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1.
Proc Natl Acad Sci U S A ; 121(37): e2404250121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39231203

RESUMEN

Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no HCMV vaccine has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize gB in its metastable prefusion conformation. One variant containing two engineered interprotomer disulfide bonds and two cavity-filling substitutions (gB-C7), displayed increased expression and thermostability. A 2.8 Å resolution cryoelectron microscopy structure shows that gB-C7 adopts a prefusion-like conformation, revealing additional structural elements at the membrane-distal apex. Unlike previous observations for several class I viral fusion proteins, mice immunized with postfusion or prefusion-stabilized forms of soluble gB protein displayed similar neutralizing antibody titers, here specifically against an HCMV laboratory strain on fibroblasts. Collectively, these results identify initial strategies to stabilize class III viral fusion proteins and provide tools to probe gB-directed antibody responses.


Asunto(s)
Citomegalovirus , Proteínas del Envoltorio Viral , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/metabolismo , Citomegalovirus/inmunología , Humanos , Animales , Ratones , Microscopía por Crioelectrón , Conformación Proteica , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Internalización del Virus , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Estabilidad Proteica , Vacunas contra Citomegalovirus/inmunología , Sustitución de Aminoácidos , Modelos Moleculares
2.
Am J Occup Ther ; 78(5)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39120609

RESUMEN

IMPORTANCE: Patients' perception of overall recovery is a critical outcome for stroke rehabilitation. However, the perception of overall recovery cannot be obtained using multidimensional measures, because satisfaction in most domains of life does not guarantee satisfaction in overall recovery. A single overall recovery score seems a straightforward measure. However, the clinical implications of overall scores are restricted, because factors affecting patients' overall recovery are unclear, which can be prioritized to optimize the effectiveness of rehabilitation. OBJECTIVE: To examine patient-reported variables affecting overall recovery scores in patients with differing stroke severity. DESIGN: The 59 items of the Stroke Impact Scale 3.0 were selected using regression analysis with a forward selection to explain the overall recovery score (0% = no recovery; 100% = full recovery). Stroke severity was determined with the National Institutes of Health Stroke Scale. SETTING: Hospitals. PARTICIPANTS: Data of 950 patients collected 90 days after stroke. RESULTS: The models explained about 55% of the variance of the overall recovery scores with five to nine variables, but merely 16% of the variance was explained for patients with moderate stroke. As stroke severity increased, the number of identified variables decreased. Most identified variables were related to social participation and self-care activities (e.g., ability to help others, control the bowels, and dress the torso). Differences in the remaining variables depended on stroke severity. CONCLUSIONS AND RELEVANCE: Patients' priorities differ depending on stroke severity. The identified variables may be set as treatment goals to optimize patients' self-perceived overall recovery. Plain-Language Summary: How patients perceive their overall recovery after a stroke is a critical outcome for their stroke rehabilitation. This study demonstrated that patients with different stroke severity may have different priorities that influence their self-perceived levels of overall recovery. The variables identified in this study may help occupational therapy practitioners identify meaningful goals to optimize patients' self-perceived overall recovery.


Asunto(s)
Recuperación de la Función , Rehabilitación de Accidente Cerebrovascular , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Índice de Severidad de la Enfermedad , Participación Social , Autoimagen , Accidente Cerebrovascular/psicología , Anciano de 80 o más Años , Actividades Cotidianas
3.
Am J Occup Ther ; 78(4)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38885526

