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Background: /aim: The aim of this study was to retrospectively compare the results of systematic preoperative coronary angiography ultimately followed by stenting in patients with asymptomatic coronary artery disease (CAD) undergoing open peripheral revascularization for peripheral arterial disease (PAD)., Patients and Methods: From January 2003 to December 2022, 276 patients having undergone open peripheral recanalization for PAD were retrospectively reviewed and divided into two groups. Patients in group A (n = 132), all without a history of coronary artery disease, had undergone standard cardiac evaluation (EKG and cardiac ultrasound) and systematic preoperative coronary angiography ultimately followed by percutaneous coronary intervention (PCI) for significant coronary artery stenoses, whereas patients in group B (n = 144) had only undergone standard cardiac evaluation prior to open peripheral revascularization. Mean length of follow-up was 60 months (range 12-130 months). The primary endpoints were occurrence of any long-term postoperative myocardial infarction (MI) and any complication related to coronary angiography and stenting. Secondary endpoints were long-term postoperative mortality, complications related to open peripheral revascularization and long-term peripheral bypass patency., Results: Fifty-three patients (40.0%; 95% CI: 32.0%, 48.0%) in group A had a significant coronary artery stenosis, 48(36.3%; 95% CI: 32.0%, 48.0%) underwent percutaneous intervention (PCI) and five (3.8%; 95% CI: 0.5 %, 7.0%) received coronary artery bypass grafting (CABG) before open revascularization. While no postoperative MI was observed in group A, seven MI occurred in group B (4.9%; 95% CI: 1.4%, 8.4%), one of which was fatal (p = 0.04). During the follow-up period, two non-fatal MI (1.5 %; 95% CI: 1.2%, 1.8%) occurred in group A, while 20 MI (14.1%; 95% CI: 8.5%, 19.7%) occurred in group B, five of which were fatal (p = 0.0001). No complications related to coronary angiography and stenting were observed. While no postoperative mortality was observed in group A, two patients (1.4%; 95% CI: -0.5%, 3.3%) in group B died, one due to a fatal MI and one due to an acute lower limb ischemia and multiple organ failure (p = 0.17). During follow-up, seven deaths (5.3%; 95% CI: 1.5%, 9.1%) occurred in group A (five related to cancer, one to lung disease and one for unknown causes) and 16 (11.0%; 95% CI: 6.0%, 16.0%) in group B (five related to MI, eight to cancer, and two of unknown causes) (p = 0.07). Concerning complications related to open peripheral revascularization, two compartmental syndromes (1.5%; 95% CI: -0.5%, 2.5%) occurred in group A and two (1.4%; 95% CI: - 0.5%, 2.5%) in group B (p = 0.93) in group B (p = 0.93), without indication to perform fasciotomy, no prosthetic infection was observed in either group, and one bypass occlusion (0.7%; 95% CI: - 0.7%, 2.1%) occurred in group B with acute lower limb ischemia (p = 0.34). Peripheral bypasses were patent in 90 patients in group A (68.0%; 95% CI: 64.0%, 72.0%) and in 96 patients (67%; 95% CI: 59.4%, 74.6%) in group B (p = 0.78)., Conclusion: Systematic preoperative coronary angiography ultimately followed by PCI in patients selected for open lower limb revascularization is safe and reduces intraoperative and postoperative risk of MI., (Copyright © 2025. Published by Elsevier Inc.)

An 11-year-old spayed female Beagle presented with tenesmus and was identified with a rectal wall mass. Diagnostic imaging (abdominal ultrasound and computed tomography) localised the mass in the right rectal wall and documented no evidence of metastatic disease. Subsequently, the dog underwent surgery for tumour excision. A histopathological diagnosis of melanoma was performed. To confirm the tumour histotype, immunohistochemistry was performed using anti-Melan A and anti-Ki67. Neoplastic cells exhibited focal Melan A immunoreactivity and widespread nuclear immunoreactivity for Ki67 with a Ki67 index of 27%. Adjuvant immunotherapy with APAVAC ® was initiated. After APAVAC administration, no local or systemic acute adverse events were observed. Four pre- and post-contrast computed tomography (CT) studies were performed in an 18-month follow-up period every 4-5 months. Follow-up rectal palpation and conscious visualisation of the surgical site have also resulted in no macroscopic signs of tumour recurrence. The dog remains alive and with no clinical evidence of tumour recurrence and/or distant progression at the time of writing, therefore, surviving over 540 days from the diagnosis.

