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1.
Front Psychol ; 14: 1265529, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38078279

RESUMEN

Introduction: The COVID-19 pandemic continues to place an unprecedented strain on the US healthcare system, and primary care is no exception. Primary care services have shifted toward a team-based approach for delivering care in the last decade. COVID-19 placed extraordinary stress on primary care teams at the forefront of the pandemic response efforts. The current work applies the science of effective teams to examine the impact of COVID-19-a crisis or adverse event-on primary care team resilience. Methods: Little empirical research has been done testing the theory of team resilience during an extremely adverse crisis event in an applied team setting. Therefore, we conducted an archival study by using large-scale national data from the Veterans Health Administration to understand the characteristics and performance of 7,023 Patient Aligned Care Teams (PACTs) during COVID-19. Results: Our study found that primary care teams maintained performance in the presence of adversity, indicating possible team resilience. Further, team coordination positively predicted team performance (B = 0.53) regardless of the level of adversity a team was experiencing. Discussion: These findings in turn attest to the need to preserve team coordination in the presence of adversity. Results carry implications for creating opportunities for teams to learn and adjust to an adverse event to maintain performance and optimize team-member well-being. Teamwork can act as a protective factor against high levels of workload, burnout, and turnover, and should be studied further for its role in promoting team resilience.

2.
BMC Health Serv Res ; 22(1): 1243, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36217148

RESUMEN

BACKGROUND/OBJECTIVE: Despite numerous extant measures assessing context-specific elements of care coordination, we are unaware of any comprehensive, team-based instrument that measures the requisite mechanisms and conditions required to coordinate successfully. In this study we develop and validate the psychometric properties of the Coordination Practices Survey, a context-agnostic measure of coordination for primary care teams. METHODS: Coordination items were developed based on a systematic literature review; items from previously developed scales were adapted and new items were created as needed; all items were refined after subject matter expert review and feedback. We collected data from Primary Care teams drawn from 1200 Veterans Health Administration (VHA) medical centers and outpatient clinics nationwide. 1645 primary care team members from 512 patient aligned care teams in the Veterans Health Administration completed the survey from 2015 to 2016. Psychometric properties were assessed after data collection using Cronbach's alpha, intraclass correlations and multilevel confirmatory factor analysis to assess the factor structure. RESULTS: Our findings confirmed the psychometric properties of two distinguishable subscales of coordination: (a) Accountability and (b) Common Understanding. The within- and between-team latent structure of each subscale exhibited adequate fit to the data, as well as appropriately high Cronbach's alpha and intraclass correlations. There was insufficient variability in responses to the predictability subscale to properly assess its psychometric properties. CONCLUSION: With context-specific validation, our subscales of accountability and common understanding may be used to assess coordination processes in other contexts for both research and operational applications.


Asunto(s)
Grupo de Atención al Paciente , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
3.
Ann R Coll Surg Engl ; 104(8): 611-617, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35639482

RESUMEN

INTRODUCTION: Appropriate patient selection within the context of a multidisciplinary team (MDT) is key to good clinical outcomes. The current evidence base for factors that guide the decision-making process in locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is limited to anatomical factors. METHODS: A registry-based, prospective cohort study was undertaken of patients referred to our specialist MDT between 2015 and 2019. Data were collected on patients and disease characteristics including performance status, Charlson Comorbidity Index, the English Index of Multiple Deprivation quintiles and MDT treatment decision. Curative treatment was defined as neoadjuvant treatment and surgical resection that would achieve a R0 resection, and/or complete treatment of distant metastatic disease. Palliative treatment was defined as non-surgical treatment. RESULTS: In total, 325 patients were identified; 72.7% of patients with LARC and 63.6% of patients with LRRC were offered treatment with curative intent (p = 0.08). Patients with poor performance status (PS > 2; p < 0.001), severe comorbidity (p < 0.001), socio-economic deprivation (p = 0.004), a positive predictive circumferential resection margin (p = 0.005) and metastatic disease (p < 0.001) were associated with palliative treatment. Overall survival in the curative cohort was 49 months (95% confidence interval [CI] 32.4-65.5) compared with 12 months (95% CI 9.1-14.9) in the palliative cohort (p < 0.001). The presence of metastatic disease was identified as a prognostic factor for patients undergoing curative treatment (p = 0.05). The only prognostic factor identified in patients treated palliatively was performance status (p < 0.001). CONCLUSIONS: Our study identifies a number of preoperative, prognostic factors that affect MDT decision-making and overall survival.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias del Recto , Humanos , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Grupo de Atención al Paciente , Estudios Prospectivos , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Estudios Retrospectivos
4.
PLoS One ; 17(1): e0261263, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35041671

