Hepatic lead and copper concentrations in dogs with chronic hepatitis and their relationship with hematology, serum biochemistry, and histopathology

Background: Although the influence of copper ([Cu]) on chronic hepatitis (CH) has been widely studied in dogs, little information is available about the accumulation of other metals. Hypothesis/Objectives: We assessed the concentration of lead ([Pb]) in the livers of dogs with CH with or without abnormal hepatic [Cu] to establish if any association existed between [Pb] and either hematologic or biochemical variables, fibrosis, necrosis and inflammation of the liver on histology. Animals: Thirty-four dogs with CH that had hepatic [Cu] and [Pb] determined. Methods: Retrospective review of medical records of dogs with CH and hepatic [Cu] and [Pb]. Chronic hepatitis was defined using current American College of Veterinary Internal Medicine consensus statement guidelines. Hepatic [Cu] and [Pb] were determined using square wave anodic stripping voltammetry. Dogs were divided into 2 groups based on [Cu]: <400 ppm (LoCu) and ≥400 ppm (HiCu). Results: The median [Cu] and [Pb] were 357 ppm (range, 100-7743 ppm) and 58.7 (range, 6.89-224.4 ppm), respectively. Nineteen dogs had LoCu and 15 dogs had HiCu. Median [Pb] was significantly higher in HiCu compared to LoCu dogs (P <.001). Hepatic [Pb] and [Cu] were significantly correlated (rho = 0.7; P <.001). Dogs with microcytosis had higher [Pb] than did dogs with normal red cell volume (P =.02). Hepatic [Pb] was not correlated with either necroinflammatory or fibrosis scores. Conclusions and Clinical Importance: Although additional studies are needed to better understand the clinical role of hepatic [Pb], dogs with abnormal hepatic [Cu] may also have higher hepatic [Pb]. In addition, in dogs with high hepatic [Pb], microcytosis may be present

Validation of p53 Immunohistochemistry (PAb240 Clone) in Canine Tumors with Next-Generation Sequencing (NGS) Analysis

In human medicine, p53 immunohistochemistry (IHC) is a common method that is used for the identification of tumors with TP53 mutations. In veterinary medicine, several studies have performed IHC for p53 in canine tumors, but it is not known how well it actually predicts the mutation. The aim of this study was to estimate the accuracy of the IHC method for p53 (clone PAb240) using a lab-developed NGS panel to analyze TP53 mutations in a subset of malignant tumors in dogs. A total of 176 tumors were analyzed with IHC and then 41 were subjected to NGS analysis; among them, 15 were IHC positive and 26 were negative, and 16 out of 41 (39%) were found to be inadequate for NGS analysis. Excluding the non-evaluable cases at NGS, of the remaining eight IHC-positive cases, six were mutants and two were wild-type. Among the 17 IHC-negative cases, 13 were wild type, and 4 were mutants. The sensitivity was 60%, specificity was 86.7%, and the accuracy was 76%. These results suggest that when using IHC for p53 with this specific antibody to predict mutation, up to 25% wrong predictions can be expected

Risk of cataract in health care workers exposed to ionizing radiation: A systematic review

Background: The eye is an important sensory organ occupationally exposed to ionizing radiation (IR) in healthcare workers (HCWs) engaged in medical imaging (MI). New evidence highlights the possible induction of cataract at IR exposure levels to be much lower than expected in the past. Objective: Conduct an updated review on the current evidence on cataract risk in healthcare workers exposed to IR. Methods: Published scientific studies on cataract risk in IR exposed healthcare workers were collected through a systematic search of two biomedical databases (MEDLINE and Scopus). Data from included studies was extracted and summarized. Study quality was also assessed. Results: All 21 eligible studies reported an increased prevalence of cataract, especially posterior subcapsular cataract, in IR exposed HCWs with a higher prevalence in interventional cardiology staff. Discussion: Our review synthesizes the latest evidence to support the hypothesis of a significantly increased risk of occupational cataract in healthcare workers operating MI and exposed to IR, especially in interventional cardiologists. Data also support a dose-response relationship between IR exposure and the prevalence of opacities, especially posterior subcapsular opacities. Con-clusions: Findings highlight the need for effective control measures including appropriate training, adherence to protective procedures, and a constant use of shields and eye personal protective equipment in healthcare workers with optical exposure to IR. Periodic health surveillance programs, possibly including lens evaluation, are also important to monitor cataract risk in these MI operators

Phytochemical analysis and antisenescence activity of Sorbus torminalis (L.) Crantz and Elaeagnus umbellata Thunb fruits

