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1.
Artículo en Inglés | MEDLINE | ID: mdl-38411869

RESUMEN

Despite collaboration among different professions being recognized as fundamentally important to contemporary and future healthcare practice, the concept is woefully undertheorized. This has implications for how health professions educators might best introduce students to interprofessional collaboration and support their transition into interprofessional, collaborative workplaces. To address this, we engage in a conceptual analysis of published collaborative, interprofessional practices and conceptual understandings in theatre, as a highly collaborative art form and industry, to advance thinking in the health professions, specifically to inform interprofessional education. Our analysis advances a conceptualization of collaboration that takes place within a work culture of creativity and community, that includes four modes of collaboration, or the ways theatre practitioners collaborate, by: (1) paying attention to and traversing roles and hierarchies; (2) engaging in reciprocal listening and challenging of others; (3) developing trust and communication, and; (4) navigating uncertainty, risk and failure. We conclude by inviting those working in the health professions to consider what might be gleaned from our conceptualization, where the embodied and human-centred aspects of working together are attended to alongside structural and organizational aspects.

2.
Ann Neurol ; 95(3): 495-506, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38038976

RESUMEN

OBJECTIVE: Biomarkers of Alzheimer disease vary between groups of self-identified Black and White individuals in some studies. This study examined whether the relationships between biomarkers or between biomarkers and cognitive measures varied by racialized groups. METHODS: Cerebrospinal fluid (CSF), amyloid positron emission tomography (PET), and magnetic resonance imaging measures were harmonized across four studies of memory and aging. Spearman correlations between biomarkers and between biomarkers and cognitive measures were calculated within each racialized group, then compared between groups by standard normal tests after Fisher's Z-transformations. RESULTS: The harmonized dataset included at least one biomarker measurement from 495 Black and 2,600 White participants. The mean age was similar between racialized groups. However, Black participants were less likely to have cognitive impairment (28% vs 36%) and had less abnormality of some CSF biomarkers including CSF Aß42/40, total tau, p-tau181, and neurofilament light. CSF Aß42/40 was negatively correlated with total tau and p-tau181 in both groups, but at a smaller magnitude in Black individuals. CSF Aß42/40, total tau, and p-tau181 had weaker correlations with cognitive measures, especially episodic memory, in Black than White participants. Correlations of amyloid measures between CSF (Aß42/40, Aß42) and PET imaging were also weaker in Black than White participants. Importantly, no differences based on race were found in correlations between different imaging biomarkers, or in correlations between imaging biomarkers and cognitive measures. INTERPRETATION: Relationships between CSF biomarkers but not imaging biomarkers varied by racialized groups. Imaging biomarkers performed more consistently across racialized groups in associations with cognitive measures. ANN NEUROL 2024;95:495-506.


Asunto(s)
Enfermedad de Alzheimer , Cognición , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Tomografía de Emisión de Positrones , Proteínas tau/líquido cefalorraquídeo , Negro o Afroamericano , Blanco
3.
Gerontologist ; 64(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37067944

RESUMEN

BACKGROUND AND OBJECTIVES: Relational caring has the capacity to reduce stigma associated with dementia by shifting the focus from dysfunction and behavior management, to attending to the interdependencies and reciprocities that underpin caring relationships, and making explicit the centrality of relationships to quality care, growth, and quality of life. Education, particularly arts-based approaches, has been identified as a key strategy to decrease stigma. Yet rarely are the arts utilized in educational initiatives, and particularly so in community care settings. With an interest in redressing this, our team evaluated the impact of a Canadian filmed research-based drama-Cracked: new light on dementia-about stigma associated with people living with dementia and their families. RESEARCH DESIGN AND METHODS: We conducted interviews with family carers of people living with dementia and formal care providers affiliated with community-based dementia care, and also the general public at 3 and 8 months postscreening. RESULTS: Our analysis of participants' perceptions/experiences illustrates the effectiveness of Cracked in reducing stigma by demonstrating changes in the understanding of dementia and changes in practice. Our analysis also includes attention to how the film, as a form of cultural production, deepened engagement and facilitated transformation. DISCUSSION AND IMPLICATIONS: Our evaluation of Cracked demonstrates that it is an effective strategy for decreasing the stigma associated with dementia by promoting relational caring. It also importantly contributes to the theoretical literature that supports film-based approaches to stigma reduction.