RESUMEN

BACKGROUND: The purpose of this article is to illustrate the application of an evidence-based, structured performance measurement methodology to identify, prioritize, and (when appropriate) generate new measures of health care quality, using primary care as a case example. Primary health care is central to the health care system and health of the American public; thus, ensuring high quality is essential. Due to its complexity, ensuring high-quality primary care requires measurement frameworks that can assess the quality of the infrastructure, workforce configurations, and processes available. This paper describes the use of the Productivity Measurement and Enhancement System (ProMES) to compile a targeted set of such measures, prioritized according to their contribution and value to primary care. METHODS: We adapted ProMES to select and rank existing primary care measures according to value to the primary care clinic. Nine subject matter experts (SMEs) consisting of clinicians, hospital leaders and national policymakers participated in facilitated expert elicitation sessions to identify objectives of performance, corresponding measures, and priority rankings. RESULTS: The SMEs identified three fundamental objectives: access, patient-health care team partnerships, and technical quality. The SMEs also selected sixteen performance indicators from the 44 pre-vetted, currently existing measures from three different data sources for primary care. One indicator, Team 2-Day Post Discharge Contact Ratio, was selected as an indicator of both team partnerships and technical quality. Indicators were prioritized according to value using the contingency functions developed by the SMEs. CONCLUSION: Our article provides an actionable guide to applying ProMES, which can be adapted to the needs of various industries, including measure selection and modification from existing data sources, and proposing new measures. Future work should address both logistical considerations (e.g., data capture, common data/programming language) and lingering measurement challenges, such as operationalizating measures to be meaningful and interpretable across health care settings.


Asunto(s)
Cuidados Posteriores
5.
BJGP Open ; 5(2)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33563700

RESUMEN

BACKGROUND: Coordination is critical to successful team-based health care. Most clinicians, however, are not trained in effective coordination or teamwork. Audit and feedback (A&F) could improve team coordination, if designed with teams in mind. AIM: The effectiveness of a multifaceted, A&F-plus-debrief intervention was tested to establish whether it improved coordination in primary care teams compared with controls. DESIGN & SETTING: Case-control trial within US Veterans Health Administration medical centres. METHOD: Thirty-four primary care teams selected from four geographically distinct hospitals were compared with 34 administratively matched control teams. Intervention-arm teams received monthly A&F reports about key coordination behaviours and structured debriefings over 7 months. Control teams were followed exclusively via their clinical records. Outcome measures included a coordination composite and its component indicators (appointments starting on time, timely recall scheduling, emergency department utilisation, and electronic patient portal enrolment). Predictors included intervention arm, extent of exposure to intervention, and degree of multiple team membership (MTM). RESULTS: Intervention teams did not significantly improve over control teams, even after adjusting for MTM. Follow-up analyses indicated cross-team variability in intervention fidelity; although all intervention teams received feedback reports, not all teams attended all debriefings. Compared with their respective baselines, teams with high debriefing exposure improved significantly. Teams with high debriefing exposure improved significantly more than teams with low exposure. Low exposure teams significantly increased patient portal enrolment. CONCLUSION: Team-based A&F, including adequate reflection time, can improve coordination; however, the effect is dose dependent. Consistency of debriefing appears more critical than proportion of team members attending a debriefing for ensuring implementation fidelity and effectiveness.

