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Broad-spectrum antiviral activities of interferon-induced transmembrane proteins (IFITMs) are primarily attributed to in vitro inhibition of viral entry. Here, we used an avian sarcoma-leukosis virus (RCAS)-based gene transfer system and successfully generated chicks that constitutively express chicken IFITM3 (chIFITM3). The chIFITM3-overexpressing chicks showed significant protection and disease tolerance against highly pathogenic avian influenza virus (HPAIV) H5N1 (Clade 2.2.1.2). The chicks, overexpressing chIFITM3, also showed delayed onset of clinical symptoms, reduced viral shedding, and alleviated histopathologic alterations compared to control and challenged chicks. These findings highlight that overexpression of chIFITM3 provide a substantial defense against zoonotic H5N1 in vivo.
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Subtipo H5N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Sarcoma Aviar , Animales , Pollos , Gripe Aviar/prevención & control , Subtipo H5N1 del Virus de la Influenza A/genéticaRESUMEN
BACKGROUND: Frailty is associated with significant morbidity and mortality and may have clinical implications in an advanced age population with atrial fibrillation undergoing left atrial appendage occlusion (LAAO). We sought to develop a novel frailty scale to predict worse outcomes in patients undergoing LAAO. METHODS: Patients in the NCDR LAAO Registry between 2016 and 2021 receiving percutaneous LAAO devices were categorized as non-frail (0 points), pre-frail (1-3 points), or frail (4-5 points) based on a 5-point scale representing multiple domains of frailty: hemoglobin <13.0 g/dL in male, <12.0 g/dL in female; creatinine ≥1.2 mg/dL; albumin <3.5 g/dL; body mass index <20 kg/m2; and increased risk of falls. RESULTS: Of 57,728 patients, 44,360 (76.8%) were pre-frail and 7693 (13.3%) were frail. Compared to non-frail, pre-frail and frail patients were older, had a higher burden of co-morbidities, and more disability based on the Modified Rankin Scale. Compared to non-frail patients after adjustment, frail patients were at higher risk of in-hospital major complication (OR 1.29, 95% 1.02-1.62, p = 0.01), any complication (OR 1.29, 95% CI 1.09-1.52, p = 0.0005), and death (OR 5.79, 95% CI 1.75-19.17, p = 0.001), while no difference was observed in pre-frail patients. At 45-day follow-up, there was no difference in the risk of complications in frail patients as compared to non-frail, although mortality was significantly higher (OR 3.01, 95% CI 1.97-4.85, p < 0.0001). CONCLUSION: A simple and practical frailty scale accurately predicts adverse events in patients undergoing LAAO. The 13% of patients considered frail were at significantly higher risk of in-hospital adverse events and 45-day mortality.
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Apéndice Atrial , Fibrilación Atrial , Fragilidad , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/cirugía , Fragilidad/epidemiología , Fragilidad/complicaciones , Estudios Retrospectivos , Sistema de Registros , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
Abstract This study was aimed to investigate Carbofuran (CF)-induced pathological changes in cattle egret. Two hundred cattle egrets were reared and equally divided into four groups and given different CF concentrations (0.03 mg/L, 0.02 mg/L, 0.01 mg/L and 0 mg/L (control group)). Hematology, serum biochemistry, histopathology, and immunological markers were studied. Our results confirm that CF induces anemic conditions, leukocytosis, elevated liver enzymatic activity, and alterations in renal biomarkers. Moreover, specific microscopic lesions such as multifocal necrosis, pyknotic nuclei, hemorrhages, congestion, and inflammatory cell proliferation were observed in the liver, kidney, spleen, and thymus. These findings suggest that CF can induce harmful effects, so the application of this pesticide in the field must be strictly monitored to mitigate the possibility of exposure to non-target species.