Asunto(s)
Demencia , Humanos , Canadá , Calidad de Vida , Cuidadores , Estigma Social
4.
Alzheimers Dement ; 19 Suppl 9: S115-S125, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37491668

RESUMEN

INTRODUCTION: One goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early-onset Alzheimer's disease (EOAD). METHODS: Cerebrospinal fluid (CSF) concentrations of Aß1-40, Aß1-42, total tau (tTau), pTau181, VILIP-1, SNAP-25, neurogranin (Ng), neurofilament light chain (NfL), and YKL-40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated. RESULTS: Biomarkers were correlated with one another. Levels of CSF Aß42/40, pTau181, tTau, SNAP-25, and Ng in EOAD differed significantly from cognitively normal and early-onset non-AD dementia; NfL, YKL-40, and VILIP-1 did not. Across groups, all biomarkers except SNAP-25 were correlated with cognition. Within the EOAD group, Aß42/40, NfL, Ng, and SNAP-25 were correlated with at least one cognitive measure. DISCUSSION: This study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/líquido cefalorraquídeo , Proteína 1 Similar a Quitinasa-3 , Péptidos beta-Amiloides/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Estudios Longitudinales , Biomarcadores/líquido cefalorraquídeo , Neurogranina/líquido cefalorraquídeo
5.
Pediatr Rev ; 43(5): e12-e14, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35490206
6.
Dementia (London) ; 21(4): 1077-1097, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34904897

RESUMEN

Despite the recognized benefits of sexual expression and its importance in the lives of people living with dementia, research demonstrates that there are multiple barriers to its positive expression (e.g., expression that is pleasurable and free of coercion, discrimination, and violence) in RLTC homes. These barriers constitute a form of discrimination based on age and ability, and violate the rights of persons living with dementia to dignity, autonomy, and participation in everyday life and society. Drawing on a human rights approach to dementia and sexual expression, we explored the experiences of diverse professionals, family members, and persons living with dementia with explicit attention to the ways in which macro-level dynamics are influencing the support, or lack thereof, for sexual expression at the micro level. Focus groups and in-depth interviews were conducted with 27 participants, and the collected data were analyzed thematically. While all participants acknowledged that intimacy and sexual expression of persons living with dementia should be supported, rarely is such expression supported in practice. Micro-level factors included negative attitudes of professionals toward sexual expression by persons living with dementia, their discomfort with facilitating intimacy and sexual expression in the context of their professional roles, their anxieties regarding potential negative reactions from family members, and concerns about sanctions for failing to prevent abuse. In our analysis, we importantly trace these micro-level factors to macro-level factors. The latter include the cultural stigma associated with dementia, ageism, ableism, and erotophobia, all of which are reproduced in, and reinforced by, professionals' education, as well as legal and professional standards that exclusively focus on managing and safeguarding residents from abuse. Our analysis demonstrates a complexity that has enormous potential to inform future research that is critically needed for the development of educational initiatives and to promote policy changes in this area.


Asunto(s)
Demencia , Cuidados a Largo Plazo , Humanos , Conducta Sexual , Parejas Sexuales , Sexualidad
7.
Foot (Edinb) ; 48: 101817, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34332397

RESUMEN

Ischemia after correction of lesser toe deformities is usually due to temporary vasospasm and can rarely cause gangrene. The published literature on dealing with the issue and been reviewed and used to suggest an algorithm for a logical step by step approach to a pale or white toe when encountered in the postoperative period.


Asunto(s)
Deformidades del Pie , Algoritmos , Humanos , Isquemia/etiología , Isquemia/cirugía , Dedos del Pie/cirugía
8.
Bone Joint J ; 103-B(6): 1127-1132, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34058886

RESUMEN

AIMS: To assess the characteristic clinical features, management, and outcome of patients who present to orthopaedic surgeons with functional dystonia affecting the foot and ankle. METHODS: We carried out a retrospective search of our records from 2000 to 2019 of patients seen in our adult tertiary referral foot and ankle unit with a diagnosis of functional dystonia. RESULTS: A total of 29 patients were seen. A majority were female (n = 25) and the mean age of onset of symptoms was 35.3 years (13 to 71). The mean delay between onset and diagnosis was 7.1 years (0.5 to 25.0). Onset was acute in 25 patients and insidious in four. Of the 29 patients, 26 had a fixed dystonia and three had a spasmodic dystonia. Pain was a major symptom in all patients, with a coexisting diagnosis of chronic regional pain syndrome (CRPS) made in nine patients. Of 20 patients treated with Botox, only one had a good response. None of the 12 patients who underwent a surgical intervention at our unit or elsewhere reported a subjective overall improvement. After a mean follow-up of 3.2 years (1 to 12), four patients had improved, 17 had remained the same, and eight reported a deterioration in their condition. CONCLUSION: Patients with functional dystonia typically presented with a rapid onset of fixed deformity after a minor injury/event and pain out of proportion to the deformity. Referral to a neurologist to rule out neurological pathology is advocated, and further management should be carried out in a movement disorder clinic. Response to treatment (including Botulinum toxin (Botox) injections) is generally poor. Surgery in this group of patients is not recommended and may worsen the condition. The overall prognosis remains poor. Cite this article: Bone Joint J 2021;103-B(6):1127-1132.


