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Neonatal and pediatric mortality in kittens could be associated with bacterial infections, complications from inadequate management, congenital malformations, neonatal isoerythrolysis, parasitic diseases, and viral diseases. The complexity of causes, coupled with kittens' physiological and immunological immaturity, complicates the diagnosis and treatment of disease, highlighting the necessity for preventive measures. This study aimed to identify the leading causes of death and the occurrence of congenital malformations in stray kittens. Necropsies were performed on 68 kittens, all aged under two months. Results indicated that respiratory lesions were the leading cause of death in the youngest group, while gastrointestinal problems were more prevalent in older groups. Infectious causes were predominant across all age groups. Congenital malformations were observed in 40% of the animals, with megaesophagus, cardiovascular anomalies, bone defects, and kidney defects being the most prevalent. The findings underscore the critical importance of hygiene in preventing infections and related complications. Promoting sterilization and sanitary control in stray cats is essential to reduce overpopulation and improve living conditions.

Solid tumours are complex and heterogeneous systems, which exist in a dynamic biophysical microenvironment. Conventional cancer research methods have long relied on two-dimensional (2D) static cultures which neglect the dynamic, three-dimensional (3D) nature of the biophysical tumour microenvironment (TME), especially the role and impact of interstitial fluid flow (IFF). To address this, we undertook a transcriptome-wide analysis of the impact of IFF-like perfusion flow using a spheroid-on-chip microfluidic platform, which allows 3D cancer spheroids to be integrated into extracellular matrices (ECM)-like hydrogels and exposed to continuous perfusion, to mimic IFF in the TME. Importantly, we have performed these studies both in experimental (normoxia) and pathophysiological (hypoxia) oxygen conditions. Our data indicated that gene expression was altered by flow when compared to static conditions, and for the first time showed that these gene expression patterns differed in different oxygen tensions, reflecting a differential role of spheroid perfusion in IFF-like flow in tumour-relevant hypoxic conditions in the biophysical TME. We were also able to identify factors primarily linked with IFF-like conditions which are linked with prognostic value in cancer patients and therefore could correspond to a potential novel biomarker of IFF in cancer. This study therefore highlights the need to consider relevant oxygen conditions when studying the impact of flow in cancer biology, as well as demonstrating the potential of microfluidic models of flow to identify IFF-relevant tumour biomarkers.

Sarcocystis is a genus of protozoa with a worldwide distribution infecting a wide range of animals, including humans. Wild boars can harbor at least two species of Sarcocystis, that is, the zoonotic Sarcocystis suihominis, using humans as definitive hosts, and Sarcocystis miescheriana, for which wild and domestic canids serve as definitive hosts. In Portugal, hunting holds significant economic and social importance, and wild boars are among the most appreciated hunted species. As the consumption of wild boar meat can expose humans to several foodborne pathogens, the presence of trained hunters can make a difference in ensuring animal health surveillance and food safety. Herein, we report the detection of macroscopic cystic lesions associated with S. miescheriana in a wild boar hunted for human consumption, resulting in carcass condemnation. To the best of the authors' knowledge, the presence of S. miescheriana in wild boar tissues has never been associated with macroscopic pathological alterations before. Although S. miescheriana cannot infect humans, carcasses affected by grossly visible pathological changes must be declared unfit for consumption. Therefore, our finding points out the potential economic damage associated with carcass rejection due to the presence of gross lesions associated with generalized sarcocystosis. Nonetheless, further studies are required to investigate these alterations that currently appear to be occasional findings., (© 2024. The Author(s).)

Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGFβ expression was assessed by immunohistochemistry in 67 malignant CMT and its correlation to previously determined FoxP3, VEGF, and CD31 markers and other clinicopathologic parameters was evaluated. The high levels of TGFβ were statistically significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), presence of neoplastic intravascular emboli and presence of lymph node metastases. The observed levels of TGFβ were positively correlated with intratumoral FoxP3 (strong correlation), VEGF (weak correlation) and CD31 (moderate correlation). Tumors that presented a concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31 markers were statistically significantly associated with parameters of tumor malignancy (high HGM, presence of vascular emboli and nodal metastasis). Additionally, shorter overall survival (OS) time was statistically significantly associated with tumors with an abundant TGFβ expression and with concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31. The presence of lymph node metastasis increased 11 times the risk of disease-related death, arising as an independent predictor of poor prognosis in the multivariable analysis. In conclusion, TGFβ and Treg cells seem involved in tumor progression emerging as potential therapeutic targets for future immunotherapy studies.

Advancements in understanding pain physiopathology have historically challenged animals' absence of pain senses. Studies have demonstrated that animals have comparable neural pain pathways, suggesting that cats and dogs likely experience pain similarly to humans. Understanding brain circuits for effective pain control has been crucial to adjusting pain management to the patient's individual responses and current condition. The refinement of analgesic strategies is necessary to better cater to the patient's demands. Cancer pain management searches to ascertain analgesic protocols that enhance patient well-being by minimizing or abolishing pain and reducing its impact on the immune system and cancer cells. Due to their ability to reduce nerve sensitivity, opioids are the mainstay for managing moderate and severe acute pain; however, despite their association with tumor progression, specific opioid agents have immune-protective properties and are considered safe alternatives to analgesia for cancer patients.

Canine cutaneous histiocytoma (CCH) represents a significant proportion of dog skin tumours, often manifesting as the most common neoplastic skin condition in young animals. Predominantly affecting dogs under four, these tumours appear primarily as solitary lesions that may regress spontaneously. This study, conducted over five years at the University of Trás-os-Montes e Alto Douro, involved a detailed histopathological and ultrastructural examination of 93 CCH cases. Histologically, these tumours showed distinct patterns of lymphoid infiltration, which contributed to their classification into four groups based on the inflammatory response and histological architecture. Most tumours displayed signs of epidermal invasion and frequent mitotic figures, with necrosis present in over half of the cases. Ultrastructurally, the neoplastic cells were characterised by pleomorphism, abundant organelles, and adherens-type junctions. This study offers significant insights into the pathophysiology and morphological characteristics of CCH, underscoring the importance of detailed histological and ultrastructural analysis in accurately diagnosing and understanding this common canine tumour.

The American crocodile ( Crocodylus acutus , Cuvier, 1807) (Class Reptilia, Family Crocodylidae) is a crocodile species inhabiting the Neotropics. Congenital defects have been described in almost every vertebrate group. In crocodiles, teratology alterations have been described in captive animals (pets, zoos, farms) such as Crocodylus niloticus or Gavialis gangeticus . The present study aimed to characterize congenital malformations of C. acutus from a farm in Lomas de Matunilla, Ballestas, Bolívar, Colombia. A total of 550 unhatched eggs were examined after embryo death. A total of 61 embryos presented malformations, with 42 different types of anomalies observed. Limb and tail malformations (29%) were the most common malformations observed. Several malformations, such as cephalothoracopagus, thoracopagus, sternopagus, xiphopagus twins, campylorrachis scoliosa, and acrania, were documented in crocodiles for the first time. Research in teratology enhances our understanding of crocodile biology. It plays a role in their conservation and management, thus helping to ensure the long-term viability of these species in their natural habitats.

