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Abstract In this study we aim to obtain a holistic view over the consequences of human-induced threats to the wild bird populations in the study area, based on data collected from a Wildlife Rehabilitation Centre (WRC) through the method of Partial Least Squares-Path Modelling (PLS-PM). The study area comprised 76 rural and urban municipalities located in northern Portugal. Within PLS-PM the threats ("anthropogenic pressures") are termed exogenous latent variables, while the final environmental consequence (wild bird mortality) is termed endogenous latent variable. Latent variables are concepts assessed by numerical parameters. The PLS-PM results identified as most significant pressures, the number of small and medium companies in the municipalities, both in traumatic and non-traumatic deaths. Although the pattern of weights is similar regardless of the general cause of death, traumatic causes seem to play a more prominent role given the larger weights in the relevant specific causes (number of companies). The high coefficients of determination (R2 > 0,8) reveal that the variance of wild bird mortality is largely explained by the variance of the pressures, which indicates a cause-effect relationship between the independent (pressures) and dependent (mortality) variables. The ample coverage of northern Portugal with a huge dataset suggests that this cause-effect relationship is typical from this region. The use of a sophisticated statistical method PLS-PM and its incorporation into a Geographic Information System (GIS) revealed to be an important tool for analysing wildlife impacts of environmental and human factors. The results obtained with this model indicate that there is a substantial negative impact of human activity on wild bird mortality. Graphical abstract Unlabelled Image Highlights • Wild birds in northern Portugal are affected by several anthropogenic factors. • Increased number of medium companies contributed to increased mortality of wild birds. • Habitat destruction and fragmentation is linked to wild bird mortality. [ABSTRACT FROM AUTHOR]

Summary: Mast cell tumours (MCTs) are among the most common cutaneous neoplasms in dogs and have a highly variable clinical behaviour. Cyclooxygenase (Cox) catalyzes the rate-limiting step in prostanoid biosynthesis and has recently gained attention as a prognostic factor and therapeutic target in human and animal oncology. In order to evaluate the potential value of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of canine MCTs, expression of Cox-2 was determined in 49 such tumours (14 of grade I, nine of grade II and 22 of grade III). Cox-2 was expressed by 86% of the tumours studied. The percentage of labelled cells ranged from isolated positive cells throughout the tumour (n =8) to localized foci of labelled cells (n =3) or diffuse labelling of >50% of the cells (n =31). The intensity of Cox-2 labelling ranged from weak (n =4) to moderate (n =16) and strong (n =22) and was greatest at the advancing margin of the tumour. The intensity of Cox-2 labelling was significantly different between the three histological groups (P =0.018). However, no significant differences were noted for the percentage of Cox-2 positive cells (P =0.122) and for the immunoreactivity score (P =0.348) between the histological grades. The results of this study suggest that NSAIDs, particularly Cox-2 inhibitors, may be of value in the treatment of canine MCTs. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: For patients diagnosed with advanced renal cell carcinoma (RCC), there are few therapeutic options. Radiation therapy is predominantly used to treat metastasis and has not proven effective in the adjuvant setting for renal cancer. Furthermore, RCC is resistant to standard cytotoxic chemotherapies. Targeted anti-angiogenics are the standard of care for RCC but are not curative. Newer agents, such as mTOR inhibitors and others that induce autophagy, have shown great promise for treating RCC. Here, we investigate the potential use of the small molecule STF-62247 to modulate radiation. Materials and methods: Using RCC cell lines, we evaluate sensitivity to radiation in addition to agents that induce autophagic cell death by clonogenic survival assays. Furthermore, these were also tested under physiological oxygen levels. Results: STF-62247 specifically induces autophagic cell death in cells that have lost VHL, an essential mutation in the development of RCC. Treatment with STF-62247 did not alter cell cycle progression but when combined with radiation increased cell killing under oxic and hypoxic/physiological conditions. Conclusions: This study highlights the possibility of combining targeted therapeutics such as STF-62247 or temsirolimus with radiation to reduce the reliance on partial or full nephrectomy and improve patient prognosis. [Copyright &y& Elsevier]

This study was designed to investigate the possible roles of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in canine mammary cancer angiogenesis. Immunohistochemistry was performed on 70 tumours (28 benign and 42 malignant) in order to detect COX-2 and VEGF expression. Microvessel density (MVD) was determined by CD31 immunolabelling to assess tumour angiogenesis. There was a significantly higher expression of COX-2 (P < 0.001), VEGF (P < 0.001) and MVD (P < 0.001) in malignant compared to benign tumours. In the malignant group, the MVD of COX-2 positive tumours was significantly higher than that of COX-2 negative tumours (P = 0.026). A similar association was observed for VEGF (P < 0.001) positive tumours. The results from this study suggested that over-expression of COX-2 and VEGF may contribute to increased angiogenesis and aggression in malignant tumours. [ABSTRACT FROM AUTHOR]

