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Background: Gamma-delta (γδ) T cells are a major immune cell subset in pigs. Approximately 50% of circulating T cells are γδ T cells in young pigs and up to 30% in adult sows. Despite this abundance, the functions of porcine γδ T cells are mostly unidentified. In humans and mice, activated γδ T cells exhibit broad innate cytotoxic activity against a wide variety of stressed, infected, and cancerous cells through death receptor/ligand-dependent and perforin/granzyme-dependent pathways. However, so far, it is unknown whether porcine γδ T cells have the ability to perform cytotoxic functions., Methods: In this study, we conducted a comprehensive phenotypic characterization of porcine γδ T cells isolated from blood, lung, and nasal mucosa. To further analyze the cytolytic potential of γδ T cells, in vitro cytotoxicity assays were performed using purified γδ T cells as effector cells and virus-exposed or mock-treated primary porcine alveolar macrophages as target cells., Results: Our results show that only CD2 + γδ T cells express cytotoxic markers (CD16, NKp46, perforin) with higher perforin and NKp46 expression in γδ T cells isolated from lung and nasal mucosa. Moreover, we found that γδ T cells can exhibit cytotoxic functions in a cell-cell contact and degranulation-dependent manner. However, porcine γδ T cells did not seem to specifically target Porcine Reproductive and Respiratory Syndrome Virus or swine Influenza A Virus-infected macrophages, which may be due to viral escape mechanisms., Conclusion: Porcine γδ T cells express cytotoxic markers and can exhibit cytotoxic activity in vitro. The specific mechanisms by which porcine γδ T cells recognize target cells are not fully understood but may involve the detection of cellular stress signals., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bettin, Darbellay, van Kessel, Dhar and Gerdts.)

SLURP1 and SLURP2 are both small secreted members of the Ly6/u-PAR family of proteins and are highly expressed in keratinocytes. Loss-of-function mutations in SLURP1 lead to a rare autosomal recessive palmoplantar keratoderma (PPK), Mal de Meleda (MdM), which is characterized by diffuse, yellowish palmoplantar hyperkeratosis. Some individuals with MdM experience pain in conjunction with the hyperkeratosis that has been attributed to fissures or microbial superinfection within the affected skin. By comparison, other hereditary PPKs such as pachyonychia congenita and Olmsted syndrome show prevalent pain in PPK lesions. Two mouse models of MdM, Slurp1 knock-out and Slurp2X knock-out, exhibit robust PPK in all four paws. However, whether the sensory experience of these animals includes augmented pain sensitivity remains unexplored. In this study, we demonstrate that both models exhibit hypersensitivity to mechanical and thermal stimuli as well as spontaneous pain behaviors in males and females. Anatomical analysis revealed slightly reduced glabrous skin epidermal innervation and substantial alterations in palmoplantar skin immune composition in Slurp2X knock-out mice. Primary sensory neurons innervating hindpaw glabrous skin from Slurp2X knock-out mice exhibit increased incidence of spontaneous activity and mechanical hypersensitivity both in vitro and in vivo. Thus, Slurp knock-out mice exhibit polymodal PPK-associated pain that is associated with both immune alterations and neuronal hyperexcitability and might therefore be useful for the identification of therapeutic targets to treat PPK-associated pain., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Gamma-Delta T cells are a prominent subset of T cells in pigs. However, developmental changes, antigen recognition, cell migration, and their contributions to pathogen clearance remain largely unknown. We have recently shown that porcine γδ T cells express Toll-like receptors (TLRs), and that TLR7/8 stimulation can function as a co-stimulatory signal that complements cytokine-induced signals to enhance INFγ production. Nonetheless, the signaling pathways behind this increased cytokine responsiveness remained unclear. Here, we analyzed the signaling pathways by measuring cellular kinase activity and selective inhibition, confirming that the TLR7/8 expression by γδ T cells is indeed functional. Moreover, TLR downstream signaling responses showed a distinct age-dependency, emphasizing the importance of age in immune function. While the TLR7/8 co-stimulation depended on activation of IRAK1/4, p38 and JNK in adult-derived γδ T cells, γδ T cells from young pigs utilized only p38, indicating the existence of an alternative signaling pathway in young pigs. Overall, this data suggests that porcine γδ T cells could be able to recognize viral RNA through TLR7/8 and subsequently support the survival and activation of the adaptive immune response by cytokine production., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Gamma-Delta (γδ) T cells represent a prominent lymphocyte subset in pigs. Their role and function, however, remains largely unknown. Toll-like receptors (TLR) are key receptors for the recognition of pathogens, but so far, it is unknown if porcine γδ T cells express TLRs and therefore have the innate ability to recognize pathogens through pattern recognition receptors. In this study, we compared γδ T cells in different age groups of pigs and investigated the functional relevance of TLR7/8 expression. We found that the major γδ T cell phenotype shifts from CD2 - CD8α -/dim CD27 + in young pigs to CD2 + CD8α high CD27 - in 3-year-old pigs impacting their ability to produce IFN-γ upon cytokine and TLR stimulation. Furthermore, we report that stimulation with TLR7/8 ligand R848 increased IFN-γ production in purified γδ T cells upon co-stimulation with IL-2 and IL-12. However, the effect of R848 as a co-activator of γδ T cells was abrogated by the addition of monocytes or within PBMCs, suggesting that γδ T cells respond to multiple direct and indirect stimulations. Thus, our results indicate that γδ T cells express TLRs, are modulated by TLR7/8 ligand R848 and have subset-specific responses., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To present the results of a nationwide survey among urological patients to evaluate their perception of the quality of care provided by residents., Methods: An anonymous survey was distributed to patients who were referred to 22 Italian academic institutions. The survey aimed to investigate the professional figure of the urology resident as perceived by the patient., Results: A total of 2587 patients were enrolled in this study. In all, 51.6% of patients were able to correctly identify a urology resident; however, almost 40% of respondents discriminated residents from fully trained urologists based exclusively on their young age. Overall, 98.2% patients rated the service provided by the resident as at least sufficient. Urology trainees were considered by more than 50% of the patients interviewed to have good communication skills, expertise and willingness. Overall, patients showed an excellent willingness to be managed by urology residents. The percentage of patients not available for this purpose showed an increasing trend that directly correlated with the difficulty of the procedure. Approximately 5-10% of patients were not willing to be managed by residents for simple procedures such as clinical visits, cystoscopy or sonography, and up to a third of patients were not prepared to undergo any surgical procedure performed by residents during steps in major surgery, even if the residents were adequately tutored., Conclusions: Our data showed that patients have a good willingness to be managed by residents during their training, especially for medium- to low-difficulty procedures. Furthermore, the majority of patients interviewed rated the residents' care delivery as sufficient. Urology trainees were considered to have good communication skills, expertise and willingness., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction and Aim: Speedy diagnosis are mandatory in testicular torsion, nevertheless some cases of irreversible ischemia still occur. In this study we analysed the results of patients undergoing surgical exploration for acute scrotum., Materials and Methods: A multicentric retrospective clinical evaluation was carried out on patients who underwent urgent scrotal exploration at 12 different departments in North-Eastern Italy. Data included complete anagraphic information, clinical presentation, numeric pain rating scale, previous testicular surgery, Doppler serial ultrasonography (US) evaluation and concordance with surgical findings, testicular mobility, surgical treatment, staged or concurrent treatment of the contralateral gonad. Statistical analysis was conducted both for descriptive and inferential statistics with SPSS v26., Results: Three hundred and sixty-eight cases were collected between January 2010 and June 2019. The time between symptom onset and ER access time was within 6 h in majority of patients. However, 17.4% of subject presented after more than 12 h. In patients undergoing US, this showed signs of ischemia in 237 patients (77.2%) and normal vascularisation in 70 (22.8%) of whom 26 had signs of testicular torsion at surgical exploration. Overall, the US data were concordant with the surgical findings in 254 cases (82.7%). A significant association was found between time-to-evaluation and time-to-treatment and the need for orchiectomy ( p  < 0.01)., Conclusion: Testicular torsion management is still challenging in terms of time-saving decision making. Scrotal US is helpful, but even in the contemporary its sensitivity is low era in a non-neglectable number of cases, therefore surgical exploration is warranted in acute scrotum when torsion cannot be ruled out, even when US shows vascularisation.