6.
Vet Immunol Immunopathol ; 233: 110194, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33530020

RESUMEN

Transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative diseases affecting humans and animals. Although many host tissues express PrPC (essential for prion replication), relatively few cell types accumulate significant levels of infectivity, including neurons and other cell types in the nervous system, and follicular dendritic cells in secondary lymphoid organs. This suggests that tissue or cell-specific receptors or cofactors could play a role in controlling differential susceptibility to infection. Endogenous retroviruses (ERV), the remnants of ancient retroviral integration into the host germline, may represent one such cofactor. We examined the effect of scrapie infection on expression of three ovine ERV families (enJSRV/ß1-OERV, γ1-OERV, γ2-OERV) in secondary lymphoid tissues of sheep at different time points following subcutaneous inoculation, using RT-qPCR. These OERVs were constitutively expressed in the prescapular lymph node and spleen of uninfected sheep. However, we were unable to find convincing evidence of specific differential expression of OERV in the same tissues following scrapie infection, in contrast to previous studies of ERV expression in brains of prion-infected mice and macaques. This study is the first to quantify the expression of potentially functional OERV transcripts in sheep lymphoid tissues, opening up interesting questions about the consequences for host immune function.


Asunto(s)
Retrovirus Endógenos/genética , Tejido Linfoide/virología , Scrapie/virología , Ovinos , Animales , Expresión Génica , Genes Virales , Ganglios Linfáticos/virología , Bazo/virología
7.
Nurs Outlook ; 69(2): 212-220, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33070980

RESUMEN

BACKGROUND: Low-income, working-age Veterans with children have risk for food insecurity. Less known is extent to which their risk compares to nonveterans. PURPOSE: To evaluate odds of food insecurity for working-age Veterans with children compared to socioeconomically-matched nonveterans with children. METHOD: We constructed a propensity score-matched cohort using 2011-2014 National Health and Nutrition Examination Survey data. Covariate-adjusted logistic regressions estimated Veterans' odds for overall food insecurity and for each level of severity compared to nonveterans. FINDINGS: We matched 155 Veterans to 310 nonveterans on gender, race/ethnicity, education, income. Models were adjusted for age, marital-status, depression, and listed matched variables. Although Veteran-status had no effect on overall food insecurity (odds ratio = 1.09, 95% confidence interval [0.62,1.93]), Veteran-status increased odds for very low food security (odds ratio = 2.71, 95% confidence interval [1.21, 6.07]). DISCUSSION: Veterans do not have higher odds of food insecurity than non-veterans, but they are more likely to have the more severe very low food security (often associated with hunger) than non-veterans. Investigation of food insecurity's impact on Veteran health/well-being is needed.


Asunto(s)
Factores de Edad , Inseguridad Alimentaria , Adulto , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estados Unidos
8.
Implement Sci ; 14(1): 22, 2019 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-30841926

RESUMEN

BACKGROUND: The science of effective teams is well documented; far less is known, however, about how specific team configurations may impact primary care team effectiveness. Further, teams experiencing frequent personnel changes (perhaps as a consequence of poor implementation) may have difficulty delivering effective, continuous, well-coordinated care. This study aims to examine the extent to which primary care clinics in the Veterans Health Administration have implemented team configurations consistent with recommendations based on the Patient-Centered Medical Home model and the extent to which adherence to said recommendations, team stability, and role stability impact healthcare quality. Specifically, we expect to find better clinical outcomes in teams that adhere to recommended team configurations, teams whose membership and configuration are more stable over time, and teams whose clinical manager role is more stable over time. METHODS/DESIGN: We will employ a combination of social network analysis and multilevel modeling to conduct a database review of variables extracted from the Veterans Health Administration's Team Assignments Report (TAR) (one of the largest, most diverse existing national samples of primary care teams (nteams > 7000)), as well as other employee and clinical data sources. To ensure the examination of appropriate clinical outcomes, we will enlist a team of subject matter experts to select a concise set of clear, prioritized primary care performance metrics. We will accomplish this using the Productivity Measurement and Enhancement System, an evidence-based methodology for developing and implementing performance measurement. DISCUSSION: We are unaware of other studies of healthcare teams that consider team size, composition, and configuration longitudinally or with sample sizes of this magnitude. Results from this study can inform primary care team implementation policy and practice in both private- and public-sector clinics, such that teams are configured optimally, with adequate staffing, and the right mix of roles within the team. TRIAL REGISTRATION: Not applicable-this study does not involve interventions on human participants.


