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Introduction Social cognition and skill deficits have been largely documented in subjects with schizophrenia (SCZs), and have a strong influence on the functional outcome of these subjects. Different behavioural interventions have been developed to target and improve social skills in SCZs. For instance, the Social Skills Training (SST) focuses on improving communication skills and assertiveness to facilitate disease management, independent living and real-life functioning of SCZs. SST seems also to have an impact on negative symptoms and social cognition. Objectives The study aims to evaluate the effectiveness of SST in improving social cognition and negative symptoms in SCZs. Methods The sample included 8 chronic SCZs (age between 18 and 60), who completed 6 months of SST. The intervention consisted of two weekly group sessions of 2 hours each. We assessed psychopathology, neurocognition, real-life functioning, functional capacity and social cognition at baseline and after training. Paired samples t-tests were performed to evaluate the differences of the variables considered after completing the treatment. Results Significant improvements in negative symptoms (p

Introduction Cognitive deficits are considered a key feature of schizophrenia due to their substantial influence on the psychosocial outcome of subjects affected by this disorder. Several studies showed that moderate to severe cognitive impairments, including dysfunctions of social cognition, are already present during the early phases of the illness, in subjects with first-episode psychosis (FEPs). Psychosocial interventions, such as social skill training (SST), could therefore be implemented already upon occurrence of the first episode of psychosis to improve the overall functional outcome of schizophrenia, which represents to date an unmet need in the care of these patients. Objectives The study aims to evaluate the use of SST to enhance social skills and real-life functioning in FEPs. Methods The sample included 7 FEPs (age between 15 and 40). The SST intervention included 30 sessions lasting 2 hours and delivered twice a week. Psychopathology, neurocognition, real life functioning, functional capacity and social cognition were assessed at baseline ad after training. Paired samples t-tests were performed to evaluate the effects of the intervention. All subjects were treated with second generation antipsychotics. Results Significant improvements were observed in negative symptoms, social cognition, problem solving skills, as well as in global functioning (all p

Abstract Background Autophagy is a highly regulated process involving the bulk degradation of cytoplasmic macromolecules and organelles in mammalian cells via the lysosomal system. Dysregulation of autophagy is implicated in the pathogenesis of many neurodegenerative diseases and integrity of the autophagosomal - lysosomal network appears to be critical in the progression of aging. Our aim was to survey the expression of autophagy markers and Amyloid precursor protein (APP) in aged bovine brains. For our study, we collected samples from the brain of old (aged 11–20 years) and young (aged 1–5 years) Podolic dairy cows. Formalin-fixed and paraffin embedded sections were stained with routine and special staining techniques. Primary antibodies for APP and autophagy markers such as Beclin-1 and LC3 were used to perform immunofluorescence and Western blot analysis. Results Histologically, the most consistent morphological finding was the age-related accumulation of intraneuronal lipofuscin. Furthermore, in aged bovine brains, immunofluorescence detected a strongly positive immunoreaction to APP and LC3. Beclin-1 immunoreaction was weak or absent. In young controls, the immunoreaction for Beclin-1 and LC3 was mild while the immunoreaction for APP was absent. Western blot analysis confirmed an increased APP expression and LC3-II/LC3-I ratio and a decreased expression of Beclin-1 in aged cows. Conclusions These data suggest that, in aged bovine, autophagy is significantly impaired if compared to young animals and they confirm that intraneuronal APP deposition increases with age.

Several reports have indicated that canine MCTs express a mutated form of a tyrosine kinase receptor, namely KIT, that is involved in abnormal mast cell growth and differentiation. Currently, the post-surgical prognosis for MCTs is related to three different KIT immunohistochemical expression patterns. However, to our knowledge, there are few studies specifically exploring the efficacy of treatment with tyrosine kinase inhibitors related to KIT staining pattern. The purpose of this study was to investigate the potential theragnostic role of KIT expression patterns by studying their correlation to the overall survival and progression-free survival in dogs treated with only tyrosine kinase inhibitors immediately after surgery. We selected 66 cases of canine cutaneous MCTs with complete clinical background. A statistical analysis was performed to assess the overall survival status. Our data suggest an important role of KIT in the etiopathogenesis of canine MCTs and indicate that the anomalous cytoplasmatic distribution of KIT is potentially related to a lower efficacy of tyrosine kinase inhibitors, thus providing a significant prognostic information about the treatment outcome.

Gunshot wound morphology and gunshot residues (GSRs) evaluation have been poorly investigated in veterinary forensic pathology. The aims of the present study were to assess the gunshot wound morphology in animals and evaluate the detectability of lead deriving from GSRs using colorimetric techniques. To these aims, cadavers were divided into four different groups. Group A comprised eight animals who died from firearm-related injuries, while groups B and C included dog limbs shot using different shooting ranges; group D comprised dog limbs stabbed with a screwdriver. Morphological analysis was performed on all entry gunshot wounds. Lead residues were investigated using a Bullet Hole Testing Kit ( BTK ) and Rhodizonate Sodium histochemical staining ( NaR-s ). Gunshot wounds in group A showed an abrasion ring associated with hemorrhages and tissue necrosis. Groups B and C showed injuries related to the shooting range. NaR-s showed positive results in both animals that died from gunshot wounds and experimentally shot limbs. However, the number of positive cases and the pattern of lead distribution varied with the shooting range. Positive results by BTK were limited to close-contact shots in group B limbs. Our results suggest that both pathological examination and NaR tests represent valid tools for investigating gunshot wounds in veterinary pathology.

Cystic echinococcosis (CE), caused by the tapeworm Echinococcus granulosus, is a zoonotic parasitic disease that still represents a serious threat to human and animal health worldwide. The Mediterranean basin is recognized as one of the major hotspots of CE due to several factors, including the presence of diverse intermediate host species as well as socio-economic and cultural conditions of local communities. This study aims to take a closer look at epidemiological data on CE in the Mediterranean area and assess the knowledge attitudes and practices of shepherds towards this disease in four countries (Algeria, Greece, Italy and Tunisia), highly endemic for CE, with the final goal of identifying highly endemic risk areas and practices in use which might potentially allow the persistence of E. granulosus infection in these areas. To update the epidemiological scenario of CE in Mediterranean areas, a comprehensive review of peer-reviewed literature on CE prevalence data published during the 2017-2023 period was carried out and, through a geographical information system (GIS), a map displaying the current CE distribution in the Mediterranean area was generated. In addition, a questionnaire survey was conducted through in-depth interviews of the farmers to collect information on their management system as well as knowledge attitudes and practices towards CE. From the farmer-participatory survey some risky practices emerged including the non-regular deworming of dogs or the use of ineffective drugs or dosing, as well as the provision of uncooked animal viscera to dogs. Finally, lower levels of knowledge and awareness of the disease was observed among farmers from North Africa compared with those of European countries. In conclusion, the results obtained highlight that CE is still a very serious problem in Mediterranean areas and increased efforts are needed to promote awareness among farmers and to turn research results into policy in order to reduce the spread of this disease, according to the One Health perspective., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Fire-related deaths are usually a consequence of carbon monoxide (CO) poisoning or shock from thermal injuries. In humans, high levels of carboxyhemoglobin (COHb) concentrations in the blood can support a diagnosis of CO poisoning. In veterinary medicine, few studies investigated the pathological changes and blood COHb% in fire victims, and no data are available on post-mortem changes in blood gas composition due to fire. This study aims to investigate the pathological changes and COHb levels in both animal victims of fire and cadavers experimentally exposed to fire. For this purpose, dogs were selected and subdivided into three groups. Group A comprised 9 adult dogs, and Group B comprised 7 puppies that died under fire-related conditions. Group C was represented by 4 dog cadavers experimentally exposed to heat and smoke. A complete macroscopic, histological, and COHb evaluation were performed on each animal. Animals in Groups A and B showed cherry-red discoloration, thermal-injuries and soot deposits along the respiratory tract. Animals in Group C showed thermal injuries and soot deposits limited to the upper respiratory tract. The mean COHb% values in cadavers in Group C were lower than those observed in the other groups but higher compared to the values detected before the heat and smoke treatment. These findings suggest that both pathological changes and COHb analysis are valid tools for investigating fire-related deaths in dogs. However, the increase of COHb levels in cadavers exposed post-mortem to heat and smoke highlights how the COHb analysis should always be evaluated together with macroscopical and microscopical findings to avoid significant misjudgments in investigating fire-related fatalities in veterinary forensic practice., 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 Piegari, d’Aquino, Salanti, Russo, De Biase, Caccia, Carfora, Campobasso and Paciello.)

