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1.
Pediatr Blood Cancer ; 71(8): e31082, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38804869

RESUMEN

INTRODUCTION: Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population. METHODS: This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21 years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy. RESULTS: Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p < .001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR] = 2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR = 4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR = 4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p = .001), but not when unrelated to neutropenia (p = .88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR = 1.20, 95% CI: 0.7-2.1). CONCLUSIONS: We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19.


Asunto(s)
COVID-19 , Síndrome de Down , Neoplasias Hematológicas , Hospitalización , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicaciones , Adolescente , Masculino , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Femenino , Niño , Adulto Joven , Hospitalización/estadística & datos numéricos , Adulto , Preescolar , Lactante
2.
Int J Cancer ; 147(11): 3152-3159, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32391579

RESUMEN

Neuroblastoma is a sympathetic nervous system tumor, primarily presenting in children under 6 years of age. The long-term prognosis for patients with high-risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapy. This report provides an update to a phase II trial evaluating DFMO as maintenance therapy in HRNB. Event-free survival (EFS) and overall survival (OS) of 81 subjects with HRNB treated with standard COG induction, consolidation and immunotherapy followed by 2 years of DFMO on the NMTRC003/003b Phase II trial were compared to a historical cohort of 76 HRNB patients treated at Beat Childhood Cancer Research Consortium (BCC) hospitals who were disease-free after completion of standard upfront therapy and did not receive DFMO. The 2- and 5-year EFS were 86.4% [95% confidence interval (CI) 79.3%-94.2%] and 85.2% [77.8%-93.3%] for the NMTRC003/003b subset vs 78.3% [69.5%-88.3%] and 65.6% [55.5%-77.5%] for the historical control group. The 2- and 5-year OS were 98.8% [96.4-100%] and 95.1% [90.5%-99.9%] vs 94.4% [89.3%-99.9%] and 81.6% [73.0%-91.2%], respectively. DFMO maintenance for HRNB after completion of standard of care therapy was associated with improved EFS and OS relative to historical controls treated at the same institutions. These results support additional investigations into the potential role of DFMO in preventing relapse in HRNB.


Asunto(s)
Eflornitina/administración & dosificación , Neuroblastoma/tratamiento farmacológico , Preescolar , Supervivencia sin Enfermedad , Eflornitina/uso terapéutico , Femenino , Humanos , Quimioterapia de Mantención , Masculino , Pronóstico , Nivel de Atención , Resultado del Tratamiento
3.
J Neurovirol ; 23(3): 422-429, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28101804

RESUMEN

Our aim was to examine the clinical relevance of white matter hyperintensities (WMH) in HIV. We used an automated approach to quantify WMH volume in HIV seropositive (HIV+; n = 65) and HIV seronegative (HIV-; n = 29) adults over age 60. We compared WMH volumes between HIV+ and HIV- groups in cross-sectional and multiple time-point analyses. We also assessed correlations between WMH volumes and cardiovascular, HIV severity, cognitive scores, and diffusion tensor imaging variables. Serostatus groups did not differ in WMH volume, but HIV+ participants had less cerebral white matter (mean: 470.95 [43.24] vs. 497.63 [49.42] mL, p = 0.010). The distribution of WMH volume was skewed in HIV+ with a high proportion (23%) falling above the 95th percentile of WMH volume defined by the HIV- group. Serostatus groups had similar amount of WMH volume growth over time. Total WMH volume directly correlated with measures of hypertension and inversely correlated with measures of global cognition, particularly in executive functioning, and psychomotor speed. Greater WMH volume was associated with poorer brain integrity measured from diffusion tensor imaging (DTI) in the corpus callosum and sagittal stratum. In this group of HIV+ individuals over 60, WMH burden was associated with cardiovascular risk and both worse diffusion MRI and cognition. The median total burden did not differ by serostatus; however, a subset of HIV+ individuals had high WMH burden.


Asunto(s)
Corteza Cerebral/patología , Cuerpo Calloso/patología , Infecciones por VIH/patología , Hipertensión/patología , ARN Viral/sangre , Sustancia Blanca/patología , Anciano , Anciano de 80 o más Años , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/virología , Cognición/fisiología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/virología , Estudios Transversales , Imagen de Difusión Tensora , Función Ejecutiva/fisiología , Femenino , Infecciones por VIH/diagnóstico por imagen , Infecciones por VIH/virología , VIH-1/patogenicidad , VIH-1/fisiología , Humanos , Hipertensión/diagnóstico por imagen , Hipertensión/virología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Índice de Severidad de la Enfermedad , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/virología
4.
Neurobiol Dis ; 92(Pt B): 175-82, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26484382