Resumo Este estudo teve como objetivo investigar as alterações patológicas induzidas por carbofurano (CF) em garças-vaqueiras. Duzentas dessas garças foram criadas e divididas igualmente em quatro grupos e receberam diferentes concentrações de CF: 0,03 mg/L; 0,02 mg/L; 0,01 mg/L; e 0 mg/L (grupo controle). Foram realizadas análises de hematologia, bioquímica sérica, histopatologia e marcadores imunológicos. Nossos resultados confirmaram que CF induz condições anêmicas, leucocitose, atividade enzimática hepática elevada e alterações nos biomarcadores renais. Além disso, lesões microscópicas específicas, como necrose multifocal, núcleos picnóticos, hemorragias, congestão e proliferação de células inflamatórias, foram observadas no fígado, rim, baço e timo. Esses achados sugerem que o CF pode causar efeitos nocivos, portanto a aplicação desse agrotóxico no campo deve ser rigorosamente monitorada para mitigar a possibilidade de exposição a espécies não alvo.
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Abstract This study was aimed to investigate Carbofuran (CF)-induced pathological changes in cattle egret. Two hundred cattle egrets were reared and equally divided into four groups and given different CF concentrations (0.03 mg/L, 0.02 mg/L, 0.01 mg/L and 0 mg/L (control group)). Hematology, serum biochemistry, histopathology, and immunological markers were studied. Our results confirm that CF induces anemic conditions, leukocytosis, elevated liver enzymatic activity, and alterations in renal biomarkers. Moreover, specific microscopic lesions such as multifocal necrosis, pyknotic nuclei, hemorrhages, congestion, and inflammatory cell proliferation were observed in the liver, kidney, spleen, and thymus. These findings suggest that CF can induce harmful effects, so the application of this pesticide in the field must be strictly monitored to mitigate the possibility of exposure to non-target species.
Resumo Este estudo teve como objetivo investigar as alterações patológicas induzidas por carbofurano (CF) em garças-vaqueiras. Duzentas dessas garças foram criadas e divididas igualmente em quatro grupos e receberam diferentes concentrações de CF: 0,03 mg/L; 0,02 mg/L; 0,01 mg/L; e 0 mg/L (grupo controle). Foram realizadas análises de hematologia, bioquímica sérica, histopatologia e marcadores imunológicos. Nossos resultados confirmaram que CF induz condições anêmicas, leucocitose, atividade enzimática hepática elevada e alterações nos biomarcadores renais. Além disso, lesões microscópicas específicas, como necrose multifocal, núcleos picnóticos, hemorragias, congestão e proliferação de células inflamatórias, foram observadas no fígado, rim, baço e timo. Esses achados sugerem que o CF pode causar efeitos nocivos, portanto a aplicação desse agrotóxico no campo deve ser rigorosamente monitorada para mitigar a possibilidade de exposição a espécies não alvo.
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Animales , Carbofurano/toxicidad , Aves , BovinosRESUMEN
Introduction Intracranial findings on imaging have long been used in assessing the severity of traumatic brain injury (TBI); the Rotterdam CT scoring (RCTS) is a more recent tool. Estimating the optic nerve sheath diameter (ONSD) at computed tomography (CT) can be another valuable predictor of the severity of the injury, especially as both ONSD and the RCTS are proven to be independent predictors of raised intracranial pressure (ICP). The study objective was to determine the correlation between ONSD at initial head CT and RCTS. Material and methods We observed 40 consecutive confirmed TBI cases at their initial head CT examinations in the emergency department for ONSD and the presence of other intracranial findings necessary to derive RCTS. The data were prospectively collected and analyzed, with statistical significance set at p ≤0.05 at 95% CI. Results The mean ONSD positively correlated with the Rotterdam CT score (r=0.368, p=0.019). A cut-off value of 6.83 mm was extrapolated from the receiver operator characteristic (ROC) curve as the mean binocular ONSD that best predicted severe RCTS (≥4) (sensitivity: 73.3%, specificity: 80%, positive predictive value: 68.7%, negative predictive value: 83.3%). The area under the curve (AUC) was 0.780 (p=0.003). Binary logistic regression analysis revealed an odd ratio (OR) of 11.000 (95% CI: 2.438-49.627; p=0.002). Conclusion TBI patients with high RCTS have wide mean binocular ONSD. Those with average binocular ONSD above the cut-off value are likelier to have severe TBI. With the documented good correlation, ONSD may become very useful in informing the clinical decision for sequential CT scans in TBI patients and, therefore, reducing the cumulative radiation burden from needless exposures. Furthermore, the non-invasive nature of its assessment will have more clinical relevance in resource-limited settings, where the skills and equipment for ICP monitoring are either not readily available or too expensive to be used routinely.