Background: Sarcoids and squamous cell carcinomas (SCCs) are the most concerning equine oncological diseases. Both tumors are challenging to manage due to their invasive behavior and high prevalence of recurrences. Furthermore, SCCs have a propensity to metastasize. Programed cell-death ligand 1 (PD-L1) has been one of the main therapeutic targets for immunotherapy in various human tumors. PD-L1 research in equine tumors is scarce and more efforts are necessary to understand the potential of this biomarker as a therapeutical target., Aim: Evaluate the immunohistochemical expression of PD-L1 in equine sarcoids and SCC., Methods: Thirteen equine tumors (seven sarcoids and 6 SCCs) were tested by immunohistochemistry and evaluated semi quantitatively to assess the percentage of positive cells., Results: None of the sarcoids presented PD-L1 expression. Regarding SCC, 2 tumors presented <10% of labeled cells; 2 tumors presented 10%-25% of labeled cells and 2 tumors presented 25%-50% of labeled cells. There were statistically significant differences between sarcoids and SCC regarding the expression of PD-L1., Conclusion: Our results point to the fact that PD-L1 could be a potential therapeutic target against SCC, and also encourage in-depth studies in this area, with larger sample sizes., Competing Interests: The authors declare that there is no conflict of interest.

Squamous cell carcinoma (SCC) stands as the second most prevalent skin cancer in dogs, primarily attributed to UV radiation exposure. Affected areas typically include regions with sparse hair and pale or depigmented skin. The significance of spontaneous canine cutaneous SCC as a model for its human counterpart is underscored by its resemblance. This study assesses the expression of key markers-Epidermal Growth Factor Receptor (EGFR), Cyclooxygenase-2 (Cox-2), and Ki-67-in canine cutaneous SCC. Our objective is to investigate the association between their expression levels and classical clinicopathological parameters, unraveling the intricate relationships among these molecular markers. In our retrospective analysis of 37 cases, EGFR overexpression manifested in 43.2% of cases, while Cox-2 exhibited overexpression in 97.3%. The EGFR, Cox-2 overexpression, and Ki-67 proliferation indices, estimated through immunohistochemistry, displayed a significant association with the histological grade, but only EGFR labeling is associated with the presence of lymphovascular emboli. The Ki-67 labeling index expression exhibited an association with EGFR and Cox-2. These findings propose that EGFR, Cox-2, and Ki-67 hold promise as valuable markers in canine SCC. EGFR, Cox-2, and Ki-67 may serve as indicators of disease progression, offering insights into the malignancy of a lesion. The implications extend to the potential therapeutic targeting of EGFR and Cox-2 in managing canine SCC. Further exploration of these insights is warranted due to their translational relevance and the development of targeted interventions in the context of canine SCC.

Paleo-oncology studies neoplastic diseases in fossilised animals, including human remains. Recent advancements have enabled more accurate diagnoses of ancient pathologies despite the inherent challenges in identifying tumours in fossils-such as the rarity of well-preserved specimens, the predominance of bone remains, and the difficulty in distinguishing neoplastic from non-neoplastic lesions. This study compiles reports of tumours in fossilised animals, highlighting that neoplasms are present in a wide range of vertebrates and drawing comparisons to modern instances of similar diseases. The findings underscore the multifactorial aetiology of tumours, which involves genetic, environmental, and lifestyle factors, and suggest that tumours have been around for at least 350 million years.

Equine melanomas are a common neoplasm in gray horses. However, scientific knowledge about their progression over time is quite scarce. Some owners and veterinarians still believe that early intervention is not necessary, stating that tumors evolve very slowly and intervention could worsen the animal's condition. This work aims to identify clinical and histological differences that may exist between equine melanomas with different excision intervals (time between tumor detection and surgical excision). A total of 42 tumors (13 benign and 29 malignant) from 34 horses were included in this study. There was a statistically significant association between excision interval and tumor size ( p = 0.038), with tumors excised later being significantly larger than the ones excised sooner. The excision interval was also statistically associated with the number of tumors ( p = 0.011), since the horses that carried a tumor for longer seemed to be prone to have multiple tumors. Furthermore, there was an association between excision interval and malignancy ( p = 0.035), with tumor excised later being fives times more likely to be malignant. This study provides evidence of delayed excision's effect on the progression of equine melanomas. Additionally, it reinforces the importance of the early excision of these tumors.

Background: Cyclo-oxygenase-2 (COX-2) and cancer associated fibroblasts (CAFs) play an important role in the development and progression of tumor malignancy in humans and animals, showing that both can influence the tumor microenvironment. However, the impact of these two markers in feline mammary carcinogenesis has not yet been addressed., Materials and Methods: In the present study, the clinicopathological significance of COX-2 immunoexpression and alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs) was determined and correlated with disease-free and overall survival of 50 felines with malignant mammary tumors., Results: COX-2 overexpression was positively associated with mitotic index (p=0.031), degree of malignancy (p≤0.001), lymph node metastasis (p≤0.001), vascular invasion (p=0.002), disease recurrence (p=0.019) and distant metastasis (p=0.036). α-SMA-positive CAFs were associated with mitotic index (p=0.004), lymph node metastasis (p=0.027), vascular invasion (p=0.05), disease recurrence (p≤0.001) and distant metastasis (p≤0.001). Additionally, both markers were correlated with disease-free and overall survival, emerging as predictors of poor prognosis., Conclusion: Our results indicate for the first time that the presence of two markers, COX-2 and α-SMA, is associated with carcinogenesis and worse prognosis in feline mammary cancer and that α-SMA-positive CAFs have a role in feline mammary tumorigenesis, cancer development, and clinical outcome., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Respiratory diseases, including the multifactorial "swine respiratory disease complex," have a significant impact on swine production. Recently, a condition manifesting primarily in the trachea, known as hemorrhagic tracheitis syndrome (HTS), has been described in pigs. HTS is characterized by severe coughing and high mortality in finishing pigs., Case Description: This report presents the first case of HTS in an adult male pig from a Portuguese farm. The animal died without any previous clinical signs. Necropsy revealed significant thickening of the trachea. Fibrinous necrotic hemorrhagic tracheitis was identified through histopathological analysis, but no bacterial infectious agents were detected during microbiological examination., Conclusion: This case underscores the need for comprehensive research, including systematic necropsies and histopathological assessments, to understand the actual prevalence of the disease, elucidate the etiology, and develop effective interventions for HTS in swine productions., Competing Interests: The authors declare that they have no conflict of interest