Asunto(s)
Grupo de Atención al Paciente/organización & administración , Atención Primaria de Salud/normas , Competencia Clínica , Humanos , Atención Dirigida al Paciente/organización & administración , Reorganización del Personal , Atención Primaria de Salud/organización & administración , Calidad de la Atención de Salud , Red Social , Estados Unidos , United States Department of Veterans Affairs
9.
Vox Sang ; 113(3): 220-231, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29359329

RESUMEN

Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal neurologic diseases affecting mammals. Human disease forms include sporadic, familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD) has been recognized for near on 100 years, variant CJD (vCJD) was first reported in 1996 and is the result of food-borne transmission of the prion of bovine spongiform encephalopathy (BSE, 'mad cow disease'). Currently, 230 vCJD cases have been reported in 12 countries, the majority in the UK (178) and France (27). Animal studies demonstrated highly efficient transmission of natural scrapie and experimental BSE by blood transfusion and fuelled concern that sCJD was potentially transfusion transmissible. No such case has been recorded and case-control evaluations and lookback studies indicate that, if transfusion transmission occurs at all, it is very rare. In contrast, four cases of apparent transfusion transmission of vCJD infectivity have been identified in the UK. Risk minimization strategies in response to the threat of vCJD include leucodepletion, geographically based donor deferrals and deferral of transfusion recipients. A sensitive and specific, high-throughput screening test would provide a potential path to mitigation but despite substantial effort no such test has yet appeared. The initial outbreak of vCJD appears to be over, but concern remains about subsequent waves of disease among those already infected. There is considerable uncertainty about the size of the infected population, and there will be at least a perception of some continuing risk to blood safety. Accordingly, at least some precautionary measures will remain in place and continued surveillance is necessary.


Asunto(s)
Seguridad de la Sangre/normas , Transfusión Sanguínea/normas , Síndrome de Creutzfeldt-Jakob/sangre , Animales , Seguridad de la Sangre/métodos , Síndrome de Creutzfeldt-Jakob/transmisión , Humanos , Priones/sangre
10.
Perm J ; 19(4): 18-28, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26222093

RESUMEN

CONTEXT: Postoperative management of pain after total joint arthroplasty remains a challenge despite advancements in analgesics. Evidence shows that complementary modalities with mind-body and tactile-based approaches are valid and effective adjuncts to reduce pain and anxiety postoperatively. OBJECTIVE: To investigate the effectiveness of the "M" Technique (M), a registered method of structured touch using a set sequence and number of strokes, and a consistent level of pressure on hands and feet, compared with guided imagery and usual care, for the reduction of pain and anxiety in patients undergoing elective total knee or hip replacement surgery. METHODS: Randomized controlled trial: M-TIJRP (MiTechnique and guided Imagery in Joint Replacement Patients [Mighty Junior P]). At a community hospital, 225 male and female patients, aged 38 to 90 years, undergoing elective total hip or knee replacement were randomly assigned to 1 of 3 groups (75 patients in each): M, guided imagery, or usual care. They were blinded to their assignment until the intervention. MAIN OUTCOME MEASURES: Reduction of pain and anxiety postoperatively. Secondary outcomes measured use of pain medication and patient satisfaction. RESULTS: This study yielded positive findings for the management of pain and anxiety in patients undergoing elective joint replacement using M and guided imagery for 18 to 20 minutes compared with usual care. M showed the largest predicted decreases in both pain and anxiety between groups. There was no significant difference in narcotic pain medication use between groups. Patient satisfaction survey ratings were highest for M, followed by guided imagery. CONCLUSION: The benefit of M may be because of the specifically structured sequence of touch by competent caring, trained providers.


