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1.
Artículo en Inglés | MEDLINE | ID: mdl-39287143

RESUMEN

OBJECTIVE: People with HIV (PWH) can demonstrate elevated cognitive intraindividual variability (IIV-dispersion) that is associated with everyday functioning problems. Higher IIV-dispersion is theorized to reflect lapses in executive aspects of cognitive control, but few studies have directly evaluated this possibility. METHOD: 72 PWH completed the Cogstate and clinical measures of executive functions, psychomotor speed, and episodic memory. IIV-dispersion was calculated with the coefficient of variation (CoV) from six age-adjusted Cogstate subtest scores. RESULTS: Multiple regression showed that the three domain-level cognitive predictors explained 8% of the variance in Cogstate CoV (p = .03). Within this model, poorer executive functions were moderately associated with higher Cogstate CoV (p = .01), but the psychomotor and episodic memory domains were not (ps > .05). CONCLUSIONS: Findings align with cognitive theory in demonstrating IIV-dispersion is uniquely associated with independent measures of executive functions among PWH. Future experimental and mechanistic studies are needed to determine the precise executive aspects of IIV-dispersion.

2.
Percept Mot Skills ; : 315125241284053, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288078

RESUMEN

Science knowledge refers to the depth and breadth of facts acquired within the life, social, and earth sciences, and it has implications for both public and personal health. Drawing from cognitive aging theory, we examine whether levels of science knowledge are associated with age, neuropsychological functioning, and personal health literacy. Fifty-two younger and fifty older healthy adults completed our telephone-based study that included a commonly used test of science knowledge, as well as measures of neuropsychological functioning, health literacy, and relevant descriptives (e.g., mood). Adjusting for other demographics and neuropsychological functioning, older adults had significantly lower science knowledge test scores than younger adults. In the full sample, lower science knowledge showed medium-to-large associations with episodic memory, executive functions, and health literacy, independent of years of education. These results suggest that older adults' science knowledge falls slightly below that of their younger counterparts and is independently associated with higher order neuropsychological functions and aspects of personal health, which may have implications for accessing, understanding, and using relevant public health information across the lifespan.

3.
Neuropsychology ; 38(7): 637-652, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39207439

RESUMEN

OBJECTIVE: Executive dysfunction is characteristic of behavioral variant frontotemporal dementia (bvFTD) but can be challenging to detect. Dispersion-based intraindividual variability (IIV-d) is hypothesized to reflect a sensitive index of executive dysfunction and has demonstrated relevance to functional decline but has not been evaluated in bvFTD. METHOD: We report on 477 demographically matched participants (159 cognitively healthy [CH], 159 clinical Alzheimer's disease [AD], 159 clinical bvFTD/prodromal bvFTD) who completed the Uniform Data Set 3.0 Neuropsychological Battery. IIV-d was measured using the coefficient of variance (CoV; raw and demographically adjusted) across 12 Uniform Data Set 3.0 Neuropsychological Battery indicators and the informant-rated Functional Activities Questionnaire assessed daily functioning. RESULTS: Analysis of covariance showed that participants in the bvFTD/prodromal bvFTD group exhibited higher raw and demographically adjusted CoV compared to CH participants, at a very large effect size (d = 1.28-1.47). Demographically adjusted (but not raw) CoV was lower in the bvFTD/prodromal bvFTD group than the AD group, though the effect size was small (d = .38). Both CoV metrics accurately differentiated the bvFTD/prodromal bvFTD and CH groups (areas under the curve = .84), but not bvFTD/prodromal bvFTD and AD groups (areas under the curve = .59). Regression analyses in the bvFTD/prodromal bvFTD group indicated that higher IIV-d on both metrics was associated with greater daily functioning impairment, over and above covariates. CONCLUSIONS: Compared to healthy adults, individuals with bvFTD/prodromal bvFTD show greater levels of performance variability across a battery of neuropsychological measures, which interferes with everyday functioning. These data demonstrate the clinical utility and ecological validity of IIV-d in bvFTD/prodromal bvFTD, though these findings should be replicated in more diverse samples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Enfermedad de Alzheimer , Función Ejecutiva , Demencia Frontotemporal , Pruebas Neuropsicológicas , Síntomas Prodrómicos , Humanos , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/psicología , Demencia Frontotemporal/diagnóstico , Femenino , Masculino , Anciano , Persona de Mediana Edad , Función Ejecutiva/fisiología , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Actividades Cotidianas
4.
J Clin Exp Neuropsychol ; 46(6): 535-556, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39120111