Equine melanocytic tumors are common and have an unusual benign behavior with low invasiveness and metastatic rates. However, tumoral mass growth is usually a concern that can have life-threatening consequences. COX-2 is related to oncogenesis, promoting neoplastic cell proliferation, invasion, and metastasis. The aim of this study was to evaluate the immunohistochemical expression of COX-2 in equine melanocytic tumors. Through extension and intensity of labeling, 39 melanocytomas and 38 melanomas were evaluated. Of the malignant tumors, 13.2% were negative and 63.2% presented a low COX-2 expression. Only 6 malignant tumors presented >50% of labeled cells, 18 malignant and 8 benign had an expression between 21 and 50%, 8 malignant and 3 benign tumors had an expression between 6 and 20%, 1 malignant tumor had an expression between 1 and 5%, and 5 malignant and 28 benign tumors had no expression. Malignant tumors showed higher COX-2 expression than did benign tumors, with statistically significant differences. The low levels of COX-2 may be one of the molecular reasons for the presence of expansive mass growth instead of the invasive pattern of other species, which is related to high COX-2 levels.

Transitional cell carcinoma of the urinary bladder is a significant neoplasm in dogs, characterized by a poor prognosis and a high metastatic potential. These canine spontaneous tumors share many characteristics with human transitional cell carcinoma, making them an excellent comparative model. The role of inflammatory infiltration in tumor development and progression is frequently contradictory, especially concerning tumor-associated tissue eosinophils (TATE) and tumor-associated macrophages (TAMs). This study aims to analyze TATE and TAMs in canine transitional cell carcinoma of the urinary bladder. Congo Red staining was used to identify TATE, and immunohistochemistry was performed to detect TAMs in 34 cases of canine transitional cell carcinoma of the bladder carcinomas, categorized into low and high grades. Statistically significant differences were observed between the number of eosinophils and macrophages in the two groups of tumors. The number of TATE was higher in low-grade malignant tumors, but the number of TAMs was higher in high-grade tumors. Our findings suggest the importance of TATEs and TAMs in the aggressiveness of canine transitional cell carcinoma and propose their potential use as therapeutic targets.

Claw diseases have a profound impact on cattle welfare, affecting behaviors such as grazing, rumination, rest, decubitus, and water consumption. This study aimed to assess the prevalence of claw lesions and classify them according to the ICAR Claw Health Atlas (International Committee of Animal Recording) in two slaughterhouses. The influence of claw lesions on carcass weight, classification, and fat deposition was also examined. Involving 343 crossbreed cattle from 103 different extensive or semi-intensive farms, this study found an animal prevalence of claw disorders at 65.8%, with a higher incidence in females (n = 207, 60.35%) compared to males (n = 136, 39.65%). Despite the observed prevalence, claw lesions were not influenced by age or sex ( p > 0.05). The main claw lesions identified, including heel horn erosion, double sole, and asymmetric claw, were consistent with the cattle management practices in the study area. These cattle were raised in small, rustic premises with uneven floors, utilizing a mix of manure and plant material as bedding and lacking access to pasture. Also, no negative economic impact was detected concerning carcass weight, classification, or fat deposition. Consequently, it was concluded that the presence of claw lesions in beef cattle raised under the characteristic management of this geographical area does not adversely affect animal health or farm economics.

This article stems from interviews conducted with Chinese women residing in Lisbon, aged 18-34, during the initial phase of fieldwork (2021/2022). As an outcome of my Anthropology Ph.D. project, the focus here is on comprehending the perception of Asian women within the realm of everyday life as fetishized entities and how they persist in (re)shaping their identities. By primarily examining visual "yellow fever" depictions (in Hollywood cinema through films like "The World of Suzie Wong", "Madame Butterfly", "Miss Saigon", and the "Year of the Dragon", along with interracial Pornography), I endeavor to delve into the impact of "race", "sexual fetishization", and the ubiquitous propagation of stereotypical imagery on the lives of the individuals I engage with.

Oral squamous cell carcinoma (OSCC) is a common and highly aggressive dog tumor known for its local invasiveness and metastatic potential. Understanding the molecular mechanisms driving the development and progression of OSCC is crucial for improving diagnostic and therapeutic strategies. Additionally, spontaneous oral squamous cell carcinomas in dogs are an excellent model for studying human counterparts. In this study, we aimed to investigate the significance of two key molecular components, Cox-2 and EGFR, in canine OSCC. We examined 34 tumor sections from various dog breeds to assess the immunoexpression of Cox-2 and EGFR. Our findings revealed that Cox-2 was highly expressed in 70.6% of cases, while EGFR overexpression was observed in 44.1%. Cox-2 overexpression showed association with histological grade of malignancy (HGM) ( p = 0.006) and EGFR with vascular invasion ( p = 0.006). COX-2 and EGFR concurrent expression was associated with HGM ( p = 0.002), as well as with the presence of vascular invasion ( p = 0.002). These data suggest that Cox-2 and EGFR could be promising biomarkers and potential therapeutic targets, opening avenues for developing novel treatment strategies for dogs affected by OSCC. Further studies are warranted to delve deeper into these findings and translate them into clinical practice.

Currently available treatments for equine melanocytic tumors have limitations, mainly due to mass localization and dimension, or the presence of metastases. Therefore, a search for new therapies is necessary. Programmed cell death-ligand 1 (PD-L1) is expressed by several tumors, blocking T cell-mediated elimination of the tumor cells by binding to programmed cell death protein 1 (PD-1). A novel therapeutic approach using PD-1/PD-L1 blockade in human melanoma resulted in tumor regression and prolonged tumor-free survival. This study aimed to evaluate the immunohistochemical expression of PD-L1 in equine melanocytic tumors. A total of 77 melanocytic tumors were classified as benign or malignant and evaluated by extension of labeling. A total of 59.7% of the tumors showed >50% of immunolabeled cells. Regarding malignant tumors, 24/38 tumors presented >50% of labeled cells, 13 tumors presented between 25-50% and one tumor presented <10%. Regarding benign tumors, 22/39 tumors presented >50% of labeled cells, nine tumors presented 25-50%, three tumors presented 10-25%, two tumors presented <10% and three tumors did not present expression. Our results suggest that PD-L1 blockade may be a potential target for immunotherapy in equine melanocytic tumors and that future clinical research trials into the clinical efficacy of the anti-PD-L1 antibody are necessary.