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Cobalt metal is considered as an essential trace element for the animals. Present investigation was undertaken in the peri-urban area to analyze the cobalt availability in animal food chain by using different indices. Cow, buffalo and sheep samples along with forage and soil samples were collected from the three different sites of District Jhang and analyzed through atomic absorption spectrophotometer. Cobalt values differed in soil samples as 0.315-0.535 mg/kg, forages as 0.127-0.333 mg/kg and animal samples as 0.364-0.504 mg/kg. Analyzed cobalt concentration in soil, forage and animal samples was found to be deficient in concentration with respect to standard limits. Soil showed the minimum cobalt level in Z. mays while maximum concentration was examined in the forage C. decidua samples. All indices examined in this study has values lesser than 1, representing the safer limits of the cobalt concentration in these samples. Enrichment factor (0.071-0.161 mg/kg) showed the highly deficient amount of cobalt enrichment in this area. Bio-concentration factor (0.392-0.883) and pollution load index (0.035-0.059 mg/kg) values were also lesser than 1 explains that plant and soil samples are not contaminated with cobalt metal. The daily intake and health risk index ranged from 0.00019-0.00064 mg/kg/day and 0.0044-0.0150 mg/kg/day respectively. Among the animals, cobalt availability was maximum (0.0150 mg/kg/day) in the buffaloes that grazed on the C. decidua fodder. Results of this study concluded that cobalt containing fertilizers must be applied on the soil and forages. Animal feed derived from the cobalt containing supplements are supplied to the animals, to fulfill the nutritional requirements of livestock.
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Cobalto , Contaminantes del Suelo , Femenino , Bovinos , Animales , Ovinos , Suelo , Cadena Alimentaria , Contaminantes del Suelo/análisis , Alimentación Animal/análisis , BúfalosRESUMEN
Background: Listeriosis is a zoonotic disease of humans, animals, birds, fish, and crustaceans worldwide. Domestic animals, especially ruminants, are more susceptible to listeriosis. This infectious disease is caused by Listeria monocytogenes, an intracellular bacterium that can cross blood-brain, placental and intestinal barriers. In Pakistan, the incidence and reliable diagnostic tools for the L. monocytogenes are unidentified in Nili-Ravi buffaloes. Aims: This study was designed to inspect listeriosis in buffaloes through molecular techniques and haemato-biochemical analyses. Methods: A total of 230 samples (115 milk and 115 faecal samples) were collected from symptomatic listeriosis cases in Nili-Ravi buffaloes of 3 geographical districts (Rawalpindi, Faisalabad, and Muzaffargarh) Punjab, Pakistan. These samples were processed for DNA extraction using commercialized kits, and L. monocytogenes was confirmed by conventional PCR. Results: The results revealed that 6.08% and 4.34% of the isolates from milk and faecal samples were found positive for L. monocytogenes, respectively. The phylogenetic analysis of these isolates showed 97-100% similarity to isolates from the USA, Switzerland, Japan, and India. The accession numbers on NCBI GenBank appeared as HF558398 (Switzerland), KP965732 (India), EU372032 (USA), and LC259850 (Japan). Haemato-biochemical examinations showed that the values of WBCs, plasma fibrinogen, ALT, and AST significantly increased (P<0.05) in diseased buffaloes compared to healthy ones. Conclusion: The occurrence of listeriosis in buffaloes urges continuous monitoring and surveillance to prevent this emerging disease in Pakistan.