RESUMEN

INTRODUCTION: Intraindividual variability across a battery of neuropsychological tests (IIV-dispersion) can reflect normal variation in scores or arise from cognitive impairment. An alternate interpretation is IIV-dispersion reflects reduced engagement/invalid test data, although extant research addressing this interpretation is significantly limited. METHOD: We used a sample of 97 older adult (mean age: 69.92), predominantly White (57%) or Black/African American (34%), and predominantly cis-gender male (87%) veterans. Examinees completed a comprehensive neuropsychological battery, including measures of reduced engagement/invalid test data (a symptom validity test [SVT], multiple performance validity tests [PVTs]), as part of a clinical evaluation. IIV-dispersion was indexed using the coefficient of variance (CoV). We tested 1) the relationships of raw scores and "failures" on SVT/PVTs with IIV-dispersion, 2) the relationship between IIV-dispersion and validity/neurocognitive disorder status, and 3) whether IIV-dispersion discriminated the validity/neurocognitive disorder groups using receiver operating characteristic (ROC) curves. RESULTS: IIV-dispersion was significantly and independently associated with a selection of PVTs, with small to very large effect sizes. Participants with invalid profiles and cognitively impaired participants with valid profiles exhibited medium to large (d = .55-1.09) elevations in IIV-dispersion compared to cognitively unimpaired participants with valid profiles. A non-significant but small to medium (d = .35-.60) elevation in IIV-dispersion was observed for participants with invalid profiles compared to those with a neurocognitive disorder. IIV-dispersion was largely accurate at differentiating participants without a neurocognitive disorder from invalid participants and those with a neurocognitive disorder (areas under the Curve [AUCs]=.69-.83), while accuracy was low for differentiating invalid participants from those with a neurocognitive disorder (AUCs=.58-.65). CONCLUSIONS: These preliminary data suggest IIV-dispersion may be sensitive to both neurocognitive disorders and compromised engagement. Clinicians and researchers should exercise due diligence and consider test validity (e.g. PVTs, behavioral signs of engagement) as an alternate explanation prior to interpretation of intraindividual variability as an indicator of cognitive impairment.


Asunto(s)
Pruebas Neuropsicológicas , Veteranos , Humanos , Masculino , Pruebas Neuropsicológicas/normas , Femenino , Anciano , Persona de Mediana Edad , Reproducibilidad de los Resultados , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiología , Anciano de 80 o más Años , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología
5.
Epilepsy Behav ; 159: 110013, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39182261

RESUMEN

OBJECTIVE: Low health literacy is common among people with epilepsy (PWE) and may play an important role in disease management and outcomes. The current study evaluated whether health literacy is related to cognition, health, and everyday functioning in PWE. METHODS: This cross-sectional, correlational study included 25 demographically comparable healthy adults retrospectively matched to a consecutive series of 89 PWE presenting for neuropsychological evaluation in a surgical setting and who completed the Newest Vital Sign and Brief Health Literacy Screener. The PWE also completed a comprehensive neuropsychological battery and measures of quality of life and everyday functioning. RESULTS: PWE had significantly lower health literacy as compared to healthy adults (ps < 0.05) at a medium-to-large effect size. In analyses covarying for education and oral word reading literacy in the PWE sample, lower health literacy was independently associated with bilateral seizure onsets, greater antiseizure medication burden, poorer performance on measures of memory and information processing speed, and difficulties with self-care (ps < 0.05). SIGNIFICANCE: Findings suggest that PWE are at risk for low health literacy, which may be partly attributable to disrupted brain-behavior relationships and contribute to poorer everyday functioning. Future studies are needed to identify effective methods to support and improve health literacy in PWE.