RESUMEN

IMPORTANCE: Effective communication skills (CS) are essential for occupational therapists. The Gap-Kalamazoo Communication Skills Assessment Form (GKCSAF) is a standard tool for assessing the CS of medical residents. However, the interrater reliability for the nine CS domain scores ranges from poor to good. The intrarater reliability remains unclear. OBJECTIVE: To examine the inter- and intrarater reliability of the GKCSAF's nine domain scores and total score among occupational therapy interns. DESIGN: Repeated assessments with the GKCSAF. SETTING: Medical center psychiatry department. PARTICIPANTS: Twenty-five interns and 49 clients with mental illness, recruited from August 2020 to December 2021. OUTCOMES AND MEASURES: The transcripts of 50 evaluation interviews between clients and interns were used. Three independent raters assessed each transcript twice, at least 3 mo apart. RESULTS: The GKCSAF demonstrated poor interrater reliability for the nine domain scores (weighted κ = .08-.30) and the total score (intraclass correlation coefficient [ICC] = .22, 95% confidence interval [CI] [.10, .35]). The GKCSAF showed poor to intermediate intrarater reliability for the nine domain scores (weighted κ = .27-.73) and fair reliability for the total score (ICC = .69, 95% CI [.60, .77]). CONCLUSIONS AND RELEVANCE: The GKCSAF demonstrates poor interrater reliability and poor to intermediate intrarater reliability for the nine domain scores. However, it demonstrates fair intrarater reliability in assessing the overall CS performance of occupational therapy interns. Significant variations were observed when different raters assessed the same interns' CS, indicating inconsistencies in ratings. Consequently, it is advisable to conservatively interpret the CS ratings obtained with the GKCSAF. Plain-Language Summary: It is essential for occupational therapists to effectively communicate with clients. The Gap-Kalamazoo Communication Skills Assessment Form (GKCSAF) is a standard tool that is used to assess the communication skills of medical residents. The study authors used the GKCSAF with occupational therapy interns in a medical center psychiatry department to assess how effectively they interviewed clients with mental illness. This study aids occupational therapy personnel in the interpretation of GKCSAF results. The study findings also highlight the importance of developing reliable and standardized measures to assess communications skills in the field of occupational therapy.


Asunto(s)
Competencia Clínica , Comunicación , Internado y Residencia , Terapia Ocupacional , Humanos , Terapia Ocupacional/educación , Reproducibilidad de los Resultados , Masculino , Femenino , Adulto , Variaciones Dependientes del Observador , Relaciones Profesional-Paciente , Trastornos Mentales/rehabilitación
4.
Front Psychol ; 15: 1274204, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650906

RESUMEN

Introduction: Theory of mind (ToM) refers to the ability to understand and attribute mental states to oneself and others. A ToM measure is warranted for preschool children to assess their ToM development from a multidimensional perspective (i.e., cognitive and affective dimensions). This study aimed to develop the Preschool Theory of Mind Assessment (ToMA-P) and to evaluate its construct validity and applicability. Methods: The ToMA-P was developed based on comprehensive literature review and revised with expert panel feedback. Its psychometric properties were evaluated in 205 typically developing preschoolers with Rasch analysis for its dimensionality, item difficulties, and convergent validity. Results: The results indicated that all ToMA-P items, except for one, fit the hypothesized two-dimensional construct. The item difficulties in the cognitive and affective dimensions followed developmental sequences. The ToMA-P scores exhibited good convergent validity, as evidenced by its significant correlations with age, verbal comprehension, adaptive functions, and daily ToM performance (p < 0.05). Children's responses and behaviors also showed that the ToMA-P has good applicability. Discussion: This study provides empirical evidence that the ToMA-P measures cognitive and affective ToM following developmental sequences, and that it has potential as a clinical tool for assessing ToM in preschool children.

5.
Phys Ther ; 104(6)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38531775

RESUMEN

OBJECTIVE: The Fugl-Meyer assessment for upper extremity (FMA-UE) is a measure for assessing upper extremity motor function in patients with stroke. However, the considerable administration time of the assessment decreases its feasibility. This study aimed to develop an accumulative assessment system of upper extremity motor function (AAS-UE) based on the FMA-UE to improve administrative efficiency while retaining sufficient psychometric properties. METHODS: The study used secondary data from 3 previous studies having FMA-UE datasets, including 2 follow-up studies for subacute stroke individuals and 1 test-retest study for individuals with chronic stroke. The AAS-UE adopted deep learning algorithms to use patients' prior information (ie, the FMA-UE scores in previous assessments, time interval of adjacent assessments, and chronicity of stroke) to select a short and personalized item set for the following assessment items and reproduce their FMA-UE scores. RESULTS: Our data included a total of 682 patients after stroke. The AAS-UE administered 10 different items for each patient. The AAS-UE demonstrated good concurrent validity (r = 0.97-0.99 with the FMA-UE), high test-retest reliability (intra-class correlation coefficient = 0.96), low random measurement error (percentage of minimal detectable change = 15.6%), good group-level responsiveness (standardized response mean = 0.65-1.07), and good individual-level responsiveness (30.5%-53.2% of patients showed significant improvement). These psychometric properties were comparable to those of the FMA-UE. CONCLUSION: The AAS-UE uses an innovative assessment method, which makes good use of patients' prior information to achieve administrative efficiency with good psychometric properties. IMPACT: This study demonstrates a new assessment method to improve administrative efficiency while retaining psychometric properties, especially individual-level responsiveness and random measurement error, by making good use of patients' basic information and medical records.