Abstract: Immunohistochemical detection of Cyclooxygenase (Cox)-1 and -2 enzymes in canine mammary tumours (CMT) has recently been described. However, the prognostic value of their expression needs to be established. The aim of this study was to investigate Cox (-1 and -2) prognostic value in malignant CMT by evaluating its correlation with clinicopathological parameters (tumour size, histological type, necrosis, lymph node metastasis) and with Disease Free Survival (DFS) and Overall Survival (OS). Twenty seven female dogs with malignant tumours were included. Cox-2 expression was associated with lymph node metastasis at surgery time, development of distant metastasis during follow-up (p =0.038), DFS (p =0.03) and OS (p =0.04). Multivariate survival analysis showed that Cox-2 did not retain its significance as an independent prognostic factor. For Cox-1 expression, no statistically significant association was observed. Present study suggests the usefulness of testing Cox-2 specific inhibitors as part of an adjuvant therapy in female dogs with malignant mammary neoplasias. [Copyright &y& Elsevier]

The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor which has been shown to have an important role in human breast cancer. Its role appears to be associated with increased angiogenesis and metastasis. In order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms were studied by using immunohistochemistry, comparing expression of EGFR, microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour aggressiveness. High EGFR immunoexpression was statistically significantly associated with tumour size, tumour necrosis, mitotic grade, histological grade of malignancy and clinical stage. High CD31 immunoreactivity was statistically significantly associated with tubule formation, histological grade of malignancy and clinical stage. A positive correlation between EGFR and CD31 immunoexpression (r = 0.843; P < 0.001) was also observed. Results suggest that an over-expression of EGFR may contribute to increased angiogenesis and aggression in malignant CMT, presenting the possibility of using EGFR inhibitors in the context of metastatic disease treatment. [ABSTRACT FROM AUTHOR]

This study was developed in order to understand the possible intervention of Campylobacter spp. as etiological agent of necrotic lesions in poultry livers. This way, Campylobacter spp. was isolated from poultry livers with and without necrotic lesions. Additionally, virulence factors ( cad F and cdt B) and antimicrobial resistance profile of the isolated strains were analyzed. From a total of 39 liver samples analyzed, 21 presented lesions and 18 were clean. Campylobacter spp. was isolated from 80.9% of liver samples with necrotic lesions (17/21) and from 38.9% of liver samples without lesions (7/18). These results indicate poultry liver as a potential source of human Campylobacter infection, since this bacteria may remain viable in the internal liver tissue in undercooked conditions. A high resistance to nalidixic acid (100%), norfloxacin (100%), ciprofloxacin (95.8%), ampicillin (91.6%) and tetracycline (75%) was observed among Campylobacter spp. isolates. Also, PCR detection of cdt B and cad F virulence and toxin genes, revealed 75% and 68.8% of positive samples, respectively. Strains isolated from livers with and without lesions presented similar results with respect to virulence factors and to antimicrobial resistance profiles, evidencing that these putative pathogenic determinants are widespread among the isolates from poultry livers. Phi coefficient calculated in order to measure the degree of association, revealed a highly significant association (Phi = 0.472; p -value < 0.01) between the presence of livers with hepatic necrosis lesions and Campylobacter isolation. This result indicates the possibility of using these macroscopic lesions as visible and reliable indicator of Campylobacter spp. presence in poultry flock, and, thus, becoming an important tool to support the implementation of corrective measures at poultry farms level. This methodology could contribute for an accurate time-efficient monitoring and the development of effective prevention and intervention measures for Campylobacter spp. infection with reduced cost. [ABSTRACT FROM AUTHOR]

• Excellent antibacterial activity of dalbavancin vs. methicillin-resistant Staphylococcus aureus (MRSA) in infection rat model. • Efficacy of dalbavancin confirmed for treatment of osteomyelitis caused by MRSA. • Efficacy shown by microbiological eradication and histological bone improvement. • The effect of dalbavancin was more pronounced in rats treated for 14 days. Bacterial osteomyelitis is a major clinical challenge in human and veterinary patients. This infection is an infrequent but feared complication of orthopedic surgery and is mainly caused by methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy of dalbavancin (dosed for either 7 or 14 days) in an MRSA-osteomyelitis tibial bone model. A total of 39 rats were included in the study. All animals received an inoculum of a clinical strain of MRSA (106 colony-forming units [CFU]) injected into the proximal tibia under general anesthesia. Dalbavancin was injected intraperitoneally for 7 or 14 days in 13 animals each; the remaining 13 animals received saline solution. After treatment, the animals were sacrificed. Infected tibiae were recovered for histological evaluation and microbiological analysis (MRSA count per gram of bone). Rats that received dalbavancin showed a statistically significant reduction of MRSA counts compared with the control group: median 0 CFU/g bone (14 days of dalbavancin) vs. 70 CFU/g bone (7 days of dalbavancin) and 1600 CFU/g bone (control). Histological evaluation showed typical signs of osteomyelitis in the control group, whereas there were no signs of bone infection in 92% of the rats that received 14 days of dalbavancin. According to this model, dalbavancin seems to have good efficacy for treating serious Gram-positive bone infections, including those caused by MRSA. [ABSTRACT FROM AUTHOR]