Cystic echinococcosis (CE), caused by the larval stage of the cestode Echinococcus granulosus, is one of the most widespread zoonoses in Mediterranean countries. Baiting not-owned dogs with praziquantel (PZQ), due to their key role in the maintaining the transmission of CE, currently appears to be the most effective way to limit the transmission of CE, as well as an important aspect to introduce for the control of this parasitic disease. Therefore, this study aims to test 3 types of PZQ-based baits by evaluating different parameters (integrity over time, attractiveness and palatability for dogs, and mechanical resistance after release to different altitudes) and the bait acceptance in field by target animals, i.e. not-owned dogs, by using camera traps. The double PZQ-laced baits (with a double layer of highly palatable chews) showed the greatest resistance in the environment while also preserving the attractiveness and palatability up to 10 days, also withstood heights of 25 m, thus resulting as the most suitable also for drone delivery. The results on the field showed that most of the baits were consumed by not-owned dogs (82.2%), while the remaining were consumed by wild boars (8.9%), foxes (6.7%), badgers (1.1%) and hedgehogs (1.1%), confirming the specific and high attractiveness of the double PZQ-laced baits for the target population and highlights how an anthelmintic baiting programme may be a viable tool for the management of E. granulosus among free-ranging dog populations in endemic rural areas.

Background and Aim: A combined microbial and cytological examination of uterine samples is the main diagnostic method for endometritis in mares. This study aimed to describe a procedure for using the same uterine cytobrush (CB) for both bacteriological and cytological evaluation., Material and Methods: The procedure consists of rolling the CB onto a sterilized glass slide immediately after collection and before the transfer into a sterile saline solution. In Experiment 1, a comparison between bacteriological results of the cotton swab (CS) and CB or pellet was made in 10 mares; in Experiment 2, bacteriological and cytological results were compared between different processing methods of CB in 28 mares; in other 6 mares, a CB was processed for cytology only, to investigate the reasons for the low cellularity of the pellet., Results: The agreement between culture results from the CB and CS was evaluated, and a comparison between the cytological data obtained by different processing methods of CB was performed. The perfect agreement between the CB and CS microbiological results was found. The described procedure enables useful diagnostic smears for cytology. Moreover, the seeding of both the tip of CB and the saline solution used for the transport produced accurate bacteriological results., Conclusion: The protocol described in this study for the use of CB for both cytological and bacteriological analysis could be used for the diagnosis of endometritis. To maximize diagnostic sample quality, cytology slides must be prepared with meticulous care in the field to preserve cellular integrity and minimize artifacts., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Prete, et al.)

Chronic kidney disease (CKD) development after acute kidney injury (AKI) involves multiple mechanisms, including inflammation, epithelial-mesenchymal transition (EMT), and extracellular matrix deposition, leading to progressive tubulointerstitial fibrosis. Recently, a central role for peroxisome-proliferator activated receptor (PPAR)-α has been addressed in preserving kidney function during AKI. Among endogenous lipid mediators, oleoylethanolamide (OEA), a PPAR-α agonist, has been studied for its metabolic and anti-inflammatory effects. Here, we have investigated OEA effects on folic acid (FA)-induced kidney injury in mice and the underlying mechanisms. OEA improved kidney function, normalized urine output, and reduced serum BUN, creatinine, and albuminuria. Moreover, OEA attenuated tubular epithelial injury, as shown by histological analysis, and decreased expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Gene expression analysis of kidney tissue indicated that OEA limited immune cell infiltration and inflammation. Moreover, OEA significantly inhibited Wnt7b and Catnb1 gene transcription and α-smooth muscle actin expression, indicating suppression of EMT. Accordingly, OEA exhibited an anti-fibrotic effect, as shown by Masson staining and the reduced levels of transforming growth factor (TGF)-β1, fibronectin, and collagen IV. Mechanistically, the nephroprotective effect of OEA was related to PPAR-α activation since OEA failed to exert its beneficial activity in FA-insulted PPAR-α -/- mice. PPAR-α involvement was also confirmed in HK2 cells where GW6471, a PPAR-α antagonist, blunted OEA activity on the TGF-β1 signalling pathway and associated pro-inflammatory and fibrotic patterns. Our findings revealed that OEA counteracts kidney injury by controlling inflammation and fibrosis, making it an effective therapeutic tool for limiting AKI to CKD progression., 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 © 2024. Published by Elsevier Masson SAS.)

Estimation of age represents a central focus in the veterinary forensic pathology field. Currently, the visual examination of the dentition and the skeletal age are the main methods to estimate the age of puppies. Nevertheless, these methods are affected by a broad range of variables. In contrast, the kidney is characterized by a specific postnatal development. In human glomerulogenesis, fetal mesangial cells change their immunohistochemical phenotypes with maturation. Therefore, we hypothesized that histological and immunohistochemical examinations of the kidney can be used together as an indirect parameter for age determination in puppies' cadavers. Forty-five puppies' cadavers were divided into five groups defined by age (Group A= 0-15 days, Group B = 16-45 days, Group C = 46-85 days, Group D = 86-105 days, Group E= 105-365 days). For each case, kidney samples were collected and processed for histopathological (for morphometrical study of the glomerulus) and immunohistochemical (for the immunolocalization of the α-SMA protein) studies. Morphometrical study allowed us to observe statistical differences in the mean glomerulus numbers per field among assessed groups. Similarly, immunohistochemical examination showed differences in SMA expression among groups. Our findings suggest a potential use of kidney morphometrical and immunohistochemical examinations together as an indirect parameter to assess the age of illegally imported puppies.

Background: Bioresorbable vascular scaffolds (BVS) were designed to improve late event-free survival compared with metallic drug-eluting stents. However, initial trials demonstrated worse early outcomes with BVS, in part due to suboptimal technique. In the large-scale, blinded ABSORB IV trial, polymeric everolimus-eluting BVS implanted with improved technique demonstrated noninferior 1-year outcomes compared with cobalt chromium everolimus-eluting stents (CoCr-EES)., Objectives: This study sought to evaluate the long-term outcomes from the ABSORB IV trial., Methods: We randomized 2,604 patients at 147 sites with stable or acute coronary syndromes to BVS with improved technique vs CoCr-EES. Patients, clinical assessors, and event adjudicators were blinded to randomization. Five-year follow-up was completed., Results: Target lesion failure at 5 years occurred in 216 (17.5%) patients assigned to BVS and 180 (14.5%) patients assigned to CoCr-EES (P = 0.03). Device thrombosis within 5 years occurred in 21 (1.7%) BVS and 13 (1.1%) CoCr-EES patients (P = 0.15). Event rates were slightly greater with BVS than CoCr-EES through 3-year follow-up and were similar between 3 and 5 years. Angina, also centrally adjudicated, recurred within 5 years in 659 patients (cumulative rate 53.0%) assigned to BVS and 674 (53.3%) patients assigned to CoCr-EES (P = 0.63)., Conclusions: In this large-scale, blinded randomized trial, despite the improved implantation technique, the absolute 5-year rate of target lesion failure was 3% greater after BVS compared with CoCr-EES. The risk period for increased events was limited to 3 years, the time point of complete scaffold bioresorption; event rates were similar thereafter. Angina recurrence after intervention was frequent during 5-year follow-up but was comparable with both devices.(Absorb IV Randomized Controlled Trial; NCT02173379)., Competing Interests: Funding Support and Author Disclosures Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, and Abbott; has served as a consultant to Daiichi-Sankyo, Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; has a daughter who is an employee at IQVIA; and his employer (Mount Sinai Hospital) receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Philips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Kereiakes has served as a consultant for Elixer Medical, Sino Medical Inc, Svelte, and Shockwave Medical Inc. Dr Gori has received speaker honoraria and research support from Abbott Vascular. Dr Metzger has received speaker honoraria and proctor fees from Abbott Vascular; has received advisory board fees from Boston Scientific; and has received speaker honoraria from Shockwave and Penumbra. Dr Stein has served a consultant for Abbott Vascular and Boston Scientific. Dr Torzewski has received speaker honoraria from Biotronik, Abbott, and Pentracor; and has received support to attend EuroPCR 2022 from Biotronik. Dr Bertolet has received speaker honoraria from Amgen, AstraZeneca, Novartis, and Shockwave Medical; and has served as a consultant to Medtronic Vascular. Drs Stockelman and West are employees of and hold equity in Abbott. Dr Choi has served as a consultant for Medtronic; and has received speaker honoraria from Shockwave. Dr Marx has served on clinical event committees for the Cardiovascular Research Foundation, including the ABSORB IV trial. Dr Spertus has served as a consultant on patient-reported outcomes and evidence evaluation for Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Myers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare; has received research grants from Bristol Myers Squibb, Abbott Vascular, and Janssen; owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire; and has served on the Board of Directors for Blue Cross Blue Shield of Kansas City. Dr Ellis has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A comprehensive pathological analysis of inbred strains is essential to define strain-specific spontaneous lesions and to understand whether a specific phenotype results from experimental intervention or reflects a naturally occurring disease. This study aimed to report and describe a novel condition affecting the skeletal muscles of an inbred C57BL/6NCrl mouse colony characterised by large sarcoplasmic vacuoles in the muscle fibres of male mice in the subsarcolemmal spaces and the intermyofibrillary network. There was no muscle weakness, loss of ambulation or cardiac/respiratory involvement. Post-mortem evaluation and histological analysis excluded the presence of pathological accumulations or lesions in other tissues and organs. Changes were seen in fibre size, with many hypotrophic and some slightly hypertrophic fibres. Histological, immunohistochemical and molecular analyses of the vacuolar content revealed dysregulation of the autophagy machinery while ruling out a morphologically similar condition marked by the accumulation of tubular aggregates.

