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Echo Research and Practice Jun 2018Congenital obstruction of the left ventricular outflow tract remains a significant problem and multilevel obstruction can often coexist. Obstruction can take several... (Review)
Review
Congenital obstruction of the left ventricular outflow tract remains a significant problem and multilevel obstruction can often coexist. Obstruction can take several morphological forms and may involve the subvalvar, valvar or supravalvar portion of the aortic valve complex. Congenital valvar stenosis presenting in the neonatal period represents a spectrum of disorders ranging from the hypoplastic left heart syndrome to almost normal hearts. Treatment options vary dependent on the severity of the left ventricular outflow tract obstruction (LVOTO) and the variable degree of left ventricular hypoplasia as well as the associated lesions such as arch hypoplasia and coarctation.
PubMed: 29681546
DOI: 10.1530/ERP-18-0016 -
Viruses Feb 2023Marek's disease virus (MDV), a highly cell-associated oncogenic α-herpesvirus, is the etiological agent of T cell lymphomas and neuropathic disease in chickens known as...
Marek's disease virus (MDV), a highly cell-associated oncogenic α-herpesvirus, is the etiological agent of T cell lymphomas and neuropathic disease in chickens known as Marek's disease (MD). Clinical signs of MD include neurological disorders, immunosuppression, and lymphoproliferative lymphomas in viscera, peripheral nerves, and skin. Although vaccination has greatly reduced the economic losses from MD, the molecular mechanism of vaccine-induced protection is largely unknown. To shed light on the possible role of T cells in immunity induced by vaccination, we vaccinated birds after the depletion of circulating T cells through the IP/IV injection of anti-chicken CD4 and CD8 monoclonal antibodies, and challenged them post-vaccination after the recovery of T cell populations post-treatment. There were no clinical signs or tumor development in vaccinated/challenged birds with depleted CD4 or CD8 T cells. The vaccinated birds with a combined depletion of CD4 and CD8 T cells, however, were severely emaciated, with atrophied spleens and bursas. These birds were also tumor-free at termination, with no virus particles detected in the collected tissues. Our data indicated that CD4 and CD8 T lymphocytes did not play a critical role in vaccine-mediated protection against MDV-induced tumor development.
Topics: Animals; Marek Disease; CD8-Positive T-Lymphocytes; Chickens; Lymphoma; Herpesvirus 2, Gallid; Viral Vaccines
PubMed: 36992357
DOI: 10.3390/v15030648 -
Viruses Jul 2023Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested...
Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread.
Topics: Animals; Chick Embryo; Hydroxycholesterols; Marek Disease; Chickens; Interferon-alpha; Antiviral Agents; Interferon Type I; Virus Replication
PubMed: 37631994
DOI: 10.3390/v15081652 -
Virology Jan 2015Marek׳s disease virus (MDV) is a widespread α-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead...
Marek׳s disease virus (MDV) is a widespread α-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead to downregulation of cell-surface MHC class I (Virology 282:198-205 (2001)), but the gene(s) involved have not been identified. Here we demonstrate that an MDV gene, MDV012, is capable of reducing surface expression of MHC class I on chicken cells. Co-expression of an MHC class I-binding peptide targeted to the endoplasmic reticulum (bypassing the requirement for the TAP peptide transporter) partially rescued MHC class I expression in the presence of MDV012, suggesting that MDV012 is a TAP-blocking MHC class I immune evasion protein. This is the first unique non-mammalian MHC class I immune evasion gene identified, and suggests that α-herpesviruses have conserved this function for at least 100 million years.
Topics: Amino Acid Sequence; Animals; Antibodies, Viral; Cell Line; Chickens; Gene Expression Regulation; Histocompatibility Antigens Class I; Immune Evasion; Mardivirus; Molecular Sequence Data; Viral Proteins
PubMed: 25462349
DOI: 10.1016/j.virol.2014.11.008 -
Biological Trace Element Research Mar 2022Selenium (Se) is an important microelement with numerous positive effects on human health and diseases. It is important to specify that the status and consumption of Se... (Review)
Review
Selenium (Se) is an important microelement with numerous positive effects on human health and diseases. It is important to specify that the status and consumption of Se are for a specific community as the levels of Se are extremely unpredictable between different populations and regions. Our existing paper was based on the impacts of Se on human health and disease along with data on the Se levels in Middle Eastern countries. Overall, the findings of this comprehensive review show that the consumption and levels of Se are inadequate in Middle Eastern nations. Such findings, together with the growing awareness of the importance of Se to general health, require further work primarily on creating an acceptable range of blood Se concentration or other measures to determine optimal Se consumption and, consequently, to guarantee adequate Se supplementation in populations at high risk of low Se intake.