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Infectious laryngotracheitis (ILT) is an economically crucial respiratory disease of poultry that affects the industry worldwide. Vaccination is the principal tool in the control of the disease outbreak. In an earlier study, we comprehensively characterized the circulating strains in Egypt and identified both CEO-like and recombinant strains are dominant. Herein, we investigated the pathogenicity of two virulent strains representing the CEO-like (Sharkia_2018) and recombinant strain (Qalubia_2018). Additionally, we evaluated the efficacy of different commercial vaccines (HVT-LT, CEO, and TCO) against the two isolates in terms of the histopathological lesion scores and the viral (gC) gene load. A total of 270 White Leghorn-specific pathogen-free male chicks were divided into nine groups of 30 birds, each housed in separate isolators. Birds were distributed as follows; one group was non-vaccinated, non-challenged, and served as a negative control. Two groups were non-vaccinated and infected with the two isolates of interest and served as a positive control to test the pathogenicity. Six groups were vaccinated and challenged; two groups were vaccinated with vector vaccine at one day old. The other four groups were vaccinated with either the CEO- or TCO- vaccine (two groups each) at four weeks of age. Three weeks after vaccination, birds were infected with the virulent ILTV isolates. The larynx, trachea, and harderian gland samples were taken at 1, 3, and 7 days post-infection for histopathological lesion score and molecular detection. Notably, The recombinant strain was more virulent and pathogenic than CEO-like ILTV strains. Moreover, the TCO vaccine was less immunogenic than the vector and CEO vaccines.
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Infecciones por Herpesviridae , Herpesvirus Gallináceo 1 , Enfermedades de las Aves de Corral , Vacunas Virales , Animales , Pollos , Egipto/epidemiología , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/veterinaria , Herpesvirus Gallináceo 1/genética , Masculino , Eficacia de las Vacunas , Vacunas Atenuadas , VirulenciaRESUMEN
New results relating to the maximum and minimum degree spectral radii of generalized splitting and shadow graphs have been constructed on the basis of any regular graph, referred as base graph. In particular, we establish the relations of extreme degree spectral radii of generalized splitting and shadow graphs of any regular graph.
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Gene therapy holds potential in the treatment of many lung pathologies, as indicated by the growing number of clinical trials in recent decades. Pulmonary delivery of gene therapies via inhalation enables localised treatment while the extensive lung surface area promotes enhanced drug absorption. However, loss of nucleic acid integrity during the aerosolisation process, pulmonary clearance, and undesirable drug deposition, pose a major challenge for local delivery. Therefore, the development of nucleic acids into a stable inhalable pharmaceutical preparation would be advantageous. Dry powder inhalers (DPIs) are considered superior compared to nebulisation and pressurised-metered dose inhalers (pMDIs) due to the production of a stable dry formulation, an easy dispensing process, and minimal physical stress. DPIs are commonly produced via spray drying with a range of excipients, solvents, and separation options which can be modified to improve the stability of the nucleic acid cargo. This review details the ideal characteristics for pulmonary delivery and formulation of DPIs for gene therapy to the lungs. The utilisation of spray drying for the production of nucleic acid-containing DPIs is evaluated, with a specific focus on the influence of instrument parameters, the nucleic acid delivery system, and excipients with respect to cargo stability and functionality.
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Excipientes , Ácidos Nucleicos , Terapia Genética , Pulmón , Polvos , Secado por PulverizaciónRESUMEN
This study was aimed to investigate Carbofuran (CF)-induced pathological changes in cattle egret. Two hundred cattle egrets were reared and equally divided into four groups and given different CF concentrations (0.03 mg/L, 0.02 mg/L, 0.01 mg/L and 0 mg/L (control group)). Hematology, serum biochemistry, histopathology, and immunological markers were studied. Our results confirm that CF induces anemic conditions, leukocytosis, elevated liver enzymatic activity, and alterations in renal biomarkers. Moreover, specific microscopic lesions such as multifocal necrosis, pyknotic nuclei, hemorrhages, congestion, and inflammatory cell proliferation were observed in the liver, kidney, spleen, and thymus. These findings suggest that CF can induce harmful effects, so the application of this pesticide in the field must be strictly monitored to mitigate the possibility of exposure to non-target species.