In order to characterize the inflammatory phenotype of livers of sheep naturally infected by cystic echinococcosis, 100 sheep livers have been macroscopically assessed for the presence of hydatid cysts and sampled for histopathological and molecular analysis. According to gross and microscopic examination, livers were subsequently classified into three groups: normal liver (Group A), liver with the presence of fertile hydatid cysts (Group B), and liver with the presence of sterile hydatid cysts (Group C). Immunohistochemical analyses were accomplished using primary antibodies anti-Iba1, anti-CD3, anti-CD20, anti-TGF-β, and anti-MMP9. Finally, real-time PCR was performed in order to estimate the concentration levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin (IL)-12, IL-10, and TGF-β. Immunohistochemical analysis showed a diffuse immunolabelling of mononuclear cells for Iba-1 and TGF-β and a higher amount of CD20+ B cells compared to CD3+ T cells in both Groups B and C. The expression levels of Th-1-like immune cytokines TNF-α, INF-γ, and IL-12 did not show significant statistical differences. However, we found a significant increase in expression levels of Th-2 immune cytokines TGF-β and IL-10 in Groups B and C compared to Group A. Taken together, our findings suggest that macrophages have a predominant role in the local immune response to cystic echinococcosis. Moreover, we can speculate that Th2 immunity may be dominant, corroborating the idea that B cells are decisively essential in the control of the immune response during parasitic infection and that the immunomodulatory role of IL-10 and TGF-β may ensure the persistence of the parasite within the host.

A new therapeutic approach for enophthalmos may be retrobulbar lipofilling. This study aims to standardize the intraconal filling technique and to evaluate the degree of eyeball displacement by computed tomography (CT). Skull CT was performed on six dog cadavers before and after intraconal injection of two 5% iodinated, viscoelastic solutions, one per eye, using an ultrasound-guided supratemporal approach. The volume to be injected was calculated using formulas for retrobulbar cone anesthesia. After CT, the dogs underwent necropsy and histopathology to evaluate damages that eventually occurred to retrobulbar structures. Eyeball displacement was estimated using two CT-based methods, named M 1 and M 2 . The Wilcoxon signed-rank test revealed no significant difference between the two injected materials in both M 1 ( p > 0.99), and M 2 (lateral p = 0.84 and rostral p = 0.84 displacement). A statistically significant difference was found between the pre- and post-injection group M 1 ( p = 0.002), M 2 ( p = 0.004) for the lateral and ( p = 0.003) for rostral displacement. Although the slight eyeball displacement, the retrobulbar filling can lead to enophthalmos resolution. Compared to M 1 , the M 2 method has better-defined anatomical landmarks. Further, preclinical in vivo studies are necessary to assess retrobulbar filling efficacy and safety.

Postmortem cadaveric changes are commonly used to estimate the postmortem interval (PMI) in humans and animals. However, these modifications have been poorly investigated in animals of interest to veterinary forensic pathology. The aim of this study was to investigate the potential use of muscle proteins (desmin and dystrophin) as biomarkers for estimating the PMI in dogs. For this study, 10 dead adult dogs were evaluated for 4 days in a temperature-controlled room at 19 ± 1 °C. For each animal, at 3, 24, 48, 72, and 96 h after death, a 1 × 1 × 1 cm cube of muscle tissue was removed from the vastus lateralis and triceps brachii. Protein expression levels were analyzed by immunohistochemical examination and immunoblot analysis. The obtained results showed rapid dystrophin degradation, with complete disappearance at 72 h after death. In contrast, desmin-positive fibers and desmin protein bands detected by immunoblot were observed on all 4 days of observation. Our findings suggest the potential use of muscle proteins as biomarkers for estimating the PMI in dogs.

The aim of this study was to evaluate the frequency of neoplasms in captive wild felids in Southern Italy zoos over a 13-year period (2008-2021) and to investigate macroscopic and histologic tumor findings in these animals. A total of 24 cases were necropsied, 9 males and 15 females, with age ranging from 6 to 19 years, including 12 tigers ( Panthera tigris ), 7 leopards ( Panthera pardus ), 4 lions ( Panthera leo ), and 1 black jaguar ( Panthera onca ). Diagnosis of neoplasm was made in 14/24 cases (58.3%). Tumors diagnosed were two cholangiocarcinomas, two hemangiosarcomas of the liver, two uterine leiomyomas, a renal adenocarcinoma, an adrenal gland adenoma, a thyroid carcinoma, an oral squamous cell carcinoma, an osteoma, a meningioma, a mesothelioma, an esophageal leiomyosarcoma, a muscoloskeletal leiomyosarcoma and a thyroid adenoma. The malignant and benign tumors were 62.5 and 37.5%, respectively. Among malignant tumors, no metastasis was observed in 50% of cases; in 10% of cases metastasis involved only regional lymph nodes; and distant metastases were found in 40% of cases. Based on our findings, the liver was the most frequent primary tumor site (25%). The high rates of malignant and widely metastatic neoplasms suggest the importance of active monitoring and management of neoplasia in these threatened and endangered species., 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 d'Aquino, Piegari, Casciaro, Prisco, Rosato, Silvestre, Degli Uberti, Capasso, Laricchiuta, Paciello and Russo.)

Subjects affected by schizophrenia present significant deficits in various aspects of social cognition, such as emotion processing, social perception and theory of mind (ToM). These deficits have a greater impact than symptoms on occupational and social functioning. Therefore, social cognition represents an important therapeutic target in people with schizophrenia. Recent meta-analyses showed that social cognition training (SCT) is effective in improving social cognition in subjects with schizophrenia; however, real-life functioning is not always ameliorated. Integration of SCT with an intervention targeting metacognitive abilities might improve the integration of social cognitive skills to daily life functioning. Our research group has implemented a new individualized rehabilitation program: the Social Cognition Individualized Activities Lab, SoCIAL, which integrates SCT with a module for narrative enhancement, an intervention targeting metacognitive abilities. The present multi-center randomized controlled study will compare the efficacy of SoCIAL and treatment as usual (TAU) in subjects diagnosed with a schizophrenia-spectrum disorder. The primary outcome will be the improvement of social cognition and real-life functioning; while the secondary outcome will be the improvement of symptoms, functional capacity and neurocognition. The results of this study will add empirical evidence to the benefits and feasibility of SCT and narrative enhancement in people with schizophrenia-spectrum disorders., 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 Palumbo, Caporusso, Piegari, Mencacci, Torriero, Giuliani, Fabrazzo, Pinto and Galderisi.)

The ICD-11 chapter on mental disorders has now been finalized. The most important changes in this chapter with respect to the ICD-10, and the most significant differences from the DSM-5, have been described comprehensively.