Asunto(s)
Aprendizaje Profundo , Evaluación de la Discapacidad , Psicometría , Rehabilitación de Accidente Cerebrovascular , Extremidad Superior , Humanos , Extremidad Superior/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Anciano , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/fisiopatología , Recuperación de la Función
6.
Nat Commun ; 15(1): 1553, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378768

RESUMEN

Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.


Asunto(s)
COVID-19 , SARS-CoV-2 , Femenino , Animales , Humanos , Ratones , Vacunas contra la COVID-19 , COVID-19/prevención & control , Antígenos Virales/genética , Ratones Endogámicos BALB C , Glicoproteína de la Espiga del Coronavirus/genética , Anticuerpos Neutralizantes , Anticuerpos Antivirales
7.
Braz J Phys Ther ; 28(1): 100595, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38394721

RESUMEN

BACKGROUND: The minimal important difference (MID) of the Postural Assessment Scale for Stroke Patients (PASS) remains unknown, limiting the interpretation of change scores. OBJECTIVES: To estimate the MID of the PASS in patients with subacute stroke. METHODS: Data at admission and discharge for 240 participants were retrieved from a longitudinal study. The "mobility" item of the Barthel Index was used as the anchor for indicating the improvement of posture control. Receiver operating characteristic (ROC) method was used to estimate the anchor-based MID of the PASS. RESULTS: The ROC method identified a MID of 3.0 points, with a sensitivity of 81.0 % and a specificity of 75.6 %. CONCLUSION: The MID of the PASS was 3.0 points, indicating that if a patient achieves an improvement of 3.0 or more points on the PASS, they have a clinically important improvement in posture control. Our results can help in interpreting change scores and aid in understanding the clinical values of treatment outcomes.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Estudios Longitudinales , Resultado del Tratamiento , Hospitalización
8.
Asian J Psychiatr ; 94: 103965, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38394743

RESUMEN

BACKGROUND AND HYPOTHESIS: The Positive and Negative Syndrome Scale (PANSS) consists of 30 items and takes up to 50 minutes to administer and score. Therefore, this study aimed to develop and validate a machine learning-based short form of the PANSS (PANSS-MLSF) that reproduces the PANSS scores. Moreover, the PANSS-MLSF estimated the removed-item scores. STUDY DESIGN: The PANSS-MLSF was developed using an artificial neural network, and the removed-item scores were estimated using the eXtreme Gradient Boosting classifier algorithm. The reliability of the PANSS-MLSF was examined using Cronbach's alpha. The concurrent validity was examined by the association (Pearson's r) between the PANSS-MLSF and the PANSS. The convergent validity was examined by the association (Pearson's r) between the PANSS-MLSF and the Clinical Global Impression-Severity, Mini-Mental State Examination, and Lawton Instrumental Activities of Daily Living Scale. The agreement of the estimated removed-item scores with their original scores was examined using Cohen's kappa. STUDY RESULTS: Our analysis included data from 573 patients with moderate severity. The two versions of the PANSS-MLSF comprised 15 items and 9 items were proposed. The PANSS-MLSF scores were similar to the PANSS scores (mean squared error=2.6-24.4 points). The reliability, concurrent validity, and convergent validity of the PANSS-MLSF were good. Moderate to good agreement between the estimated removed-item scores and the original item scores was found in 60% of the removed items. CONCLUSION: The PANSS-MLSF offers a viable way to reduce PANSS administration time, maintain score comparability, uphold reliability and validity, and even estimate scores for the removed items.