Antibiotic resistance is a global concern that affects not only human health but also the health of wildlife and the environment. Wildlife can serve as reservoirs for antibiotic-resistant bacteria, and antibiotics in veterinary medicine and agriculture can contribute to the development of resistance in these populations. Several European carnivore species, such as wolves, foxes, otters, and bears, can be exposed to antibiotics by consuming contaminated food, water, or other resources in their habitats. These animals can also be indirectly exposed to antibiotics through interactions with domestic animals and human activities in their environment. Antibiotic resistance in wildlife can harm ecosystem health and also impact human health indirectly through various pathways, including zoonotic disease transmission. Moreover, the spread of resistant bacteria in wildlife can complicate conservation efforts, as it can threaten already endangered species. This review aims to describe the presence of antibiotic-resistant bacteria in wild carnivores in Europe.

Among the transmissible spongiform encephalopathies (TSEs), chronic wasting disease (CWD) in cervids is now a rising concern in wildlife within Europe, after the detection of the first case in Norway in 2016, in a wild reindeer and until June 2022 a total of 34 cases were described in Norway, Sweden and Finland. The definite diagnosis is post-mortem , performed in target areas of the brain and lymph nodes. Samples are first screened using a rapid test and, if positive, confirmed by immunohistochemistry and Western immunoblotting. The study of the genetics of the prion protein gene, PRNP , has been proved to be a valuable tool for determining the relative susceptibility to TSEs. In the present study, the exon 3 of PRNP gene of 143 samples from red deer ( Cervus elaphus ) and fallow deer ( Dama dama ) of Portugal was analysed. Three single nucleotide polymorphisms (SNPs) were found in red deer - codon A136A, codon T98A, codon Q226E - and no sequence variation was detected in fallow deer. The low genetic diversity found in our samples is compatible with previous studies in Europe. The comparison with results from North America suggests that the free-ranging deer from our study may present susceptibility to CWD, although lack of experimental data and the necessity of continuous survey are necessary to evaluate these populations.

Throughout the course of oncological disease, the majority of patients require surgical, anaesthetic and analgesic intervention. However, during the perioperative period, anaesthetic agents and techniques, surgical tissue trauma, adjuvant drugs for local pain and inflammation and other non-pharmacological factors, such as blood transfusions, hydration, temperature and nutrition, may influence the prognosis of the disease. These factors significantly impact the oncologic patient's immune response, which is the primary barrier to tumour progress, promoting a window of vulnerability for its dissemination and recurrence. More research is required to ascertain which anaesthetics and techniques have immunoprotective and anti-tumour effects, which will contribute to developing novel anaesthetic strategies in veterinary medicine.

Background: In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC., Results: Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside., Conclusion: Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Agonic aspiration of blood (AAB) may result from an inadequate exsanguination with accidental trachea severing, that can be favoured by ineffective stunning of pigs ( Sus scrofa domesticus ). This study aimed to evaluate AAB as an animal-based indicator of electrical stunning ineffectiveness, which could be used by official veterinarians during the post-mortem inspection of pigs. Information on 3584 finishing pigs was collected at a Portuguese abattoir that performs head-to-body electrical stunning with horizontal bleeding. Of them, 15.5% of the pigs presented signs of ineffective stunning. AAB lung lesions were found in 27.8% of lungs. Despite what was predicted, a strong correlation was found between well stunned animals and the presence of blood lesions in lungs ( p = 0.006). Statistical significances were found between pigs' lateral recumbency at the conveyor and the presence of blood affecting one lung. Under the conditions of this study, the authors cannot point to AAB lung lesions as an animal-based indicator of electrical stunning ineffectiveness. Further studies should be conducted to establish a better understanding of the causes of aspiration of blood, in particular how horizontal bleeding may affect the occurrence of similar lesions.

Melanocytic tumors are an important neoplastic disease in human and veterinary medicine, presenting large differences regarding tumor behavior between species. In horses, these tumors present a prolonged benign behavior, with rare invasiveness and metastases. In humans and small animals, invasion and metastasis have been associated with an Epithelial-Mesenchymal Transition, where the loss of E-cadherin expression plays a key role in tumor progression. This process and the role of E-cadherin have not yet been evaluated in equine melanocytic tumors. This study aimed to assess the immunolabeling of E-cadherin in equine melanocytic tumors and relate this with clinicopathological variables. A total of 72 equine melanocytic tumors were classified as benign and malignant and evaluated by immunohistochemistry for E-cadherin expression. A different pattern of immunostaining was found, contrasting with other species. A total of 69.4% of tumors presented raised immunolabeling of E-cadherin, with 70.7% of melanomas remaining with high expression. The typical loss of immunostaining was not seen in malignant melanomas and no differences were found between benign and malignant melanomas regarding E-cadherin immunostaining. The high immunolabeling of E-cadherin may contribute to the low invasiveness of these tumors, and it is in accordance with the benign behavior of equine melanoma and with the genetic factors associated with its development.

Portugal is the habitat of three species of vultures. According to the IUCN Red List of Threatened Species, Neophron percnopterus is an Endangered species, Aegypius monachus is nearly Threatened, and Gyps fulvus is of Least Concern. This study aims to investigate the admission causes, morbidity, and outcomes of vultures admitted to a wildlife rehabilitation centre and necropsy service in Northern Portugal. Over 17 years (2005-2022), 84 animals were admitted: 10 A. monachus , 69 G. fulvus , and 5 N. percnopterus . The main causes of admission to the centre were 80% ( n = 63) unknown cause, 13% ( n = 10) found debilitated, 6 % ( n = 5) vehicle collision, 4% ( n = 3) captivity, 1% ( n = 1) gunshot, and 1% ( n = 1) electrocution. Most animals were admitted during the summer (45.2%) and autumn (36.9%). Analysis of outcome data showed that 73% ( n = 58) of the animals that arrived alive at the centre could be rehabilitated and released back into the wild. Thirteen animals died during treatment and five were found dead. This is the first time that such a lengthy study of results and mortality has been carried out for these species in Portugal. Although the data are limited, they can already provide some information about these populations, particularly for the endangered species that are so rare to observe.

Abnormal prion proteins (PrP Sc ) are the disease-associated isoform of cellular prion protein and diagnostic markers of transmissible spongiform encephalopathies (TSEs). These neurodegenerative diseases affect humans and several animal species and include scrapie, zoonotic bovine spongiform encephalopathy (BSE), chronic wasting disease of cervids (CWD), and the newly identified camel prion disease (CPD). Diagnosis of TSEs relies on immunodetection of PrP Sc by application of both immunohistochemistry (IHC) and western immunoblot methods (WB) on encephalon tissues, namely, the brainstem (obex level). IHC is a widely used method that uses primary antibodies (monoclonal or polyclonal) against antigens of interest in cells of a tissue section. The antibody-antigen binding can be visualized by a color reaction that remains localized in the area of the tissue or cell where the antibody was targeted. As such, in prion diseases, as in other fields of research, the immunohistochemistry techniques are not solely used for diagnostic purposes but also in pathogenesis studies. Such studies involve detecting the PrP Sc patterns and types from those previously described to identify the new prion strains. As BSE can infect humans, it is recommended that biosafety laboratory level-3 (BSL-3) facilities and/or practices are used to handle cattle, small ruminants, and cervid samples included in the TSE surveillance. Additionally, containment and prion-dedicated equipment are recommended, whenever possible, to limit contamination. The PrP Sc IHC procedure consists of a formic acid epitope-demasking step also acting as a prion inactivation measure, as formalin-fixed and paraffin-embedded tissues used in this technique remain infectious. When interpreting the results, care must be taken to distinguish non-specific immunolabeling from target labeling. For this purpose, it is important to recognize artifacts of immunolabeling obtained in known TSE-negative control animals to differentiate those from specific PrP Sc immunolabeling types, which can vary between TSE strains, host species, and prnp genotype, further described herein.