Bisphenol A (BPA) is largely used as a monomer in some types of plastics. It accumulates in tissues and fluids and is able to bypass the placental barrier, affecting various organs and systems. Due to huge developmental processes, children, foetuses, and neonates could be more sensitive to BPA-induced toxicity. To investigate the multi-systemic effects of chronic exposure to a low BPA dose (100 μg/L), pregnant Wistar rats were exposed to BPA in drinking water during gestation and lactation. At weaning, newborn rats received the same treatments as dams until sex maturation. Free and conjugated BPA levels were measured in plasma and adipose tissue; the size of cerebral ventricles was analysed in the brain; morpho-functional and molecular analyses were carried out in the liver with a focus on the expression of inflammatory cytokines and Sirtuin 1 (Sirt1). Higher BPA levels were found in plasma and adipose tissue from BPA treated pups (17 PND) but not in weaned animals. Lateral cerebral ventricles were significantly enlarged in lactating and weaned BPA-exposed animals. In addition, apart from microvesicular steatosis, liver morphology did not exhibit any statistically significant difference for morphological signs of inflammation, hypertrophy, or macrovesicular steatosis, but the expression of inflammatory cytokines, Sirt1, its natural antisense long non-coding RNA ( Sirt1-AS LncRNA ) and histone deacetylase 1 (Hdac1) were affected in exposed animals. In conclusion, chronic exposure to a low BPA dose could increase the risk for disease in adult life as a consequence of higher BPA circulating levels and accumulation in adipose tissue during the neonatal period.

White striping (WS) is an emerging myopathy of broiler chickens characterized by white striation of muscle. Despite the recent advances, the pathomechanism underlying the WS remains elusive. The aim of this study was to characterize morphological and molecular features of WS in broiler chickens. 50 pectoralis muscles were collected from 55 days old ROSS 308 broiler chickens with a mean weight of 3.5 kg. Samples were snap frozen and analyzed by histopathology, immunohistochemistry, and immunofluorescence. Real-time-PCR was used to evaluate the expression of different cytokines. Histological lesions were observed in all examined animals, both with and without macroscopic evidence of WS. WS muscles showed endomysial and perivascular inflammatory infiltrates of macrophages and cluster of differentiation (CD)8-positive T lymphocytes with severe myofiber atrophy, necrosis, fibrosis and replacement by adipose tissue. There was diffuse sarcoplasmic and sarcolemmal overexpression of the major histocompatibility complex class I (MHC I). The severity of the histologic lesions was positively correlated with the macroscopic degree of white striations. IL-6, IL-17 and lipopolysaccharide-induced TNF-α factor (LITAF) were overexpressed in severe lesions of WS. The presence of the CD8/MHC I complexes, together with the higher expression of IL-6, IL-17 and LITAF in severe degree of WS, suggest that the immune response may be involved in the progression of this myopathy and can be consistent with a hypoxia-induced inflammatory myopathy. These results help to understand the pathomechanism of WS contributing to the reduction of economic losses and improving poultry welfare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Accelerated endothelial healing after targeted antiproliferative drug delivery may limit the long-term inflammatory response of drug-eluting stents (DESs). The novel Supreme DES is designed to synchronize early drug delivery within 4 to 6 weeks of implantation, leaving behind a prohealing permanent base layer. Whether the Supreme DES is safe and effective in the short term and can improve long-term clinical outcomes is not known., Methods: In an international, 2:1 randomized, single-blind trial, we compared treatment with Supreme DES to durable polymer everolimus-eluting stents (DP-EES) in patients with acute and chronic coronary syndromes. The primary end point was target lesion failure-a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. The trial was designed to demonstrate noninferiority (margin of 3.58%) of the Supreme DES at 12 months compared with DP-EES (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03168776)., Results: From October 2017 to July 2019, a total of 1629 patients were randomly assigned (2:1) to the Supreme DES (N=1086) or DP-EES (N=543). At 12 months, target lesion failure occurred in 57 of 1057 patients (5.4%) in the Supreme DES group and in 27 of 532 patients (5.1%) in the DP-EES group (absolute risk difference, 0.32% [95% CI, -1.87 to 2.5]; P non inferiority =0.002]. There were no significant differences in rates of device success, clinically driven target lesion revascularization, or stent thrombosis at 12 months, and the safety composite of cardiovascular death and target vessel myocardial infarction was 3.5% versus 4.6% (hazard ratio, 0.76 [95% CI, 0.46-1.25]) with Supreme DES compared with DP-EES, although rates of combined clinically and non-clinically driven target lesion revascularization at 12 months were higher with Supreme DES., Conclusions: Among patients with acute and chronic coronary syndromes undergoing percutaneous coronary intervention, the Supreme DES proved to be noninferior to the standard DP-EES. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03168776.

Perosomus elumbis (PE) is a rare congenital condition characterized by agenesis of the lumbar, sacral and coccygeal vertebrae. Perosomus elumbis has rarely been reported in literature as morphological description of singles or few cases. Here we report the first extensive description of eight cases of PE detected in two consecutive litters from the same parents of Casertana pig breed. In August 2018, eight piglets were investigated for multiple malformations. All malformed animals, but one, died in the first day of life. The survivor piglet died at 23 days of age. Pathological, radiological and cytogenetic examination was performed. Furthermore, a farm epidemiological investigation was carried out to investigate the percentage of piglets born dead or with malformations in 2018. The radiological and pathological exams showed skeletal abnormalities at the spinal cord level and visceral malformations. Cytogenetic investigations showed a normal chromosome arrangement. Finally, epidemiological investigation revealed a low prevalence of malformations in newborn pigs, equal to 0.5% of the total birth rate of the farm. Our findings report the first extensive description of PE cases in pigs and suggest an underestimation of this malformation in veterinary medicine. Our findings also suggest a specific genetic etiological basis as cause of PE in pigs and exclude chromosomal abnormalities. Further studies will be performed to confirm this hypothesis.

Leishmania spp. infection is associated with an inflammatory myopathy (IM) in dogs. The pathomechanism underlying this disorder is still elusive, however, the pattern of cellular infiltration and MHC I and II upregulation indicate an immune-mediated myositis. This study aimed to investigate the presence of autoantibodies targeting the skeletal muscle in sera of leishmania-infected dogs and individuate the major autoantigen. We tested sera from 35 leishmania-infected dogs and sera from 10 negative controls for the presence of circulating autoantibodies with indirect immunofluorescence. Immunoblot and mass spectrometry were used to identify the main target autoantigen. Immunocolocalization and immunoblot on immunoprecipitated muscle proteins were performed to confirm the individuated major autoantigen. We identified circulating autoantibodies that recognize skeletal muscle antigen(s) in sera of leishmania-infected dogs. The major antigen was identified as the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase 1 (SERCA1). We also found that canine SERCA1 presents several identical traits to the calcium-translocating P-type ATPase of Leishmania infantum . In the present study, we defined circulating anti-SERCA1 autoantibodies as part of the pathogenesis of the leishmania-associated IM in dogs. Based on our data, we hypothesize that antigen mimicry is the mechanism underlying the production of these autoantibodies in leishmania-infected dogs.

Sarcopenia is defined as the age-related loss of skeletal muscle mass, quality, and strength. The pathophysiological mechanisms underlying sarcopenia are still not completely understood. The aim of this work was to evaluate, for the first time, the expression of NLRP3 inflammasome in bovine skeletal muscle in order to investigate the hypothesis that inflammasome activation may trigger and sustain a pro-inflammatory environment leading to sarcopenia. Samples of skeletal muscle were collected from 60 cattle belonging to three age-based groups. Morphologic, immunohistochemical and molecular analysis were performed to assess the presence of age-related pathologic changes and chronic inflammation, the expression of NLRP3 inflammasome and to determine the levels of interleukin-1β, interleukin-18 and tumor necrosis factor alpha in muscle tissue. Our results revealed the presence of morphologic sarcopenia hallmark, chronic lymphocytic inflammation and a type II fibers-selective NLRP3 expression associated to a significant decreased number of immunolabeled-fibers in aged animals. Moreover, we found a statistically significant age-related increase of pro-inflammatory cytokines such as interleukin-1β and interleukin-18 suggesting the activation of NLRP3 inflammasome. Taken together, our data suggest that NLRP3 inflammasome components may be normally expressed in skeletal muscle, but its priming and activation during aging may contribute to enhance a pro-inflammatory environment altering normal muscular anabolism and metabolism.