The cannabinoid 2 receptor (CB2R) is a crucial element of the endocannabinoid system (ECS), which is predominantly expressed on cells of the reticuloendothelial system. Alterations in CB2R expression have shown a prognostic role in various human neoplastic diseases and its expression has been studied in canine mast cell tumours (MCT). Canine diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in dogs and has a variable clinical behaviour. Expression of CB2R was assessed by means of immunohistochemistry in fifteen dogs with proven histological diagnosis of DLBCL. A semiquantitative and quantitative assessment of immunoreactivity (IR) by digital analysis was performed in all cases. Our results indicate that CB2R expression is conserved in canine DLBCL but does not correlate with clinical outcome., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A cutaneous mast cell tumor (cMCT) is among the most common tumors in dogs. Endocannabinoids (eCBs) belong to the endocannabinoid system (ECS), which involves also cannabinoid receptors and an enzymatic system of biosynthesis and degradation. In this study, plasma levels of N -arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), N -palmitoylethanolamine (PEA), and N -oleoylethanolamine (OEA) were evaluated in 17 dogs with MCTs of varying histological grades and clinical stages, as well as in a control group of 11 dogs. Dogs affected by cMCT had higher plasma levels of 2-AG ( p = 0.0001) and lower levels of AEA ( p = 0.0012) and PEA ( p = 0.0075) compared to the control group, while no differences were observed at the OEA level between healthy and cMCT dogs ( p = 0.9264). The ability of eCBs to help discriminate between healthy and cMCT dogs was interrogated through the area under the ROC curve (AUC). An accuracy of 0.98 (95% confidence interval [CI], 0.94-1.02) was found for 2-AG, of 0.85 (95% CI, 0.71-0.99) for AEA, and of 0.81% for PEA (95% CI, 0.64-0.69). Values > 52.75 pmol/mL for 2-AG showed 94% sensitivity and 90% specificity in distinguishing cMCT. This is the first study to demonstrate alterations in plasmatic levels of eCBs in dogs affected by MCTs, suggesting the significance of these biomarkers in the tumorigenic process and their potential use as biomarkers in the future.

Objectives: In cats affected by severe thoracolumbar spinal cord pathologies, paraplegia and paraparesis, often accompanied by urinary retention, pose significant challenges, impacting both the cats' welfare and owners' lives. This study aimed to assess the quality of life (QoL) of cats affected by these conditions, and to evaluate the social and familial implications for caregivers., Methods: The study was structured into two parts. The first part comprised direct observations of aspects of QoL in cats both in household and shelter settings, while the second part involved the distribution of questionnaires to cat owners and shelter operators., Results: Cats with paraplegia/paraparesis and urinary retention can maintain a good QoL, with hindlimb mobility significantly influencing QoL scores. Shelter cats showed a comparable QoL to household cats, challenging the anecdotal beliefs that shelter cats with severe neurological impairments are destined to lead substandard lives. Operator surveys highlighted the feasibility of managing these cats in shelter environments, emphasising the importance of collaboration between caregivers and veterinary professionals. Likewise, owner surveys revealed a manageable time commitment for care, with most owners achieving proficiency in manual bladder expression within 1 month. Despite challenges, most of the owners reported positive experiences and did not contemplate euthanasia for their cats. Regular veterinary visits and occasional physiotherapy were common practices among caregivers., Conclusions and Relevance: Owners who respond to the questionnaire and shelter operators have a high commitment to cats with paraplegia/paraparesis. Although the study acknowledges this potential bias, it suggests that dedicated care can ensure a good QoL for cats with severe spinal injuries, both in shelter and household settings. Effective communication between caregivers and veterinary professionals is essential for accurate information dissemination and optimal care provision. This research contributes to raising awareness of managing these conditions and emphasises the importance of collaborative care approaches in veterinary medicine., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/Objectives : Giant splenic artery aneurysms (SAAs) and pseudoaneurysms (SAPs) represent rare conditions, characterized by a diameter greater than or equal to 5 cm. The risk of rupture is increased compared to common SAAs and SAPs, necessitating urgent treatments to prevent it. Methods : This systematic review was conducted through a comprehensive search involving the PubMed, Google Scholar, and Scopus databases. A total of 82 patients and 65 articles were included in the analysis. For each patient, we investigated age, sex, symptoms, comorbidities, the presence of a true or a false aneurysm, the dimensional criteria used to define dilations as giant aneurysms or pseudoaneurysms, the dimension of the two greatest diameters, imaging studies, surgical treatment, post-operative length of stay (LOS), and post-operative follow-up. Results : The results revealed a similar incidence in both genders (43 males vs. 39 females) with a median age of 55.79 years. The most frequently described symptom was pain (59.76%). Thirteen cases were false aneurysms and 69 were true aneurysms. The mean greatest diameter was 9.90 cm. The CT scan was the most utilized imaging study (80.49%). Open, endovascular, and hybrid surgery were performed in 47, 26, and 9 patients, respectively, with complication rates of 14.89%, 23.08%, and 22.22% occurring for each treatment. The post-operative LOS was 12.29 days, 2.36 days, and 5 days, respectively. The median follow-up was 17.28 months overall. No recanalization was observed after endovascular procedures during the follow-up period. Conclusions : The dimensional criterion to define SAAs and SAPs as giant was most frequently that at least one diameter was ≥ 5 cm. The CT scan was the most frequently utilized radiological study to diagnose giant SAAs and SAPs. Finally, endovascular procedures, open surgeries, and hybrid treatments presented similar post-operative complication rates. The post-operative LOS was lower for the endovascular group, and the follow-up period did not show aneurysm recanalization in any patients.