Asunto(s)
Actividades Cotidianas , Epilepsia , Alfabetización en Salud , Pruebas Neuropsicológicas , Humanos , Femenino , Masculino , Adulto , Epilepsia/psicología , Persona de Mediana Edad , Estudios Transversales , Cognición/fisiología , Calidad de Vida/psicología , Adulto Joven , Estudios Retrospectivos , Trastornos del Conocimiento/etiología
6.
AIDS Behav ; 28(10): 3238-3248, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38904928

RESUMEN

Clinically notable apathy occurs in approximately one-third of persons living with HIV (PLWH). Drawing from psychological theory, this cross-sectional study examined the interplay between apathy and social support in persons with (n = 143) and without (n = 61) HIV disease. Analyses were conducted using multiple regression and mediation procedures with 95th percentile bootstrap confidence intervals. Positive HIV serostatus and lower social support were associated with more frequent apathy, independent of other mood symptoms. Social support did not moderate apathy's associations with everyday functioning among PLWH, but post hoc analyses revealed that apathy mediated the relationship between social support and everyday functioning among PLWH. Stronger social support may provide a buffer against the frequency of apathy symptoms in persons with and without HIV disease. The relationship between lower social support and poorer everyday functioning in HIV might be partly explained by apathy. Longitudinal research is needed to examine the mechanisms of these relationships.


RESUMEN: La apatía clínicamente notable se produce en aproximadamente un tercio de las personas que viven con el VIH (PVVS). A partir de la teoría psicológica, este estudio transversal examinó la interacción entre la apatía y el apoyo social en personas con (n = 143) y sin (n = 61) enfermedad de VIH. Los análisis se llevaron utilizando procedimientos de regresión múltiple y mediación con intervalos de confianza bootstrap del 95º percentil. El estado serológico positivo respecto al VIH y un menor apoyo social se asociaron con una apatía más frecuente, independientemente de otros síntomas del estado de ánimo. El apoyo social no moderó las asociaciones de la apatía con el funcionamiento cotidiano entre las PVVS, pero los análisis post hoc revelaron que la apatía mediaba la relación entre el apoyo social y el funcionamiento cotidiano entre las PVVS. Un apoyo social más fuerte puede atenuar la frecuencia de los síntomas de apatía en personas con y sin VIH. La relación entre un menor apoyo social y un peor funcionamiento cotidiano en personas con VIH podría explicarse en parte por la apatía. Se necesitan investigaciones longitudinales para examinar los mecanismos de estas relaciones.


Asunto(s)
Apatía , Infecciones por VIH , Apoyo Social , Humanos , Masculino , Estudios Transversales , Femenino , Infecciones por VIH/psicología , Persona de Mediana Edad , Adulto , Actividades Cotidianas/psicología , Encuestas y Cuestionarios
7.
Clin Neuropsychol ; 38(5): 1085-1108, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38914007

RESUMEN

Objective: HIV is associated with elevated performance-based cognitive intra-individual variability (IIV) in the laboratory that can reflect difficulty regulating cognitive resources over time (i.e., cognitive fluctuations) and disrupt everyday functioning. Whether persons living with HIV (PLWH) experience appreciable cognitive fluctuations in their daily lives is unclear. This study examined the presence of cognitive fluctuations and their relationship to everyday functioning in PLWH. Methods: Participants were 145 PLWH and 61 seronegative individuals age ≥ 50 years who completed a self-report version of the Mayo Fluctuations Scale (MFS), structured psychiatric interview, medical evaluation, and well-validated measures of mood, cognitive symptoms, and activities of daily living (ADLs). A confirmatory factor analysis of the MFS yielded three factors, including a 7-item cognitive fluctuations scale. Results: Univariable analyses showed that HIV was associated with moderately higher MFS Cognitive Fluctuation subscale scores (d = 0.46), but this effect was no longer significant a multiple regression model that included medical comorbidities and affective disorders, which emerged as unique predictors. Of clinical relevance, higher MFS Cognitive Fluctuation subscale scores were independently associated with more frequent cognitive symptoms and dependence in ADLs in the full sample. Conclusions: Higher frequency of self-perceived cognitive fluctuations disrupts management of ADLs among middle-aged and older adults independent of HIV status and general cognitive symptoms. Future studies are needed to understand the full clinical significance of self-perceived cognitive fluctuations among PLWH and their impact on daily life.