Asunto(s)
Tobillo/fisiopatología , Síndromes de Dolor Regional Complejo/fisiopatología , Distonía/fisiopatología , Pie/fisiopatología , Adolescente , Adulto , Anciano , Comorbilidad , Síndromes de Dolor Regional Complejo/diagnóstico , Distonía/diagnóstico , Distonía/terapia , Femenino , Humanos , Londres , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
9.
J Peripher Nerv Syst ; 26(2): 187-192, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33650166

RESUMEN

Foot deformities are frequently observed in patients with Charcot Marie tooth disease (CMT) and orthopaedic surgery is often required. Currently there is no evidence-based guideline on surgical management and only a few studies which have evaluated long-term outcomes of surgical procedures. The aim of the study was to evaluate longitudinally the effect of foot surgery in a cohort of CMT patients. Twenty-five CMT adult patients were assessed using a comprehensive group of validated scales and questionnaires before and after surgery. A wide range of surgical procedures was performed by one team of dedicated foot ankle orthopaedic surgeons. Foot alignment as measured by the foot posture index, pain, quality of life and callosities significantly improved after one year and the improvement was maintained up to 4 years after surgery. There was a trend towards a reduction in the number of falls post-operatively. Surgery had no effect on fatigue, balance and CMT examination score. Our findings showed significant improvement of pain, foot alignment, callosities and quality of life after surgery and suggested that foot deformity correction in adults with CMT performed in a specialised foot and ankle unit is beneficial.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Deformidades del Pie , Callosidades , Enfermedad de Charcot-Marie-Tooth/complicaciones , Enfermedad de Charcot-Marie-Tooth/cirugía , Deformidades del Pie/cirugía , Humanos , Dolor , Estudios Prospectivos , Calidad de Vida
10.
J Med Humanit ; 42(3): 453-469, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31332591

RESUMEN

This paper interrogates and reclaims clown practices in children's rehabilitation as 'foolish.' Attempts to legitimize and 'take seriously' clown practices in the health sciences frame the work of clowns as secondary to the 'real' work of medical professionals and diminish the ways clowns support emotional vulnerability and bravery with a willingness to fail and be ridiculous as fundamental to their work. Narrow conceptualizations of clown practices in hospitals as only happy and funny overlook the ways clowns also routinely engage with sadness, despair, discomfort and many other ways of being and doing. Our exploration of clown practices as foolish exposes the ways children's rehabilitation upholds particular neoliberal models of success and invites a re-centring of rehabilitation and health care research and practice towards relationship building, supporting meaningful projects and a continued nurturing of aesthetic and pleasurable ways of being-in-the-world in the present moment as valuable unto themselves.


Asunto(s)
Hospitales , Niño , Humanos
11.
Toxicol Pathol ; 49(3): 634-646, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33349160

RESUMEN

Fusion of biologic therapeutics to hyaluronic acid binding proteins, such as the link domain (LD) of Tumor necrosis factor (TNF)-Stimulated Gene-6 (TSG-6), is expected to increase vitreous residence time following intravitreal injection and provide for long-acting delivery. The toxicity of a single intravitreal dose of free TSG-6-LD and fusion proteins of TSG-6-LD and a nonbinding rabbit antibody fragment (RabFab) were assessed in New Zealand White rabbits. Animals administered free TSG-6-LD exhibited extensive lens opacities and variable retinal vascular attenuation, correlated with microscopic findings of lens and retinal degeneration. Similar but less severe findings were present in animals dosed with the RabFab-TSG-6-LD fusion proteins. In-life ocular inflammation was noted in all animals from 7-days postdose and was associated with high anti-RabFab antibody titers in animals administered fusion proteins. Inflammation and retinal degeneration were multifocally associated with evidence of retinal detachment, and hypertrophy and migration of vimentin, glial fibrillary acidic protein, and glutamine synthetase positive Müller cells to the outer nuclear layer. Further assessment of alternative hyaluronic acid binding protein fusions should consider the potential for retinal degeneration and enhanced immune responses early in development.