Asunto(s)
Ansiedad/terapia , Artroplastia de Reemplazo de Cadera/métodos , Artroplastia de Reemplazo de Rodilla/métodos , Imágenes en Psicoterapia/métodos , Dolor Postoperatorio/terapia , Tacto , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Satisfacción del Paciente
11.
Otol Neurotol ; 35(6): 1111-7, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24853238

RESUMEN

OBJECTIVE: This study examined the effects of symptom reports of dizziness and imbalance on cognitive function in concussed collegiate football players. DESIGN: Retrospective, descriptive. SETTING: University athletic medicine facility. SUBJECTS: Twenty-seven collegiate football players were included in the final analysis: 16 with symptoms of dizziness/imbalance resulting from concussion and 11 without dizziness/imbalance resulting from concussion. MAIN OUTCOME MEASURES: Participants completed the Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) at baseline, at 1 to 2 days postconcussion and 5 to 7 days postconcussion. The ImPACT neurocognitive assessment consists of 6 modules, yielding 4 composite scores: verbal memory, visual memory, visual-motor processing speed, and reaction time. In addition, it includes a postconcussion symptom scale total score. RESULTS: Results revealed that participants with reports of dizziness and imbalance had significantly lower scores on the ImPACT composite scores; however, these individuals also had an overall higher symptom inventory. When accounting for the additional postconcussion symptoms, time was the only significant effect. CONCLUSION: Dizziness and imbalance are common symptoms postconcussion; however, these symptoms did not predict performance on acute ImPACT scores. Further research is needed to understand the mechanisms causing postconcussion symptoms, including symptoms of dizziness and imbalance, and influence on outcomes postconcussion.


Asunto(s)
Conmoción Encefálica/diagnóstico , Mareo/diagnóstico , Fútbol Americano/lesiones , Desempeño Psicomotor , Adolescente , Adulto , Conmoción Encefálica/complicaciones , Conmoción Encefálica/fisiopatología , Mareo/etiología , Mareo/fisiopatología , Humanos , Masculino , Memoria , Pruebas Neuropsicológicas , Equilibrio Postural , Trastornos de la Pupila , Aprendizaje Verbal , Adulto Joven
12.
J Oral Rehabil ; 38(7): 501-8, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21133984

RESUMEN

This study was undertaken in a young Irish population to determine the dimensions and ratios of the six maxillary anterior teeth. One hundred and nine Irish subjects (age 18-25 inclusive) had irreversible hydrocolloid impressions made of their maxillary dentition poured in type V stone. Clinical crown dimensions were measured with a digital calliper. The stone casts were digitally photographed in a standardised manner enabling calculation of various ratios between the maxillary anterior teeth. Sexual dimorphism existed for various tooth dimensions; most notably canine teeth were in the region of 0·8 mm longer and 0·6 mm wider in males. Central and lateral incisors were found to be 0·5 mm wider in males. It is, therefore, recommended that dimensional tooth guidelines should be given for each of the sexes and not on a population basis. With regard to tooth proportion ratios, no significant differences were found between genders or the left and right sides for any of the measurements or ratios measured. The digitally recorded tooth proportions were similar for both sexes, and the Golden Proportion guidelines could only be applied to the lateral incisor/central incisor widths (0·618). Identified width proportions for the canine/central incisor were 0·58 and for canine/lateral incisor 0·89.