Background : Performing percutaneous coronary intervention (PCI) and endovascular aneurysm repair (EVAR) at the same time represents a groundbreaking development in the multidisciplinary treatment of cardiovascular disease. This combined PCI-EVAR approach bridges a critical gap by offering treatment for patients who have both coronary artery disease and aortic aneurysms. This innovative strategy exemplifies the evolving landscape of cardiovascular care, providing a new solution for complex clinical situations that previously required separate procedures. Methods : Six patients with critical coronary artery lesions and asymptomatic infrarenal aortic aneurysms (AAAs) ≥ 6 cm diameter, as well as one patient with critical coronary artery lesions and endoleak type 1A with aneurysms ≥ 6 cm, underwent simultaneous coronary artery revascularization through percutaneous intervention (PCI) and endovascular aneurysm repair (EVAR). The occurrence of any intraoperative or postoperative complication was considered to be the primary endpoint of the study, including the abortion or failure of either PCI or EVAR, bleeding requiring a conversion to open surgical procedures, the failure of local anesthesia, postoperative myocardial or lower limb ischemia, and a postoperative serum creatinine level of >125 mmol/L or of >180 mmol/L in patients affected by chronic renal failure. The overall length of the procedure, X-ray exposure, the quantity of iodine contrast medium administered, and the length of recovery were considered to be secondary endpoints. Results : Postoperative complications included two episodes of acute renal failure in the two patients already affected by chronic renal failure, which were easily resolved with adequate daily hydration and the elimination of nephrotoxic drugs. In no cases did cardiac ischemia or lower limb ischemia occur. The average procedure duration was 198 min (range: 180-240 min), the average fluoroscopy duration was 41.7 min (range: 35-50 min), the average amount of iodinated contrast medium was 34.8 mL (range: 30-40 mL), and the mean length of hospitalization was 2.7 days (range: 2-5 days). Conclusions : In selected patients, this surgical approach has demonstrated safety, reduced hospitalization times, minimized risks associated with complications from the untreated condition if procedures were performed at different times, and facilitated the effective management of intraoperative complications due to the presence of a multidisciplinary team. However, the limited number of patients necessitates further research.