The aim of this study was to investigate the correlation between infection by Dicrocoelium dendriticum (class Trematoda) and the animal host response in terms of macroscopic lesions, the immunopathological response, and histological changes in the livers of naturally infected sheep. Twenty-four sheep were selected on the basis of positive D. dendriticum fecal egg counts (FECs). Gross and histological injuries were scored. A positive significant association was observed between the number of adult worms recovered from the liver, FEC, macroscopic lesions, fibrosis, and bile duct hyperplasia. A significant negative association was observed among these variables and the degree of leukocyte infiltration. In addition, immunophenotyping of the inflammatory cells was carried out using primary antibodies against T cell epitopes (CD3+, CD4+, and CD8+), B cell epitopes (CD79α), and the ionized calcium-binding adapter molecule 1 (IBA-1) antigen. Independently of the severity of the D. dendriticum infection, the predominant cell population was CD3-positive and associated with lesser numbers of CD79α- and Iba-I-positive cells. An increase in Iba-1-positive cells was observed in the livers of animals with a high worm burden. Our results provide a reference basis to better understand the local immune response in sheep naturally infected by D. dendriticum in relation to the FEC and parasitic burden.

RNA is considered as an indicator of the dynamic genetic expression changes in a cell. RNAScope is a commercially available in situ hybridization assay for the detection of RNA in formalin-fixed paraffin-embedded tissue. In this work, we describe the use of RNAScope as a sensitive and specific method for the evaluation of c-KIT messenger RNA (mRNA) in canine mast cell tumor. We investigated the expression of c-KIT mRNA with RNAscope in 60 canine mast cell tumors (MCTs), comparing it with the histological grade and KIT immunohistochemical expression patterns. Our results showed an overall good expression of c-KIT mRNA in neoplastic cells if compared with control probes. We also observed a statistically significant correlation between histological grade and c-KIT mRNA expression. No correlations were found between KIT protein immunohistochemical distribution pattern and c-KIT mRNA expression or histological grade. Our results provide a reference basis to better understand c-KIT mRNA expression in canine MCTs and strongly encourage further studies that may provide useful information about its potential and significant role as a prognostic and predictive biological marker for canine MCTs clinical outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 De Biase, Prisco, Piegari, Ilsami, d'Aquino, Baldassarre, Zito Marino, Franco, Papparella and Paciello.)

Ochratoxin A (OTA) is a powerful mycotoxin found in various foods and feedstuff, responsible for subchronic and chronic toxicity, such as nephrotoxicity, hepatotoxicity, teratogenicity, and immunotoxicity to both humans and several animal species. The severity of the liver damage caused depends on both dose and duration of exposure. Several studies have suggested that oxidative stress might contribute to increasing the hepatotoxicity of OTA, and several antioxidants, including curcumin (CURC), have been tested to counteract the toxic hepatic action of OTA in various classes of animals. Therefore, the present study was designed to evaluate the protective effect of CURC, a bioactive compound with different therapeutic properties on hepatic injuries caused by OTA in rat animal models. CURC effects were examined in Sprague Dawley rats treated with CURC (100 mg/kg), alone or in combination with OTA (0.5 mg/kg), by gavage daily for 14 days. At the end of the experiment, rats treated with OTA showed alterations in biochemical parameters and oxidative stress in the liver. CURC dosing significantly attenuated oxidative stress and lipid peroxidation versus the OTA group. Furthermore, liver histological tests showed that CURC reduced the multifocal lymphoplasmacellular hepatitis, the periportal fibrosis, and the necrosis observed in the OTA group. This study provides evidence that CURC can preserve OTA-induced oxidative damage in the liver of rats.

In human medicine, "sudden death" has been defined by the World Health Organization (WHO) as a non-violent, unexpected death occurring less than 24 h from the onset of symptoms. The aims of this study were: (1) to estimate the proportional mortality ratio for "sudden and unexpected death" (SUD) in young dogs; (2) to investigate the pathological and microbiological findings in SUD cases in young dogs. For these purposes, a retrospective study of a total of 145 cases of young dead dogs was performed. For each case, we collected information about the age, medical history and the gross and microbiological findings of the animals. The results of this study found 21 cases of SUD. The most frequently observed clinical symptoms in the cases of sudden death were acute respiratory symptoms, followed by acute gastroenteric symptoms, non-specific symptoms and neurological symptoms. The evaluation of necropsy reports allowed us to observe enteritis in 18 out of 21 cases and pneumonia in seven out of 21 cases. Viral infection with Canine parvovirus type 2 was the most common cause of SUD observed. These results could provide a valuable tool for the investigation of sudden death in young dogs., Competing Interests: The authors declare no conflict of interest.

Infectious diseases are a common cause of death in young dogs. Several factors are thought to predispose young dogs to microbiological infections. Identifying the cause of death is often a challenge, and broad diagnostic analysis is often needed. Here, we aimed to determine the infectious causes of death in young dogs aged up to 1 year, examining how it relates to age (under and over 6 months), lifestyle (owned versus ownerless), breed (purebred and crossbreed), and gender. A retrospective study was conducted in a 3-year period (2015-2017) on 138 dead dogs that had undergone necropsy and microbiological diagnostics. Enteritis and pneumonia were the most commonly observed lesions. Polymicrobism was more prevalent (62.3%) than single-agent infections and associated with a higher rate of generalised lesions. Ownerless dogs showed over a three-fold higher predisposition to viral coinfections than owned dogs. Above all, canine parvovirus was the most prevalent agent (77.5%), followed by canine coronavirus (31.1%) and canine adenovirus (23.9%); ownerless pups had a higher predisposition to these viruses. Escherichia coli (23.9%), Clostridium perfringens type A (18.1%), and Enterococcus spp. (8.7%) were the most commonly identified bacteria, which mostly involved in coinfections. A lower prevalence of CDV and Clostridium perfringens type A was observed in puppies under 6 months of age. In conclusion, this study is the first comprehensive survey on a wide panel of microbiological agents related to necropsy lesions. It lays the groundwork for future studies attempting to understand the circulation of infectious agents in a determined area., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Lorena Cardillo et al.)

NLRP3 inflammasome is a multiprotein complex that can sense several stimuli such as autophagy dysregulation and increased reactive oxygen species production stimulating inflammation by priming the maturation of proinflammatory cytokines interleukin-1β and interleukin-18 in their active form. In the aging brain, these cytokines can mediate the innate immunity response priming microglial activation. Here, we describe the results of immunohistochemical and molecular analysis carried out on bovine brains. Our results support the hypothesis that the age-related impairment in cellular housekeeping mechanisms and the increased oxidative stress can trigger the inflammatory danger sensor NLRP3. Moreover, according to the recent scientific literature, we demonstrate the presence of an age-related proinflammatory environment in aged brains consisting in an upregulation of interleukin-1β, an increased microglial activation and increased NLRP3 expression. Finally, we suggest that bovine may potentially be a pivotal animal model for brain aging studies., (© 2020 Wiley Periodicals, Inc.)

Sarcocystosis is a protozoal disease affecting a wide range of animals. The aims of this study were to characterize the following in sheep: (1) the muscle pathology in Sarcocystis infection, (2) the inflammatory infiltrate and its relationship to severity of infection, and (3) immune markers expressed by parasitized muscle fibers and parasitic cysts. Skeletal muscle samples from 78 sheep slaughtered in southern Italy were snap frozen and analyzed by histopathology, immunohistochemistry, and immunofluorescence. Polymerase chain reaction (PCR) and sequencing were used for Sarcocystis species identification. All 40 muscle samples tested were PCR-positive for Sarcocystis tenella. Histologically, cysts were identified in 76/78 cases (97%), associated with an endomysial infiltrate of lymphocytes and plasma cells. The T cells were predominantly CD8+, with fewer CD4+ or CD79α+ cells. Eosinophils were absent. Notably, sarcolemmal immunopositivity for major histocompatibility complex (MHC) I and II was found in 76/78 cases (97%) and 75/78 cases (96%), respectively, both in samples with and in those without evident inflammatory infiltrate. The number of cysts was positively correlated with inflammation. In addition, MHC I was detected in 55/78 cyst walls (72%), and occasionally co-localized with the membrane-associated protein dystrophin. The findings suggest that muscle fibers respond to the presence of cysts by expression of MHC I and II. The possible role of MHC I and II in the inflammatory response and on the cyst wall is also discussed.