Asunto(s)
Diente Canino/anatomía & histología , Maxilar/anatomía & histología , Adolescente , Adulto , Análisis de Varianza , Femenino , Humanos , Irlanda/etnología , Masculino , Odontometría , Linaje , Fotografía Dental , Valores de Referencia , Reproducibilidad de los Resultados , Población Blanca/etnología , Adulto Joven
13.
J Gen Virol ; 91(Pt 10): 2642-50, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20573855

RESUMEN

Scrapie control in Great Britain (GB) was originally based on the National Scrapie Plan's Ram Genotyping scheme aimed at reducing the susceptibility of the national flock. The current official strategy to control scrapie in the national flock involves culling susceptible genotypes in individual, known affected flocks (compulsory scrapie flock scheme or CSFS). However, the recent development of preclinical test candidates means that a strategy based on disease detection may now be feasible. Here, a deterministic within-flock model was used to demonstrate that only large flocks with many home-bred ewes are likely to be a significant risk for flock-to-flock transmission of scrapie. For most other flocks, it was found that the CSFS could be replaced by a strategy using a currently available live test without excessive risk to other farmers, even if the proportion of susceptible genotypes in the flock is unusually large. Even for flocks that represent a high risk of harbouring a high prevalence of infection, there would be limited probability of onward transmission if scrapie is detected soon after disease introduction (typically less than 5 years). However, if detection of disease is delayed, the existing CSFS strategy may be the most appropriate control measure in these cases.


Asunto(s)
Transmisión de Enfermedad Infecciosa/prevención & control , Tamizaje Masivo/métodos , Scrapie/diagnóstico , Scrapie/epidemiología , Animales , Modelos Estadísticos , Scrapie/prevención & control , Ovinos , Reino Unido/epidemiología
14.
J Comp Pathol ; 142(1): 27-35, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19625026

RESUMEN

Blood transfusion practices have resulted in iatrogenic cases of variant Creutzfeldt-Jakob disease (vCJD) and it is known that sheep blood is also infectious in the pre-clinical stages of natural scrapie and experimentally induced bovine spongiform encephalopathy (BSE). Further investigations have also shown that the pathological phenotype of sheep BSE and human vCJD is maintained after blood transfusion. The present study describes the pathological phenotype, in terms of accumulation of the disease-associated prion protein in brain and lymphoreticular tissues, in sheep receiving blood from donors infected with natural scrapie. The immunohistochemical examinations undertaken showed a degree of phenotypic variability within and between scrapie donors and recipients, which might be attributable to the presence of more than one scrapie strain amongst the donor sheep or to a host adaptation process, or to the interaction of both, rather than to the influence of the route of infection.


Asunto(s)
Encéfalo/patología , Proteínas PrPSc/metabolismo , Scrapie/patología , Scrapie/transmisión , Reacción a la Transfusión , Animales , Encéfalo/metabolismo , Inmunohistoquímica , Fenotipo , Ovinos
15.
Eur J Dent Educ ; 13(3): 184-8, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19630938

RESUMEN

Recordings of patient satisfaction with provision of dental implant treatment are scarce. This study aimed to evaluate satisfaction amongst patients attending for provision of implant treatment by training undergraduate and postgraduate students at Dublin Dental School and Hospital (DDSH). A questionnaire was formulated and distributed to 100 individuals randomly selected from records of patients who had received implant treatment via student clinics in the previous 5 years. The response rate was 68%. Results showed a high overall level of satisfaction with treatment received.