Asunto(s)
Actividades Cotidianas , Infecciones por VIH , Humanos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por VIH/psicología , Infecciones por VIH/complicaciones , Anciano , Autoimagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Pruebas Neuropsicológicas , Cognición/fisiología , Autoinforme
8.
J Clin Exp Neuropsychol ; 46(4): 341-351, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38704612

RESUMEN

INTRODUCTION: People living with HIV (PLWH) often experience difficulties in everyday functioning, which can arise in part from deficits in the strategic/executive aspects of prospective memory (PM). Using Suchy's Contextually Valid Executive Assessment (ConVExA) framework, this study sought to determine whether the contextual factors of busyness and routine moderate the relationship between the strategic/executive aspects of PM and everyday functioning in older PLWH. METHODS: Participants in this cross-sectional analysis were 145 PLWH aged 50 years and older who had completed the Martin and Park Environmental Demands (MPED) questionnaire of routine and busyness, the performance-based Cambridge Test of Prospective Memory, and self-report measures of activities of daily living (ADLs) and cognitive symptoms in daily life. RESULTS: Multiple regression analyses covarying for relevant comorbidities showed that higher levels of busyness - but not routine - were associated with more frequent cognitive symptoms in daily life. Neither busyness nor routine interacted with PM in association with cognitive symptoms. However, routine and a strategic/executive measure of PM interacted in predicting ADLs; specifically, the association between time-based PM and ADLs was stronger in persons with higher levels of routine in their daily lives. Parallel analyses with less executively-demanding event-based PM were null and small. CONCLUSIONS: Overall, findings provided mixed - and unexpected - evidence for the associations between contextual factors (i.e. routine and busyness), everyday functioning, and PM in this sample of older adults with HIV disease. Results and clinical implications are interpreted and discussed in the framework of the ConVExA model.


Asunto(s)
Actividades Cotidianas , Infecciones por VIH , Memoria Episódica , Humanos , Masculino , Femenino , Infecciones por VIH/psicología , Infecciones por VIH/fisiopatología , Infecciones por VIH/complicaciones , Persona de Mediana Edad , Anciano , Estudios Transversales , Función Ejecutiva/fisiología , Pruebas Neuropsicológicas
9.
Stem Cell Reports ; 19(6): 859-876, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38788724

RESUMEN

Hepatocyte nuclear factor 1B (HNF1B) encodes a transcription factor expressed in developing human kidney epithelia. Heterozygous HNF1B mutations are the commonest monogenic cause of dysplastic kidney malformations (DKMs). To understand their pathobiology, we generated heterozygous HNF1B mutant kidney organoids from CRISPR-Cas9 gene-edited human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) reprogrammed from a family with HNF1B-associated DKMs. Mutant organoids contained enlarged malformed tubules displaying deregulated cell turnover. Numerous genes implicated in Mendelian kidney tubulopathies were downregulated, and mutant tubules resisted the cyclic AMP (cAMP)-mediated dilatation seen in controls. Bulk and single-cell RNA sequencing (scRNA-seq) analyses indicated abnormal Wingless/Integrated (WNT), calcium, and glutamatergic pathways, the latter hitherto unstudied in developing kidneys. Glutamate ionotropic receptor kainate type subunit 3 (GRIK3) was upregulated in malformed mutant nephron tubules and prominent in HNF1B mutant fetal human dysplastic kidney epithelia. These results reveal morphological, molecular, and physiological roles for HNF1B in human kidney tubule differentiation and morphogenesis illuminating the developmental origin of mutant-HNF1B-causing kidney disease.