Asunto(s)
Retina , Degeneración Retiniana , Animales , Proteína Ácida Fibrilar de la Glía , Inyecciones Intravítreas , Conejos , Degeneración Retiniana/inducido químicamente
12.
Foot Ankle Surg ; 27(8): 865-868, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33272751

RESUMEN

Charcot Marie Tooth disease (CMT) is the most common inherited neuropathy and is also called Hereditary Motor Sensory Neuropathy (HMSN). Whilst both motor and sensory deficits are present, motor deficits tend to predominate over sensory deficits. Charcot neuroarthropathic joints occur in conditions, most commonly diabetes nowadays, where joints are destroyed in association with reduced protective sensation, pain in particular. Three cases of development of Charcot joint disorders in patients with CMT are discussed and the literature is reviewed. Orthopaedic surgeons should be aware that Charcot joints can occur in CMT and surgery can be complicated by Charcot joints.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Enfermedad de Charcot-Marie-Tooth/complicaciones , Enfermedad de Charcot-Marie-Tooth/genética , Humanos
13.
Alzheimers Dement ; 16(1): 144-152, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31914216

RESUMEN

INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers can identify individuals with Alzheimer's disease (AD) pathology (eg, amyloid plaques, neurofibrillary tangles), but defined analyte cut-points using high-throughput automated assays are necessary for general clinical use. METHODS: CSF amyloid ß42 peptide (Aß42), t-tau, and t-tau/Aß42 were quantified by the Lumipulse platform in two test cohorts (A/B: Eisai BAN2401-201/MISSION AD E2609-301/302, n = 138; C: Knight Alzheimer's Disease Research Center (ADRC), n = 198), and receiver operating characteristic (ROC) curve analyses defined cut-points corresponding best to amyloid determinations using positron emission tomography (PET) imaging. The best-performing cut-point was then validated as a predictor of amyloid status in an independent cohort (D: MISSION AD E2609-301/302, n = 240). RESULTS: Virtually identical t-tau/Aß42 cut-points (∼0.54) performed best in both test cohorts and with similar accuracy (areas under ROC curve [AUCs] [A/B: 0.95; C: 0.94]). The cut-point yielded an overall percent agreement with amyloid PET of 85.0% in validation cohort D. DISCUSSION: Lumipulse CSF biomarker measures with validated cut-points have clinical utility in identifying AD pathology.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Amiloide/metabolismo , Biomarcadores/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Anciano , Péptidos beta-Amiloides/metabolismo , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/metabolismo , Tomografía de Emisión de Positrones , Reproducibilidad de los Resultados
14.
Alzheimers Dement ; 15(5): 655-665, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30846386

RESUMEN

INTRODUCTION: Four less well-studied but promising "emerging" cerebrospinal fluid (CSF) biomarkers are elevated in late-onset Alzheimer disease (AD): neurogranin, synaptosomal-associated protein-25 (SNAP-25), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). METHODS: CSF neurogranin, SNAP-25, VILIP-1, and YKL-40 were measured in families carrying autosomal-dominant AD mutations. RESULTS: The four emerging CSF biomarkers were significantly elevated in the mutation carriers (n = 235) versus noncarriers (n = 145). CSF SNAP-25, VILIP-1, and YKL-40 were altered very early in the AD time course, approximately 15-19 years before estimated symptom onset. All CSF biomarkers predicted important AD-related outcomes including performance on a cognitive composite, brain amyloid burden as measured by amyloid positron emission tomography, and the estimated years from symptom onset. DISCUSSION: Early abnormalities in CSF tTau, pTau, SNAP-25, VILIP-1, and YKL-40 suggest that synaptic damage, neuronal injury, and neuroinflammation begin shortly after the commencement of brain amyloid accumulation.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/genética , Biomarcadores/líquido cefalorraquídeo , Progresión de la Enfermedad , Mutación/genética , Anciano , Péptidos beta-Amiloides/líquido cefalorraquídeo , Proteína 1 Similar a Quitinasa-3/líquido cefalorraquídeo , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Neurocalcina/líquido cefalorraquídeo , Neurogranina/líquido cefalorraquídeo , Tomografía de Emisión de Positrones , Proteína 25 Asociada a Sinaptosomas/líquido cefalorraquídeo
15.
Alzheimers Dement ; 14(11): 1460-1469, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29501462