C-terminal tensin-like (tensin-4/TNS4/CTEN) is the fourth member of the tensin family, frequently described as displaying oncological functions, including cellular migration, invasion, adhesion, growth, metastasis, epithelial to mesenchymal transition, and apoptosis, in several different types of cancer. To investigate, for the first time, the clinical significance of CTEN in squamous cell carcinoma (SCC) of dogs, we studied a total of 45 SCC sections from various dog breeds. The mean age of the affected dogs was 8.9 ± 3.6 years. Immunohistochemistry confirmed strong cytoplasmatic CTEN expression in the basal layer of the epidermis next to the tumor. We detected high CTEN expression associated with the highest grade of the tumor (grade III) and observed 100% of immunopositivity for this tumor grading ( p < 0.0001). These data suggest that CTEN is an oncogene in SCC of dogs and a promising biomarker and a therapeutic target for dogs affected by SCC.

Chromosomal instability (CIN) plays a key role in the carcinogenesis of several human cancers and can be related to the deregulation of core components of the spindle assembly checkpoint (SAC) including BUBR1 protein kinase. These proteins have been related to tumor development and poor survival rates in human patients with oral squamous cell carcinoma (OSCC). To investigate the expression of the SAC proteins BUBR1, BUB3 and SPINDLY and also Ki-67 in canine OSCC, we performed an immunohistochemical evaluation in 60 canine OSCCs and compared them with clinical and pathological variables. BUBR1, Ki-67, BUB3 and SPINDLY protein expressions were detected in all cases and classified as with a high-expression extent score in 31 (51.7%) cases for BUBR1, 33 (58.9%) cases for BUB3 and 28 (50.9%) cases for SPINDLY. Ki-67 high expression was observed in 14 (25%) cases. An independent prognostic value for BUBR1 was found, where high BUBR1 expression was associated with lower survival ( p = 0.012). These results indicate that BUBR1 expression is an independent prognostic factor in these tumors, suggesting the potential use for clinical applications as a prognostic biomarker and also as a pharmacological target in canine OSCC.

A local drug delivery system that attempts to find a suitable balance between antimicrobial and regenerative actions was developed for osteomyelitis treatment (OM). This system combines the angiogenic and immunomodulatory peptide LLKKK18 (LL18) and vancomycin hydrochloride (VH), loaded into an injectable oxidized dextrin (ODEX)-based hydrogel (HG). In vitro cytotoxicity was analyzed in MC3T3-E1 pre-osteoblasts and erythrocytes. The kinetics of LL18 release was studied. Antimicrobial activity was assessed in vitro against a clinical Methicillin-Resistant Staphylococcus aureus (MRSA) strain. A rat model of acute OM was developed by direct inoculation into a tibia defect, concomitantly with the implantation of the drug-loaded HG. The local bioburden was quantified and damage in surrounding tissues was examined histologically. In vitro, ODEX-based HG displayed a safe hemolytic profile. Half of LL18 (53%) is released during the swelling phase at physiological pH, then being gradually released until complete HG degradation. LL18-loaded HG at 300 μM was the most effective peptide formulation in decreasing in vivo infection among concentrations ranging from 86 to 429 μM. The histopathological scores observed in vivo varied with the LL18 concentration in a dose-dependent manner. VH at 28 mM completely eradicated bacteria, although with substantial tissue injury. We have found that sub-millimolar doses of VH combined with LL18 at 300 μM may suffice to eradicate the infection, with reduced tissue damage. We propose an easy-to-handle, shape-fitting HG formulation with the potential to treat MRSA-infected bone with low VH doses associated with LL18., (© 2022 Wiley Periodicals LLC.)

Analysis of canine and feline tumor malignancy data can help clinicians identify high-risk patients and make more accurate decisions. Based on a sample of 16,272 cancer records, including 3266 cats and 13,006 dogs, collected from January 2019 to December 2021 in the Vet-OncoNet Network database, this study aimed to compare the tumor malignancy profile between cats and dogs, considering animal-related factors (sex, age, and breed), topography, and geographic location using a mixed-effects logistic regression model. Cats had a higher proportion of malignant tumors (78.7%) than dogs (46.2%), and the malignancy profile was very different regarding tumors' topographies. The mean age of malignant tumors occurred eight months later than benign ones (9.1, SD = 3.4; 9.8, SD = 3.2), in general. Species (OR = 3.96, 95%CI 3.57: 4.39) and topography (MOR = 4.10) were the two most important determinants of malignancy risk. Female dogs had a higher risk than male dogs (OR = 1.19, 95%CI 1.08: 1.31), which does not appear to be the case in cats (OR = 0.98, 95%CI 0.77: 1.23). Breed contributed significantly to differences in malignancy risk in dogs (MOR = 1.56), particularly in pit bulls and boxers. District of residence was not so relevant in predicting malignancy risk (MOR = 1.14). In both species, the risk of malignancy increased by approximately 20% every three years. It could be hypothesized that species differences in genetic structure may contribute to tumor malignancy.

Scarce information exists on the role of mTOR pathway proteins and their association to aggressiveness and prognosis of patients with canine oral cancers. We aimed to investigate the activated form of mTOR and its downstream S6 protein in canine oral squamous cell carcinoma (OSCC), and to evaluate potential associations between protein expression and clinic-pathologic variables and survival. For that we analysed p-mTOR and p-S6 protein expression by immunohistochemistry in 61 canine OSCCs. Multivariate analysis was conducted to examine their role in patients' cancer-specific survival (CSS). p-mTOR and p-S6 expression were present in almost all cases. High-expression of p-mTOR was observed in 44 (72.1%) cases using extent score and 52 (85.2%) cases using intensity score. For p-S6, high expression was observed in 53 (86.9%) cases using extent score and in 54 (88.5%) cases using intensity score. An independent prognostic value for p-S6 extension ( p = 0.027), tumour stage ( p = 0.013) and treatment ( p = 0.0009) was found in patients' CSS analysis. Our data suggest that p-mTOR and p-S6 proteins are commonly expressed in canine OSCC and p-S6 expression is correlated with poor CSS in dogs with OSCC. More studies should be performed to identify possible therapeutic targets related with mTOR pathway for these patients.