Feline chronic enteropathies (FCE), include food-responsive-enteropathy (FRE), inflammatory bowel disease (IBD), and low-grade intestinal T-cell lymphoma (LGITL), and are common causes of chronic gastrointestinal signs in cats. Distinguishing between different subgroups of FCE can be challenging due to the frequent overlap of anamnestic, clinical, and laboratory data. While dysregulation in lipid metabolism has been reported in humans and dogs with chronic IBD, similar changes in cats are not yet completely understood. Assessing the fatty acid (FA) profile of red blood cell (RBC) membranes offers a valuable method for evaluating the quantity and quality of structural and functional molecular components in the membranes. Therefore, this study aimed to examine the FA composition of RBC membranes in FCE in comparison to healthy cats (HC). Gas-chromatography was used to quantitatively analyze a cluster of 11 FA, and based on these results, parameters of lipid homeostasis and enzyme activity indexes were calculated. A total of 41 FCE cats (17 FRE, 15 IBD, 9 LGITL) and 43 HC were enrolled. In FCE cats, the values of docosapentaenoic acid (p = 0.0002) and docosahexaenoic acid (p = 0.0246), were significantly higher, resulting in an overall increase in ω-3 polyunsaturated fatty acids (PUFA) (p = 0.006), and that of linoleic acid (p = 0.0026) was significantly lower. Additionally, FCE cats exhibited an increased PUFA balance (p = 0.0019) and Δ6-desaturase index (p = 0.0151), along with a decreased ω-6/ω-3 ratio (p = 0.0019). No differences were observed among cats affected by FRE, IBD and LGITL. Like humans and dogs, the results of this study indicate that FCE cats also display changes in their FA lipid profile at the level of the RBC membrane. The non-invasive analysis of RBC membrane shows promise as a potential tool for gaining a better understanding of lipid imbalances in this disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Crisi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ocrelizumab (OCR), an anti-CD20 monoclonal antibody, is approved for treating relapsing remitting (RR) and primary progressive (PP) multiple sclerosis (MS). The standard interval dosing (SID) regimen requires intravenous infusions every six months. Experience of extended dosing due to COVID-19 pandemic-related issues suggests that this strategy may provide comparable efficacy while reducing treatment burden and healthcare costs. This study aimed to evaluate clinical effectiveness, changes in B- and T-cell count, and immunoglobulin dynamics associated with extended interval dosing (EID) of ocrelizumab in a real-world setting. We retrospectively included RRMS or PPMS patients treated with OCR that had already received two OCR cycles and with at least 6 months of follow up after the last infusion. EID was defined as a ≥4 weeks delay compared to SID. Clinical outcomes were occurrence of relapses, MRI activity, 6-months confirmed disability progression (CDP) and their combination (No Evidence of Disease Activity, NEDA-3). We also evaluated changes in CD19+ B cell count, CD4+ and CD8+ T cell count, immunoglobulin titers, and occurrence of hypogammaglobulinemia (hypo-Ig). Frequency tests, multivariate regression models, and survival analysis were applied as appropriate. We analyzed data on 93 subjects (75.3% RRMS) for a total of 389 infusions (272 SID, 117 EID). Clinical and MRI activity, CDP, and NEDA 3 did not significantly differ between EID and SID. EID was associated with lower rates of B-cell depletion. T-cell dynamics and incidence of hypo-Ig were comparable following EID and SID. Hypo-IgG at index infusion was associated with further occurrence of hypo-IgG; male sex and hypo-IgM at index infusion were independently associated with hypo-IgM. In conclusion, OCR EID does not impact MS clinical and radiological outcomes, although it interferes with B-cell dynamics. These findings provide support for a tailored schedule of OCR in MS.

During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory cells in this tissue, identifying a relatively homogeneous population of the epithelial cells which are responsible for producing the majority of seminal fluid. We also define the immune cell populations - including large populations of macrophages, dendritic cells, T cells, and NKT cells - which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.

Diverticular disease is common in Western countries; one-third of patients with diverticular disease develop diverticulitis during their lifetime of whom 5% may experience serious complications. We describe a rare complication of diverticulitis: a duodeno-colic fistula in a patient with an elongated sigmoid colon (dolicosigma). The patient complained of abdominal pain, diarrhea, weight loss, and feculent vomiting. Radiological studies and gastroscopy demonstrated a fistula between the second portion of the duodenum and the sigmoid colon. Curative surgery cured the fistula and completely resolved its associated signs and symptoms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The increasing knowledge about multiple sclerosis (MS) pathophysiology has reinforced the need for an improved description of disease phenotypes, connected to disease biology. Growing evidence indicates that complex diseases constitute phenotypical and genetic continuums with "simple," monogenic disorders, suggesting shared pathomechanisms., Objectives: The objective of this study was to depict a novel MS phenotypical framework leveraging shared physiopathology with Mendelian diseases and to identify phenotype-specific candidate drugs., Methods: We performed an enrichment testing of MS-associated variants with Mendelian disorders genes. We defined a "MS-Mendelian network," further analyzed to define enriched phenotypic subnetworks and biological processes. Finally, a network-based drug screening was implemented., Results: Starting from 617 MS-associated loci, we showed a significant enrichment of monogenic diseases ( p  < 0.001). We defined an MS-Mendelian molecular network based on 331 genes and 486 related disorders, enriched in four phenotypic classes: neurologic, immunologic, metabolic, and visual. We prioritized a total of 503 drugs, of which 27 molecules active in 3/4 phenotypical subnetworks and 140 in subnetwork pairs., Conclusion: The genetic architecture of MS contains the seeds of pathobiological multiplicities shared with immune, neurologic, metabolic and visual monogenic disorders. This result may inform future classifications of MS endophenotypes and support the development of new therapies in both MS and rare diseases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.S. receives research support and has received fees as speaker from Sanofi, Biogen, Roche, Novartis, Bayer Schering, and Merck Serono. M.C.B. has received fees as speaker from Sanofi, Biogen, Roche, Merck Serono, and Novartis. 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.