Asunto(s)
Actividades Cotidianas , Humanos , Reproducibilidad de los Resultados , Psicometría
9.
Am J Occup Ther ; 78(2)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38271640

RESUMEN

IMPORTANCE: The machine learning-based Stroke Impact Scale (ML-SIS) is an efficient short-form measure that uses 28 items to provide domain scores comparable to those of the original 59-item Stroke Impact Scale-Third Edition (SIS 3.0). However, its utility is largely unknown because it has not been cross-validated with an independent sample. OBJECTIVE: To examine the ML-SIS's comparability and test-retest reliability with that of the original SIS 3.0 in an independent sample of people with stroke. DESIGN: Comparability was examined with the coefficient of determination (R2), mean absolute error, and root-mean-square error (RMSE). Test-retest reliability was examined using the intraclass correlation coefficient (ICC). SETTING: Five hospitals in Taiwan. PARTICIPANTS: Data of 263 persons with stroke were extracted from a previous study; 144 completed repeated assessments after a 2-wk interval. RESULTS: High R2 (.87-.95) and low mean absolute error or RMSE (about 2.4 and 3.3) of the domain scores, except for the Emotion scores (R2 = .08), supported the comparability of the two measures. Similar ICC values (.39-.87 vs. .46-.87) were found between the two measures, suggesting that the ML-SIS is as reliable as the SIS 3.0. CONCLUSIONS AND RELEVANCE: The ML-SIS provides scores mostly identical to those of the original measure, with similar test-retest reliability, except for the Emotion domain. Thus, it is a promising alternative that can be used to lessen the burden of routine assessments and provide scores comparable to those of the original SIS 3.0. Plain-Language Summary: The machine learning-based Stroke Impact Scale (ML-SIS) is as reliable as the original Stroke Impact Scale-Third Edition, except for the Emotion domain. Thus, the ML-SIS can be used to improve the efficiency of clinical assessments and also relieve the burden on people with stroke who are completing the assessments.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Reproducibilidad de los Resultados , Comparación Transcultural , Accidente Cerebrovascular/psicología , Lenguaje
10.
Arch Clin Neuropsychol ; 39(6): 724-731, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-38163920

RESUMEN

Patients with schizophrenia tend to have deficits in emotion recognition (ER) that affect their social function. However, the commonly-used ER measures appear incomprehensive, unreliable and invalid, making it difficult to comprehensively evaluate ER. The purposes of this study were to develop the Computerized Emotion Recognition Video Test (CERVT) evaluating ER ability in patients with schizophrenia. This study was divided into two phases. First, we selected candidate CERVT items/videos of 8 basic emotion domains from a published database. Second, we validated the selected CERVT items using Rasch analysis. Finally, the 269 patients and 177 healthy adults were recruited to ensure the participants had diverse abilities. After the removal of 21 misfit (infit or outfit mean square > 1.4) items and adjustment of the item difficulties of the 26 items with severe differential item functioning, the remaining 217 items were finalized as the CERVT items. All the CERVT items showed good model fits with small eigenvalues (≤ 2) based on the residual-based principal components analysis for each domain, supporting the unidimensionality of these items. The 8 domains of the CERVT had good to excellent reliabilities (average Rasch reliabilities = 0.84-0.93). The CERVT contains items of the 8 basic emotions with individualized scores. Moreover, the CERVT showed acceptable reliability and validity, and the scores were not affected by examinees' gender. Thus, the CERVT has the potential to provide a comprehensive, reliable, valid, and gender-unbiased assessment of ER for patients with schizophrenia.


Asunto(s)
Emociones , Psicometría , Esquizofrenia , Humanos , Masculino , Femenino , Adulto , Emociones/fisiología , Esquizofrenia/diagnóstico , Psicometría/normas , Psicometría/instrumentación , Persona de Mediana Edad , Reproducibilidad de los Resultados , Psicología del Esquizofrénico , Reconocimiento en Psicología/fisiología , Pruebas Neuropsicológicas/normas , Adulto Joven
11.
Commun Biol ; 6(1): 1250, 2023 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-38082099

RESUMEN

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Anticuerpos Neutralizantes
12.
Hong Kong J Occup Ther ; 36(2): 110-117, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38027052

