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To characterize the clinicopathologic features of recently described genotypes of Newcastle disease virus (NDV), 1 representative strain of genotype XIV and 2 of genotype XVII, all isolated from West Africa, were used to infect groups of ten 4-week-old specific pathogen-free chickens. The pathobiology of these 3 strains was compared to a South African NDV strain classified within genotype VII. All chickens infected with the 4 viruses died or were euthanized by day 4 postinfection due to the severity of clinical signs. Gross and histologic lesions in all infected chickens included extensive necrosis of lymphoid tissues (thymus, spleen, bursa of Fabricius, cecal tonsils, gut-associated lymphoid tissue), gastrointestinal necrosis and hemorrhages, and severe hemorrhagic conjunctivitis. Immunohistochemical staining revealed systemic viral distribution, and the most intense staining was in the lymphoid organs. Results demonstrate that the 3 West African strains from the previously uncharacterized genotypes XIV and XVII are typical velogenic viscerotropic NDV strains with lesions similar to the South African strain. Under experimental conditions, QV4 and LaSota NDV vaccine strains successfully protected chickens from morbidity and mortality against the genotype VII and one genotype XVII NDV strain, with no significant differences in the amount of virus shed when 2 vaccine schemes were compared. [ABSTRACT FROM PUBLISHER]

Aims: To investigate the effect of 16 weeks of aerobic training performed at two different intensities on nitric oxide (tNOx) availability and iNOS/nNOS expression, oxidative stress (OS) and inflammation in obese humans with or without type 2 diabetes mellitus (T2DM).Methods: Twenty-five sedentary, obese (BMI > 30 kg/m2) males (52.8 ± 7.2 years); 12 controls versus 13 T2DM were randomly allocated to four groups that exercised for 30 min, three times per week either at low (Fat-Max; 30-40% VO(2max)) or moderate (T(vent); 55-65 % VO(2max)) intensity. Before and after training, blood and muscle samples (v. lateralis) were collected.Results: Baseline erythrocyte glutathione was lower (21.8 ± 2.8 vs. 32.7 ± 4.4 nmol/ml) and plasma protein oxidative damage and IL-6 were higher in T2DM (141.7 ± 52.1 vs. 75.5 ± 41.6 nmol/ml). Plasma catalase increased in T2DM after T(vent) training (from 0.98 ± 0.22 to 1.96 ± 0.3 nmol/min/ml). T2DM groups demonstrated evidence of oxidative damage in response to training (elevated protein carbonyls). Baseline serum tNOx were higher in controls than T2DM (18.68 ± 2.78 vs. 12.34 ± 3.56 μmol/l). Training at T(vent) increased muscle nNOS and tNOx in the control group only. Pre-training muscle nNOS was higher in controls than in T2DMs, while the opposite was found for iNOS. No differences were found after training for plasma inflammatory markers.Conclusion: Exercise training did not change body composition or aerobic fitness, but improved OS markers, especially when performed at T(vent). Non-diabetics responded to T(vent) training by increasing muscle nNOS expression and tNOx levels in skeletal muscle while these parameters did not change in T2DM, perhaps due to higher insulin resistance (unchanged after intervention). [ABSTRACT FROM AUTHOR]

The article provides information on a study which investigated an experimental canine model of Lyme disease. The study tested the hypothesis that histologic scoring of synovial lesions would be a useful method for evaluating the severity of the disease and provide standardization among studies. The study was also aimed at establishing a standardized synovial histologic grading system to confirm infection and evaluate the severity of synovial lesions in Borrelia burgdorferi-infected dogs.

The article presents information about recognition and diagnosis of Newcastle disease virus (NDV), including field presentation of the disease and traditional bench diagnostics, as well as some of the newer methods used in the laboratory. NDV is believed to be one of the most important animal diseases in the world. The researchers emphasize the need for rapid and reliable detection of the disease to help avoid economic losses and contain the disease.

The article analyzes several isolates of the Newcastle disease found usually in poultry. The authors report that phylogenetic studies have shown that the isolate from Australia belongs to class II genotype I, while the one found in the Long Bien, Vietnam outbreak belongs to class II genotype VIId. The one found in Nevada, was under class II genotype V, the authors also reported. They reveal that the isolates differ in their ability to cause clinical signs, in the characteristics of lesions and in terms of viral distribution among body tissues.