RESUMEN

BACKGROUND: Deficits in lexical retrieval, present in approximately 40% of HIV+ patients, are thought to reflect disruptions to frontal-striatal functions and may worsen with immunosuppression. Coupling frontal-striatal tasks such as lexical retrieval with functional neuroimaging may help delineate the pathophysiologic mechanisms underlying HIV-associated neurological dysfunction. OBJECTIVE: We examined whether HIV infection confers brain functional changes during lexical access and retrieval. It was expected that HIV+ individuals would demonstrate greater brain activity in frontal-subcortical regions despite minimal differences between groups on neuropsychological testing. Within the HIV+ sample, we examined associations between indices of immunosuppression (recent and nadir CD4+ count) and task-related signal change in frontostriatal structures. Method16 HIV+ participants and 12 HIV- controls underwent fMRI while engaged in phonemic/letter and semantic fluency tasks. Participants also completed standardized measures of verbal fluency RESULTS: HIV status groups performed similarly on phonemic and semantic fluency tasks prior to being scanned. fMRI results demonstrated activation differences during the phonemic fluency task as a function of HIV status, with HIV+ individuals demonstrating significantly greater activation in BG structures than HIV- individuals. There were no significant differences in frontal brain activation between HIV status groups during the phonemic fluency task, nor were there significant brain activation differences during the semantic fluency task. Within the HIV+ group, current CD4+ count, though not nadir, was positively correlated with increased activity in the inferior frontal gyrus and basal ganglia. CONCLUSION: During phonemic fluency performance, HIV+ patients recruit subcortical structures to a greater degree than HIV- controls despite similar task performances suggesting that fMRI may be sensitive to neurocompromise before overt cognitive declines can be detected. Among HIV+ individuals, reduced activity in the frontal-subcortical structures was associated with lower CD4+ count.


Asunto(s)
Encéfalo/fisiopatología , Infecciones por VIH/fisiopatología , Infecciones por VIH/psicología , Fonética , Semántica , Habla/fisiología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Circulación Cerebrovascular/fisiología , Femenino , Infecciones por VIH/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Oxígeno/sangre
5.
Pediatr Blood Cancer ; 63(7): 1296-9, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26970537

RESUMEN

Central nervous system (CNS) involvement in the context of hemophagocytic lymphohistiocytosis (HLH) is not uncommon. Given the immunosuppressive nature of HLH therapy, infectious complications are also seen. We describe a 9-year-old male who developed acute neurological decline secondary to aspergillosis while undergoing HLH therapy. The significant overlap observed in CNS neuroimaging of HLH and aspergillosis and the subtleties that may help differentiate the two are discussed. The importance of obtaining tissue for definitive diagnosis is underscored.


Asunto(s)
Aspergilosis/diagnóstico , Enfermedades del Sistema Nervioso Central/diagnóstico , Linfohistiocitosis Hemofagocítica/diagnóstico , Aspergilosis/diagnóstico por imagen , Aspergilosis/terapia , Enfermedades del Sistema Nervioso Central/diagnóstico por imagen , Enfermedades del Sistema Nervioso Central/terapia , Niño , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico por imagen , Linfohistiocitosis Hemofagocítica/terapia , Masculino , Neuroimagen
6.
J Transl Med ; 13: 110, 2015 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-25889105

RESUMEN

BACKGROUND: Osteosarcoma (OS) is the most common type of solid bone cancer, with latent metastasis being a typical mode of disease progression and a major contributor to poor prognosis. For this to occur, cells must resist anoikis and be able to recapitulate tumorigenesis in a foreign microenvironment. Finding novel approaches to treat osteosarcoma and target those cell subpopulations that possess the ability to resist anoikis and contribute to metastatic disease is imperative. Here we investigate anchorage-independent (AI) cell growth as a model to better characterize anoikis resistance in human osteosarcoma while using an expression profiling approach to identify and test targetable signaling pathways. METHODS: Established human OS cell lines and patient-derived human OS cell isolates were subjected to growth in either adherent or AI conditions using Ultra-Low Attachment plates in identical media conditions. Growth rate was assessed using cell doubling times and chemoresistance was assessed by determining cell viability in response to a serial dilution of either doxorubicin or cisplatin. Gene expression differences were examined using quantitative reverse-transcription PCR and microarray with principal component and pathway analysis. In-vivo OS xenografts were generated by either subcutaneous or intratibial injection of adherent or AI human OS cells into athymic nude mice. Statistical significance was determined using student's t-tests with significance set at α=0.05. RESULTS: We show that AI growth results in a global gene expression profile change accompanied by significant chemoresistance (up to 75 fold, p<0.05). AI cells demonstrate alteration of key mediators of mesenchymal differentiation (ß-catenin, Runx2), stemness (Sox2), proliferation (c-myc, Akt), and epigenetic regulation (HDAC class 1). AI cells were equally tumorigenic as their adherent counterparts, but showed a significantly decreased rate of growth in-vitro and in-vivo (p<0.05). Treatment with the pan-histone deacetylase inhibitor vorinostat and the DNA methyltransferase inhibitor 5-azacytidine mitigated AI growth, while 5-azacytidine sensitized anoikis-resistant cells to doxorubicin (p<0.05). CONCLUSIONS: These data demonstrate remarkable plasticity in anoikis-resistant human osteosarcoma subpopulations accompanied by a rapid development of chemoresistance and altered growth rates mirroring the early stages of latent metastasis. Targeting epigenetic regulation of this process may be a viable therapeutic strategy.


