephali, detected only twice in Italy. These are the first data available on SFG Rickettsiae circulation in the study area and they can be considered as starting point to assess the possible risk for humans.

Este trabajo busca ser un aporte a los estudios centrados en reponer las perspectivas de los trabajadores respecto de los años setenta. Por ende, se privilegiará un enfoque que integre aspectos de la vida cotidiana para, así, lograr comprender la complejidad de esos años, ya que ?como han demostrado diversos autores? la última dictadura militar implicó para muchas personas experiencias violentas y traumáticas, mientras que para otras fue una etapa de “normalidad”. A partir del caso de la fábrica Jabón Federal ubicada en La Matanza (Buenos Aires) se indagará, en primer lugar, en las representaciones de los trabajadores sin militancia política sobre los trabajadores víctimas del terrorismo estatal y, para ello, se contemplarán sus recuerdos sobre el clima fabril. Luego, se buscará reponer tanto las identidades de los trabajadores desaparecidos como la trama política en la que estaban insertos con el propósito de reconstruir al menos una pequeña parte de las historias destruidas por la dictadura. Para abordar ambos objetivos, utilizaremos diversas fuentes: entrevistas orales a ex trabajadores (empleados y obreros) y a personal jerárquico; entrevistas a familiares y compañeros de los trabajadores desaparecidos; prensa de las organizaciones armadas; legajos policiales y bases de datos de organismos de Derechos Humanos.

Background and Objectives: Emotional dysregulation is central to the problem of the overlap between attention-deficit/hyperactivity disorder (ADHD) and cyclothymia. The aim of the study was to evaluate comorbidity rates between ADHD and cyclothymic disorder and to explore demographic and clinical differences among the groups, focusing on affective temperament and emotional dysregulation. Materials and Methods: One hundred sixty-five outpatients attending the Second Psychiatry Unit at the Santa Chiara University Hospital (Pisa) were consecutively recruited: 80 were diagnosed with ADHD, 60 with cyclothymic disorder, and 25 with both conditions. Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-M) and the 40-item version of Reactivity, Intensity, Polarity, and Stability questionnaire (RI-PoSt-40) were administered. Results: Cyclothymic patients were more frequently female and older with respect to the ADHD groups. Both comorbid and non-comorbid ADHD patients showed significantly lower educational attainment and more frequently had substance use disorders. Panic disorder was common in non-comorbid cyclothymic patients, who showed significantly higher rates of familial panic disorder, major depressive disorder and suicide attempts in comparison with patients only diagnosed with ADHD. Cyclothymic patients without ADHD were also characterized by fewer hyperthymic temperamental traits, higher depressive and anxious dispositions, and a greater negative emotionality. No significant differences among groups were observed for cyclothymic temperament and overall negative emotional dysregulation, but comorbid patients with both conditions scored the highest in these subscales. This group also showed significantly higher affective instability with respect to ADHD patients without cyclothymia and was less frequently diagnosed with bipolar disorder type II than patients from both the other groups. Conclusions: ADHD and cyclothymia often co-occur and show similar levels of emotional dysregulation. However, cyclothymic patients may be more prone to negative emotionality in clinical settings. Subjects with “sunny” cyclothymic features might escape the attention of clinicians unless ADHD is present.

EHV1 and EHV4 are the most important herpesviruses in horses. Repeated cases of abortion in mares regularly vaccinated, prompted us to investigate the immune response after vaccination with the same inactivated vaccine, but with three different protocols. Eighteen mares were chosen and randomly divided in three study groups (G1-G2-G3) and a control group (Ctrl). For serologic and PCR investigations nasal swabs, sera and blood were collected. The protocol used in G3 (4 doses) increased the titer recorded by ELISA and seroneutralization (SN). Poor agreement and no correlation were observed in titer values between ELISA and SN and between SN and PCR. A very weak positive correlation between ELISA and PCR was obtained. Seven out of 18 nasal swabs were positive by PCR; none showed viremia and no abortion occurred, regardless of vaccination status and despite active circulation of EHV-1 in the farm at the time of the study. The study was conducted in field conditions, in a susceptible population with a known history of infection and abortion, and among the three protocols, the one proposed in the G1 was the least efficient while the one proposed for the G3, seems to have induced a higher antibody titer in both SN and ELISA.

Este trabajo se propone reflexionar sobre la forma de militancia de Marcos, un obrero fabril, delegado sindical y militante trotskista. Para ello, se trabajará con registros etnográficos y fragmentos de entrevistas. Asimismo, se fundamentará la importancia de analizar los bares como lugares centrales para nuestro interlocutor y, a través de los cuales, se vislumbrarán otras facetas de su modo de hacer polí­tica. Entonces, situados en un bar matancero en pleno contexto electoral, veremos cómo las transformaciones en la militancia, que Marcos señalaba discursivamente, se pondrí­an en evidencia allí­ y me interpelarí­an en mi rol de investigadora. Por lo tanto, poner en práctica la reflexividad será una excelente ví­a para aprender aún más de su forma de militancia. Así­, concluiremos en la necesidad de matizar aquellas visiones que reconstruyen las prácticas de militancia trotskista a partir, esencialmente, de la discusión polí­tica.

Pathogens transmitted to humans by phlebotomine sand flies are neglected, as they cause infectious diseases that are not on the priority list of national and international public health systems. However, the infections caused by protozoa of the Leishmania genus and viruses belonging to the Phlebovirus genus (family Phenuiviridae)-the most significant group of viruses transmitted by sand flies-have a relevant role for human pathology. These infections are emerging in the Mediterranean region and will likely spread in forthcoming decades, posing a complex threat to human health. Four species and 2 hybrid strains of Leishmania are pathogenic for humans in the Mediterranean Basin, with an estimated annual incidence of 239,500-393,600 cases of cutaneous leishmaniasis and 1,200-2,000 cases of visceral leishmaniasis. Among the phleboviruses, Toscana virus can cause neuroinvasive infections, while other phleboviruses are responsible for a typical "3-day fever"; the actual incidence of Phlebovirus infections in the Mediterranean area is unknown, although at least 250 million people are exposed. Here, we reviewed the current literature on epidemiology of sand fly-borne infections in the Mediterranean Basin, with a focus on humans. Our analysis indicates the need for increased public health activities directed to determine the disease burden of these infections as well as to improve their surveillance. Among the emerging challenges concerning sand fly-borne pathogens, the relationships between sand fly-borne protozoa and viruses should be considered in future studies, including epidemiological links between Leishmania and phleboviruses as well as the conditional capacity for these pathogens to be involved in interactions that may evolve towards increased virulence.