Recent evidence suggests that stressful experiences may be related to deficits in inhibitory functions and temporo-limbic epileptic-like activity. The latter may produce psychosensory seizure-like symptoms that may also appear in nonepileptic conditions. This study assesses whether the increased presence of the seizure-like symptoms in 113 unipolar depressive patients treated with SSRIs is as- sociated with significantly more severe symptoms of depression, traumatic stress, and dissociation in comparison with 86 healthy controls. Results indicate that seizure-like symptoms in depressive patients have significant association with depression, symptoms of dissociation, and traumatic stress. This association suggests that processess generating seizure-like symptoms may be related to symptoms of depression, traumatic stress, and dissociation. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that stressful experiences may be related to deficits in inhibitory functions and temporo-limbic epileptic-like activity. The latter may produce psychosensory seizure-like symptoms that may also appear in nonepileptic conditions. This study assesses whether the increased presence of the seizure-like symptoms in 113 unipolar depressive patients treated with SSRIs is as- sociated with significantly more severe symptoms of depression, traumatic stress, and dissociation in comparison with 86 healthy controls. Results indicate that seizure-like symptoms in depressive patients have significant association with depression, symptoms of dissociation, and traumatic stress. This association suggests that processess generating seizure-like symptoms may be related to symptoms of depression, traumatic stress, and dissociation. [ABSTRACT FROM AUTHOR]

Simple Summary: The generation of tumor-specific T cells remains a pillar of modern cancer immunotherapy. Exogenous vaccines often rely on targeting tumor-associated antigens. The anti-apoptotic protein survivin has been deemed a high priority target due to its overexpression in a wide variety of tumor types. To support the analysis of tumor-associated T cell responses, optimization of epitope mapping would be valuable. A heterologous prime-boost vaccination strategy was designed to target survivin to induce anti-tumor immune responses. However, survivin-specific T cell responses could not be detected in mice. Potential mechanisms to explain this failure were explored. To confirm the robustness of the vaccination platform, enhanced green fluorescent protein (eGFP) was targeted since it has been defined as a protein with relatively low immunogenicity. In this context the vaccination strategy uncovered novel T cell epitopes from eGFP in two strains of mice. This research highlighted the utility of the vaccine platform to triage potential target antigens based on their immunogenicity. Survivin is a member of the inhibitor of apoptosis family of proteins and has been reported to be highly expressed in a variety of cancer types, making it a high priority target for cancer vaccination. We previously described a heterologous prime-boost strategy using a replication-deficient adenovirus, followed by an oncolytic rhabdovirus that generates unprecedented antigen-specific T cell responses. We engineered each vector to express a mutated version of full-length murine survivin. We first sought to uncover the complete epitope map for survivin-specific T cell responses in C57BL/6 and BALB/c mice by flow cytometry. However, no T cell responses were detected by intracellular cytokine staining after re-stimulation of T cells. Survivin has been found to be expressed by activated T cells, which could theoretically cause T cell-mediated killing of activated T cells, known as fratricide. We were unable to recapitulate this phenomenon in experiments. Interestingly, the inactivated survivin construct has been previously shown to directly kill tumor cells in vitro. However, there was no evidence in our models of induction of death in antigen-presenting cells due to treatment with a survivin-expressing vector. Using the same recombinant virus-vectored prime-boost strategy targeting the poorly immunogenic enhanced green fluorescent protein proved to be a highly sensitive method for mapping T cell epitopes, particularly in the context of identifying novel epitopes recognized by CD4+ T cells. Overall, these results suggested there may be unusually robust tolerance to survivin in commonly used mouse strains that cannot be broken, even when using a particularly potent vaccination platform. However, the vaccination method shows great promise as a strategy for identifying novel and subdominant T cell epitopes. [ABSTRACT FROM AUTHOR]