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon ® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

Ionising radiotherapy is a well-established, effective cancer treatment modality, whose efficacy has improved with the application of newer technological modalities. However, patient outcomes are governed and potentially limited by aspects of tumour biology that are associated with radioresistance. Patients also still endure treatment-associated toxicities owed to the action of ionising radiation in normoxic tissue adjacent to the tumour mass. Tumour hypoxia is recognised as a key component of the tumour microenvironment and is well established as leading to therapy resistance and poor prognosis. In this review, we outline the current understanding of hypoxia-mediated radiotherapy resistance, before exploring targeting tumour hypoxia for radiotherapy sensitisation to improve treatment outcomes and increase the therapeutic window. This includes increasing oxygen availability in solid tumours, the use of hypoxia-activated prodrugs, targeting of hypoxia-regulated or associated signalling pathways, as well as the use of high-LET radiotherapy modalities. Ultimately, targeting hypoxic radiobiology combined with precise radiotherapy delivery modalities and modelling should be associated with improvement to patient outcomes.

The animal cancer burden is essential for the translational value of companion animals in comparative oncology. The present work aims to describe, analyze, and compare frequencies and associations of tumors in dogs and cats based on the Animal Cancer Registry created by Vet-OncoNet. With 9079 registries, regarding 2019 and 2020, 81% ( n = 7355) belonged to dogs. In comparison, cats have a general one-year right advance in the mean age of cancer diagnosis compared to dogs. The multivariate topography group analysis shows a distinct pattern between the two species: dogs have higher odds of cancer in the genito-urinary system, spleen, soft tissue tumors and skin, while cats show higher odds for tumors in the eyes, digestive organs, nasal cavity, lymph nodes, bones and mammary glands. Regarding morphologies, dogs are overrepresented in mast cell tumors (MCT), melanomas, and hemangiosarcomas. While cats are overrepresented in fibrosarcomas, lymphomas (T and B-cell), in malignant mammary tumors, and squamous cell carcinoma (SCC). Females have greater odds only in the mammary gland, with males having greater odds in six of twelve topographies. This study is the first outcome of continuous animal cancer registration studies in Portugal.

Cancer registries are fundamental tools for collecting epidemiological cancer data and developing cancer prevention and control strategies. While cancer registration is common in the human medical field, many attempts to develop animal cancer registries have been launched over time, but most have been discontinued. A pivotal aspect of cancer registration is the availability of cancer coding systems, as provided by the International Classification of Diseases for Oncology (ICD-O). Within the Global Initiative for Veterinary Cancer Surveillance (GIVCS), established to foster and coordinate animal cancer registration worldwide, a group of veterinary pathologists and epidemiologists developed a comparative coding system for canine neoplasms. Vet-ICD-O-canine-1 is compatible with the human ICD-O-3.2 and is consistent with the currently recognized classification schemes for canine tumors. It comprises 335 topography codes and 534 morphology codes. The same code as in ICD-O-3.2 was used for the majority of canine tumors showing a high level of similarity to their human counterparts ( n = 408). De novo codes ( n = 152) were created for specific canine tumor entities ( n = 126) and topographic sites ( n = 26). The Vet-ICD-O-canine-1 coding system represents a user-friendly, easily accessible, and comprehensive resource for developing a canine cancer registration system that will enable studies within the One Health space.

Objectives . Increased radiation doses could improve local control and overall survival of lung cancer patients, however, this could be challenging without exceeding organs at risk (OAR) dose constraints, especially for patients with advanced-stage disease. Increasing OAR doses could reduce the therapeutic ratio and quality of life. It is therefore important to investigate methods to increase the dose to target volume without exceeding OAR dose constraints. Methods . Gross tumour volume (GTV) was contoured on synthetic computerised tomography (sCT) datasets produced using the Velocity adaptive radiotherapy software for eleven patients. The fractions where GTV volume decreased compared to that prior to radiotherapy (reference plan) were considered for personalised progressive dose escalation. The dose to the adapted GTV (GTV Adaptive ) was increased until OAR doses were affected (as compared to the original clinical plan). Planning target volume (PTV) coverage was maintained for all plans. Doses were also escalated to the reference plan (GTV Clinical ) using the same method. Adapted, dose-escalated, plans were combined to estimate accumulated dose, D 99 (dose to 99%) of GTV Adapted , PTV D 99 and OAR doses and compared with those in the original clinical plans. Knowledge-based planning (KBP) model was developed to predict D 99 of the adapted GTV with OAR doses and PTV coverage kept similar to the original clinical plans; prediction accuracy and model verification were performed using further data sets. Results . Compared to the original clinical plan, the dose to GTV was significantly increased without exceeding OAR doses. Adaptive dose-escalation increased the average D 99 to GTV Adaptive by 15.1Gy and 8.7Gy compared to the clinical plans. The KBP models were verified and demonstrated prediction accuracy of 0.4% and 0.7% respectively. Conclusion . Progressive adaptive dose escalation can significantly increase the dose to GTV without increasing OAR doses or compromising the dose to microscopic disease. This may increase overall survival without increasing toxicities., (© 2022 IOP Publishing Ltd.)

Vet-OncoNet is a replicable tripartite animal cancer database with the scientific and academic purposes of collecting data and producing evidence-based knowledge for cancer science in general. Inspired by the One Health vision, Vet-OncoNet uses business intelligence tools to optimize the process of capturing, treating, and reporting animal cancer data to a national level in three interfaces: ACR (animal cancer registry, pathology-based), COR (clinical oncology registry, vet practice-based) and RFR (risk factor registry, owner-based). The first results show that skin and mammary gland are by far the most affected systems. Mast cell tumors and complex adenoma of the mammary gland are the most frequent histologic type in dogs, while in cats they are squamous cell carcinomas, tubular adenocarcinoma of the mammary gland and lymphomas. Regarding COR, it provides valuable information on the landscape of veterinary oncology practices, therapeutics options, outcomes and owners' drivers' adherence towards therapies, which range from 30% up to 80% upon vet practices. Furthermore, being aware of the role of animals within the family and as possible sentinels of environmental risks to cancer in humans, the network built an interface (Pet-OncoNet) dedicated to owners and a database (RFR) that receives information regarding pets and owners' daily habits.