Asunto(s)
Factor Nuclear 1-beta del Hepatocito , Células Madre Pluripotentes Inducidas , Organoides , Humanos , Factor Nuclear 1-beta del Hepatocito/genética , Factor Nuclear 1-beta del Hepatocito/metabolismo , Organoides/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Diferenciación Celular/genética , Heterocigoto , Túbulos Renales/patología , Túbulos Renales/metabolismo , Mutación , Riñón/patología , Riñón/metabolismo , Riñón/anomalías , Sistemas CRISPR-Cas , Células Madre Pluripotentes/metabolismo , Edición Génica
10.
J Clin Exp Neuropsychol ; 46(4): 316-328, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38695312

RESUMEN

INTRODUCTION: Episodic memory disruptions in epilepsy stem from shared neurocircuitry. While prior research has focused on retrospective memory (RM), prospective memory (PM; i.e. remembering to remember) also deserves consideration given its critical role in the management of daily activities. The current investigation assessed whether PM is associated with disability and quality of life in people with epilepsy. METHODS: This cross-sectional, correlational study included a consecutive series of 50 people with epilepsy presenting for neuropsychological evaluation who completed the Royal Prince Alfred Prospective Memory Test (RPA) and Prospective and Retrospective Memory Questionnaire (PRMQ) and 63 demographically comparable healthy adults. The participants with epilepsy also completed clinical measures of neuropsychological ability and questionnaires assessing disability and quality of life. RESULTS: People with epilepsy had significantly more frequent memory symptoms as compared to healthy adults at a very large effect size. Worse mood was associated with lower PM ability at a medium effect size and more frequent PM symptoms at a large effect size. A hierarchical linear regression indicated that PM explained 52% of the variance in disability and 43% of the variance in quality of life after accounting for RM ability. CONCLUSIONS: PM is associated with poorer everyday functioning among people with epilepsy and shows evidence of incremental value beyond RM ability in that regard. Future studies are needed to understand the complex pathways from PM to functional limitations to inform clinical intervention.


Asunto(s)
Epilepsia , Trastornos de la Memoria , Memoria Episódica , Calidad de Vida , Humanos , Calidad de Vida/psicología , Femenino , Masculino , Epilepsia/psicología , Epilepsia/fisiopatología , Epilepsia/complicaciones , Adulto , Persona de Mediana Edad , Estudios Transversales , Trastornos de la Memoria/etiología , Trastornos de la Memoria/fisiopatología , Pruebas Neuropsicológicas , Adulto Joven , Actividades Cotidianas , Personas con Discapacidad/psicología
11.
Artículo en Inglés | MEDLINE | ID: mdl-38727240

RESUMEN

The current study evaluated the reliability and validity of a novel, performance-based banking task in 60 younger (18-34 years) and 60 older (50-85 years) adults. All participants completed the Telephone-based Daily Instrumental Activities of Living (T-DIAL) using interactive voice response technology to complete a series of mock actions with a financial institution via telephone. The T-DIAL showed strong inter-rater reliability and internal consistency. T-DIAL accuracy was significantly and independently related to better self-reported instrumental activities of daily living and executive functions at a large effect size. Findings from this study provided preliminary supportive evidence for the reliability and validity of the T-DIAL, which had robust associations with manifest everyday functioning and higher-order cognitive ability. Future work is needed on the psychometrics (e.g. test-retest reliability, normative standards), and construct validity (e.g. diagnostic accuracy) of the T-DIAL in neurocognitive disorders and under-served communities for whom remote evaluations might be particularly relevant.

