Heat shock protein 90 is associated with hyperplasia and neoplastic transformation of canine prostatic epithelial cells

Heat shock protein 90 (HSP90) is a molecular chaperone that regulates critical signalling proteins of cancer development and progression. Abnormal levels of HSP90 have been observed in human prostatic carcinoma (PC), with prognostic and therapeutic implications. Since spontaneously arising canine PC is a valuable model for the human disease, the aim of this study was to evaluate the immunohistochemical expression of HSP90 in two normal canine prostates, 17 canine prostates with benign prostatic hyperplasia (BPH) and five canine prostates with PC. HSP90 was expressed in the cytoplasm of epithelial cells in all samples, with a significant increase in labelled cells in PCs. Nuclear labelling was observed occasionally in normal tissue, but was increased in BPH and PC. HSP90 immunoreactivity in preneoplastic lesions (proliferative inflammatory atrophy and prostatic intraepithelial neoplasia) was similar to that in PCs. Increased HSP90 expression in canine PCs suggests the involvement of this molecule in carcinogenesis and tumour progression, supporting HSP90 as a potential target for therapeutic intervention

VP41.09: Value of umbilical vein flow as a predictor of wellbeing in small‐for‐gestational‐age fetuses

n/

A strontium isoscape of Italy for provenance studies

We present a novel database of biological and geological 87Sr/86Sr values (n = 1920) from Italy, using literature data and newly analysed samples, for provenance purposes. We collected both bioavailable and non-bioavailable (i.e. rocks and bulk soils) data to attain a broader view of the Sr isotope variability of the Italian territory. These data were used to build isotope variability maps, namely isoscapes, through Kriging interpolations. We employed two different Kriging models, namely Ordinary Kriging and Universal Kriging, with a geolithological map of Italy categorized in isotope classes as external predictor. Model performances were evaluated through a 10-fold cross validation, yielding accurate 87Sr/86Sr predictions with root mean squared errors (RMSE) ranging between 0.0020 and 0.0024, dependent on the Kriging model and the sample class. Overall, the produced maps highlight a heterogeneous distribution of the 87Sr/86Sr across Italy, with the highest radiogenic values (>0.71) mainly localized in three areas, namely the Alps (Northern Italy), the Tuscany/Latium (Central Italy) and Calabria/Sicily (Southern Italy) magmatic/metamorphic terrains. The rest of the peninsula is characterized by values ranging between 0.707 and 0.710, mostly linked to sedimentary geological units of mixed nature. Finally, we took advantage of the case study of Fratta Polesine, to underscore the importance of choosing appropriate samples when building the local isoscape and of exploring different end-members when interpreting the local Sr isotope variability in mobility and provenance studies. Our user-friendly maps and database are freely accessible through the Geonode platform and will be updated over time to offer a state-of-the-art reference in mobility and provenance studies across the Italian landscape

The role of the capping agent and nanocrystal size in photoinduced hydrogen evolution using CdTe/CdS quantum dot sensitizers

Hydrogen production via light-driven water splitting is a key process in the context of solar energy conversion. In this respect, the choice of suitable light-harvesting units appears as a major challenge, particularly as far as stability issues are concerned. In this work, we report on the use of CdTe/CdS QDs as photosensitizers for light-assisted hydrogen evolution in combination with a nickel bis(diphosphine) catalyst (1) and ascorbate as the sacrificial electron donor. QDs of different sizes (1.7-3.4 nm) and with different capping agents (MPA, MAA, and MSA) have been prepared and their performance assessed in the above-mentioned photocatalytic reaction. Detailed photophysical studies have been also accomplished to highlight the charge transfer processes relevant to the photocatalytic reaction. Hydrogen evolution is observed with remarkable efficiencies when compared to common coordination compounds like Ru(bpy)32+ (where bpy = 2,2′-bipyridine) as light-harvesting units. Furthermore, the hydrogen evolution performance under irradiation is strongly determined by the nature of the capping agent and the QD size and can be related to the concentration of the surface defects within the semiconducting nanocrystal. Overall, the present results outline how QDs featuring large quantum yields and long lifetimes are desirable to achieve sustained hydrogen evolution upon irradiation and that a precise control of the structural and photophysical properties thus appears as a major requirement towards profitable photocatalytic applications

Old subjects with sepsis in the emergency department: Trend analysis of case fatality rate

