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1.
J Opioid Manag ; 20(3): 260-262, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39017618

RESUMEN

Transitioning a patient with chronic pain from a fentanyl patch to a buprenorphine patch has not been well described in the literature. Even after a patient removes their fentanyl patch, the residual fentanyl in the skin continues to be absorbed for hours. Due to the risk of precipitated withdrawal when initiating buprenorphine, this transition is a more challenging opioid rotation to plan safely. We report a case of a patient who had been using a fentanyl patch for over 10 years and was successfully rotated directly to a buprenorphine patch.


Asunto(s)
Analgésicos Opioides , Buprenorfina , Dolor Crónico , Fentanilo , Parche Transdérmico , Humanos , Buprenorfina/administración & dosificación , Buprenorfina/efectos adversos , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Dolor Crónico/tratamiento farmacológico , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Administración Cutánea , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Tratamiento de Sustitución de Opiáceos , Femenino
2.
J Virol ; : e0062224, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953377

RESUMEN

African swine fever virus causes a lethal hemorrhagic disease in domestic swine and wild boar for which currently licensed commercial vaccines are only available in Vietnam. Development of subunit vaccines is complicated by the lack of information on protective antigens as well as suitable delivery systems. Our previous work showed that a pool of eight African swine fever virus genes vectored using an adenovirus prime and modified vaccinia virus boost could prevent fatal disease after challenge with a virulent genotype I isolate of the virus. Here, we identify antigens within this pool of eight that are essential for the observed protection and demonstrate that adenovirus-prime followed by adenovirus-boost can also induce protective immune responses against genotype I African swine fever virus. Immunization with a pool of adenoviruses expressing individual African swine fever virus genes partially tailored to genotype II virus did not protect against challenge with genotype II Georgia 2007/1 strain, suggesting that different antigens may be required to induce cross-protection for genetically distinct viruses. IMPORTANCE: African swine fever virus causes a lethal hemorrhagic disease in domestic pigs and has killed millions of animals across Europe and Asia since 2007. Development of safe and effective subunit vaccines against African swine fever has been problematic due to the complexity of the virus and a poor understanding of protective immunity. In a previous study, we demonstrated that a complex combination of eight different virus genes delivered using two different viral vector vaccine platforms protected domestic pigs from fatal disease. In this study, we show that three of the eight genes are required for protection and that one viral vector is sufficient, significantly reducing the complexity of the vaccine. Unfortunately, this combination did not protect against the current outbreak strain of African swine fever virus, suggesting that more work to identify immunogenic and protective viral proteins is required to develop a truly effective African swine fever vaccine.

3.
SAGE Open Med ; 12: 20503121241254941, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38826827

RESUMEN

Objective: The study aims to investigate the patient perspective on the pathway from healthcare practitioners' presentations of their cases at a Project ECHO (Extension for Community Healthcare Outcomes) tele-clinic to the management of those patients' chronic pain. Introduction: Managing patients with chronic and complex pain constitutes a prevalent, stressful challenge in the primary care setting. Primary care physicians typically have received little training in treating such patients and, until recently, have relied heavily on opioid and other pharmaceutical therapies as part of their regimen. Project ECHO Ontario Chronic Pain and Opioid Stewardship is an interprofessional telementoring program connecting pain specialists to primary care practitioners with the aim of supporting them in managing their patients with chronic pain, although the patients concerned do not generally participate in the telementoring sessions. While a number of papers have described the benefits accruing to healthcare professionals through participating in Project ECHO, there has been little exploration concerning patients' perceptions of their care subsequent to case presentation. Methods: Using data from in-depth interviews with 20 patients along with their associated case presentation forms and the recommendations following the presentation, we look at the alignment of patient and practitioner views and inquire about the patient's perceptions of how Project ECHO affects them. Results: Results suggest that the impact on patients is indirect but positive: most respondents express pleasure in contributing to research around chronic pain management, though only two of them identified a direct impact on their own treatment. They also appreciated their practitioner's efforts to bring expert attention to the patient's situation. Conclusions: Patients whose cases are presented to Project ECHO sessions experience positive emotions at being part of the process of research and quality improvement, regardless of changes in their own conditions. This study highlights the importance to patients of their practitioners' commitment to managing their chronic pain.