12.
Clin Neuropsychol ; : 1-26, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38453891

RESUMEN

Objective: Doctoral education is a cornerstone in the training of clinical neuropsychologists. However, we know little about perceptions, practices, and needs of the faculty who oversee doctoral training in clinical neuropsychology (CN). Method: Seventy-one faculty from 45 doctoral programs providing CN training completed at least part of a survey assessing characteristics of their programs, current training practices and views, and challenges to CN doctoral training. Results: Over half of CN faculty reported having zero or only one CN colleague. CN faculty reported that the goals of CN doctoral training are research training, clinical training, and acquisition of knowledge and skills reflected in the Houston Conference Guidelines (HCG). CN faculty reported that doctoral trainees obtain more clinical hours than faculty would like and endorsed alternative clinical metrics, including competency-based ratings. CN faculty are divided about the benefits of a required two-year postdoctoral CN fellowship. Conclusions: The HCG states that specialization in CN begins at the doctoral level. CN faculty in doctoral programs are fully immersed in the early development and education of future CN researchers and practitioners. Tensions between clinical and research training in CN at the doctoral level-and student overemphasis on accruing clinical hours-might place CN at risk for failing to make research innovations necessary for our field to evolve and thrive. More CN doctoral faculty are needed to serve as mentors to students, especially for students from backgrounds that have been historically excluded and marginalized. A greater voice from CN doctoral faculty in CN governance is needed.

13.
J Neurovirol ; 30(2): 1-11, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38546936

RESUMEN

Although older adults with HIV are at high risk for mild neurocognitive disorders, a subset experience successful cognitive aging (SCA). HIV is associated with an increased risk of vascular depression (VasDep), which can affect cognitive and daily functioning. The current study examined whether VasDep impedes SCA among older adults with HIV. 136 persons with HIV aged 50 years and older were classified as either SCA+ (n = 37) or SCA- (n = 99) based on a battery of demographically adjusted neurocognitive tests and self-reported cognitive symptoms. Participants were also stratified on the presence of vascular disease (e.g., hypertension) and current depression as determined by the Composite International Diagnostic Interview and the Depression/Dejection scale of the Profile of Mood States. A Cochran-Armitage test revealed a significant additive effect of vascular disease and depression on SCA in this sample of older adults with HIV (z = 4.13, p <.0001). Individuals with VasDep had the lowest frequency of SCA+ (0%), which differed significantly from the group with only vascular disease (30%, OR = 0.04, CI = 0.002,0.68)) and the group with neither vascular disease nor depression (47% OR = 0.02, CI = 0.33,0.001). Findings were not confounded by demographics, HIV disease severity, or other psychiatric and medical factors (ps > 0.05). These data suggest that presence of VasDep may be a barrier to SCA in older adults with HIV disease. Prospective, longitudinal studies with neuroimaging-based operationalizations of VasDep are needed to further clarify this risk factor's role in the maintenance of cognitive and brain health in persons with HIV disease.


Asunto(s)
Envejecimiento Cognitivo , Depresión , Infecciones por VIH , Humanos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Infecciones por VIH/psicología , Infecciones por VIH/fisiopatología , Infecciones por VIH/virología , Anciano , Depresión/fisiopatología , Depresión/psicología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/virología , Pruebas Neuropsicológicas , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/fisiopatología , Factores de Riesgo
14.
Nanoscale ; 16(11): 5653-5664, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38414413

RESUMEN

Graphene Oxide (GO) has been shown to increase the expression of key cartilage genes and matrix components within 3D scaffolds. Understanding the mechanisms behind the chondroinductive ability of GO is critical for developing articular cartilage regeneration therapies but remains poorly understood. The objectives of this work were to elucidate the effects of GO on the key chondrogenic signalling pathway - TGFß and identify the mechanism through which signal activation is achieved in human chondrocytes. Activation of canonical signalling was validated through GO-induced SMAD-2 phosphorylation and upregulation of known TGFß response genes, while the use of a TGFß signalling reporter assay allowed us to identify the onset of GO-induced signal activation which has not been previously reported. Importantly, we investigate the cell-material interactions and molecular mechanisms behind these effects, establishing a novel link between GO, the plasma membrane and intracellular signalling. By leveraging fluorescent lifetime imaging (FLIM) and a membrane tension probe, we reveal GO-mediated increases in plasma membrane tension, in real-time for the first time. Furthermore, we report the activation of mechanosensory pathways which are known to be regulated by changes in plasma membrane tension and reveal the activation of endogenous latent TGFß in the presence of GO, providing a mechanism for signal activation. The data presented here are critical to understanding the chondroinductive properties of GO and are important for the implementation of GO in regenerative medicine.