The detection of diatoms into the organs is considered an important "biological marker" for the diagnosis of drowning in human pathology, but it still has a high possibility for false positive results. The aims of this study were: (1) to evaluate the contribution of pathological examination in drowning cases and (2) to investigate the differences in the number and location of diatoms between animals who died in drowning and non-drowning conditions. For these purposes, 30 dead adult dogs were selected for the study and subdivided into five groups. The group A comprised six cadavers dead for drowning; the group B comprised six control animals; the groups C, D, and E comprised six animals dead for causes other than drowning and subsequently immersed in water for 24, 48, and 72 h, respectively. On each animal, a complete macroscopic and histological examination and diatom test were performed. Diatoms test and quantification were also performed on drowning mediums. Pathological findings of the animals in the group A showed pulmonary congestion, oedema, and hemorrages in the lung. However, similar injuries were also observed in control and experimentally submerged cadavers. In contrast, we observed a statistically differences between drowning animals and all experimentally submerged groups and control animals regarding diatom numbers recovered from organ tissue samples ( p < 0.05). Therefore, these findings suggest that the number of diatoms may be used as a valid tool to differentiate animals who died in drowning and non-drowning conditions, even if the latter were found in an aquatic environment., (Copyright © 2019 Piegari, De Biase, d'Aquino, Prisco, Fico, Ilsami, Pozzato, Genovese and Paciello.)

Introduction: The Computerized Interactive Remediation of Cognition - Training for Schizophrenia (CIRCuiTS) is a form of cognitive remediation therapy developed to target neurocognitive and metacognitive deficits of people with schizophrenia, which have a detrimental impact on real-life functioning. The English version of CIRCuiTS demonstrated good acceptability and feasibility. A recent randomized controlled trial provided evidence that the program improves memory and functioning, and that the impact on functional outcome is mediated by metacognition. The next steps in the development of CIRCuiTS include both: 1) the translation and adaptation of the program in different cultural settings; and 2) the demonstration of feasibility, acceptability and effectiveness of a standardized method to administer CIRCuiTS remotely., Purpose: To implement the CIRCuiTS Italian version and to assess acceptability, feasibility and efficacy of a standardized method to administer CIRCuiTS remotely., Methods: Participants were assessed at baseline and received up to 40 CIRCuiTS therapy sessions, three times a week, for about 1 hr over a three-month period. Participants were reassessed post-treatment., Results: The program demonstrated good feasibility and high acceptability when assessed by the number of dropouts and evaluation of patients' satisfaction. Participants improved in learning, speed of processing, working memory and executive control. They showed a reduction in disorganization and improvement in self-esteem, functional capacity, and real-life functioning., Conclusion: In this study, a standardized protocol for using CIRCuiTS from home was implemented. The first set of data showed in the paper is encouraging. The proposed procedure could lead to a dropout reduction while maintaining the efficacy of the program., 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. General sources of potential conflict of interest, considered unrelated to this work, include the following: Armida Mucci has received fees as consultant and/or advisor to Janssen Pharmaceutica NV, Gedeon Bulgaria, Pierre Fabre and Lundbeck; Silvana Galderisi has been a consultant and/or advisor to or has received honoraria or grants from: Millennium Pharmaceuticals, Innova Pharma - Recordati Group, Janssen Pharmaceutica NV, Sunovion Pharmarmaceuticals, Janssen-Cilag Polska Sp. z o.o., Gedeon Richter-Recordati, Pierre Fabre, Otsuka, Angelini. Davide Palumbo, Giulia Maria Giordano, Giuseppe Piegari, Carmen Aiello, Daria Pietrafesa, Nicola Annarumma, Marcello Chieffi and Matteo Cella reported no conflicts of interest., (© 2019 Palumbo et al.)

Background: Previous studies showed more adverse events with coronary bioresorbable vascular scaffolds (BVS) than with metallic drug-eluting stents (DES), although in one randomised trial angina was reduced with BVS. However, these early studies were unmasked, lesions smaller than intended for the scaffold were frequently enrolled, implantation technique was suboptimal, and patients with myocardial infarction, in whom BVS might be well suited, were excluded., Methods: In the active-controlled, blinded, multicentre, randomised ABSORB IV trial, patients with stable coronary artery disease or acute coronary syndromes aged 18 years or older were recruited from 147 hospitals in five countries (the USA, Germany, Australia, Singapore, and Canada). Enrolled patients were randomly assigned (1:1) to receive polymeric everolimus-eluting BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) with optimised implantation technique or cobalt-chromium everolimus-eluting stents (EES; Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetic status, whether patients would have been eligible for enrolment in the previous ABSORB III trial, and site. Patients and clinical assessors were masked to randomisation. The primary endpoint was target lesion failure (cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation) at 30 days, tested for non-inferiority with a 2·9% margin for the risk difference. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02173379, and is closed to accrual., Findings: Between Aug 15, 2014, and March 31, 2017, we screened 18 722 patients for eligibility, 2604 of whom were enrolled. 1296 patients were assigned to BVS, and 1308 patients were assigned to EES. Follow-up data at 30 days and 1 year, respectively, were available for 1288 and 1254 patients with BVS and for 1303 and 1272 patients with EES. Biomarker-positive acute coronary syndromes were present in 622 (24%) of 2602 patients, and, by angiographic core laboratory analysis, 78 (3%) of 2893 of lesions were in very small vessels. Target lesion failure at 30 days occurred in 64 (5·0%) patients assigned to BVS and 48 (3·7%) patients assigned to EES (difference 1·3%, upper 97·5% confidence limit 2·89; one-sided p non-inferiority =0·0244). Target lesion failure at 1 year occurred in 98 (7·8%) patients assigned to BVS and 82 (6·4%) patients assigned to EES (difference 1·4%, upper 97·5% confidence limit 3·4; one-sided p non-inferiority =0·0006). Angina, adjudicated by a central events committee at 1 year, occurred in 270 (20·3%) patients assigned to BVS and 274 (20·5%) patients assigned to EES (difference -0·3%, 95% CI -3·4% to 2·9%; one-sided p non-inferiority =0·0008; two-sided p superiority =0·8603). Device thrombosis within 1 year occurred in nine (0·7%) patients assigned to BVS and four (0·3%) patients assigned to EES (p=0·1586)., Interpretation: Polymeric BVS implanted with optimised technique in an expanded patient population resulted in non-inferior 30-day and 1-year rates of target lesion failure and angina compared with metallic DES., Funding: Abbott Vascular., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Google Glass is a head-mounted device designed in the shape of a pair of eyeglasses equipped with a 5.0-megapixel integrated camera and capable of taking pictures with simple voice commands., Objective: The objective of our study was to determine whether Google Glass is fit for veterinary forensic pathology purposes., Methods: A total of 44 forensic necropsies of 2 different species (22 dogs and 22 cats) were performed by 2 pathologists; each pathologist conducted 11 necropsies of each species and, for each photographic acquisition, the images were taken with a Google Glass device and a Nikon D3200 digital single-lens reflex (DSLR) camera. The pictures were collected, divided into 3 groups (based on the external appearance of the animal, organs, and anatomical details), and evaluated by 5 forensic pathologists using a 5-point score system. The parameters assessed were overall color settings, region of interest, sharpness, and brightness. To evaluate the difference in mean duration between necropsies conduced with Google Glass and DSLR camera and to assess the battery consumption of the devices, an additional number of 16 necropsies were performed by the 2 pathologists. In these cases, Google Glass was used for photographic reports in 8 cases (4 dogs and 4 cats) and a Nikon D3200 reflex camera in the other 8 cases. Statistical evaluations were performed to assess the differences in ratings between the quality of the images taken with both devices., Results: The images taken with Google Glass received significantly lower ratings than those acquired with reflex camera for all 4 assessed parameters (P<.001). In particular, for the pictures of Groups A and B taken with Google Glass, the sum of frequency of ratings 5 (very good) and 4 (good) was between 50% and 77% for all 4 assessed parameters. The lowest ratings were observed for the pictures of Group C, with a sum of frequency of ratings 5 and 4 of 21.1% (342/1602) for region of interest, 26% (421/1602) for sharpness, 35.5% (575/1602) for overall color settings, and 61.4% (995/1602) for brightness. Furthermore, we found a significant reduction in the mean execution time for necropsy conduced with the Google Glass with respect to the reflex group (P<.001). However, Google Glass drained the battery very quickly., Conclusions: These findings suggest that Google Glass is usable in veterinary forensic pathology. In particular, the image quality of Groups A and B seemed adequate for forensic photographic documentation purposes, although the quality was lower than that with the reflex camera. However, in this step of development, the high frequency of poor ratings observed for the pictures of Group C suggest that the device is not suitable for taking pictures of small anatomical details or close-ups of the injuries., (©Giuseppe Piegari, Valentina Iovane, Vincenzo Carletti, Rosario Fico, Alessandro Costagliola, Davide De Biase, Francesco Prisco, Orlando Paciello. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 21.09.2018.)