4.
NPJ Vaccines ; 9(1): 98, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830899

RESUMEN

A recombinant, replication-defective, adenovirus-vectored vaccine expressing the H surface glycoprotein of peste des petits ruminants virus (PPRV) has previously been shown to protect goats from challenge with wild-type PPRV at up to 4 months post vaccination. Here, we present the results of a longer-term trial of the protection provided by such a vaccine, challenging animals at 6, 9, 12 and 15 months post vaccination. Vaccinated animals developed high levels of anti-PPRV H protein antibodies, which were virus-neutralising, and the level of these antibodies was maintained for the duration of the trial. The vaccinated animals were largely protected against overt clinical disease from the challenge virus. Although viral genome was intermittently detected in blood samples, nasal and/or ocular swabs of vaccinated goats post challenge, viral RNA levels were significantly lower compared to unvaccinated control animals and vaccinated goats did not appear to excrete live virus. This protection, like the antibody response, was maintained at the same level for at least 15 months after vaccination. In addition, we showed that animals that have been vaccinated with the adenovirus-based vaccine can be revaccinated with the same vaccine after 12 months and showed an increased anti-PPRV antibody response after this boost vaccination. Such vaccines, which provide a DIVA capability, would therefore be suitable for use when the current live attenuated PPRV vaccines are withdrawn at the end of the ongoing global PPR eradication campaign.

5.
Can J Pain ; 8(1): 2337074, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38938328

RESUMEN

Background: Chronic pain is a complex disease that requires interprofessional care for effective management. Despite the need for multidisciplinary care, disease and health care inequities can prevent individuals from attaining adequate treatment. Factors such as mental health, cost, and distance to a health care center can contribute to health care accessibility inequality. The aim of this study is to examine declined referrals at the Toronto Academic Pain Medicine Institute (TAPMI) to determine the reason for declining care and number of declined referrals. Methods: A retrospective chart review of all declined referrals at TAPMI in 2018 and 2022 was conducted. Referral documentation and the intake decision were extracted from the electronic medical charts by the research team and verified by the clinical intake team. Chi-square tests were conducted to determine whether the proportion of declined referrals changed between the years reviewed. Results: The number of declined referrals due to mental health complexities increased significantly from 51 (11%) in 2018 to 180 (18%) in 2022 (χ2 = 10.9, P = 0.0009). A significant rise in the number of declines due to mental health service requests was also observed (χ2 = 24.53, P < 0.00001). Other common reasons for declined referrals in 2018 and 2022 included duplicate service, no primary care provider, and health care service changes. Conclusion: Mental health complexities continue to be a significant barrier to health care service acquisition for individuals living with chronic pain. The increase in patient complexity from 2018 to 2022 highlights the need for integrated health care resources.


Contexte: La douleur chronique est une maladie complexe qui nécessite des soins interprofessionnels pour une prise en charge efficace. Malgré la nécessité de soins multidisciplinaires, les maladies et les iniquités en matière de soins de santé peuvent empêcher les individus d'obtenir un traitement adéquat. Des facteurs tels que la santé mentale, le coût et la distance d'un centre de soins de santé peuvent contribuer aux inégalités en matière d'accessibilité des soins de santé. Le but de cette étude est d'examiner les demandes de consultation refusées à l'Institut universitaire de médecine de la douleur de Toronto (TAPMI) afin de déterminer la raison du refus des soins et le nombre de demandes de consultation refusées.Méthodes: Un examen rétrospectif de toutes les demandes de consultation refusées au TAPMI en 2018 et 2022 a été effectué. La documentation relative à la demande de consultation et la décision d'admission ont été extraites du dossier médical électronique par l'équipe de recherche et vérifiées par l'équipe d'admission clinique. Des tests de chi-carré ont été effectués pour déterminer si la proportion de demandes de consultation refusées avait changé entre les années examinées.Résultats: Le nombre de demandes de consultation refusées en raison des complexités de la santé mentale a considérablement augmenté, passant de 51 (11 %) en 2018 à 180 (18%) en 2022 (χ2 = 10,9, P = 0,0009). Une augmentation significative du nombre de refus attribuables aux demandes de services de santé mentale a également été observée (χ2 = 24,53, P < 0,00001). Parmi les autres raisons courantes pour lesquelles les demandes de consultation ont été refusées en 2018 et 2022, on compte la duplication du service, l'absence de prestataire de soins primaires et les changements dans les services de soins de santé.Conclusion: Les complexités de la santé mentale continuent d'être un obstacle important à l'acquisition de services de soins de santé pour les personnes vivant avec une douleur chronique. L'augmentation de la complexité des patients de 2018 à 2022 souligne la nécessité de ressources de soins de santé intégrées.