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Carbofurano , Animales , Aves , Carbofurano/toxicidad , BovinosRESUMEN
BACKGROUND: Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare condition where a mutation in the transthyretin gene leads to systemic deposition of amyloid. The manifestations and prognosis of ATTR amyloidosis depends on the specific ATTR mutation, with over 100 mutations reported in the literature. The manifestations of many rare forms of ATTR amyloidosis have not been well described, particularly the late-onset ophthalmic findings. CASE PRESENTATION: We present the case of a 43-year-old Caucasian male with a diagnosis of ATTRD18E amyloidosis confirmed by fat pad biopsy. He had diffuse systemic involvement, including cardiovascular, pulmonary, and gastrointestinal symptoms. He also had significant ocular involvement including vitreous opacities, retinal angiopathy, and conjunctival lymphangiectasia. These ocular findings modestly progressed at 2-year follow-up. DISCUSSION: The ATTRD18E mutation is a rare variant, with few described cases. To our knowledge, this is the first documented case of ATTRD18E amyloidosis with significant ocular involvement. These ocular findings may serve as a relevant biomarker for severe disease prognosis in ATTRD18E amyloidosis. With improving treatments addressing the systemic symptoms of ATTR amyloidosis, a better understanding of the late-onset ocular symptoms is becoming increasingly relevant.
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Convalescent plasma therapy (CP) has long been used to prevent and treat various infectious diseases before COVID-19 such as SARS, MERS, and H1N1. Because the viral and clinical characteristics of COVID-19 share the similarities between SARS and MERS, CP treatment could be a promising treatment option to save COVID-19. With only low quality medical evidence, but massive media support and a very significant public demand for the use of convalescent plasma for COVID-19, we are now faced with an ethical dilemma. Therefore, this paper uses a structured analysis that focuses on the preferred reporting items for a systematic review of ethical issues regarding the use of Convalescent Plasma Therapy for COVID-19. The use of convalescent plasma must meet the ethical principles of autonomy; such as voluntary, informed consent, and confidentiality. Consideration of the risk-benefit ratio for potential donor recipients also needs to be considered in order to meet the beneficence and non-maleficence principles. The principle of justice also needs to be applied both to donors, donor recipients and health workers, such as determining the priority of donor recipients, due to the increasing demand for convalescent plasma amid the limited circumstances of patients who have recovered from Covid-19 who voluntarily donate.
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COVID-19/terapia , SARS-CoV-2 , Adolescente , Adulto , Altruismo , Donantes de Sangre , COVID-19/prevención & control , Niño , Confidencialidad , Selección de Donante/ética , Selección de Donante/normas , Personal de Salud , Humanos , Inmunización Pasiva/ética , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Consentimiento Informado , Autonomía Personal , Equipo de Protección Personal , Medición de Riesgo , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Justicia Social , Voluntarios , Sueroterapia para COVID-19RESUMEN
This study focused on producing high quality and yield of biodiesel from novel non-edible seed oil of abundantly available wild Raphnus raphanistrum L. using an efficient, recyclable and eco-friendly copper modified montmorillonite (MMT) clay catalyst. The maximum biodiesel yield of 83% was obtained by base catalyzed transesterification process under optimum operating conditions of methanol to oil ratio of 15:1, reaction temperature of 150 °C, reaction time of 5 h and catalyst loading of 3.5%. The synthesized catalyst and biodiesel were characterized for their structural features and chemical compositions using various state-of-the-art techniques, including x-ray diffraction, scanning electron microscopy, energy dispersive x-ray spectroscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance (1H, 13C) and gas chromatography-mass spectroscopy. The fuel properties of the biodiesel were estimated including kinematic viscosity (4.36 cSt), density (0.8312 kg/L), flash point (72 °C), acid value (0.172 mgKOH/g) and sulphur content (0.0002 wt.%). These properties were compared and found in good agreement with the International Biodiesel Standards of American (ASTM-951, 6751), European Committee (EN-14214) and China GB/T 20828 (2007). The catalyst was re-used in five consecutive transesterification reactions without losing much catalytic efficiency. Overall, non-edible Raphnus raphanistrum L.. seed oil and Cu doped MMT clay catalyst appeared to be highly active, stable, and cheap contenders for future biofuel industry. However, detailed life cycle assessment (LCA) studies of Raphnus raphanistrum L. seed oil biodiesel are highly recommended to assess the technical, ecological, social and economic challenges.