Cardiac laceration with non-penetrating chest trauma is reported as a common cause of death in human following rapid deceleration in high-speed vehicular accident. In contrast, in veterinary medicine, traumatic rupture of heart and great-vessel structures appears to be an uncommon cause of death. Here we report three cases of cardiac laceration following non-penetrating chest trauma in a one cat and two dogs. In two of these cases, necropsy revealed a rupture of the heart associated with fractures of the ribs and lung contusion; only one case did not exhibit any external chest injury but revealed pericardial tear associated with hemothorax following rupture of the right auricle of the heart. However, in all three presented cases, the thoracic location of the injuries allowed to conclude that the cause of the cardiac rupture was due to a direct impact of the chest wall with a high speed object and consequent transmission of the kinetic force and compression of the heart between left and right thorax. These case reports underline the importance of a systematic and complete macroscopic evaluation of the heart in all cases of death following non-penetrating chest trauma in dog and cat such as in human. They also highlight how, in clinical and forensic practice, the cardiac injury following blunt chest trauma should be ruled out even in the cases of absence of external chest injury., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A 56-year-old nulliparous female Asian elephant (Elephas maximus) living at the zoological garden of Naples (Italy), with a clinical history of recurrent colic, was found in agonal state and humane euthanasia was elected. At necropsy the uterine body was moderately increased in size and the lumen was reduced due to a poorly demarcated and infiltrative neoplasm. Furthermore, multiple, whitish, firm nodules were present in both lungs. Histological examination of the uterine mass revealed epithelial cells arranged in tubular or solid pattern infiltrating the endometrium and the muscular layer. Immunohistochemical examination showed immunoreactivity of neoplastic cells to oestrogen receptors antibody. Pulmonary lesions were histologically and immunohistochemically superimposable to the epithelial uterine neoplasm. A definitive diagnosis of uterine adenocarcinoma with pulmonary metastases was made.

The purpose of this pilot study was to assess the efficacy of a new social cognition (SC) remediation intervention, the Social Cognition Individualized Activities Lab (SoCIAL), for subjects with schizophrenia. The training includes a module for emotion recognition and one for theory of mind. A comparison with a validated cognitive remediation intervention, the Social Skills And Neurocognitive Individualized Training (SSANIT), was conducted to verify the efficacy of the SoCIAL in improving SC. Ten stabilized patients with schizophrenia accepted to participate. Five patients were randomized to SoCIAL and five to SSANIT. The SoCIAL intervention includes individual sessions of neurocognitive individualized training (NIT) and group sessions of SC training. SSANIT includes individual sessions of NIT and group sessions of social skills individualized training. The interventions were matched for the overall treatment duration (20 weeks) and for the frequency of the sessions (two times a week, one for SoCIAL or social skills individualized training and one for NIT, with a duration of 80 minutes for each session). Results showed a significant treatment effect (effect size: Cohen's d 0.32) on the primary outcome; in fact, only the SoCIAL intervention improved theory of mind. Patients receiving the SoCIAL intervention also showed an improvement of avolition. These preliminary findings support further development of the SoCIAL and suggest that cognitive remediation should include an SC module., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions.

Background: Autophagy is a highly regulated process involving the bulk degradation of cytoplasmic macromolecules and organelles in mammalian cells via the lysosomal system. Dysregulation of autophagy is implicated in the pathogenesis of many neurodegenerative diseases and integrity of the autophagosomal - lysosomal network appears to be critical in the progression of aging. Our aim was to survey the expression of autophagy markers and Amyloid precursor protein (APP) in aged bovine brains. For our study, we collected samples from the brain of old (aged 11-20 years) and young (aged 1-5 years) Podolic dairy cows. Formalin-fixed and paraffin embedded sections were stained with routine and special staining techniques. Primary antibodies for APP and autophagy markers such as Beclin-1 and LC3 were used to perform immunofluorescence and Western blot analysis., Results: Histologically, the most consistent morphological finding was the age-related accumulation of intraneuronal lipofuscin. Furthermore, in aged bovine brains, immunofluorescence detected a strongly positive immunoreaction to APP and LC3. Beclin-1 immunoreaction was weak or absent. In young controls, the immunoreaction for Beclin-1 and LC3 was mild while the immunoreaction for APP was absent. Western blot analysis confirmed an increased APP expression and LC3-II/LC3-I ratio and a decreased expression of Beclin-1 in aged cows., Conclusions: These data suggest that, in aged bovine, autophagy is significantly impaired if compared to young animals and they confirm that intraneuronal APP deposition increases with age.

Several pathogenetic factors have been involved in the onset and progression of Parkinson's disease (PD), including inflammation, oxidative stress, unfolded protein accumulation, and apoptosis. Palmitoylethanolamide (PEA), an endogenous N-acylethanolamine, has been shown to be a neuroprotective and anti-inflammatory molecule, acting as a peroxisome proliferator activated receptor (PPAR)-α agonist. In this study we investigated the effects of PEA on behavioral alterations and the underlying pathogenic mechanisms in the 6-hydroxydopamine (6-OHDA)-induced model of PD in male mice. Additionally, we showed the involvement of PPAR-α in PEA protective effect on SH-SY5Y neuroblastoma against 6-OHDA damage. Here, we report that PEA (3-30mg/kg/days.c.) improved behavioral impairments induced by unilateral intrastriatal injection of 6-OHDA. This effect was accompanied by a significant increase in tyrosine hydroxylase expression at striatal level, indicating PEA preserving effect on dopaminergic neurons. Moreover, we found a reduction in the expression of pro-inflammatory enzymes, i.e. inducible nitric oxide synthase and cyclooxygenase-2, a modulation between pro- and anti-apoptotic markers, suggestive of PEA capability in controlling neuroinflammation and cell death. Interestingly, PEA also showed protective scavenging effect, through superoxide dismutase induction, and dampened unfolding protein response, interfering on glucose-regulated protein 78 expression and PERK-eIF2α pathway. Similar data were found in in vitro studies, where PEA treatment was found to rescue SH-SY5Y neuroblastoma cells from 6-OHDA-induced damage and death, partly by inhibiting endoplasmic reticulum stress detrimental response. Therefore, PEA, counteracting the pathogenetic aspects involved in the development of PD, showed its therapeutic potential, possibly integrating current treatments correcting dopaminergic deficits and motor dysfunction., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Impaired premorbid adjustment has been reported in patients with schizophrenia, generally in association with unfavorable aspects of the illness (e.g., poor outcome and severe negative symptoms). Several studies attempted to define the domains of premorbid dysfunction associated with negative symptoms and poor outcome; however, most of them assessed broadly defined negative symptoms. The present study was aimed to characterize premorbid functioning in a group of patients with deficit schizophrenia (DS), characterized by the presence of at least two primary and persistent negative symptoms (PPNS), and one of patients with a diagnosis of schizophrenia who did not meet criteria for DS (NDS). The presence of emotional/behavioral problems during childhood was investigated using the Childhood Behavior Checklist (CBCL) in both patient groups and in their respective healthy siblings. The Premorbid Adjustment Scale (PAS) was also used to assess premorbid functioning during childhood in the two patient groups. PPNS were also treated as a continuous variable and correlated with the indices of premorbid functioning regardless the DS/NDS categorization. DS patients, as compared to NDS, showed higher scores on the CBCL subscale "Withdrawn". Both DS and NDS patients showed, as compared to their healthy siblings, a greater impairment on almost all CBCL subscales. PAS findings revealed that DS patients had poorer premorbid adjustment than NDS. No significant correlation between premorbid functioning and PPNS was observed. These findings support the hypothesis that DS has a different developmental trajectory with respect to NDS, and that premorbid adjustment is one of the essential aspects of its characterization., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to assess the safety and efficacy of the Misago stent (Terumo Corp, Tokyo, Japan) in occlusive and stenotic superficial femoral artery (SFA) disease., Methods: The safety and efficacy of the Misago SFA stent were evaluated prospectively in this initial collaboration trial between Japan and the United States. Because this trial enrolled patients mainly from Japan and the United States and because there is a question as to whether a race difference exists in SFA stent performance, the race difference on outcome was also analyzed. In addition, results were compared with a prior SFA stent trial., Results: The Misago stent was implanted in 261 subjects with TransAtlantic Inter-Society Consensus (TASC) type A and type B SFA lesions (201 subjects in the United States, 50 in Japan, 9 in Taiwan, 1 in South Korea). The mean age of the patients was 69.3 ± 10.0 years, and the mean lesion length was 83.8 ± 41.3 mm. The overall 12-month primary patency rate and clinically driven target lesion revascularization were 82.9% and 13.0%, respectively. Regional differences within the Occlusive/Stenotic Peripheral Artery Revascularization Study (OSPREY) and outcomes between U.S. and Asian patients were similar, including primary patency (82.9% vs 83.0%; P = .889), clinically driven target lesion revascularization (13.4% vs 11.7%; P = .829), stent fracture rate (1.3% vs 0.0%; P = 1.000), and stent thrombosis rate (0.5% vs 0.0%; P = 1.000)., Conclusions: OSPREY 12-month data showed satisfactory outcome of the Misago stent for the treatment of TASC type A and type B SFA lesions and appears to be comparable to recent stent trials. In addition, the lack of difference in outcome among races supports the value of international trials., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection.