The changes are as follows: (1) Replacing the heading of "Section 2.2.5." on page 3: "EMPA Analysis" with "EMPA and LA-ICP-MS Analyses" (2) The authors wish to add an explanation along with a reference in "Section 2.2.5." on page 4. Multi-Scale Minero-Chemical Analysis of Biomass Ashes: A Key to Evaluating Their Dangers vs. Minor and trace elements were analysed at the Department of Physics and Geology (Perugia University) by LA-ICP-MS using the analytical protocol reported in Ref. [25]. [Extracted from the article]

The ongoing COVID-19 pandemic drew global attention to infectious diseases, attracting numerous resources for development of pandemic preparedness plans and vaccine platforms—technologies with robust manufacturing processes that can quickly be pivoted to target emerging diseases. Newcastle Disease Virus (NDV) has been studied as a viral vector for human and veterinary vaccines, but its production relies heavily on embryonated chicken eggs, with very few studies producing NDV in cell culture. Here, NDV is produced in suspension Vero cells, and analytical assays (TCID50 and ddPCR) are developed to quantify infectious and total viral titer. NDV-GFP and NDV-FLS (SARS-CoV-2 full-length spike protein) constructs were adapted to replicate in Vero and HEK293 suspension cultures using serum-free media, while fine-tuning parameters such as MOI, temperature, and trypsin concentration. Shake flask productions with Vero cells resulted in infectious titers of 1.07 × 108 TCID50/mL for NDV-GFP and 1.33 × 108 TCID50/mL for NDV-FLS. Production in 1 L batch bioreactors also resulted in high titers in culture supernatants, reaching 2.37 × 108 TCID50/mL for NDV-GFP and 3.16 × 107 TCID50/mL for NDV-FLS. This shows effective NDV production in cell culture, building the basis for a scalable vectored-vaccine manufacturing process that can be applied to different targets. [ABSTRACT FROM AUTHOR]

This study is part of a 2 year disease surveillance project conducted to establish the prevalence of poultry and zoonotic pathogens, including Campylobacter spp., among small poultry flocks in Ontario, Canada. For each post-mortem submission to the Animal Health Laboratory, a pooled sample of cecal tissue was cultured for Campylobacter spp., and a husbandry and biosecurity questionnaire was completed by the flock owner (n = 153). Using both laboratory and questionnaire data, our objective was to investigate demographic, husbandry, and biosecurity factors associated with the presence of Campylobacter spp. in small flocks. Two multivariable logistic regression models were built. In the farm model, the odds of Campylobacter spp. were higher in turkeys, and when birds were housed in a mixed group with different species and/or types of birds. The odds were lower when antibiotics were used within the last 12 months, and when birds had at least some free-range access. The effect of pest control depended on the number of birds at risk. In the coop model, the odds of Campylobacter spp. were lower when owners wore dedicated clothing when entering the coop. These results can be used to limit the transmission of Campylobacter spp. from small poultry flocks to humans. [ABSTRACT FROM AUTHOR]

The emergence and re-emergence of pathogens with pandemic potential has been a persistent issue throughout history. Recent decades have seen significant outbreaks of zoonotic viruses from members of the Coronaviridae, Filoviridae, Paramyxoviridae, Flaviviridae, and Togaviridae families, resulting in widespread infections. The continual emergence of zoonotic viral pathogens and associated infections highlights the need for prevention strategies and effective treatments. Central to this effort is the availability of suitable animal models, which are essential for understanding pathogenesis and assessing transmission dynamics. These animals are also critical for evaluating the safety and efficacy of novel vaccines or therapeutics and are essential in facilitating regulatory approval of new products. Rapid development of animal models is an integral aspect of pandemic response and preparedness; however, their establishment is fraught by several rate-limiting steps, including selection of a suitable species, the logistical challenges associated with sharing and disseminating transgenic animals (e.g., the time-intensive nature of breeding and maintaining colonies), the availability of technical expertise, as well as ethical and regulatory approvals. A method for the rapid development of relevant animal models that has recently gained traction, in large part due to the COVID-19 pandemic, is the use of gene therapy vectors to express human viral receptors in readily accessible laboratory animals to enable virus infection and development of clinical disease. These models can be developed rapidly on any genetic background, making mechanistic studies and accelerated evaluation of novel countermeasures possible. In this review, we will discuss important considerations for the effective development of animal models using viral vector approaches and review the current vector-based animal models for studying viral pathogenesis and evaluating prophylactic and therapeutic strategies, with an emphasis on models of SARS-CoV-2 infection based on the vectorized expression of human angiotensin-converting enzyme 2. [ABSTRACT FROM AUTHOR]