6.
Microorganisms ; 12(5)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38792762

RESUMEN

African horse sickness is a severe and often fatal disease affecting all species of equids. The aetiological agent, African horse sickness virus (AHSV), can be differentiated into nine serotypes. The identification of AHSV serotypes is vital for disease management, as this can influence vaccine selection and help trace disease incursion routes. In this study, we report the development and optimisation of a novel, molecular-based assay that utilises multiplex PCR and microsphere-based technology to expedite detection and differentiation of multiple AHSV serotypes in one assay. We demonstrated the ability of this assay to identify all nine AHSV serotypes, with detection limits ranging from 1 to 277 genome copies/µL depending on the AHSV serotype. An evaluation of diagnostic sensitivity and specificity revealed a sensitivity of 88% and specificity of 100%. This method can serotype up to 42 samples per run and can be completed in approximately 4-6 h. It provides a powerful tool to enhance the rapidity and efficiency of AHSV serotype detection, thereby facilitating the generation of epidemiological data that can help understand and control the incidence of AHSV worldwide.

7.
Can J Pain ; 8(1): 2297561, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562673

RESUMEN

Background: Despite the established efficacy of multidisciplinary chronic pain care, barriers such as inflated referral wait times and uncoordinated care further hinder patient health care access. Aims: Here we describe the evolution of a single-entry model (SEM) for coordinating access to chronic pain care across seven hospitals in Toronto and explore the impact on patient care 6 years after implementation. Methods: In 2017, an innovative SEM was implemented for chronic pain referrals in Toronto and surrounding areas. Referrals are received centrally, triaged by a clinical team, and assigned an appointment according to the level of urgency and the most appropriate care setting/provider. To evaluate the impact of the SEM, a retrospective analysis was undertaken to determine referral patterns, patient characteristics, and referral wait times over the past 6 years. Results: Implementation of an SEM streamlined the number of steps in the referral process and led to a standardized referral form with common inclusion and exclusion criteria across sites. Over the 6-year period, referrals increased by 93% and the number of unique providers increased by 91%. Chronic pain service wait times were reduced from 299 (±158) days to 176 (±103) days. However, certain pain diagnoses such as chronic pelvic pain and fibromyalgia far exceed the average. Conclusions: The results indicate that the SEM helped reduce wait times for pain conditions and standardized the referral pathway. Continued data capture efforts can help identify gaps in care to enable further health care refinement and improvement.


Contexte: Malgré l'efficacité établie des soins multidisciplinaires dans le traitement de la douleur chronique, des obstacles tels que des délais d'attente prolongés et l'absence de coordination des soins entravent davantage l'accès des patients aux services de santé.Objectifs: Nous décrivons ici l'évolution d'un modèle à entrée unique visant à coordonner l'accès aux soins pour la douleur chronique dans sept hôpitaux de Toronto. Nous examinons également l'effet de ce modèle sur les soins aux patients six ans après sa mise en œuvre.Méthodes: En 2017, un modèle à entrée unique novateur a été mis en place pour orienter les patients souffrant de douleur chronique à Toronto et dans les régions avoisinantes. Les patients sont reçus de manière centralisée, triés par une équipe clinique et un rendez-vous leur est attribué en fonction du degré d'urgence et de l'établissement de soins ou du prestataire le plus approprié.Pour évaluer l'impact du modèle à entrée unique, une analyse rétrospective a été entreprise afin de déterminer les schémas de consultation, les caractéristiques des patients et les temps d'attente pour les demandes de consultation au cours des six dernières années.Résultats: La mise en œuvre d'un modèle à entrée unique a permis de rationaliser le nombre d'étapes du processus de demande de consultation et a conduit à l'élaboration d'un formulaire de demande de consultation normalisé comprenant des critères d'inclusion et d'exclusion communs à tous les sites. Au cours de la période de six ans, le nombre de demandes de consultation a augmenté et le nombre de prestataires uniques a augmenté de 91 %.Les temps d'attente pour les services de traitement de la douleur chronique ont diminué de 299 (±158) jours à 176 (±103) jours. Cependant, certains diagnostics de douleur, comme la douleur pelvienne chronique et la fibromyalgie, dépassent de loin la moyenne.Conclusions: Les résultats indiquent que le modèle à entrée unique a contribué à réduire les temps d'attente pour les affections douloureuses et à normaliser le parcours de consultation. La poursuite des efforts de collecte des données peut aider à recenser les lacunes dans les soins, permettant ainsi une amélioration continue des soins de santé.