Background: The burden of sepsis represents a global health care problem. We aimed to assess the case fatality rate (CFR) and its predictors in subjects with sepsis admitted to a general Italian hospital from 2009 to 2016, stratified by risk score. Methods: We performed a retrospective analysis of all sepsis-related hospitalizations after Emergency Department (ED) visit in a public Italian hospital in an 8-year period. A risk score to predict CFR was computed by logistic regression analysis of selected variables in a training set (2009-2012), and then confirmed in the whole study population. A trend analysis of CFR during the study period was performed dividing patient as high-risk (upper tertile of risk score) or low-risk. Results: Two thousand four hundred ninety-two subjects were included. Over time the incidental admission rate (no. of sepsis-related admissions per 100 total admissions) increased from 4.1% (2009-2010) to 5.4% (2015-2016); P < 0.001, accompanied by a reduced CFR (from 38.0 to 18.4%; P < 0.001). A group of 10 variables (admission to intensive care unit, cardio-vascular dysfunction, HIV infection, diabetes, age 65 80 years, respiratory diseases, number of organ dysfunction, digestive diseases, dementia and cancer) were selected by the logistic model to predict CFR with good accuracy: AUC 0.873 [0.009]. Along the years CFR decreased from 31.8% (2009-2010) to 25.0% (2015-2016); P = 0.007. The relative proportion of subjects 6580 years (overall, 52.9% of cases) and classified as high-risk did not change along the years. CFR decreased only in low-risk subjects (from 13.3 to 5.2%; P < 0.001), and particularly in those aged 6580 (from 18.2 to 6.6%; P = 0.003), but not in high-risk individuals (from 69.9 to 64.2%; P = 0.713). Conclusion: Between 2009 and 2016 the incidence of sepsis-related hospitalization increased in a general Italian hospital, with a downward trend in CFR, only limited to low-risk patients and particularly to subjects 6580 years

Angiogenesis in Spontaneous Tumors and Implications for Comparative Tumor Biology.

Blood supply is essential for development and growth of tumors and angiogenesis is the fundamental process of new blood vessel formation from preexisting ones. Angiogenesis is a prognostic indicator for a variety of tumors, and it coincides with increased shedding of neoplastic cells into the circulation and metastasis. Several molecules such as cell surface receptors, growth factors, and enzymes are involved in this process. While antiangiogenic therapy for cancer has been proposed over 20 years ago, it has garnered much controversy in recent years within the scientific community. The complex relationships between the angiogenic signaling cascade and antiangiogenic substances have indicated the angiogenic pathway as a valid target for anticancer drug development and VEGF has become the primary antiangiogenic drug target. This review discusses the basic and clinical perspectives of angiogenesis highlighting the importance of comparative biology in understanding tumor angiogenesis and the integration of these model systems for future drug development

Canine placenta histological findings and microvascular density: The histological basis of a negative neonatal outcome?

Placenta is essential for the development of the fetus, and its impaired function can lead to a negative outcome (i.e., neonatal mortality). In dogs, investigations on placenta histology and neonatal outcome in healthy bitches are lacking, and a contribution is provided in this study to emphasize the use of placenta histology in practice. Fifty-one placentas from 11 litters were collected during cesarean section, classified according to the litter size (large (L) or small (S)) and the outcome, this latter as healthy (Group 1) or dead within 7 days (Group 2). The placenta/puppy weight ratio (PPR) was calculated, and specimens were formalin-fixed and paraffin-wax embedded, and on the resulting histological slides, capillary density (CD) was quantified. Among necrosis, calcification, and intravascular leucocytes, only the presence of multifocal-confluent necrosis (significantly more frequent in Group 2) was associated with a higher risk of death within 7 days (odds ratio = 30.7). Mixed logistic regression ruled out the effect on death both of a bitch and cesarean type (programmed vs. emergency). PPR and CD values were associated with litter size; large litters had lower PPR (p < 0.01) and higher CD (p < 0.05) than small litters. The relationship between PPR and CD was negative and significant (p < 0.01). Necrosis was a frequent finding in canine placentas, but only when multifocal-confluent was it associated with a poor outcome. The litter size influenced PPR (lower in L) and CD (higher in L), and this is likely due to the plasticity of placenta adaptation

Deletion in the EVC2 gene causes chondrodysplastic dwarfism in Tyrolean grey cattle