Asunto(s)
Implantación Dental/educación , Educación en Odontología/métodos , Satisfacción del Paciente , Competencia Clínica , Comunicación , Relaciones Dentista-Paciente , Educación de Posgrado en Odontología , Femenino , Humanos , Irlanda , Masculino , Proyectos Piloto , Encuestas y Cuestionarios , Resultado del Tratamiento
16.
Neuropathol Appl Neurobiol ; 35(3): 247-58, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19207266

RESUMEN

UNLABELLED: Decreased rates of transmission of transmissible spongiform encephalopathies (TSEs) to sheep have been attributed to some polymorphisms of the prion protein (PrP) and to a 'species barrier' on interspecies experiments. In addition, the blood-brain barrier may be a further impediment to TSE neuroinvasion. The intracerebral (I/C) route is generally considered the most efficient for TSE transmission, as it may help to bypass those factors. Therefore, susceptibility of particular species to specific TSE agents is conducted by this route. AIMS: This study characterizes the traumatic brain lesions associated with the I/C injection of the bovine spongiform encephalopathy agent in sheep, assesses the relevance of such lesions in the outcome of clinical disease and provides insight into the mechanisms of PrP(d) conversion and amplification following I/C challenge. METHODS: A total of 27 hemibrains have been macroscopically and immunohistochemically examined to investigate the presence of lesions compatible with the needle track and the PrP(d) distribution, respectively. RESULTS: No residual inoculum was found and the extension and severity of the traumatic brain lesions were unrelated to the clinical outcome. Sheep with PrP(d) accumulation in the brain also showed conspicuous focal aggregates in the porencephalic lesions and in the circumventricular organs. In contrast, sheep without PrP(d) deposits in the brain were also negative in the traumatic lesions. CONCLUSION: Overall, these findings suggest that the efficiency of the I/C route is due to effective absorption and blood recirculation of infection, rather than to primary amplification at the site of injection.


Asunto(s)
Encéfalo/metabolismo , Encéfalo/patología , Encefalopatía Espongiforme Bovina/patología , Priones/metabolismo , Enfermedades de las Ovejas/patología , Animales , Bovinos , Ventrículos Cerebrales , Encefalopatía Espongiforme Bovina/metabolismo , Inmunohistoquímica , Ovinos , Enfermedades de las Ovejas/metabolismo
17.
J Immunol Methods ; 298(1-2): 119-28, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15847802

RESUMEN

The diagnosis of prion diseases, such as scrapie and BSE, has traditionally relied upon the identification of the disease-associated form of the prion protein, PrP(Sc), based on its resistance to digestion by proteinase K (PK). A more recent development is the conformation-dependent immunoassay (CDI), which distinguishes between PrP Sc and normal PrP (PrP C) based on their differing solubility in guanidine hydrochloride rather than resistance or sensitivity to PK. We have developed a CDI-formatted sandwich immunoassay for the measurement of PrP Sc in sheep brain, which discriminates between clinically affected scrapie cases (natural or experimental) and uninfected controls of the same PrP genotype. Using this method, we have shown for the first time that, in sheep, the PrP genotype has a significant influence on the amount of PrP Sc deposited in the brains of animals experimentally infected with scrapie.


Asunto(s)
Inmunoensayo/métodos , Proteínas PrPC/genética , Proteínas PrPSc/análisis , Scrapie/diagnóstico , Scrapie/genética , Animales , Western Blotting , Encéfalo/patología , Química Encefálica , Genotipo , Ovinos
18.
J Gen Virol ; 86(Pt 5): 1571-1579, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15831971

RESUMEN

PrP(C), a glycosylphosphatidylinositol-linked glycoprotein, plays a central role in the pathogenesis of transmissible spongiform encephalopathies (TSEs), undergoing a conformational alteration to the disease-associated isoform, commonly designated PrP(Sc). PrP(C) is expressed in many tissues other than the nervous system, although its precise function(s) remains unclear. It has previously been demonstrated that TSEs can be transmitted by blood transfusion in sheep. The aim of this work was to identify which components of blood carried the infection. As an initial step, the distribution of PrP(C) on cellular components of sheep blood was examined to identify potential targets for infection. Cell-surface expression of PrP(C) was found only on peripheral blood mononuclear cells (PBMCs); however, platelets also contained significant amounts of intracellular PrP(C). The level of PrP(C) expressed on the cell surface of PBMCs was influenced by PrP genotype, with the highest levels found in scrapie-susceptible VRQ/VRQ sheep and the lowest levels in scrapie-resistant ARR/ARR sheep. In susceptible sheep, PrP(C) was expressed at varying levels on all major subsets of PBMCs, with the highest levels on the CD21(+) subset of B cells, and PrP expression was upregulated dramatically on CD21(+) B cells in some scrapie-infected sheep.