Asunto(s)
Cartílago Articular , Condrocitos , Grafito , Humanos , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular , Membrana Celular/metabolismo
15.
Sci Rep ; 14(1): 2696, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302538

RESUMEN

Osteoarthritis is the most common degenerative joint condition, leading to articular cartilage (AC) degradation, chronic pain and immobility. The lack of appropriate therapies that provide tissue restoration combined with the limited lifespan of joint-replacement implants indicate the need for alternative AC regeneration strategies. Differentiation of human pluripotent stem cells (hPSCs) into AC progenitors may provide a long-term regenerative solution but is still limited due to the continued reliance upon growth factors to recapitulate developmental signalling processes. Recently, TTNPB, a small molecule activator of retinoic acid receptors (RARs), has been shown to be sufficient to guide mesodermal specification and early chondrogenesis of hPSCs. Here, we modified our previous differentiation protocol, by supplementing cells with TTNPB and administering BMP2 at specific times to enhance early development (referred to as the RAPID-E protocol). Transcriptomic analyses indicated that activation of RAR signalling significantly upregulated genes related to limb and embryonic skeletal development in the early stages of the protocol and upregulated genes related to AC development in later stages. Chondroprogenitors obtained from RAPID-E could generate cartilaginous pellets that expressed AC-related matrix proteins such as Lubricin, Aggrecan, and Collagen II, but additionally expressed Collagen X, indicative of hypertrophy. This protocol could lay the foundations for cell therapy strategies for osteoarthritis and improve the understanding of AC development in humans.


Asunto(s)
Benzoatos , Cartílago Articular , Osteoartritis , Células Madre Pluripotentes , Retinoides , Humanos , Condrocitos/metabolismo , Tretinoina/farmacología , Condrogénesis/genética , Diferenciación Celular , Cartílago Articular/metabolismo , Colágeno/metabolismo , Osteoartritis/metabolismo
16.
Arch Clin Neuropsychol ; 39(6): 732-746, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-38364295

RESUMEN

OBJECTIVE: Cognitive dispersion indexes intraindividual variability in performance across a battery of neuropsychological tests. Measures of dispersion show promise as markers of cognitive dyscontrol and everyday functioning difficulties; however, they have limited practical applicability due to a lack of normative data. This study aimed to develop and evaluate normed scores for cognitive dispersion among older adults. METHOD: We analyzed data from 4,283 cognitively normal participants aged ≥50 years from the Uniform Data Set (UDS) 3.0. We describe methods for calculating intraindividual standard deviation (ISD) and coefficient of variation (CoV), as well as associated unadjusted scaled scores and demographically adjusted z-scores. We also examined the ability of ISD and CoV scores to differentiate between cognitively normal individuals (n = 4,283) and those with cognitive impairment due to Lewy body disease (n = 282). RESULTS: We generated normative tables to map raw ISD and CoV scores onto a normal distribution of scaled scores. Cognitive dispersion indices were associated with age, education, and race/ethnicity but not sex. Regression equations were used to develop a freely accessible Excel calculator for deriving demographically adjusted normed scores for ISD and CoV. All measures of dispersion demonstrated excellent diagnostic utility when evaluated by the area under the curve produced from receiver operating characteristic curves. CONCLUSIONS: Results of this study provide evidence for the clinical utility of sample-based and demographically adjusted normative standards for cognitive dispersion on the UDS 3.0. These standards can be used to guide interpretation of intraindividual variability among older adults in clinical and research settings.