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Bentonita , Biocombustibles , Biocombustibles/análisis , Catálisis , China , Arcilla , Cobre , Aceites de PlantasRESUMEN
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The authors retract the above paper due to: 1) conflict of interest among the authors; and 2) addition of coauthor Dr. Muhammad Younus without his knowledge or permission. The authors apologize for these two grave mistakes.
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A self-administered validated (Cronbach's alpha=0.077) questionnaire was used to assess knowledge, attitude and practice among healthcare workers (HCWs) in Pakistan regarding coronavirus disease 2019 (COVID-19). Findings showed that HCWs have good knowledge (93.2%, N=386), a positive attitude [mean 8.43 (standard deviation 1.78)] and good practice (88.7%, N=367) regarding COVID-19. HCWs perceived that limited infection control material (50.7%, N=210) and poor knowledge regarding transmission (40.6%, N=168) were the major barriers to infection control. Regression analysis indicated that pharmacists were more likely to demonstrate good practice than other HCWs (odds ratio 2.247, 95% confidence interval 1.11-4.55, P=0.025). This study found that HCWs in Pakistan have good knowledge, but there are gaps in specific aspects of knowledge and practice that warrant attention.
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Betacoronavirus , Infecciones por Coronavirus/psicología , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/estadística & datos numéricos , Neumonía Viral/psicología , COVID-19 , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Estudios Transversales , Femenino , Personal de Salud/psicología , Humanos , Masculino , Persona de Mediana Edad , Enfermeras y Enfermeros/psicología , Enfermeras y Enfermeros/estadística & datos numéricos , Pakistán , Pandemias/prevención & control , Farmacéuticos/psicología , Farmacéuticos/estadística & datos numéricos , Médicos/psicología , Médicos/estadística & datos numéricos , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
The impact of liquid electrolyte soaking on the interfacial resistance between the garnet-structured Li7La3Zr2O12 (LLZO) solid electrolyte and metallic lithium has been studied. Lithium carbonate (Li2CO3) formed by inadvertent exposure of LLZO to ambient conditions is generally known to increase interfacial impedance and decrease lithium wettability. Soaking LLZO powders and pellets in the electrolyte containing lithium tetrafluoroborate (LiBF4) shows a significantly reduced interfacial resistance and improved contact between lithium and LLZO. Raman spectroscopy, X-ray diffraction, and soft X-ray absorption spectroscopy reveal how Li2CO3 is continuously removed with increasing soaking time. On-line mass spectrometry and free energy calculations show how LiBF4 reacts with surface carbonate to form carbon dioxide. Using a very simple and scalable process that does not involve heat-treatment and expensive coating techniques, we show that the Li-LLZO interfacial resistance can be reduced by an order of magnitude.
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Newcastle disease (ND) and avian influenza (AI) are economically important infectious diseases of poultry. Sometime, concomitant secondary viral/or bacterial infections significantly alters the pathobiology of ND and AI in poultry. As of now, the disease patterns and dynamics of co-infections caused by ND virus (NDV, genotype XIII) and Low Pathogenic AI viruses (LPAI, H9N2) are explicitly elusive. Thus, we examined the clinicopathological disease conditions due to these two economically important viruses to understand the complex disease outcomes by virus-virus interactions in vaccinated flocks. The findings of clinicopathological and molecular investigations carried on 37 commercial ND vaccinated poultry flocks revealed simultaneous circulation of NDV and AIV in same flock/bird. Further, molecular characterization of hemagglutinin (HA) and neuraminidase (NA) genes confirmed that all the identified AIVs were of low pathogenicity H9N2 subtype and fusion (F) gene analysis of detected NDVs belong to NDV class II, genotype XIII, a virulent type. The NDV and H9N2 alone or co-infected flocks (NDV + LPAI) exhibit clinical signs and lesions similar to that of virulent NDV except the degree of severity, which was higher in H9N2-NDV co-infected flocks. Additionally, avian pathogenic E. coli and mycoplasma infections were detected in majority of the ailing/dead birds from the co-infected flocks during progression of the clinical disease. Overall, the findings highlight the multi-factorial disease complexity in commercial poultry and suggest the importance of NDV genotype XIII in intensifying the clinical disease in vaccinated birds.