Asunto(s)
Plaquetas/química , Leucocitos Mononucleares/química , Proteínas PrPC/análisis , Animales , Linfocitos B/química , Femenino , Masculino , Receptores de Complemento 3d/análisis , Ovinos
19.
Neuroscience ; 130(2): 519-26, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15664708

RESUMEN

One of several tenable hypotheses that can be proposed to explain the complex dynamics of spatially selective hippocampal neural activity postulates that the region of space over which a given cell receives its external input is actually much smaller than the classical 'place field.' According to this notion, the later portions of the field reflect some form of network hysteresis resulting from 'reverberatory' activity within reentrant, synaptically coupled cell assemblies within the hippocampus. This hypothesis predicts that transient, global inhibition, induced after the onset of firing, might truncate the remainder of the place field. To test this hypothesis, principal afferents to the hippocampus were stimulated bilaterally in rats running on a circular track, evoking widespread inhibition throughout the hippocampus, and abolishing all spike activity from simultaneously recorded populations of CA1 pyramidal cells for periods of 150-300 ms. Stimulation at any point within the place field of a given cell suppressed firing only for such brief intervals, followed by an immediate resumption for the remainder of the field. These results suggest that without additional cellular and/or synaptic mechanisms, reverberatory activity alone within the hippocampus does not account for the shape and spatial extent of place fields.


Asunto(s)
Potenciales de Acción/fisiología , Hipocampo/fisiología , Red Nerviosa/fisiología , Orientación/fisiología , Percepción Espacial/fisiología , Transmisión Sináptica/fisiología , Vías Aferentes/fisiología , Animales , Estimulación Eléctrica , Masculino , Modelos Neurológicos , Inhibición Neural/fisiología , Células Piramidales/fisiología , Ratas , Ratas Endogámicas F344 , Sinapsis/fisiología
20.
J Gen Virol ; 84(Pt 12): 3503-3512, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14645932

RESUMEN

The experimental infection of sheep with bovine spongiform encephalopathy (BSE) by the oral route and the likelihood that sheep were fed BSE-infected meat and bone meal has led to extensive speculation as to whether or not sheep are naturally infected with BSE. In response, the UK government has initiated the National Scrapie Plan (NSP), an ambitious pound 120 million per year project to create a BSE- and scrapie-resistant national sheep flock, by selectively breeding for a genotype of sheep believed to be resistant to both diseases. This genotype has recently been shown to be susceptible to BSE by intracerebral (i.c.) inoculation. Should these sheep be sufficiently susceptible to BSE via natural transmission, the NSP might fail. Here we estimate the susceptibility of this genotype to horizontal (sheep-to-sheep) transmission of BSE by comparison with more extensive oral and i.c. exposure data for other sheep genotypes. We show that a previous estimate of the risk of BSE transmission to sheep via the feedborne route remains robust. However, using a mathematical model for the within-flock transmission of BSE, we show that, while the best estimate indicates that the NSP should be successful, current data cannot exclude the failure of the NSP.


Asunto(s)
Encefalopatía Espongiforme Bovina/epidemiología , Enfermedades de las Ovejas/epidemiología , Animales , Bovinos , Susceptibilidad a Enfermedades , Transmisión de Enfermedad Infecciosa , Encefalopatía Espongiforme Bovina/genética , Encefalopatía Espongiforme Bovina/transmisión , Enfermedades Transmitidas por los Alimentos/epidemiología , Modelos Biológicos , Factores de Riesgo , Ovinos , Enfermedades de las Ovejas/genética , Reino Unido/epidemiología
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