8.
Front Immunol ; 15: 1328820, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38357545

RESUMEN

Introduction: Bluetongue virus (BTV) is an arthropod-borne Orbivirus that is almost solely transmitted by Culicoides biting midges and causes a globally important haemorrhagic disease, bluetongue (BT), in susceptible ruminants. Infection with BTV is characterised by immunosuppression and substantial lymphopenia at peak viraemia in the host. Methods: In this study, the role of cell-mediated immunity and specific T-cell subsets in BTV pathogenesis, clinical outcome, viral dynamics, immune protection, and onwards transmission to a susceptible Culicoides vector is defined in unprecedented detail for the first time, using an in vivo arboviral infection model system that closely mirrors natural infection and transmission of BTV. Individual circulating CD4+, CD8+, or WC1+ γδ T-cell subsets in sheep were depleted through the administration of specific monoclonal antibodies. Results: The absence of cytotoxic CD8+ T cells was consistently associated with less severe clinical signs of BT, whilst the absence of CD4+ and WC1+ γδ T cells both resulted in an increased clinical severity. The absence of CD4+ T cells also impaired both a timely protective neutralising antibody response and the production of IgG antibodies targeting BTV non-structural protein, NS2, highlighting that the CD4+ T-cell subset is important for a timely protective immune response. T cells did not influence viral replication characteristics, including onset/dynamics of viraemia, shedding, or onwards transmission of BTV to Culicoides. We also highlight differences in T-cell dependency for the generation of immunoglobulin subclasses targeting BTV NS2 and the structural protein, VP7. Discussion: This study identifies a diverse repertoire of T-cell functions during BTV infection in sheep, particularly in inducing specific anti-viral immune responses and disease manifestation, and will support more effective vaccination strategies.


Asunto(s)
Arbovirus , Virus de la Lengua Azul , Lengua Azul , Ceratopogonidae , Ovinos , Animales , Ganado , Viremia , Linfocitos T CD8-positivos , Rumiantes , Subgrupos de Linfocitos T , Lengua Azul/prevención & control , Ceratopogonidae/fisiología
9.
Pathogens ; 12(8)2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37623982

RESUMEN

African swine fever virus (ASFV) is known to be very stable and can remain infectious over long periods of time especially at low temperatures and within different matrices, particularly those containing animal-derived organic material. However, there are some gaps in our knowledge pertaining to the survivability and infectivity of ASFV in groundwater. This study aims to determine the stability and infectivity of the cell culture-adapted ASFV strain BA71V by plaque assay after incubation of the virus within river water samples at three different environmentally relevant temperatures (4 °C, 15 °C, and 21 °C) over the course of 42 days. The results from this study indicate that ASFV can remain stable and infectious when maintained at 4 °C in river water for more than 42 days, but as incubation temperatures are increased, the stability is reduced, and the virus is no longer able to form plaques after 28 days and 14 days, respectively, when stored at 15 °C and 21 °C. Characterizing the survivability of ASFV in groundwater can allow us to develop more appropriate inactivation and disinfection methods to support disease control and mitigate ASFV outbreaks.