Vinorelbine (VRL), a semi-synthetic vinca alkaloid commonly used in humans with advanced lung cancer, reaches high concentrations in the lung tissue, has proven antineoplastic activity and a low toxicity profile in dogs. Treatment-naïve, client-owned dogs with a cyto/histological diagnosis of advanced pulmonary carcinoma, selected from a laboratory database and previously subjected to imaging, were enrolled in the study. Vinorelbine (15 mg/m 2 ) was administered weekly for 4 weeks and then fortnightly until progressive disease was documented. Staging work-up was repeated by means of diagnostic imaging after the fourth VRL (i.e., 28 days) and monthly thereafter; response to treatment was evaluated according to the RECIST. Toxicity was graded following the VCOGC group. Ten dogs met the inclusion criteria. Partial response was documented in eight dogs. Median time to progression was 88 days (range: 7-112) and median survival time for all dogs was 100 days (range 7-635). The most common side effect was neutropenia. The main limitations of the study were the absence of histological diagnosis in eight cases and the limited number of treated dogs. VRL is well tolerated with an adequate toxicity profile and may be useful in the management of advanced lung tumours if used as a first-line treatment strategy.

This report describes the pathological findings in a 15-year-old spayed female Domestic Shorthaired cat with a pulmonary adenocarcinoma characterized by feline lung-digit syndrome (FLDS) and unusual tongue metastasis. Felis catus papillomavirus type 3 (FcaPV-3) DNA was amplified from the lingual sample but not from samples of the pulmonary mass or digital or splenic metastatic lesions, indicating the presence of FcaPV-3 in the oral cavity but not suggesting a role for FcaPVs in tumour pathogenesis. FLDS is a clinical entity in which primary lung tumours present because of metastatic digital lesions. In humans, tongue metastasis may be a rare initial presentation of lung cancer, whereas, to the best of our knowledge, tongue metastasis of feline tumours has not been reported. Although lingual metastases are rare, the present findings serve to remind clinicians that metastatic manifestations of primary lung tumours in cats may involve multiple extrapulmonary sites, including the tongue., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The analysis of knuckle creases is part of the multifactorial assessment of digital images of the hand used to assist in the identification of perpetrators captured in images depicting child sexual abuse and other offending behaviours. To quantify the impact of finger flexion on the appearance of the dorsal knuckle creases associated with the proximal interphalangeal joint (PIP) joint in digital images, the collection of knuckle crease images, at different points of flexion, was facilitated through an app-based Citizen Science project, Knuckle Down ID. A method of knuckle crease classification was adapted to assess the images collected and was used to assess the impact of finger flexion on the frequency of different knuckle crease features observed in manual analysis. The results show that the adapted methodology had good intra-observer repeatability when the entire method was assessed (ICC.81). Specifically, the recording of the knuckle crease features had good inter-observer reliability (ICC.99) whereas the tracing aspect of the methodology was less repeatable (DSC of whole trace.24). The impact of flexion on the recorded frequency of knuckle creases was shown to be significant (p = .00). However, when comparing two hands at different points of flexion, only when comparing fingers held at 0⁰ vs 45⁰ (p = .04) as well as fingers held at 90⁰ vs any other finger position was the differences in the knuckle crease feature frequencies significant (p = .00). The comparison of knuckle crease image pairs at 20⁰ of hyperflexion vs 0⁰ (p = .10) and 20⁰ of hyperflexion vs 45⁰ (p = .09) showed that the difference in knuckle crease feature frequencies was not significant. This has implications for examiners and improves understanding of the limitations of the 1:1 comparison of knuckle creases in casework evidence in which perpetrator's hands are unconstrained., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Interferon-beta (IFN-β) for Multiple Sclerosis (MS) is turning 30. The COVID-19 pandemic rejuvenated the interest in interferon biology in health and disease, opening translational opportunities beyond neuroinflammation. The antiviral properties of this molecule are in accord with the hypothesis of a viral etiology of MS, for which a credible culprit has been identified in the Epstein-Barr Virus. Likely, IFNs are crucial in the acute phase of SARS-CoV-2 infection, as demonstrated by inherited and acquired impairments of the interferon response that predispose to a severe COVID-19 course. Accordingly, IFN-β exerted protection against SARS-CoV-2 in people with MS (pwMS). In this viewpoint, we summarize the evidence on IFN-β mechanisms of action in MS with a focus on its antiviral properties, especially against EBV. We synopsize the role of IFNs in COVID-19 and the opportunities and challenges of IFN-β usage for this condition. Finally, we leverage the lessons learned in the pandemic to suggest a role of IFN-β in long-COVID-19 and in special MS subpopulations., Competing Interests: MS receives research support and has received fees as speaker from Sanofi, Biogen, Roche, Novartis, Bayer Schering, and Merck Serono. VR, GB and GR 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. AA and CR are employees of Merck Serono S.p.A., Rome, Italy, an affiliate of Merck KGaA, Darmstadt, Germany., (Copyright © 2023 Bellucci, Albanese, Rizzi, Rinaldi, Salvetti and Ristori.)