During the summer of 2013 seven Italian Tyrolean Grey calves were born with abnormally short limbs. Detailed clinical and pathological examination revealed similarities to chondrodysplastic dwarfism. Pedigree analysis showed a common founder, assuming autosomal monogenic recessive transmission of the defective allele. A positional cloning approach combining genome wide association and homozygosity mapping identified a single 1.6 Mb genomic region on BTA 6 that was associated with the disease. Whole genome re-sequencing of an affected calf revealed a single candidate causal mutation in the Ellis van Creveld syndrome 2 (EVC2) gene. This gene is known to be associated with chondrodysplastic dwarfism in Japanese Brown cattle, and dwarfism, abnormal nails and teeth, and dysostosis in humans with Ellis-van Creveld syndrome. Sanger sequencing confirmed the presence of a 2 bp deletion in exon 19 (c.2993_2994ACdel) that led to a premature stop codon in the coding sequence of bovine EVC2, and was concordant with the recessive pattern of inheritance in affected and carrier animals. This loss of function mutation confirms the important role of EVC2 in bone development. Genetic testing can now be used to eliminate this form of chondrodysplastic dwarfism from Tyrolean Grey cattle

P-Glycoprotein and Breast Cancer Resistance Protein in Canine Inflammatory and Noninflammatory Grade III Mammary Carcinomas

P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) expression are frequently related to multidrug resistance (MDR) in neoplastic cells. Canine inflammatory and grade III noninflammatory mammary carcinomas (IMC and non-IMC) are aggressive tumors that could benefit from chemotherapy. This study describes the immunohistochemical detection of P-gp and BCRP in 20 IMCs and 18 non-IMCs from dogs that had not received chemotherapy. Our aim was to determine if P-gp and BCRP expression was related to the \u201cinflammatory\u201d phenotype, to establish a basis for future studies analyzing the response to chemotherapy in dogs with highly malignant mammary cancer. Immunolabeling was primarily membranous for P-gp with a more intense labeling in emboli, and immunolabeling was membranous and cytoplasmic for BCRP. P-gp was expressed in 17 of 20 (85%) IMCs compared to 7 of 18 (39%) non-IMCs (P = 0.006). BCRP was expressed within emboli in 15 of 19 (79%) emboli in IMC, 12 of 15 (80%) primary IMCs, and 12 of 18 (67%) non-IMCs, without statistically significant differences (P >.05). All IMCs and 67% of non-IMCs expressed at least 1 of the 2 transporters, and 63% (12/19) of IMCs and 39% (7/18) of non-IMCs expressed both P-gp and BCRP. P-gp and BCRP evaluation might help select patients for chemotherapy. P-gp, expressed in a significantly higher percentage of IMCs vs non-IMCs, might play a specific role in the chemoresistance of IMC

Construction and validation of a dimensional scale exploring mood disorders: MAThyS (Multidimensional Assessment of Thymic States)

<p>Abstract</p> <p>Background</p> <p>The boundaries between mood states in bipolar disorders are not clear when they are associated with mixed characteristics. This leads to some confusion to define appropriate therapeutic strategies. A dimensional approach might help to better define bipolar moods states and more specifically those with mixed features.</p> <p>Therefore, we proposed a new tool based on a dimensional approach, built with a priori five sub-scales and focus on emotional reactivity rather than exclusively on mood tonality. This study was designed to validate this MAThyS Scale (Multidimensional Assessment of Thymic States).</p> <p>Methods</p> <p>One hundred and ninety six subjects were included: 44 controls and 152 bipolar patients in various states: euthymic, manic or depressed. The MAThyS is a visual analogic scale consisting of 20 items. These items corresponded to five quantitative dimensions ranging from inhibition to excitation: emotional reactivity, thought processes, psychomotor function, motivation and sensory perception. They were selected as they represent clinically relevant quantitative traits.</p> <p>Results</p> <p>Confirmatory analyses demonstrated a good validity for this scale, and a good internal consistency (Cronbach's alpha coefficient = 0.95). The MathyS scale is moderately correlated of both the MADRS scale (depressive score; r = -0.45) and the MAS scale (manic score; r = 0.56).</p> <p>When considering the Kaiser-Guttman rule and the scree plot, our model of 5 factors seems to be valid. The four first factors have an eigenvalue greater than 1.0 and the eigenvalue of the factor five is 0.97. In the scree plot, the "elbow", or the point at which the curve bends, indicates 5 factors to extract. This 5 factors structure explains 68 per cent of variance.</p> <p>Conclusion</p> <p>The characterisation of bipolar mood states based on a global score assessing inhibition/activation process (total score of the MATHyS) associated with descriptive analysis on sub-scores such as emotional reactivity (rather than the classical opposition euphoria/sadness) can be useful to better understand the broad spectrum of mixed states.</p