RESUMEN

INTRODUCTION: Levels of amyloid ß peptide 42 (Aß42), total tau, and phosphorylated tau-181 are well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, but variability in manual plate-based assays has limited their use. We examined the relationship between CSF biomarkers, as measured by a novel automated immunoassay platform, and amyloid positron emission tomography. METHODS: CSF samples from 200 individuals underwent separate analysis for Aß42, total tau, and phosphorylated tau-181 with automated Roche Elecsys assays. Aß40 was measured with a commercial plate-based assay. Positron emission tomography with Pittsburgh Compound B was performed less than 1 year from CSF collection. RESULTS: Ratios of CSF biomarkers (total tau/Aß42, phosphorylated tau-181/Aß42, and Aß42/Aß40) best discriminated Pittsburgh Compound B-positive from Pittsburgh Compound B-negative individuals. DISCUSSION: CSF biomarkers and amyloid positron emission tomography reflect different aspects of Alzheimer's disease brain pathology, and therefore, less-than-perfect correspondence is expected. Automated assays are likely to increase the utility of CSF biomarkers.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Amiloide/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Inmunoensayo , Tomografía de Emisión de Positrones , Anciano , Péptidos beta-Amiloides/líquido cefalorraquídeo , Compuestos de Anilina , Biomarcadores/líquido cefalorraquídeo , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/líquido cefalorraquídeo , Radiofármacos , Tiazoles , Proteínas tau/líquido cefalorraquídeo
16.
Can J Occup Ther ; 85(2): 128-136, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29463135

RESUMEN

BACKGROUND: Theatre-based interventions use artistic media to facilitate social and emotional awareness and have therapeutic benefits for persons with developmental disabilities and mental health problems. The role of these interventions with Indigenous youth who have emotional, behavioural, and cognitive sequelae related to fetal alcohol spectrum disorder (FASD) has not been explored. PURPOSE: The purpose of this study was to explore the experiences and acceptability of a theatre-based approach for facilitating social communication and engagement in youth with FASD. METHOD: Participants were three Indigenous youth with FASD. A qualitative exploration of the experiences and acceptability of the intervention was conducted via focus groups held 2 weeks post-program participation with the participants, their caregivers, and program facilitators. The transcripts were analyzed using an inductive thematic approach. FINDINGS: Our results identified perceived postintervention improvements in participants' development of self-esteem, social skills, and emotional awareness. IMPLICATIONS: A theatre-based arts intervention has the potential to support improvements in social skills for youth with FASD.


Asunto(s)
Trastornos del Espectro Alcohólico Fetal/rehabilitación , Indígenas Norteamericanos , Terapia Ocupacional/métodos , Psicodrama/métodos , Adolescente , Canadá , Niño , Creatividad , Emociones , Femenino , Grupos Focales , Humanos , Masculino , Autoeficacia , Habilidades Sociales
17.
Dementia (London) ; 15(3): 358-80, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27170587

RESUMEN

Healthcare literature, public discourse, and policy documents continue to represent persons with dementia as "doomed" and "socially dead." This tragedy meta-narrative produces and reproduces misunderstandings about dementia and causes stigma, oppression, and discrimination for persons living with dementia. With few opportunities to challenge the dominant discourse, persons with dementia continue to be denied their citizenship rights. Drawing on the concept of narrative citizenship, we describe a community-based, critical arts-based project where persons with dementia, family members, visual and performance artists, and researchers came together to interrogate the tragedy discourse and construct an alternative narrative of dementia using the arts. Our research demonstrates the power of the arts to create transformative spaces in which to challenge dominant assumptions, foster critical reflection, and envision new possibilities for mutual support, caring, and relating. This alternative narrative supports the reclamation of citizenship for persons living with dementia and fosters the relational citizenship of all.


Asunto(s)
Arte , Demencia/psicología , Narración , Autonomía Personal , Justicia Social , Participación de la Comunidad , Investigación Participativa Basada en la Comunidad , Femenino , Humanos , Masculino , Participación Social , Estigma Social
18.
MAbs ; 6(2): 460-73, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24492306