Topics: Humans; Nutritional Status; Selenium; Selenoproteins
PubMed: 33884538
DOI: 10.1007/s12011-021-02716-z -
Neurology Apr 2023The University of Pennsylvania Smell Identification Test (UPSIT) is commonly used to assess olfaction and screen for early detection of disorders including Parkinson... (Clinical Trial)
Clinical Trial
BACKGROUND AND OBJECTIVES
The University of Pennsylvania Smell Identification Test (UPSIT) is commonly used to assess olfaction and screen for early detection of disorders including Parkinson (PD) and Alzheimer disease. Our objective was to develop updated percentiles, based on substantially larger samples than previous norms, to more finely discriminate age- and sex-specific UPSIT performance among ≥50-year-old adults who may be candidates for studies of prodromal neurodegenerative diseases.
METHODS
The UPSIT was administered cross-sectionally to participants recruited between 2007-2010 and 2013-2015 for the Parkinson Associated Risk Syndrome (PARS) and Parkinson's Progression Markers Initiative (PPMI) cohort studies, respectively. Exclusion criteria included age <50 years and a confirmed or suspected PD diagnosis. Demographics, family history, and prodromal features of PD including self-reported hyposmia were collected. Normative data including mean, SDs, and percentiles were derived by age and sex.
RESULTS
The analytic sample included 9,396 individuals (5,336 female and 4,060 male), aged 50-95 years, who were predominantly White, non-Hispanic US residents. UPSIT percentiles were derived and are provided across 7 age categories (50-54, 55-59, 60-64, 65-69, 70-74, 75-79, and ≥80 years) for female and male participants separately; relative to existing norms, subgroups included between 2.4 and 20 times as many participants. Olfactory function declined with age and was better among women than men; accordingly, the percentile corresponding to a given raw score varied markedly by age and sex. UPSIT performance was comparable among individuals with vs without first-degree family history of PD. Comparisons of self-reported hyposmia vs UPSIT percentiles indicated a strong association (χ < 0.0001) but minimal agreement (Cohen simple kappa [95% CI]: = 0.32 [0.28-0.36] for female participants; 0.34 [0.30-0.38] for male participants).
DISCUSSION
Updated age/sex-specific UPSIT percentiles are provided for ≥50-year-old adults who reflect a population likely to be recruited into studies of prodromal neurodegenerative diseases. Our findings highlight the potential advantages of evaluating olfaction relative to age and sex instead of in absolute terms (i.e., based on raw UPSIT scores) or based on subjective (i.e., self-reported) measures. This information addresses the need to support studies of disorders including PD and Alzheimer disease by providing updated normative data from a larger sample of older adults.
TRIAL REGISTRATION INFORMATION
NCT00387075 and NCT01141023.
Topics: Aged; Female; Humans; Male; Middle Aged; Alzheimer Disease; Anosmia; Olfaction Disorders; Parkinson Disease; Smell; Cross-Sectional Studies
PubMed: 36849448
DOI: 10.1212/WNL.0000000000207077 -
Viruses Dec 2022Marek's disease virus (MDV) infection results in Marek's disease (MD) in chickens, a lymphoproliferative and oncogenic deadly disease, leading to severe economic losses....
Marek's disease virus (MDV) infection results in Marek's disease (MD) in chickens, a lymphoproliferative and oncogenic deadly disease, leading to severe economic losses. The spleen and bursa are the most important lymphoid and major target organs for MDV replication. The immune response elicited by MDV replication in the spleen and bursa is critical for the formation of latent MDV infection and reactivation. However, the mechanism of the host immune response induced by MDV in these key lymphoid organs during the latent and reactivation infection phases is not well understood. In the study, we focused on the replication dynamics of a vaccine MDV strain MDV/CVI988 and a very virulent MDV strain MDV/RB1B in the spleen and bursa in the latent and reactivation infection phases (7-28 days post-inoculation [dpi]), as well as the expression of some previously characterized immune-related molecules. The results showed that the replication ability of MDV/RB1B was significantly stronger than that of MDV/CVI988 within 28 days post-infection, and the replication levels of both MDV strains in the spleen were significantly higher than those in the bursa. During the latent and reactivation phase of MDV infection (7-28 dpi), the transcriptional upregulation of chicken IL-1β, IL6, IL-8L1 IFN-γ and PML in the spleen and bursa induced by MDV/RB1B infection was overall stronger than that of MDV/CVI988. However, compared to MDV/RB1Binfection, MDV/CVI988 infection resulted in a more effective transcriptional activation of CCL4 in the latent infection phase (7-14 dpi), which may be a characteristic distinguishing MDV vaccine strain from the very virulent strain.