The development of tools to manipulate the mouse genome, including knockout and transgenic technology, has revolutionized our ability to explore gene function in mammals. Moreover, for genes that are expressed in multiple tissues or at multiple stages of development, the use of tissue-specific expression of the Cre recombinase allows gene function to be perturbed in specific cell types and/or at specific times. However, it is well known that putative tissue-specific promoters often drive unanticipated 'off-target' expression. In our efforts to explore the biology of the male reproductive tract, we unexpectedly found that expression of Cre in the central nervous system resulted in recombination in the epididymis, a tissue where sperm mature for ~1-2 weeks following the completion of testicular development. Remarkably, we not only observed reporter expression in the epididymis when Cre expression was driven from neuron-specific transgenes, but also when Cre expression in the brain was induced from an AAV vector carrying a Cre expression construct. A surprisingly wide range of Cre drivers - including six different neuronal promoters as well as the adipose-specific Adipoq Cre promoter - exhibited off-target recombination in the epididymis, with a subset of drivers also exhibiting unexpected activity in other tissues such as the reproductive accessory glands. Using a combination of parabiosis and serum transfer experiments, we find evidence supporting the hypothesis that Cre may be trafficked from its cell of origin to the epididymis through the circulatory system. Together, our findings should motivate caution when interpreting conditional alleles, and suggest the exciting possibility of inter-tissue RNA or protein trafficking in modulation of reproductive biology., Competing Interests: VR, KM, KD, FS, BB, SK, AT, OR No competing interests declared, AW is a scientific advisor for Kate Therapeutics and Frequency Therapeutics and a cofounder, advisor, and holder of private equity in Elevian, Inc, which also provides sponsored research to the Wagers Lab. Is a co-inventor on patents that include the use of AAVs for research and therapeutic applications (application numbers: 17/614,327, 63/332,655, 17/743,444, 63/344,328, 63/388,920), (© 2023, Rinaldi et al.)

Early and accurate visualisation of a crime scene is highly desirable such that a rapid, agile, and informed decision-making process can be undertaken by an investigative team. We present a new standard operating procedure for imaging an indoor scene using DSLR cameras conventionally used by crime scene investigators and examiners. The standard operating procedure (SOP) enables the systematic photography of indoor spaces in such a way that the Structure from Motion (SfM) photogrammetry technique can be implemented, allowing the scene to be recreated in Virtual Reality (VR). To demonstrate the method's validity, we compare two VR-rendered representations of an example scene using (a) photographs taken by an experienced crime scene examiner using a conventional photographic method and (b) photographs taken by a novice photographer following the developed SOP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Pharyngoplasty represents one of the most widely performed surgical procedures for the treatment of obstructive sleep apnea (OSA) in the presence of palate-oropharyngeal collapse. The learning curve for pharyngoplasties is steep and success is conditional on the correct use of the sutures and the careful application of the surgical steps in a narrow surgical field. The use of synthetic models may be conveniently and safely employed for hands-on surgical practice in pharyngoplasties, especially when fresh frozen cadaveric specimens are not available. We present the "Pharyngolab", a new simulator for pharyngoplasties., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Feline calicivirus (FCV) infection in cats can led to several diverse clinical presentations, ranging from mild upper respiratory signs to virulent systemic disease. Herein, we report a paw and mouth disease case in a 7-year-old household cat due to an FCV infection. An asymptomatic cat living in the same household was also infected with FCV. Clinical and pathological investigations were combined with the molecular and phenotypical characterization of the FCV strains. The RNA of the FCV was detected using qualitative and quantitative reverse transcription (RT)-PCR assays, and FCV antigen was confirmed by immunohistochemistry. After the whole genome analysis, the strains detected in the two cats appeared to be genetically diverse from FCVs previously detected in association with paw and mouth disease and with virulent systemic disease. Interestingly, the isolates obtained in this study were resistant to low pH conditions and slightly susceptible to bile salts, but they were susceptible to a trypsin treatment, revealing a phenotype pattern that is different from that which has been observed for respiratory FCVs.