The gastrointestinal (GI) tract is composed of rapidly renewing cells, which increase the likelihood of cancer. Colorectal cancer is one of the most frequently diagnosed GI cancers and currently stands in second place regarding cancer-related mortality. Unfortunately, the treatment of GI is limited, and few developments have occurred in the field over the years. With this in mind, new therapeutic strategies involving biologically active phytocompounds are being evaluated as anti-cancer agents. Vegetables such as broccoli, brussels sprouts, cabbage, cauliflower, and radish, all belonging to the Brassicaceae family, are high in dietary fibre, minerals, vitamins, carotenoids, polyphenols, and glucosinolates. The latter compound is a secondary metabolite characteristic of this family and, when biologically active, has demonstrated anti-cancer properties. This article reviews the literature regarding the potential of Cruciferous vegetables in the prevention and/or treatment of GI cancers and the relevance of appropriate compound formulations for improving the stability and bioaccessibility of the major Cruciferous compounds, with a particular focus on glucosinolates.

Importance: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed., Methods: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT)., Results: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms., Conclusions and Relevance: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study., Trial Registration: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the use of hypoxia pre-equilibrated tubes, higher platelet concentrations (>2 × 10 8 /mL versus 2 × 10 7 /mL), smaller volumes (600 µL versus 3 mL), and presence of plasma reduced the time for samples to reach 2% oxygen. Notably, oxygen levels decreased below 2% in most suspensions, but also in WP maintained at atmospheric 21% oxygen. Additionally, platelet spreading on fibrinogen was decreased when using hypoxic fibrinogen-coated culture plates regardless of the oxygen percentage (2% or 21%) in which platelet incubation took place. Thus, sample handling and experimental conditions should be carefully monitored in platelet-hypoxia studies as they might compromise results interpretation and comparison across studies.

This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose doxorubicin or surgery alone in cats with mammary carcinoma. Medical records of 228 female cats treated for mammary carcinoma between 2008 and 2018, were reviewed in eight veterinary institutions. Only cats with complete tumour staging and radical mastectomy were included in the study. One hundred and thirty-seven cats were divided into three treatment groups: group 1 (n = 80) cats treated with surgery, group 2 (n = 34) cats that had surgery and adjuvant treatment with doxorubicin, and group 3 (n = 23) cats with surgery and adjuvant treatment with low dose metronomic cyclophosphamide and meloxicam. The study endpoints were disease free interval (DFI) and overall survival (OS). Toxicity was evaluated according to the VCOG-CTCAE criteria. The median DFI was 270, 226 and 372 days in groups 1, 2 and 3, respectively. The median OS was 338 (group 1), 421 (group 2) and 430 (group 3) days. The differences between groups were not significant (DFI P = .280 and OS P = .186). Toxicity was observed in 52.9% (n = 18) of cats in group 2 and 39.1% (n = 9) of cats in group 3, with mild to moderate intensity. Differences were not significant (P = .306). In conclusion, adjuvant chemotherapy treatment did not improve survival and the overall benefit remains unproven. Randomized prospective trials are necessary to clarify the effectiveness of adjuvant chemotherapy treatment for feline mammary carcinomas., (© 2020 John Wiley & Sons Ltd.)

The presence of methicillin-resistant Staphylococcus aureus (MRSA) in bone infections difficults its treatment and is a sign of concern. The aim of this study was to evaluate in vitro activity of dalbavancin on pre-established adhered cells and 24 h old biofilms of MRSA strains isolated from a human bone infection. Thirty-three MRSA were isolated from osteomyelitis episodes. The antimicrobial susceptibility of these strains was assessed by the Kirby-Bauer disc diffusion method and the presence of resistance genes was screened by PCR. MRSA planktonic minimum inhibitory concentration and minimum bactericidal concentration were assessed. Minimum biofilm eradication concentration (MBEC) was performed by the microtiter biofilm formation assay. All 33 MRSA strains were classified as multidrug-resistant strains and susceptible to dalbavancin. Dalbavancin inhibited the growth of 54.6% and 52% of strains at the concentrations of 0.05 µg/mL and 1 µg/mL, respectively. The MBEC values up to 0.4 µg/mL demonstrated that dalbavancin was active against most strains in pre-established adhered cells and 24 h old biofilms. The current results show that dalbavancin is active against adhered cells and biofilms in vitro , suggesting that this antimicrobial agent may be an option for the treatment of bone infections caused by MRSA.

Wasting disease in small ruminants is frequently detected at slaughterhouses. The wasting disorder is manifested by the deterioration of the nutritional and physiological state of the animal indicated by thinness, emaciation, and cachexia. Evidence of emaciation and cachexia, alone, are pathological conditions leading to carcass condemnation during an inspection. Several diseases are associated with a wasting condition, including scrapie, pseudotuberculosis, tuberculosis, paratuberculosis, Maedi Visna, and tumor diseases. On the other hand, parasitic diseases, nutrition disorders, exposure or ingestion of toxins, metabolic conditions, inadequate nutrition due to poor teeth, or poor alimentary diet are conditions contributing to poor body condition. Classical and atypical scrapie is naturally occurring transmissible spongiform encephalopathies in small ruminants. The etiological agent for each one is prions. However, each of these scrapie types is epidemiologically, pathologically, and biochemically different. Though atypical scrapie occurs at low incidence, it is consistently prevalent in the small ruminant population. Hence, it is advisable to include differential diagnosis of this disease, from other possibilities, as a cause of wasting conditions detected during meat inspection at the abattoir. This manuscript is a review of the measures in force at the abattoir for scrapie control, focusing on the differential diagnosis of gross lesions related to wasting conditions detected in small ruminants during meat inspection.

Objectives . Volumetric modulated arc therapy (VMAT) allows for reduction of organs at risk (OAR) volumes receiving higher doses, but increases OAR volumes receiving lower radiation doses and can subsequently increasing associated toxicity. Therefore, reduction of this low-dose-bath is crucial. This study investigates personalizing the optimization of VMAT arc parameters (gantry start and stop angles) to decrease OAR doses. Materials and Methods . Twenty previously treated locally advanced non-small cell lung cancer (NSCLC) patients treated with half-arcs were randomly selected from our database. These plans were re-optimized with seven different arcs parameters; optimization objectives were kept constant for all plans. All resulting plans were reviewed by two clinicians and the optimal plan (lowest OAR doses and adequate target coverage) was selected. Furthermore, knowledge-based planning (KBP) model was developed using these plans as 'training data' to predict optimal arc parameters for individual patients based on their anatomy. Treatment plan complexity scores and deliverability measurements were performed for both optimal and original clinical plans. Results. The results show that different arc geometries resulted in different dose distributions to the OAR but target coverage was mostly similar. Different arc geometries were required for different patients to minimize OAR doses. Comparison of the personalized against the standard (2 half-arcs) plans showed a significant reduction in lung V 5 (lung volume receiving 5 Gy), mean lung dose and mean heart doses. Reduction in lung V 20 and heart V 30 were statistically insignificant. Plan complexity and deliverability measurements show the test plans can be delivered as planned. Conclusions. Our study demonstrated that personalizing arc parameters based on an individual patient's anatomy significantly reduces both lung and heart doses. Dose reduction is expected to reduce toxicity and improve the quality of life for these patients., (© 2021 IOP Publishing Ltd.)