Topics: Animals; Cytokines; Spleen; Marek Disease; Chickens; Herpesvirus 2, Gallid; Marek Disease Vaccines; Latent Infection
PubMed: 36680047
DOI: 10.3390/v15010006 -
Virology Feb 2023Marek's disease, caused by herpes virus infection, is a highly contagious disease characterized by latent infection. Here, we aimed to study the pathology, viremia and...
Marek's disease, caused by herpes virus infection, is a highly contagious disease characterized by latent infection. Here, we aimed to study the pathology, viremia and apoptosis during the Marek's Disease Virus (MDV) latency in vaccinated chickens. Vaccinated chickens were inoculated with the MD5 strain and were dissected at different time points. The viremia occurs in the spleen and thymus during the latency period of MD5 infection, however, lesions can be observed in the liver tissue. The latency-associated early gene of MDV, i.e., ICP4, was highly expressed in the spleen and thymus during the early latency. Compared with the early cytolytic stage, apoptosis of splenocytes was remarkably downregulated in the latency period. This study suggests that MDV latency could occur in the spleen and thymus in vaccinated chickens and there is a negative correlation between the MDV latency and apoptosis of spleen. MDV latency can resist the apoptosis of spleen.
Topics: Animals; Marek Disease; Chickens; Viremia; Herpesvirus 2, Gallid; Apoptosis
PubMed: 36696868
DOI: 10.1016/j.virol.2023.01.003 -
Veterinarni Medicina Nov 2023Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The...
Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The purpose of this study was to describe non-classical gross lesions observed in broilers and laying hens that suggest the disease emergence and re-emergence. The survey was conducted on 10 broiler and 4 laying hen flocks. All of the dead birds were necropsied in order to obtain a comprehensive diagnosis of lesions, analysing both macroscopic and microscopic alterations. Marek's disease occurred in 80% of cases in broilers and 100% of cases in layer hens. The disease struck 26-day-old broilers and hens at 2 weeks of age, causing a total mortality of 6% and 15%, respectively. There were no clinical indications of the classical neurological form of the disease in either rearing type, and tumour lesions were mostly detected in the liver, spleen, and ovarian follicles in layers, and in the proventriculus in broilers. These findings demonstrated that MD is widespread and that its resurgence is primarily manifested in visceral rather than neurological manifestations. Despite MD immunization, biosecurity remains critical.
PubMed: 38163046
DOI: 10.17221/75/2023-VETMED -
Epidemics Jun 2019The industrialization of farming has had an enormous impact. To most, this impact is viewed solely in the context of productivity, but the denser living conditions and...
The industrialization of farming has had an enormous impact. To most, this impact is viewed solely in the context of productivity, but the denser living conditions and shorter rearing periods of industrial livestock farms provide pathogens with an ideal opportunity to spread and evolve. For example, the industrialization of poultry farms drove the Marek's disease virus (MDV) to evolve from a mild paralytic syndrome to a highly contagious, globally prevalent, deadly disease. Fortunately, the economic catastrophe that would occur from MDV evolution is prevented through the widespread use of live imperfect vaccines that limit disease symptoms, but fail to prevent transmission. Unfortunately, the continued rollout of such imperfect vaccines is steering MDV evolution towards even greater virulence, and the ability to evade vaccine protection. Thus, there is a need to investigate alternative economically viable control measures for their ability to inhibit MDV spread and evolution. In what follows we examine the economic viability of standard husbandry practices for their ability to inhibit the spread of both virulent MDV and very virulent MDV throughout an industrialized egg farm. To do this, we parameterize a MDV transmission model and calculate the loss in egg production due to MDV. We find that MDV strain and the cohort duration have the greatest influence on both disease burden and egg production. Additionally, our findings show that for long cohort durations, conventional cages result in the least per capita loss in egg production due to MDV infection, while Aviary systems perform best over shorter cohort durations. Finally, we find that the least per capita loss in egg production for flocks infected with the more virulent MDV strains occurs when cohort durations are sufficiently short. These results highlight the important decisions that managers will face when implementing new hen husbandry practices.
Topics: Animals; Chickens; Eggs; Food Industry; Marek Disease; Virulence
PubMed: 30745241
DOI: 10.1016/j.epidem.2019.01.004