There is evidence that chicken IL4 (chIL4) functions similarly to its mammalian analogue by enhancing type 2 T helper (Th2) humoral immunity and promoting protection against parasitic infections; however, no studies have been performed to assess the effect of chIL4 on the pathogenesis of Newcastle disease (ND). To assess the role of chIL4 in velogenic NDV pathogenesis we created a vNDV infectious clone expressing chIL4. We hypothesized that co-expression of chIL4 during virus replication would result in decreased inflammation caused by the Th1 response and thereby increasing survival to challenge with vNDV. To evaluate the effect of chIL4 during early infection with velogenic Newcastle disease virus (NDV) in chickens, recombinant NDV clones expressing either chIL4 (rZJ1-IL4) or a control expressing green fluorescent protein (rZJ1-GFP) were created by inserting an expression cassette in an intergenic region of the NDV genome. The pathogenesis of rZJ1-IL4 was assessed in 4-week-old specific pathogen free chickens. The extent of virus replication was evaluated by titration in mucosal secretions and immunohistochemistry in multiple tissues. Expression of chIL4 was confirmed in tissues using immunohistochemistry. Infection of birds with the rZJ1-IL4 resulted in successful viral replication in vivo and in vitro and generation of the chIL4 in tissues. All birds were clinically normal 2 DPI, with one bird in each group showing conjunctival swelling and enlarged spleens grossly. At 5 DPI, moderate or severe depression was observed in birds infected with rZJ1-GFP or rZJ1-IL4, respectively. Neurological signs and thymic atrophy were observed in one bird infected with rZJ1-IL4. Grossly, conjunctival swelling, mottled spleen and proventricular hemorrhages were observed at 5 DPI in one bird from each group. At 5 DPI, severe necrosis in the spleen, bursa and cecal tonsils were observed in birds infected with rZJ1-GFP, along with minimal evidence of chIL4 expression. In contrast, splenic atrophy, and moderate necrosis in the bursa and cecal tonsils were observed in birds infected with rZJ1-IL4. In addition, chIL4 signal was found in all tissues of rZJ1-IL4 birds at 5DPI. The production of chIL4 by a recombinant NDV strain resulted in the activation of the positive feedback loop associated with IL4 production. Insertion of chIL4 into NDV may decrease necrosis to lymphoid organs while increasing the severity of lymphoid atrophy and prolonged disease. However, with a low number of birds it is difficult to determine whether these results are significant to disease outcome. • Infection with rZJ1-IL4 resulted in successful viral replication in vivo and in vitro. • ChIL4 signal was found in the tissues of birds infected with rZJ1-IL4. • Production of chIL4 by a recombinant NDV strain decreased necrosis to lymphoid organs. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) vector mediated expression of therapeutic monoclonal antibodies is an alternative strategy to traditional vaccination to generate immunity in immunosuppressed or immunosenescent individuals. In this study, we vectorized a human monoclonal antibody (31C2) directed against the spike protein of SARS-CoV-2 and determined the safety profile of this AAV vector in mice and sheep as a large animal model. In both studies, plasma biochemical parameters and hematology were comparable to untreated controls. Except for mild myositis at the site of injection, none of the major organs revealed any signs of toxicity. AAV-mediated human IgG expression increased steadily throughout the 28-day study in sheep, resulting in peak concentrations of 21.4–46.7 µg/ mL, demonstrating practical scale up from rodent to large animal models. This alternative approach to immunity is worth further exploration after this demonstration of safety, tolerability, and scalability in a large animal model. [ABSTRACT FROM AUTHOR]