Objectives . anatomical changes are inevitable during the course of radiotherapy treatments and, if significant, can severely alter expected dose distributions and affect treatment outcome. Adaptive radiotherapy (ART) is employed to maintain the planned distribution and minimise detriment to predicted treatment outcome. Typically, patients who may benefit from adaptive planning are identified via a re-planning process, i.e., re-simulation, re-contouring, re-planning and treatment plan quality assurance (QA). This time-intensive process significantly increases workload, can introduce delays and increases unnecessary stress to those patients who will not actually gain benefit. We consider it crucial to develop efficient models to predict changes to target coverage and trigger ART, without the need for re-planning. Methods. knowledge-based planning (KBP) models were developed using data for 20 patients' (400 fractions) to predict changes in PTV V 95 coverageΔV95PTV.Initially, this change in coverage was calculated on the synthetic computerised tomography (sCT) images produced using the Velocity adaptive radiotherapy software. Models were developed using patient (cell death bio-marker) and treatment fraction (PTV characteristic) specific parameters to predictΔV95PTVand verified using five patients (100 fractions) data. Results . three models were developed using combinations of patient and fraction specific terms. The prediction accuracy of the model developed using biomarker (PD-L1 expression) and the difference in 'planning' and 'fraction' PTV centre of the mass (characterised by mean square difference, MSD) had the higher prediction accuracy, predicting theΔV95PTVwithin ± 1.0% for 77% of the total fractions; with 59% for the model developed using, PTV size, PD-L1 and MSD and 48% PTV size and MSD respectively. Conclusion . the KBP models can predictΔV95PTVvery effectively and efficiently for advanced-stage NSCLC patients treated using volumetric modulated arc therapy and to identify patients who may benefit from adaption for a specific fraction., (© 2021 IOP Publishing Ltd.)

Purpose: This study aims to analyze the retinal layers and choroidal thickness in a large set of eyes with early age-related macular degeneration (AMD), in order to detect differences by stage suggestive of early neurodegeneration, and to explore biomarkers of different phenotypes., Methods: This study is a population-based, cross-sectional study. Patients from the incidence AMD study (NCT02748824) with early AMD (Rotterdam 2a, 2b, 3) were included. All performed spectral-domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Germany) and automatic segmentation of all retinal layers was obtained with built-in software. Manual correction was performed whenever necessary. The mean thicknesses (ETDRS grid) and volume of each layer were recorded. Subfoveal choroidal thickness was manually measured. Estimates for each layer thickness were calculated with linear mixed models and tested for pairwise differences between stages. Associations between layer thickness and microstructural findings were assessed by multivariate regression analysis., Results: The final cohort comprised 346 eyes (233 patients): 82.66% (n = 286) in stage 2a, 5.49% (n = 19) in stage 2b, and 11.85% (n = 41) in stage 3. A global tendency for lower/inferior thickness of the neuroretinal layers was found comparing stage 3 to 2a: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were inferior in the inner/outer ETDRS circles and the outer nuclear layer (ONL) and photoreceptors' segments layer in the central circle (p ≤ 0.002). The retinal pigment epithelium-Bruch's membrane (RPE/BrM) layer was thicker in stage 3 (p ≤ 0.001). Subretinal drusenoid deposits (SDD) were associated with thinner neuroretinal layers and choroid (p < 0.05)., Conclusions: Our results showed in a large population-based dataset that several inner and outer neuroretinal layers were thinner with a higher stage in early AMD. These findings support the existence of early and progressive neurodegeneration. Neuronal retinal layer thicknesses might thus be used as quantitative biomarkers of disease progression in AMD. The presence of SDD is possibly associated to more prominent and faster neurodegeneration., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Blood leukocyte counts and respective derived ratios have been described as potential prognostic markers in several tumours in veterinary oncology. This study aimed to evaluate peripheral blood leukocyte subpopulations and neutrophil-to-lymphocyte ratio (NLR) as prognostic factors for feline mammary carcinomas (FMC). Medical records from cats diagnosed with FMC between 2017 to 2019 were reviewed. Cats were included if fully staged, classified as WHO stage I to III, and submitted to mastectomy. Cats were excluded if they had evidence of other diseases. Forty-nine cats were included. The study endpoints were disease-free interval (DFI) and tumour-specific survival (TSS). The median DFI and TSS were 389 days and 528 days respectively. In the univariate analysis, higher values of total white blood cell count (WBC), neutrophil count (NEU) and NLR were identified as significant prognostic factors for both endpoints (P < .05). On the multivariate analysis, NLR remained an independent prognostic factor for TSS (P = .024). In the receiver operating characteristic curve analysis, the estimated cut-off for WBC was 8.49 × 10 9 /L (DFI and TSS); for NEU was 4.62 × 10 9 /L (DFI) and 6.65 × 10 9 /L (TSS) and for NLR was 2.46. These cut-offs were significant prognostic factors for DFI and TSS (P < .05). NLR cut-off remained an independent prognostic factor for both DFI (P = .032) and TSS (P = .043) in the multivariable analysis. Our results suggest that NLR, NEU, and WBC can be important non-invasive presurgical prognostic markers, and that NLR is an independent prognostic marker for FMC. Prospective studies are warranted to validate its clinical use., (© 2021 John Wiley & Sons Ltd.)

The majority of cancer deaths are linked to tumor spread, or metastasis, but 3D in vitro metastasis models relevant to the tumor microenvironment (including interstitial fluid flow) remain an area of unmet need. Microfluidics allows us to introduce controlled flow to an in vitro cancer model to better understand the relationship between flow and metastasis. Here, we report new hybrid spheroid-on-chip in vitro models for the impact of interstitial fluid flow on cancer spread. We designed a series of reusable glass microfluidic devices to contain one spheroid in a microwell under continuous perfusion culture. Spheroids derived from established cancer cell lines were perfused with complete media at a flow rate relevant to tumor interstitial fluid flow. Spheroid viability and migratory/invasive capabilities were maintained on-chip when compared to off-chip static conditions. Importantly, using flow conditions modeled in vitro , we are the first to report flow-induced secretion of pro-metastatic factors, in this case cytokines vascular endothelial growth factor and interleukin 6. In summary, we have developed a new, streamlined spheroid-on-chip in vitro model that represents a feasible in vitro alternative to conventional murine in vivo metastasis assays, including complex tumor environmental factors, such as interstitial fluid flow, extracellular matrices, and using 3D models to model nutrient and oxygen gradients. Our device, therefore, constitutes a robust alternative to in vivo early-metastasis models for determination of novel metastasis biomarkers as well as evaluation of therapeutically relevant molecular targets not possible in in vivo murine models., (© 2021 Author(s).)