Background: The Brief Negative Symptom Scale (BNSS) was developed to address the main limitations of the existing scales for the assessment of negative symptoms of schizophrenia. The initial validation of the scale by the group involved in its development demonstrated good convergent and discriminant validity, and a factor structure confirming the two domains of negative symptoms (reduced emotional/verbal expression and anhedonia/asociality/avolition). However, only relatively small samples of patients with schizophrenia were investigated. Further independent validation in large clinical samples might be instrumental to the broad diffusion of the scale in clinical research., Methods: The present study aimed to examine the BNSS inter-rater reliability, convergent/discriminant validity and factor structure in a large Italian sample of outpatients with schizophrenia., Results: Our results confirmed the excellent inter-rater reliability of the BNSS (the intraclass correlation coefficient ranged from 0.81 to 0.98 for individual items and was 0.98 for the total score). The convergent validity measures had r values from 0.62 to 0.77, while the divergent validity measures had r values from 0.20 to 0.28 in the main sample (n=912) and in a subsample without clinically significant levels of depression and extrapyramidal symptoms (n=496). The BNSS factor structure was supported in both groups., Conclusions: The study confirms that the BNSS is a promising measure for quantifying negative symptoms of schizophrenia in large multicenter clinical studies., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Rehabilitation programs integrating cognitive remediation (CR) and psychosocial rehabilitation are often implemented as they seem to yield greater improvements in functional outcome than stand alone treatment approaches. Mechanisms underlying synergistic effects of combining CR with psychosocial interventions are not fully understood. Disentangling the relative contribution of each component of integrated programs might improve understanding of underlying mechanisms. In the present study we compared the efficacy of two components of our rehabilitation program [the Neurocognitive Individualized Training (NIT) and the Social Skills Individualized Training (SSIT)]. Seventy-two patients with schizophrenia or schizoaffective disorder were randomly assigned to one of two treatment groups. Changes in cognitive, psychopathological and real-world functioning indices after 6 and 12 months were compared between the two groups. After both 6 and 12 months, NIT produced an improvement of attention, verbal memory and perseverative aspects of executive functioning, while SSIT produced a worsening of visuo-spatial memory and attention and no significant effect on the other cognitive domains. As to the real-world functioning, NIT produced a significant improvement of interpersonal relationships, while SSIT yielded a significant improvement of QLS instrumental role subscale. According to our findings, cognitive training is more effective than social skills training on several cognitive domains and indices of real-world functioning relevant to subject's relationships with other people. Integrated approaches might target different areas of functional impairment but should be planned carefully and individually to fully exploit the synergistic potential., (© 2013.)

Background: Relatively few studies have examined how patients with schizophrenia and depression view psychiatric research and what influences their readiness to participate., Methods: A total of 763 patients (48% schizophrenia, 52% depression) from 7 European countries were examined using a specifically designed self-report questionnaire ["Hamburg Attitudes to Psychiatric Research Questionnaire" (HAPRQ)]., Results: Most patients (98%) approved of psychiatric research, in general, at least "a little". There was a tendency to approve psychosocial rather than biological research topics (e.g. research on the role of the family by 91% of patients compared to 79% in genetics). Reasons to participate were mainly altruistic. Only a minority (28%) considered monetary incentives important. Patients wanted extensive background information and a feedback of the results; both were significantly more expressed by schizophrenia as compared to depressive patients, although these findings need to be interpreted with care because of age and gender differences between the diagnostic groups., Conclusion: While patients expressed discerning views of psychiatric research, only few differences were apparent between the two diagnostic groups. Patients' research priorities are not the same as those of many professionals and funding bodies. Their demonstrated critical appraisal should inform future research ensuring an increased patient role in the research process.

Cognitive impairment and deficits in social skills have been largely documented in patients with schizophrenia and are increasingly recognized as rate-limiting factors for recovery. Evidence has been provided that cognitive training and social skills training (SST) are effective to treat cognitive and social skills impairment in schizophrenia; however, the translation of improved performance on cognitive or social skills tasks into improved functional outcome is controversial. According to recent reviews, interventions providing cognitive training in conjunction with psychosocial rehabilitation have a greater impact on functional outcome than either intervention alone suggesting that the two treatment approaches may work together in a synergistic fashion. The present pilot study was designed to test the hypothesis that an integrated rehabilitation program, including individualized cognitive and SST, is more effective than the structured leisure activities (SLA) carried out in many Italian Mental Health Departments. The primary outcome measure was subjects' personal and social functioning as assessed by the Interview for the assessment of disability. The study is based on a controlled design including randomization to treatment groups, blind assessments and stable pharmacological treatment. Subjects were recruited among patients attending three psychiatric facilities located in the Italian region Campania. Thirty patients were randomized to the experimental program "social skills and neurocognitive individualized training" (SSANIT), and 30 to SLA. The two programs were matched for the overall duration as well as frequency and duration of the sessions. The two groups of patients did not differ at baseline on psychopathology, neurocognitive and personal/social functioning. After 6 months of treatment, personal and social functioning was significantly better in patients assigned to SSANIT than in those assigned to usual rehabilitation activities practiced in Mental Health Departments. No advantage was observed for either program on psychopathological and cognitive outcome indices. As for other integrated programs, also for SSANIT further studies are needed to verify generalization and persistence of the observed gains, and to clarify most adequate length and doses of the therapeutic intervention as well as the relative contribution of each program component to its impact on subjects' disability.

Patients with schizophrenia often present mild to severe cognitive deficits which contribute to their social disability. Second-generation antipsychotics have shown only mild to moderate beneficial effects on cognition. The present case report suggests cognitive enhancing effects of aripiprazole, a dopamine partial agonist, shown to increase dopamine release in prefrontal cortex in animal studies.The patient was in his first-episode of schizophrenia, and had no previous exposure to first-generation antipsychotics. Before schizophrenia onset his cognitive functioning was poor and he could not attend regular courses to reach his high school degree; he started but was not able to attend the University courses for several years.After schizophrenia onset, he was treated, in sequence, with olanzapine, amisulpride and aripiprazole. During treatment with the first two second-generation antipsychotics, positive symptoms markedly improved while cognitive functioning remained poor. During treatment with aripiprazole, clinical remission was obtained and the patient was able to attend university courses and pass several examinations. Social functioning was markedly improved.Aripiprazole demonstrated cognitive enhancing effects in this patient. These effects were long-lasting and paralleled by a positive impact on social functioning.