RESUMEN

Viral entry targets with therapeutic neutralizing potential are subject to multiple escape mechanisms, including antigenic drift, immune dominance of functionally irrelevant epitopes, and subtle variations in host cell mechanisms. A surprising finding of recent years is that potent neutralizing antibodies to viral epitopes independent of strain exist, but are poorly represented across the diverse human population. Identifying these antibodies and understanding the biology mediating the specific immune response is thus difficult. An effective strategy for meeting this challenge is to incorporate multiplexed antigen screening into a high throughput survey of the memory B cell repertoire from immune individuals. We used this approach to discover suites of cross-clade antibodies directed to conformational epitopes in the stalk region of the influenza A hemagglutinin (HA) protein and to select high-affinity anti-peptide antibodies to the glycoprotein B (gB) of human cytomegalovirus. In each case, our screens revealed a restricted VH and VL germline usage, including published and previously unidentified gene families. The in vivo evolution of paratope specificity with optimal neutralizing activity was understandable after correlating biological activities with kinetic binding and epitope recognition. Iterative feedback between antigen probe design based on structure and function information with high throughput multiplexed screening demonstrated a generally applicable strategy for efficient identification of safe, native, finely tuned antibodies with the potential for high genetic barriers to viral escape.


Asunto(s)
Anticuerpos Bloqueadores/metabolismo , Antígenos Virales/metabolismo , Subgrupos de Linfocitos B/inmunología , Linfocitos B/inmunología , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Epítopos/metabolismo , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Proteínas del Envoltorio Viral/metabolismo , Anticuerpos Bloqueadores/inmunología , Afinidad de Anticuerpos , Antígenos Virales/inmunología , Línea Celular , Infecciones por Citomegalovirus/terapia , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Ensayos Analíticos de Alto Rendimiento , Humanos , Evasión Inmune/efectos de los fármacos , Inmunidad Humoral , Inmunidad Innata , Memoria Inmunológica , Gripe Humana/terapia , Conformación Proteica , Proteínas del Envoltorio Viral/inmunología
19.
Dev Neurorehabil ; 17(1): 44-63, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24180636

RESUMEN

OBJECTIVE: Previous research has demonstrated the value of arts-based programs for adolescents with childhood brain disorder to facilitate social skills and participation. The current study extends this work by examining the feasibility and effectiveness of an arts-based intervention for youth with acquired brain injuries (ABI). METHODS: A case study approach was used with four adolescent participants and one case control. A battery of quantitative measures were administered four and one week pre-intervention, one week post-intervention, as well six to eight month post-intervention. RESULTS: Improvements in pragmatic communication skills and social and participation goals were observed across intervention participants. Similar improvements were not seen with the case control participant. CONCLUSION: Results support the use of an arts-based intervention for youth with ABI to facilitate social skills and participation. Findings also highlight the need for more sensitive measures of these skills for these youth. Suggested guidelines for program implementation are provided.


Asunto(s)
Arteterapia/métodos , Lesiones Encefálicas/rehabilitación , Comunicación , Participación Social , Adolescente , Emociones , Estudios de Factibilidad , Femenino , Objetivos , Humanos , Masculino , Proyectos Piloto , Autoimagen , Conducta Social , Apoyo Social
20.
Vet Immunol Immunopathol ; 155(1-2): 129-34, 2013 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-23838470

RESUMEN

The passive transfer of antibodies from dams to offspring via colostrum is believed to play an important role in protecting neonatal mammals from infectious disease. The study presented here investigates the uptake of colostrum by 548 calves in western Kenya maintained under smallholder farming, an important agricultural system in eastern Africa. Serum samples collected from the calves and dams at recruitment (within the first week of life) were analysed for the presence of antibodies to four tick-borne haemoparasites: Anaplasma marginale, Babesia bigemina, Theileria mutans and Theileria parva. The analysis showed that at least 89.33% of dams were seropositive for at least one of the parasites, and that 93.08% of calves for which unequivocal results were available showed evidence of having received colostrum. The maternal antibody was detected up until 21 weeks of age in the calves. Surprisingly, there was no discernible difference in mortality or growth rate between calves that had taken colostrum and those that had not. The results are also important for interpretation of serosurveys of young calves following natural infection or vaccination.


Asunto(s)
Bovinos/inmunología , Inmunidad Materno-Adquirida , Anaplasma marginale/inmunología , Anaplasmosis/inmunología , Anaplasmosis/prevención & control , Animales , Animales Recién Nacidos , Anticuerpos Antibacterianos/metabolismo , Anticuerpos Antiprotozoarios/metabolismo , Babesia/inmunología , Babesiosis/inmunología , Babesiosis/prevención & control , Babesiosis/veterinaria , Bovinos/crecimiento & desarrollo , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/prevención & control , Estudios de Cohortes , Calostro/inmunología , Femenino , Kenia , Estudios Longitudinales , Embarazo , Theileria/inmunología , Theileria parva/inmunología , Theileriosis/inmunología , Theileriosis/prevención & control
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