In Italy, many spontaneous plants are used as food in folk traditions and are now being re-evaluated as healthy products with high nutritional value. In the ethnobotanical field, we selected a fruit tree that modern gastronomy has forgotten: the "Ciavardello" (Sorbus torminalis (L.) Crantz). The Italian phyto-alimentary tradition (1) uses its fruits to make jams, jellies, syrups, fresh snacks and, less often, alcoholic beverages. The "Ciavardello" is a species of Sorbus native to Europe, North Africa, and Asia Minor and it is a member of the Rosaceae family. It is a deciduous tree or shrub which grows 1-7 m tall (sometimes reaching 20 m) and it is a slow-growing and long-lived species found in forests of broadleaf trees. The trunk is straight and the crown is expanded, globose and dense, while the bark is smooth and greyish. The leaves are alternate, simple, glabrous, petiole, ovate (4–10 cm long and 2–8 cm wide), with five to nine acute lobes, serrate and dark green colored on both sides. The flowers are hermaphrodite, 5-merous, with white petals and they are produced in corymbs. It blooms in spring (April-May) and bears fruit in autumn (September-October). The fruit is a globose to ovoid pome 10–15 mm in diameter and it is greenish to russet or brown and patterned with small and pale lenticel spots when ripe, with a pleasantly acidulous taste (2). Another interesting plant is ‘Albero dei coralli’ (Elaeagnus umbellata Thunb.), an allochthonous species belonging to the Elaeagnaceae family. It is cultivated in Italy for ornamental purposes, while the fruits are eaten fresh, a custom that was imported from tropical and temperate Asia, its native region. The "Albero dei coralli" is a deciduous shrub or tree, more or less spiny, which grows 3-5 m tall. The leaves are alternate, lanceolate (4-10 cm x 2-4 cm), with wavy margins, green colored above and covered with silvery scales below. The flowers are hermaphrodite, fragrant, whitish, tubular and 4-lobed and they are found in the leaf axils in clusters of 1-7 elements. The fruits are small roundish drupes (3-9 mm diameter), reddish to pink, dotted with scales and they are pulpy, juicy and sweet. It blooms in the spring and its fruits ripen in the fall (2). Both fresh fruits, collected in the Tuscany region (Italy), were extracted at room temperature with EtOH-H2O 80% (three times, every 24 h) and obtained residues were partitioned between n-BuOH and H2O. The n-butanolic extracts were finally analyzed by HPLC-PDA/UV-ESI-MS/MS techniques. The chemical profile of S. torminalis revealed the presence of phenolic acids and flavonol glycosides (3), while E. umbellata extract was rich especially in quercetin and kaempferol derivatives. In the scenario of regenerative medicine, the gingival mesenchymal stem cells (GMSCs) have arisen as a promising tool to repair damaged tissues. Herein, the GMSCs were used to investigate the beneficial effects of n-butanolic extract of investigated fruits. Both extracts were able to increase the GMSC proliferation and decrease the intracellular accumulation of ROS. Furthermore, the extracts were able to counteract the senescence phenomena in GMSC with different extent. In particular, they contrast the ROS production mediated by hydroxyurea and hydrogen peroxide and reduced the age-related phenotypic changes (SA-β-gal staining). In conclusion, these results highlight S. torminalis and E. umbellata fruit extracts as novel sources of antioxidant phytocomplexes able to decrease the senescence process in mesenchymal cells. The ability of both extracts per se to ameliorate the GMSC well-being and decrease cellular senescence shed light on their possible use in regenerative medicine and in particular in all the GMSC in vitro application

HER2 Overexpression and Cytogenetical Patterns in Canine Mammary Carcinomas

Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that promotes tumor cell growth and is implicated in the pathogenesis of human breast cancer. The role of HER2 in canine mammary carcinomas (CMCs) is not clear. Therefore, this study aimed to examine the protein expression and cytogenetic changes of HER2 and their correlation with other clinical-pathological parameters in CMC. We retrospectively selected 112 CMCs. HER2, ER, and Ki67 were assessed by immunohistochemistry. HER2 antibody validation was investigated by immunoblot on mammary tumor cell lines. Fluorescence in situ hybridization (FISH) was performed with probes for HER2 and CRYBA1 (control gene present on CFA9). HER2 protein overexpression was detected in 15 carcinomas (13.5%). A total of 90 carcinomas were considered technically adequate by FISH, and 8 out of 90 CMC (10%) were HER2 amplified, 3 of which showed a cluster-type pattern. HER2 overexpression was correlated with an increased number of HER2 gene copies (p = 0.01; R = 0.24) and overall survival (p = 0.03), but no correlation with ER, Ki67, grade, metastases, and tumor-specific survival was found. Surprisingly, co-amplification or polysomy was identified in three tumors, characterized by an increased copy number of both HER2 and CRYBA1. A morphological translocation-fusion pattern was recognized in 20 carcinomas (22%), with a co-localized signal of HER2 and CRYBA1. HER2 is not associated with clinical-pathological parameters of increased malignancy in canine mammary tumors, but it is suitable for studying different amplification patterns