10.
Artículo en Inglés | MEDLINE | ID: mdl-36376079

RESUMEN

Blindness due to rod-cone dystrophies is a significant comorbidity and cause of reduced quality of life worldwide. Optogenetics uses adeno-associated viral (AAV) vectors to bypass lost photoreceptors and transfect remnant cell populations of the degenerated retina aiming to restore vision via the ectopic expression of opsins. The optogenetic targeting of retinal ganglion cells (RGCs) has been remarkably successful and several studies have advanced to clinical trials over the recent years. The inner retina and specifically ON bipolar cells represent even more appealing targets due to their intrinsically coded tasks in parallel processing and fine-tuning of visual signals before reaching the output: RGCs. However, present success with pursuing inner and outer retinal cells for optogenetic vision restoration is limited by multiple factors, including AAV tropism, promoter specificity, and retinal morphofunctional remodeling. Here we provide a review of the evolution of optogenetics, its greatest challenges, and solutions from bench to bedside.


Asunto(s)
Optogenética , Degeneración Retiniana , Humanos , Invenciones , Calidad de Vida , Células Ganglionares de la Retina/metabolismo , Retina/metabolismo , Degeneración Retiniana/metabolismo
11.
Vaccines (Basel) ; 10(11)2022 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-36366345

RESUMEN

Solid dose vaccine formulation and delivery systems offer potential advantages over traditional liquid vaccine formulations. In addition to enhanced thermostability, needle-free delivery of unit solid dose injectable (USDI) vaccines offers safe, rapid, and error-free administration, with applicability to both human and animal health. Solid dose formulation technologies can be adapted for delivery of different vaccine formats including live attenuated vaccines, which remain the 'gold standard' for many disease targets. Porcine reproductive and respiratory syndrome viruses (PRRSV) cause one of the most economically important diseases affecting the global pig industry. Despite several shortcomings, live attenuated vaccines are widely used to control PRRSV. We optimised a freeze-dried USDI formulation of live attenuated PRRSV-1, which fully retained infectious titre, and evaluated its immunogenicity in comparison to virus delivered in liquid suspension via intramuscular and subcutaneous needle inoculation. Pigs vaccinated with the USDI formulation displayed vaccine viraemia, and PRRSV-specific antibody and T cell responses comparable to animals immunised with the liquid vaccine. The USDI vaccine formulation was stable for at least 6 months when stored refrigerated. These data demonstrate the potential for a solid dose vaccine delivery system as an alternative to conventional needle-syringe delivery of live attenuated PRRSV vaccines.

12.
Ophthalmic Res ; 2022 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-36103843

RESUMEN

The recent approval of voretigene neparvovec (Luxturna®) for patients with biallelic RPE65 mutation-associated inherited retinal dystrophy with viable retinal cells represents an important step in the development of ocular gene therapies. Herein, we review studies investigating the episomal persistence of different recombinant adeno-associated virus (rAAV) vector genomes and the pre-clinical and clinical evidence of long-term effects of different RPE65 gene replacement therapies. A targeted review of articles published between 1974 and January 2021 in Medline®, Embase®, and other databases, was conducted, followed by a descriptive longitudinal analysis of the clinical trial outcomes of voretigene neparvovec. Following an initial screening, 14 publications examining the episomal persistence of different rAAV genomes and 71 publications evaluating gene therapies in animal models were included. Viral genomes were found to persist for at least 22 months (longest study follow-up) as transcriptionally active episomes. Treatment effects lasting almost a decade were reported in canine disease models, with more pronounced effects the earlier the intervention. The clinical trial outcomes of voretigene neparvovec are consistent with pre-clinical findings and reveal sustained results for up to 7.5 years for the full-field light sensitivity threshold test and 5 years for the multi-luminance mobility test in the Phase I and Phase III trials, respectively. In conclusion, the therapeutic effect of voretigene neparvovec lasts for at least a decade in animal models and 7.5 years in human subjects. Since retinal cells can retain functionality over their lifetime after transduction, these effects may be expected to last even longer in patients with a sufficient number of outer retinal cells at the time of intervention.