Cannabinoid receptors (CB1 and CB2) belong to endocannabinoid system (ECS), which is also composed from endocannabinoids and the enzymatic systems involved in their biosynthesis and degradation. The expression of CB1 and CB2 have been previously identified in normal canine mast cell and in atopic dermatitis. Canine cutaneous mast cell tumours (cMCTs) are among the most common cutaneous neoplasms in dogs and have a highly variable clinical behaviour. Expression of CB1-CB2 was assessed by means of immunohistochemistry in thirty-seven dogs (from 2019 to 2021) with proven histological diagnosis of cMCT. Dogs were divided in two groups according to the Kiupel's grading system: high-grade (HG) cMCT and low-grade (LG) cMCT. A semiquantitative (score 0-3) and quantitative assessment of immunoreactivity (IR) was performed for each case. Our results show that there CB1 and CB2 are highly expressed in LG- cMCT, in contrast to HG- cMCT., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Vaccinations provided the most effective tool to fight the SARS-CoV-2 pandemic. It is now well established that COVID-19 vaccines are safe for the general population; however, some cases of rare adverse events following immunization have been described, including CNS Inflammatory Demyelinating Events (CIDEs). Although observational studies are showing that these events are rare and vaccines' benefits highly outweigh the risks, collecting and characterizing post-COVID-19 vaccine CIDEs might be relevant to single out potential risk factors and suggest possible underlying mechanisms., Methods: Here we describe six CIDEs, including two acute transverse myelitis (ATM), three multiple sclerosis (MS), and one neuromyelitis optica spectrum disorder (NMOSD), occurring between 8 and 35 days from a COVID-19 vaccine. Moreover, we performed a systematic literature search of post-COVID-19 vaccines CIDEs, including ATM, ADEM, MS, and NMOSD/MOGAD, published worldwide between December 2020 and December 2021, during 1 year of the vaccination campaign. Clinical/MRI and CSF/serum characteristics were extracted from reviewed studies and pooled-analyzed., Results: Forty-nine studies were included in the systematic review, reporting a total amount of 85 CIDEs. Considering our additional six cases, 91 CIDEs were summarized, including 24 ATM, 11 ADEM, 47 MS, and nine NMOSD/MOGAD. Overall, CIDEs occurred after both mRNA ( n = 46), adenoviral-vectored ( n = 37), and inactivated vaccines ( n = 8). Adenoviral-vectored vaccines accounted for the majority of ADEM (55%) and NMOSD/MOGAD (56%), while mRNA vaccines were more frequent in MS new diagnoses (87%) and relapses (56%). Age was heterogeneous (19-88) and the female sex was prevalent. Time from vaccine to symptoms onset was notably variable: ADEM and NMOSD/MOGAD had a longer median time of onset (12.5 and 10 days) compared to ATM and MS (6 and 7 days) and further timing differences were observed between events following different vaccine types, with ATM and MS after mRNA-vaccines occurring earlier than those following adenoviral-vectored ones., Conclusion: Both the prevalence of vaccine types for certain CIDEs and the heterogeneity in time of onset suggest that different mechanisms-with distinct dynamic/kinetic-might underly these events. While epidemiological studies have assessed the safety of COVID-19 vaccines, descriptions and pooled analyses of sporadic cases may still be valuable to gain insights into CIDE's pathophysiology., 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 Rinaldi, Bellucci, Buscarinu, Reniè, Marrone, Nasello, Zancan, Nistri, Palumbo, Salerno, Salvetti and Ristori.)

Introduction: Oropharyngeal surgery for Obstructive Sleep Apnea (OSA) has evolved from a radical excision of "redundant" soft tissue for the enlargment of the airway to a minimally invasive reconstruction to fulfill both preservation of pharyngeal function and improvement of sleep apnea. Recently, Alianza surgical technique has been successfully introduced as a new, non-resective procedure aimed to treat concentric pharyngeal collapse at the velum using Barbed Sutures. The aim of this study was to show the effectiveness and safety of Alianza technique as standalone surgical treatment in selected patients with moderate-severe OSA and concentric pharyngeal collapse that refused or did not tolerate Continuous Positive Airway Pressure therapy., Materials and Methods: Effectiveness of the surgical procedure was assessed by means of the Epworth Sleepiness Scale (ESS), Home Sleep Test, and a 0-10 snoring VAS., Results: At the end of our selection process, 26 patients were enrolled, with a mean age of 52.7 ± 9.2 years, that undergone Alianza tecnique. There was a statistically significant reduction in mean post-operative apnea-hypopnea indexes (34.1 ± 11.5-16.3 ± 10.3; p  <0.01), mean oxygen desaturation index (29.0 ± 14.5-13.1 ± 9.2; p < 0.01), and mean ESS scores (12.1 ± 5.8 and 5.8 ± 4.4; p < 0.01).There was also a significant decrease in mean post-operative snoring VAS scores (7.85 ± 1.23 vs 3.2 ± 1.7, p < 0.01). There were no major complications., Conclusions: Our preliminary results suggest that Alianza technique is a safe and repeatable surgery. Further studies on a larger scale are needed to confirm these encouraging data supporting the role of Alianza alone or in OSA multilevel surgery in selected OSA patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mast cell tumour (MCT) is a common cutaneous and subcutaneous neoplasia in dogs. It can metastasise to lymph nodes (LNs), and this adversely affects the prognosis and treatment. The study aims to evaluate the SLN mapping of MCTs with radiographic indirect lymphography. Dogs that underwent clinical staging were prospectively enrolled. Lipiodol was injected around the MCT or the surgical scar. After 24 h, LNs that picked up contrast were radiographically assessed. Twenty-six dogs with 29 MCTs were included. MCTs were confirmed histologically, while SLNs were evaluated either by cytology and/or histology. SLNs were detectable in 23 dogs with 26 MCTs. Lymphatic vessels were visible in 19 MCTs. In nine MCTs, at least two SLNs picked up contrast. In particular, seven MCTs involved two SLNs, and two MCTs involved three different SLNs. In nine MCTs, at least a SLN was metastatic. This study indicates that the lymph drainage pattern of the MCTs may be different for each MCT, and more than one SLN can be involved. Indirect lymphangiography with Lipiodol allowed the detection of the SLN in 90% of MCTs. This provided clinically relevant information to remove the LN and stage the patient.