An Autonomous Power Controller for the NASA Human Deep Space Gateway

Autonomous control of a spacecraft is an enabling technology that must be developed for deep space human exploration. NASA's current long term human space platform, the International Space Station which is in Low Earth Orbit, is in almost continuous communication with ground based mission control. This allows near real-time control of all the vehicle core systems, including power, to be controlled by the ground. As the focus shifts from Low Earth Orbit, communication time-lag and bandwidth limitations beyond geosynchronous orbit does not permit this type of ground based operation. This paper presents the ongoing work at NASA to develop an architecture for autonomous power control system and a vehicle manager which monitors, coordinates, and delegates all the onboard subsystems to enable autonomous control of the complete spacecraft

Pathological features and molecular phenotype of mmtv like‐positive feline mammary carcinomas

In the last few years MMTV‐like nucleotide sequences were detected in some feline and canine mammary tumours. Due to the confirmed role of cats in the epidemiology of the MMTV‐like virus, the aim of this study was to investigate the main pathological features of positive feline mammary carcinomas (FMCs). Twenty‐four FMCs were collected at the University of Bologna, submitted to laser microdissection and analysed by nested fluorescence‐PCR using primer sets specific for MMTV env sequence. For immunohistochemistry, an antibody against MMTV protein 14 (p14) was used. MMTV‐like sequences were detected in three out of 24 FMCs (12.5%), one tubular carcinoma, one tubulopapillary carcinoma and one ductal carcinoma. All PCR‐positive tumours were also positive for p14. Multiple nucleotide alignment has shown similarity to MMTV ranging from 98% to 100%. All the 102 examined FMCs were submitted to immunohistochemistry for molecular pheno-typing. Of the nine MMTV‐like positive FMCs, six were basal‐like and three luminal‐like. Our results demonstrate MMTV‐like sequences and protein in FMCs of different geographic areas. Molecular phenotyping could contribute to understand the possible role of MMTV‐like virus in FMC tumor biology

Plasma Proteomic Variables Related to COVID-19 Severity: An Untargeted nLC-MS/MS Investigation

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to a wide range of clinical manifestations and determines the need for personalized and precision medicine. To better understand the biological determinants of this heterogeneity, we explored the plasma proteome of 43 COVID-19 patients with different outcomes by an untargeted liquid chromatography-mass spectrometry approach. The comparison between asymptomatic or pauci-symptomatic subjects (MILDs), and hospitalised patients in need of oxygen support therapy (SEVEREs) highlighted 29 proteins emerged as differentially expressed: 12 overexpressed in MILDs and 17 in SEVEREs. Moreover, a supervised analysis based on a decision-tree recognised three proteins (Fetuin-A, Ig lambda-2chain-C-region, Vitronectin) that are able to robustly discriminate between the two classes independently from the infection stage. In silico functional annotation of the 29 deregulated proteins pinpointed several functions possibly related to the severity; no pathway was associated exclusively to MILDs, while several only to SEVEREs, and some associated to both MILDs and SEVEREs; SARS-CoV-2 signalling pathway was significantly enriched by proteins up-expressed in SEVEREs (SAA1/2, CRP, HP, LRG1) and in MILDs (GSN, HRG). In conclusion, our analysis could provide key information for 'proteomically' defining possible upstream mechanisms and mediators triggering or limiting the domino effect of the immune-related response and characterizing severe exacerbations

Porcine Lawsonia intracellularis Ileitis in Italy and Its Association with Porcine Circovirus Type 2 (PCV2) Infection

The objective of this study was to employ a diagnostic algorithm, which involves detecting positive farms by stool PCR followed by PCR and histology/immunohistochemistry on ileum samples, for diagnosing Lawsonia intracellularis proliferative enteritis in Northern Italy. The primary aim was to examine the relationship between the gold standard of L. intracellularis diagnostics, namely histology and immunohistochemistry, and PCR in acute and chronic cases of L. intracellularis enteritides. An additional goal was to investigate the coinfection of L. intracellularis with porcine circovirus type 2 (PCV2). Twenty-eight ileum samples, including four from acute cases and 24 from chronic cases, were collected. PCR yielded positive results in 19 cases (four acute and 15 chronic cases). In comparison, immunohistochemistry was positive in 16 cases (four acute and 12 chronic cases), with an observed agreement of 89%. The findings suggest that performing the two tests in series can increase the specificity of the causal diagnosis. PCR may be used as a screening tool to identify the presence of the microorganism, and only positive cases will be examined by histology and immunohistochemistry to confirm the causative role of L. intracellularis. Co-infection with PCV2 was demonstrate in two out of four acute cases and in two out of 24 chronic cases, providing further evidence to support the hypothesis that when the infection starts with ubiquitous pathogens such as L. intracellularis, it may boost the possibility of PCV2 replication, especially in acute cases. As a result, this may trigger a transition from subclinical to clinical forms of PCV2 disease