13.
BMC Genomics ; 23(1): 406, 2022 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-35644636

RESUMEN

BACKGROUND: Non-targeted whole genome sequencing is a powerful tool to comprehensively identify constituents of microbial communities in a sample. There is no need to direct the analysis to any identification before sequencing which can decrease the introduction of bias and false negatives results. It also allows the assessment of genetic aberrations in the genome (e.g., single nucleotide variants, deletions, insertions and copy number variants) including in noncoding protein regions. METHODS: The performance of four different random priming amplification methods to recover RNA viral genetic material of SARS-CoV-2 were compared in this study. In method 1 (H-P) the reverse transcriptase (RT) step was performed with random hexamers whereas in methods 2-4 RT incorporating an octamer primer with a known tag. In methods 1 and 2 (K-P) sequencing was applied on material derived from the RT-PCR step, whereas in methods 3 (SISPA) and 4 (S-P) an additional amplification was incorporated before sequencing. RESULTS: The SISPA method was the most effective and efficient method for non-targeted/random priming whole genome sequencing of SARS-CoV-2 that we tested. The SISPA method described in this study allowed for whole genome assembly of SARS-CoV-2 and influenza A(H1N1)pdm09 in mixed samples. We determined the limit of detection and characterization of SARS-CoV-2 virus which was 103 pfu/ml (Ct, 22.4) for whole genome assembly and 101 pfu/ml (Ct, 30) for metagenomics detection. CONCLUSIONS: The SISPA method is predominantly useful for obtaining genome sequences from RNA viruses or investigating complex clinical samples as no prior sequence information is needed. It might be applied to monitor genomic virus changes, virus evolution and can be used for fast metagenomics detection or to assess the general picture of different pathogens within the sample.


Asunto(s)
COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Virus ARN , Genoma Viral , Humanos , SARS-CoV-2/genética , Secuenciación Completa del Genoma
14.
Curr Opin Pharmacol ; 65: 102259, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35749908

RESUMEN

Blinding diseases that are caused by degeneration of rod and cone photoreceptor cells often spare the rest of the retinal circuit, from bipolar cells, which are directly innervated by photoreceptor cells, to the output ganglion cells that project axons to the brain. A strategy for restoring vision is to introduce light sensitivity to the surviving cells of the retina. One approach is optogenetics, in which surviving cells are virally transfected with a gene encoding a signaling protein that becomes sensitive to light by binding to the biologically available chromophore retinal, the same chromophore that is used by the opsin photo-detectors of rods and cones. A second approach uses photopharmacology, in which a synthetic photoswitch associates with a native or engineered ion channel or receptor. We review these approaches and look ahead to the next generation of advances that could reconstitute core aspects of natural vision.


Asunto(s)
Retina , Células Fotorreceptoras Retinianas Conos , Humanos , Optogenética , Células Fotorreceptoras Retinianas Conos/metabolismo , Opsinas de Bastones/genética , Opsinas de Bastones/metabolismo
15.
Methods Mol Biol ; 2503: 95-104, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35575888

RESUMEN

Real-time polymerase chain reaction (PCR) for the detection of African swine fever virus (ASFV) is the tool of choice for the diagnostic laboratory and is a robust and easily scalable method for the researcher analyzing viral replication both in vitro and in vivo. In this chapter, we describe protocols for both quantitative real-time polymerase chain reactions (qPCR) and non-quantitative real-time polymerase chain reactions (real-time PCR) for the detection of African swine fever virus genome in a range of samples.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Fiebre Porcina Africana/diagnóstico , Virus de la Fiebre Porcina Africana/genética , Animales , Técnicas de Laboratorio Clínico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Sensibilidad y Especificidad , Porcinos
16.
Proc Natl Acad Sci U S A ; 119(13): e2117038119, 2022 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-35316139

RESUMEN

SignificanceCanine models of inherited retinal diseases have helped advance adeno-associated virus (AAV)-based gene therapies targeting specific cells in the outer retina for treating blinding diseases in patients. However, therapeutic targeting of diseases such as congenital stationary night blindness (CSNB) that exhibit defects in ON-bipolar cells (ON-BCs) of the midretina remains underdeveloped. Using a leucine-rich repeat, immunoglobulin-like and transmembrane domain 3 (LRIT3) mutant canine model of CSNB exhibiting ON-BC dysfunction, we tested the ability of cell-specific AAV capsids and promotors to specifically target ON-BCs for gene delivery. Subretinal injection of one vector demonstrated safety and efficacy with robust and stable rescue of electroretinography signals and night vision up to 1 y, paving the way for clinical trials in patients.