RESUMEN

Purpose: To examine the consistency between patient- and occupational therapist-reported judgments of patients' ability and change in ADL abilities. Materials: Patient- and therapist-reported ADL abilities were assessed using a Visual Analogue Scale, whilst the changes in patients' ADL abilities were reported by patients and therapists using a 15-point Likert-type scale. Methods: Repeated assessments at a 3-week interval were used. 88 inpatients with stroke and 16 occupational therapists were recruited from rehabilitation wards in a medical center. Results: Moderate correlations (rs = .53-.56) were found between the patient- and therapist-reported ADL abilities. The patient-reported scores were significantly lower (ds = .45; ps < .001 at follow-up) than the therapist-reported scores. Only low correlation (r = .33) was found for the change scores. Conclusions: Our findings indicated that there was only a moderate to low correlation between the patients' reports and the therapists' judgments regarding the patients' ADL ability and its change. Because both patients' reports and therapists' judgments affect decisions on rehabilitation, frequent communication may be beneficial for reaching consensus and helpful in managing the interventions.

13.
Am J Occup Ther ; 77(5)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37824724

RESUMEN

IMPORTANCE: Performance of coloring, origami, and copying activities reflects children's visual-motor integration (VMI), but the levels of association remain unclear. OBJECTIVE: To use artificial intelligence (AI) to investigate associations of performance of coloring, origami, and copying activities with VMI. DESIGN: Cross-sectional study. SETTING: Kindergartens. PARTICIPANTS: A sample of 370 children (182 boys and 188 girls) in the second and third years of kindergarten. OUTCOMES AND MEASURES: Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition (VMI-6). RESULTS: Data for preschool children from an ongoing project were retrieved. AI models were trained to use photographs of activity products to predict total score on the VMI-6. R2 values were used to identify the variance in VMI-6 standardized scores explained by predicted scores from the activities. That is, R2 values reflected associations between activity performance and VMI. The R2 values for the combination of origami and copying were the largest (.390-.577). These R2 values were larger than those for each individual activity (.340-.473) and similar to those for the combination of all three activities (.400-.550). CONCLUSIONS AND RELEVANCE: Because moderate R2 values were found between performance of the three activity products and VMI, the three activities have high potential for use in identifying children's level of VMI or as teaching materials to facilitate the development of children's VMI. Furthermore, combining origami and copying activities is recommended for teachers and clinicians who need to address VMI. What This Article Adds: A combination of origami and copying activities had the strongest associations with children's VMI. Teachers and clinicians can use these two activities when addressing VMI development among preschool children.


Asunto(s)
Inteligencia Artificial , Desarrollo Infantil , Masculino , Femenino , Preescolar , Humanos , Estudios Transversales , Desempeño Psicomotor , Pruebas Neuropsicológicas
14.
mBio ; 14(4): e0090223, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37535402

RESUMEN

While immune correlates against SARS-CoV-2 are typically defined at peak immunogenicity following vaccination, immunologic responses that expand selectively during the anamnestic response following infection can provide mechanistic and detailed insights into the immune mechanisms of protection. Moreover, whether anamnestic correlates are conserved across variants of concern (VOC), including the Delta and more distant Omicron VOC, remains unclear. To define the anamnestic correlates of immunity, across VOCs, we deeply profiled the humoral immune response in individuals infected with sequence-confirmed Delta or Omicron VOC after completing the vaccination series. While limited acute N-terminal domain and receptor-binding domain (RBD)-specific immune expansion was observed following breakthrough infection, a significant immunodominant expansion of opsonophagocytic Spike-specific antibody responses focused largely on the conserved S2-domain of SARS-CoV-2 was observed. This S2-specific functional humoral response continued to evolve over 2-3 weeks following Delta or Omicron breakthrough, targeting multiple VOCs and common coronaviruses. Strong responses were observed on the fusion peptide (FP) region and the heptad repeat 1 (HR1) region adjacent to the RBD. Notably, the FP is highly conserved across SARS-related coronaviruses and even non-SARS-related betacoronavirus. Taken together, our results point to a critical role of highly conserved, functional S2-specific responses in the anamnestic antibody response to SARS-CoV-2 infection across VOCs. These humoral responses linked to virus clearance can guide next-generation vaccine-boosting approaches to confer broad protection against future SARS-related coronaviruses. IMPORTANCE The Spike protein of SARS-CoV-2 is the primary target of antibody-based recognition. Selective pressures, be it the adaption to human-to-human transmission or evasion of previously acquired immunity, have spurred the emergence of variants of the virus such as the Delta and Omicron lineages. Therefore, understanding how antibody responses are expanded in breakthrough cases of previously vaccinated individuals can provide insights into key correlates of protection against current and future variants. Here, we show that vaccinated individuals who had documented COVID-19 breakthrough showed anamnestic antibody expansions targeting the conserved S2 subdomain of Spike, particularly within the fusion peptide region. These S2-directed antibodies were highly leveraged for non-neutralizing, phagocytic functions and were similarly expanded independent of the variant. We propose that through deep profiling of anamnestic antibody responses in breakthrough cases, we can identify antigen targets susceptible to novel monoclonal antibody therapy or vaccination-boosting strategies.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2/genética , Anticuerpos , Anticuerpos Antivirales , Anticuerpos Neutralizantes
15.
Arch Phys Med Rehabil ; 104(10): 1676-1682, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37419234