An evaluation of the hemorheologic parameters and an ultrasonographic study of the extracranial carotid tract were performed on 48 patients, age range: sixty to seventy-five years, affected by acute stroke, 23 of whom had hypertension, while 27 were smokers. None of them was suffering from hyperlipidemia, diabetes mellitus, or symptomatic coronary heart or peripheral artery disease. The echotomographic analysis, using B-mode real-time echotomography revealed atherosclerotic lesions in 26 patients. The hemorheologic pattern (hematocrit, fibrinogen, whole blood filterability, whole blood and plasma viscosity) was determined in all the patients three months after the clinical event. Statistical analysis of the results indicates a possible link between atherosclerotic lesions of the extracranial carotid tract and age, fibrinogen levels, and whole blood filterability. [ABSTRACT FROM AUTHOR]

The effects of 3-glucosaminoglycan sulfate on lipids and the hemorheologic parameters were observed in a preliminary double-blind crossover study in 30 hyperlipidemic peripheral vascular disease (PYD) patients. Parenteral administration of the test drug was associated with a reduction in serum lipids, especially in triglyceride levels, and a lowering of fibrinogen, plasma viscosity, and whole blood viscosity levels. These effects justify the drug's use in the treatment of PYD, especially when associated with hypertriglyceridemia and hemorheologic disturbances. [ABSTRACT FROM AUTHOR]

High-resolution real-time echotomography was used in a longitudinal study on 118 atherosclerotic plaques of the extracranial carotid tract with the aim of identifying those most likely to cause a cerebrovascular event. Seventy patients (average age 61 ± 7 years), referred to our Clinical Vascular Laboratory because suffering from transient cerebral ischemic attacks (TIA), coronary heart disease (CHD), peripheral artery disease (PAD), or cervical bruits (CB), were followed up for two years. Medical treatment remained that of the referring physician. Ten patients suffered from clinical events caused by stroke, TIA, and/or carotid occlusion during the follow-up. The echostructural profile of the lesions most often correlated with the clinical event was characterized by a mixed or hard echogenic pattern, an irregular surface, and an initial vascular stenosis of more than 50%. [ABSTRACT FROM AUTHOR]

A two-year follow-up on 118 atherosclerotic lesions of the extracranial carotid tract observed in 70 patients was carried out using real-time high-reso- lution echotomography. The following plaque characteristics were monitored: the echogenic patterns (soft, intermediate, hard, and mixed), the surface aspects, and the degree of stenosis. The aim of the study was to evaluate plaque evolution, in relation both to the degree of vessel stenosis produced and to the echostructural characteris- tics of the lesion. After two years 68% of the lesions remained unchanged while the degree of vessel stenosis increased in 32%; no case of regression was observed. Intrinsic factors appearing to condition an increase in degree of stenosis were ‘mixed’ and ‘hard’ echogenic pattern, an irregular lesion surface, and an initial degree of stenosis of more than 50%. A modification in the echogenic pattern, which generally tended to progress toward more highly reflecting echogenic levels was observed in 27% of the lesions studied. [ABSTRACT FROM AUTHOR]

An ultrasonographic study was performed in 187 hyperlipoproteinaemia patients to evaluate the incidence of atheromatous lesions in the extracranial carotid tract. A high-resolution, real-time, B-mode instrument with two probes (4- and 8- MHz) was used. Fifty-five subjects had high blood cholesterol levels, 70 high triglyceride values, and 62 both. Arteriosclerotic disease was present at other sites in 39% of the patients. Atheromatous carotid lesions were revealed in 37% of the patients, and there seemed to he no significant correlation with the type of hyperlipoproteinaemia. There was also no correlation between blood cholesterol levels and the presence or absence of atheromatous lesions. Increasing age and arteriosclerotic disease at other sites were the factors most frequently associated with atheromatous lesions in the extracranial carotid tract. [ABSTRACT FROM AUTHOR]

The article presents a case study of a one-year old calico spayed female domestic shorthair cat with history of anaemia, who was taken to the University of Georgia Small Animal Teaching Hospital after reporting severe inappetence and lethargy. The cat underwent abdominal and thoracic ultrasonography which showed abdominal and pericardial effusion while it was diagnosed effusive feline infectious peritonitis (FIP) with fibrinous epicarditis.