Asunto(s)
Enfermedades Genéticas Ligadas al Cromosoma X , Ceguera Nocturna , Animales , Dependovirus/genética , Perros , Electrorretinografía , Enfermedades Hereditarias del Ojo , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Terapia Genética , Humanos , Proteínas de la Membrana/genética , Miopía , Ceguera Nocturna/genética , Ceguera Nocturna/terapia
18.
Transbound Emerg Dis ; 69(4): e336-e343, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34448540

RESUMEN

Lumpy skin disease virus (LSDV) is an emerging poxviral pathogen of cattle that is currently spreading throughout Asia. The disease situation is of high importance for farmers and policy makers in Asia. In October 2020, feral cattle in Hong Kong developed multi-focal cutaneous nodules consistent with lumpy skin disease (LSD). Gross and histological pathology further supported the diagnosis and samples were sent to the OIE Reference Laboratory at The Pirbright Institute for confirmatory testing. LSDV was detected using quantitative polymerase chain reaction (qPCR) and additional molecular analyses. This is the first report of LSD in Hong Kong. Whole genome sequencing (WGS) of the strain LSDV/Hong Kong/2020 and phylogenetic analysis were carried out in order to identify connections to previous outbreaks of LSD, and better understand the drivers of LSDV emergence. Analysis of the 90 core poxvirus genes revealed LSDV/Hong Kong/2020 was a novel strain most closely related to the live-attenuated Neethling vaccine strains of LSDV and more distantly related to wildtype LSDV isolates from Africa, the Middle East and Europe. Analysis of the more variable regions located towards the termini of the poxvirus genome revealed genes in LSDV/Hong Kong/2020 with different patterns of grouping when compared to previously published wildtype and vaccine strains of LSDV. This work reveals that the LSD outbreak in Hong Kong in 2020 was caused by a different strain of LSDV than the LSD epidemic in the Middle East and Europe in 2015-2018. The use of WGS is highly recommended when investigating LSDV disease outbreaks.


Asunto(s)
Enfermedades de los Bovinos , Dermatosis Nodular Contagiosa , Virus de la Dermatosis Nodular Contagiosa , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Brotes de Enfermedades/veterinaria , Hong Kong/epidemiología , Filogenia , Vacunas Atenuadas
19.
Transbound Emerg Dis ; 69(4): 1837-1846, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34033248

RESUMEN

Sheeppox is a transboundary disease of small ruminants caused by infection with the capripoxvirus sheeppox virus. Sheeppox is found in Africa, the Middle East and Asia and is characterized by fever, multifocal cutaneous raised lesions and death. Vaccination with live attenuated capripoxvirus (CPPV) strains is an effective and widely used strategy to contol sheeppox outbreaks; however, there are few reports of post-vaccination field surveillance studies. This study used a commercially available enzyme-linked immunosorbent assay (ELISA) to examine quantitative and temporal features of the humoral response of sheep vaccinated with a live-attenuated CPPV strain in Mongolia. Four hundred samples were tested using the ELISA commercial kit, and a subset of 45 samples were also tested with a virus neutralization test (VNT). There was substantial agreement between the VNT and ELISA tests. Antibodies to CPPV were detected between 40 and 262 days post-vaccination. There was no significant difference between serological status (positive/negative) and sex or age; however, an inverse correlation was found between the length of time since vaccination and serological status. Animals between 90 and 180 days post-vaccination were more likely to be positive than animals greater than 180 days post-vaccination. Our results show that a commercial CPPV ELISA kit is a robust and reliable assay for post-CPPV vaccination surveillance in resource-restricted settings and provide temporal parameters to be considered when planning sheeppox post-vaccination monitoring programmes.


Asunto(s)
Capripoxvirus , Infecciones por Poxviridae , Enfermedades de las Ovejas , Animales , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Inmunidad Humoral , Infecciones por Poxviridae/epidemiología , Infecciones por Poxviridae/prevención & control , Infecciones por Poxviridae/veterinaria , Sensibilidad y Especificidad , Ovinos , Enfermedades de las Ovejas/epidemiología
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