RESUMEN

OBJECTIVE: To examine the test-retest reliability, responsiveness, and clinical utility of the Computerized Adaptive Testing System of the Functional Assessment of Stroke (CAT-FAS) in persons with stroke. DESIGN: Repeated measurements design. SETTING: A department of rehabilitation in a medical center. PARTICIPANTS: 30 persons with chronic stroke (for test-retest reliability) and 65 persons with subacute stroke (for responsiveness) were recruited. To examine the test-retest reliability, the participants received measurements twice at 1-month intervals. To examine the responsiveness, the data were collected at admission and discharge from hospital. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENT TOOL: CAT-FAS. RESULTS: The intra-class correlation coefficients of the CAT-FAS were ≥0.82, indicating good to excellent test-retest reliability. The Kazis' effect size and standardized response mean of the CAT-FAS were ≥0.96, indicating good group-level responsiveness. For individual-level responsiveness, approximately two-thirds of the participants exceeded the conditional minimal detectable change. On average, the CAT-FAS was completed within 9 items and 3 minutes per administration. CONCLUSIONS: Our results suggest the CAT-FAS is an efficient measurement tool with good to excellent test-retest reliability and responsiveness. In addition, the CAT-FAS can be used routinely in clinical settings to monitor progress of the crucial 4 domains for persons with stroke.

16.
Arch Phys Med Rehabil ; 104(9): 1432-1438, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37028696

RESUMEN

OBJECTIVE: To examine the test-retest reliability, minimal detectable change (MDC), responsiveness, and efficiency of the Computerized Adaptive Test of Social Functioning (Social-CAT) in patients with stroke. DESIGN: Repeated-assessments design. SETTING: A department of rehabilitation of a medical center. PARTICIPANTS: In total, 31 patients with chronic stroke and 65 patients with subacute stroke were recruited. INTERVENTION: Not available. MAIN OUTCOME MEASURE: Social-CAT. RESULTS: The Social-CAT showed acceptable test-retest reliability (intraclass correlation coefficient, 0.80) and small random measurement error (MDC%: 18.0%). However, heteroscedasticity was found (r between the means and the absolute change scores: 0.32), so the MDC% adjusted cut-off score is recommended for determining real improvement. Regarding responsiveness, the Social-CAT showed large differences (Kazis' effect size and standardized mean response: 1.15 and 1.09, respectively) in subacute patients. Regarding efficiency, the Social-CAT required an average of 5 items and less than 2 minutes for completion. CONCLUSIONS: Our findings indicate that the Social-CAT is a reliable and efficient measure with good test-retest reliability, small random measurement error, and good responsiveness. Thus, the Social-CAT is a useful outcome measure for routine monitoring of the changes in social function of patients with stroke.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Reproducibilidad de los Resultados , Interacción Social , Actividades Cotidianas , Evaluación de la Discapacidad
18.
Elife ; 122023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36942851

RESUMEN

To address the ongoing SARS-CoV-2 pandemic and prepare for future coronavirus outbreaks, understanding the protective potential of epitopes conserved across SARS-CoV-2 variants and coronavirus lineages is essential. We describe a highly conserved, conformational S2 domain epitope present only in the prefusion core of ß-coronaviruses: SARS-CoV-2 S2 apex residues 980-1006 in the flexible hinge. Antibody RAY53 binds the native hinge in MERS-CoV and SARS-CoV-2 spikes on the surface of mammalian cells and mediates antibody-dependent cellular phagocytosis and cytotoxicity against SARS-CoV-2 spike in vitro. Hinge epitope mutations that ablate antibody binding compromise pseudovirus infectivity, but changes elsewhere that affect spike opening dynamics, including those found in Omicron BA.1, occlude the epitope and may evade pre-existing serum antibodies targeting the S2 core. This work defines a third class of S2 antibody while providing insights into the potency and limitations of S2 core epitope targeting.