Clinical staging is a fundamental step in the clinical assessment of canine cutaneous mast cell tumor (cMCT), and it is recommended to evaluate the tumor draining lymph node (eTDLN), perform diagnostic imaging, and fine needle aspiration (FNA) of the spleen and liver to determine the presence of metastatic disease, thereby refining the prognosis. The aim of this retrospective study was to evaluate the prevalence of splenic and hepatic involvement in newly diagnosed canine low-grade cMCT (Patnaik grade I-II, Kiupel low-grade). Medical records of dogs that underwent a clinical staging work-up and surgical excision for a low-grade cMCT between December 2019 and December 2021 were reviewed at five veterinary centers. Only dogs with a histological diagnosis of low-grade cMCT, FNA or histology of the eTDLN, FNA of the spleen and liver, and one year of follow up were included. One hundred and thirty-six dogs met the inclusion criteria. Only 1 out of 136 dogs (0.7%) had the presence of visceral metastases at diagnosis, suggesting that the prevalence of visceral metastases in low-grade cMCT is extremely low. The results of this study are consistent with previous literature and suggest that after a diagnosis of low-grade cMCT, cytology of visceral organs may not represent an essential step in the clinical staging work-up.

Osteoid osteoma (OO) is a primary benign tumor that accounts for up to 3% of all bone tumors. The cervical spine is less affected by OOs, and very few cases of C2 OOs have been reported in the literature, both in adults and children. Surgery may be required in case of functional torticollis, stiffness, and reduced range of motion (ROM) due to cervical OOs refractory to medical therapy. Several posterior and anterior surgical techniques have been described to remove C2 OOs. In particular, anterior approaches to the cervical spine represent the most used surgical route for treating C2 OOs. We describe the first case of OO of the odontoid process removed through a transnasal endoscopic approach with the aid of neuronavigation in a 6-year-old child. No intraoperative complications occurred, and the post-operative course was uneventful. The patient had immediate relief of neck pain and remained pain-free throughout the follow-up period, with complete functional recovery of the neck range of motion (ROM). In this case, based on the favorable anatomy, the transnasal endoscopic approach represented a valuable strategy for the complete removal of an anterior C2 OO without the need for further vertebral fixation since the preservation of ligaments and paravertebral soft tissue.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS), clinically defined by an acute polyfocal neurological syndrome usually with monophasic course. ADEM often occurs after infections, but 5%-10% of cases are preceded by vaccinations. Several cases of ADEM have been described after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas no case has been reported after adenovirus-vectored or mRNA COVID-19 vaccine administration. Here we describe a case of ADEM presenting 2 weeks after receiving the first dose of ChAdOx1 nCoV-19 vaccine. Patient clinical/magnetic resonance imaging (MRI) status spontaneously improved and rapidly resolved with corticosteroids. A 4-month follow-up showed complete recovery and no relapses.

A clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. Our previous investigations suggested heterogeneity in etiology components and stochasticity in the interaction between genetic and non-genetic factors. To find a unifying model for this evidence, we focused on the recently mapped transient transcriptome (TT), that is mostly coded by intergenic and intronic regions, with half-life of minutes. Through a colocalization analysis, here we demonstrate that genomic regions coding for the TT are significantly enriched for MS-associated GWAS variants and DNA binding sites for molecular transducers mediating putative, non-genetic, determinants of MS (vitamin D deficiency, Epstein Barr virus latent infection, B cell dysfunction), indicating TT-coding regions as MS etiopathogenetic hotspots. Future research comparing cell-specific transient and stable transcriptomes may clarify the interplay between genetic variability and non-genetic factors causing MS. To this purpose, our colocalization analysis provides a freely available data resource at www.mscoloc.com ., (© 2022. The Author(s).)