Asunto(s)
Disfunción Cognitiva , Pruebas Neuropsicológicas , Humanos , Masculino , Femenino , Pruebas Neuropsicológicas/normas , Pruebas Neuropsicológicas/estadística & datos numéricos , Anciano , Persona de Mediana Edad , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Valores de Referencia , Anciano de 80 o más Años , Reproducibilidad de los Resultados , Enfermedad por Cuerpos de Lewy/diagnóstico , Cognición/fisiología
17.
Clin Neuropsychol ; : 1-22, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38414159

RESUMEN

Introduction: Gay and bisexual men (GBM) account for the highest rates of incident infection with HIV in the U.S., and experience social, systemic barriers to accessing and engaging in healthcare services. Interacting with healthcare providers can be a complex process for some GBM with HIV disease. The current study examined the contributions of cognition and health literacy to perceived interactions with healthcare providers among GBM with HIV disease. Methods: The sample included 100 adults with HIV disease (ages 24-75) who identified as GBM. All participants completed the Dealing with Health Professionals subscale of the Beliefs Related to Medication Adherence survey, as well as the Cogstate neuropsychological battery, self-report measures of cognitive symptoms, and well-validated measures of health literacy. Results: Worse performance-based cognition and subjective cognitive symptoms were both associated with perceived difficulties dealing with healthcare providers, but these associations were fully mediated by lower health literacy. Conclusion: Health literacy may play a role in the association between poorer cognitive functioning and difficulties navigating healthcare interactions among GBM with HIV disease. Further studies are needed to determine whether cognitive approaches to enhancing the access, understanding, and use of health information in GBM with HIV disease improves healthcare interactions and outcomes.

18.
J Affect Disord ; 350: 133-147, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38224740

RESUMEN

BACKGROUND: Apathy was identified as a feature of HIV early in the epidemic; however, there are no systematic reviews of the diverse literature on the sociodemographic and clinical correlates of apathy in HIV disease. METHODS: The current study adopted a hybrid systematic-narrative review methodology in which we used PRISMA guidelines to identify, summarize, and critique peer-reviewed, empirical studies of apathy in HIV disease in the era of combination antiretroviral therapy. RESULTS: A total of 34 studies of apathy in persons living with HIV (PLWH) were identified. Findings across these studies showed that apathy was reliably related to the structure of grey and white matter pathways commonly implicated in apathy, poorer everyday functioning, education, and other neuropsychiatric symptoms (e.g., depression). Apathy was not reliably associated with age, sex, race/ethnicity, cognition, and clinical markers of HIV disease. LIMITATIONS: The current review does not provide rigorous quantitative estimates of clinical correlates of apathy, and the exclusion criteria of non-English and non-peer reviewed publications introduces risk of bias and Type I error. CONCLUSIONS: Apathy occurs at higher rates in PLWH and is linked to neuroanatomical differences, as well as negative outcomes for everyday functions, aspects of neurocognition, and neuropsychiatric symptoms. As such, apathy is an important component to consider in the clinical assessment, diagnosis, and management of neurocognitive disorders in PLWH. Future work is needed to replicate existing findings with larger sample sizes and longitudinal designs, examine apathy as a multi-dimensional construct, and develop evidence-based treatments for apathy in PLWH.


Asunto(s)
Apatía , Infecciones por VIH , Humanos , Infecciones por VIH/psicología , Infecciones por VIH/tratamiento farmacológico
20.
AIDS Behav ; 28(3): 811-819, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37792230

RESUMEN

People with HIV (PWH) are susceptible to neurocognitive, physical, and mental health problems that may decrease their likelihood of experiencing successful aging. This cross-sectional, retrospective study estimated the extent to which health literacy is associated with successful aging among 116 older PWH and 60 persons without HIV. Successful aging was defined using indicators of biological health, cognitive efficiency, mental health, and productivity. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine, Newest Vital Sign, Brief Health Literacy Screening, and Beliefs Related to Medication Adherence. A series of logistic regressions covarying for education showed that better health literacy was associated with a higher frequency of successful aging among older PWH. Older PWH were approximately three times less likely to experience successful aging as compared to older adults without HIV. Future studies may examine whether improving health literacy among younger PWH increases the likelihood of successful aging.


Asunto(s)
Infecciones por VIH , Alfabetización en Salud , Humanos , Anciano , Estudios Transversales , Estudios Retrospectivos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Envejecimiento
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