Purpose: The prognosis of stage I nonseminomatous germ cell tumor of the testis is favorable. Early and late side effects of treatment may affect quality of life and survival. We determined the tolerability, safety and efficacy of laparoscopic retroperitoneal lymph node dissection in patients with stage I nonseminomatous germ cell tumor of the testis at a high volume center., Materials and Methods: Unilateral laparoscopic retroperitoneal lymph node dissection was prospectively recorded in 225 patients from 2000 to 2014. Since 2007, patients have been treated at a multidisciplinary clinic and were proposed surgery as an alternative to surveillance or adjuvant chemotherapy. The indication for adjuvant chemotherapy changed during the study period. Descriptive statistics and regression analyses were used to evaluate the domains of safety and oncologic outcomes., Results: A total of 221 patients were evaluable. Median operative time was 200 minutes. Conversion to open surgery was done in 20 cases (9%). A median of 14 nodes (IQR 11-20) was retrieved. Grade greater than 2 complications in 8 cases (3.6%) increased as the number of retrieved nodes increased. Antegrade ejaculation was maintained in 98.6% of patients. Nodal metastases were found in 29 patients (13%), of whom 7 underwent adjuvant chemotherapy. There were 14 recurrences (6.3%), including 8 of 192 (4.2%) associated with no nodal metastases and 6 of 22 (27.3%) associated with nodal metastases in patients not undergoing adjuvant chemotherapy. At regression analyses lymph node ratio was the only significant factor predictive of recurrence and of the administration of any chemotherapy (each p <0.001). Operative time, the number of retrieved nodes and conversions improved with time., Conclusions: In the context of a high volume center laparoscopic retroperitoneal lymph node dissection was safe and its oncologic efficacy was comparable to that of open surgery. Select patients with stage I nonseminomatous germ cell tumor could be offered laparoscopic retroperitoneal lymph node dissection as an alternative to other options., (Copyright © 2018. Published by Elsevier Inc.)

Chyluria is the passage of chyle in the urine. The cause seems to be the rupture of retroperitoneal lymphatics into the pyelocaliceal system, giving urine a milky appearance. This communication is caused by the obstruction of lymphatic drainage proximal to intestinal lacteals, resulting in dilatation of distal lymphatics and the eventual rupture of lymphatic vessels into the urinary collecting system.This condition, if left untreated, leads to significant morbidity because of hematochyluria, recurrent renal colic, nutritional problems due to protein losses and immunosuppression resulting from lymphocyturia.In this review, we summarize the state of the art of this condition and the newest treatments available.