Asunto(s)
COVID-19 , Glicoproteína de la Espiga del Coronavirus , Animales , Glicoproteína de la Espiga del Coronavirus/genética , SARS-CoV-2 , Anticuerpos , Epítopos , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Mamíferos
19.
Arch Phys Med Rehabil ; 104(8): 1219-1226, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36736809

RESUMEN

OBJECTIVE: To develop and validate a short form of the Fugl-Meyer Assessment of Upper Extremity Scale (FMA-UE) using a machine learning approach (FMA-UE-ML). In addition, scores of items not included in the FMA-UE-ML were predicted. DESIGN: Secondary data from a previous study, which assessed individuals post-stroke using the FMA-UE at 4 time points: 5-30 days post-stroke screen, 2-month post-stroke baseline assessment, 6-month post-stroke assessment, and 12-month post-stroke assessment. SETTING: Rehabilitation units in hospitals. PARTICIPANTS: A total of 408 individuals post-stroke (N=408). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The 30-item FMA-UE. RESULTS: We established 29 candidate versions of the FMA-UE-ML with different numbers of items, from 1 to 29, and examined their concurrent validity and responsiveness. We found that the responsiveness of the candidate versions obviously declined when the number of items was less than 13. Thus, the 13-item version was selected as the FMA-UE-ML. The concurrent validity was good (intra-class correlation coefficients ≥0.99). The standardized response means of the FMA-UE-ML and FMA-UE were 0.54-0.88 and 0.52-0.91, respectively. The Pearson's rs between the change scores of the FMA-UE-ML and those of the FMA-UE were 0.96-0.98. The predicted item scores had acceptable to good accuracy (Kappa=0.50-0.92). CONCLUSIONS: The FMA-UE-ML seems a promising short form to improve administrative efficiency while retaining good concurrent validity and responsiveness. In addition, the FAM-UE-ML can provide all item scores of the FMA-UE for users.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Evaluación de la Discapacidad , Recuperación de la Función/fisiología , Extremidad Superior , Accidente Cerebrovascular/complicaciones
20.
Disabil Rehabil ; 45(22): 3748-3754, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36288467

RESUMEN

PURPOSE: We examined the unidimensionality and Rasch reliability of both Jenkinson's and MacIsaac's eight-item short versions of the Stroke Impact Scale (SF-SIS), a questionnaire for assessing overall health-related quality of life (HRQOL). METHODS: This study was a secondary data analysis in which 263 persons with stroke completed the SIS. The 263 persons, on average, had age of 60 years, mild stroke, and moderate disability of self-care. The unidimensionality of both versions was validated via testing of model fitting and principal component analysis (PCA) of residuals using the Rasch analysis to determine the Rasch reliability and measures. RESULTS: The eight items in both SF-SIS versions met the criteria of infit and outfit MNSQ (<1.4 and >0.6), indicating good data-model fit. The PCA showed that no dominant factors existed in the residuals of the items. The person reliability of Jenkinson's and MacIsaac's SF-SIS versions was 0.80 and 0.79, respectively. The Rasch measures (i.e., person measure in logits) ranged from -1.06 to 1.87 in Jenkinson's SF-SIS and -0.82 to 1.88 in MacIsaac's version. CONCLUSIONS: The unidimensionality of both versions was supported. The Rasch measures of both appear valid for representing overall HRQOL levels. Both versions also showed acceptable reliability for research purposes.Implications for rehabilitationThe unidimensionality was justified for both versions (Jenkinson's and MacIsaac's eight-item short-versions of Stroke Impact Scale).The Rasch scores of both versions appear valid for representing overall health-related quality of life.Both versions showed acceptable reliability for research purposes, but not sufficiently reliable for clinical use.

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