Asunto(s)
Anoicis , Neoplasias Óseas/genética , Epigénesis Genética , Perfilación de la Expresión Génica , Osteosarcoma/genética , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Humanos , Osteosarcoma/tratamiento farmacológico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
7.
iScience ; 27(2): 108949, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38357666

RESUMEN

Heliconius butterflies exhibit expanded mushroom bodies, a key brain region for learning and memory in insects, and a novel foraging strategy unique among Lepidoptera - traplining for pollen. We tested visual long-term memory across six Heliconius and outgroup Heliconiini species. Heliconius species exhibited greater fidelity to learned colors after eight days without reinforcement, with further evidence of recall at 13 days. We also measured the plastic response of the mushroom body calyces over this time period, finding substantial post-eclosion expansion and synaptic pruning in the calyx of Heliconius erato, but not in the outgroup Heliconiini Dryas iulia. In Heliconius erato, visual associative learning experience specifically was associated with a greater retention of synapses and recall accuracy was positively correlated with synapse number. These results suggest that increases in the size of specific brain regions and changes in their plastic response to experience may coevolve to support novel behaviors.

8.
J Int Neuropsychol Soc ; 19(8): 925-37, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23809097

RESUMEN

Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as mild cognitive impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and diffusion tensor imaging scans were completed. Tract-Based Spatial Statistics was applied and a priori selected regions of interest were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for corticalthic kness, the MCI group showed decreased average fractional anisotropy (FA) and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes.


Asunto(s)
Corteza Cerebral/patología , Disfunción Cognitiva/patología , Fibras Nerviosas Mielínicas/patología , Pruebas Neuropsicológicas , Adulto , Anciano , Apolipoproteínas E/genética , Disfunción Cognitiva/genética , Imagen de Difusión por Resonancia Magnética , Función Ejecutiva , Análisis Factorial , Femenino , Genotipo , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Memoria , Persona de Mediana Edad
9.
J Immunother Cancer ; 11(11)2023 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-38007236

RESUMEN

Focused ultrasound (FUS) is a powerful emerging tool for non-invasive, non-ionizing targeted destruction of tumors. The last two decades have seen a growing body of preclinical and clinical literature supporting the capacity of FUS to increase nascent immune responses to tumors and to potentiate cancer immunotherapies (e.g. checkpoint inhibitors) through a variety of means, including immune modulation and drug delivery. With the rapid acceleration of this field and a multitude of FUS immunotherapy clinical trials having now been deployed worldwide, there is a need to streamline and standardize the methodology for immunological analyses field-wide. Recently, the Focused Ultrasound Foundation and Cancer Research Institute partnered to convene a group of over 85 leaders to discuss the nexus of FUS and immuno-oncology. The guidelines documented herein were assembled in response to recommendations that emerged from this discussion, emphasizing the urgent need for heightened accessibility of immune analysis methods and standardized protocols unique to the field. These guidelines are designated for existing stakeholders in the FUS immuno-oncology domain or those newly entering the field, to provide guidance on collection, storage, and immunological profiling of tissue or blood specimens in the context of FUS immunotherapy studies, and additionally offer templates for standardized deployment of these methods based on collective experience gained within the field to date. These guidelines are tumor-agnostic and provide evidence-based, consensus-based recommendations for both preclinical and clinical immune analysis of tissue and blood specimens.


Asunto(s)
Inmunoterapia , Neoplasias , Humanos , Inmunoterapia/métodos , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/terapia
10.
J Neuropsychiatry Clin Neurosci ; 23(3): 324-31, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21948894

RESUMEN

The authors investigated the relationship between antiretroviral adherence and HIV-associated verbal memory impairment. HIV-positive participants demonstrated poorer verbal memory than HIV-negative participants. Both good (≥90%) and poor (<90%) adherers displayed encoding deficits as compared with controls, but only poor adherers exhibited retrieval deficits. Encoding deficits primarily accounted for reduced delayed recall in good adherers, but both encoding and retrieval deficits accounted for reduced delayed recall in poor adherers. The retrieval difference between the adherence groups might be explained by a neuroprotective effect of good antiretroviral adherence or preexisting HIV-related retrieval deficits that result in poorer adherence.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH , Trastornos de la Memoria/etiología , Cooperación del Paciente/psicología , Aprendizaje Verbal/fisiología , Adulto , Análisis de Varianza , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Análisis de Regresión
11.
Appl Neuropsychol Adult ; 28(6): 685-696, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-31661322

RESUMEN

Both Human Immunodeficiency Virus (HIV) and cocaine use have been associated with impairment in neuropsychological functioning. The high comorbidity between HIV and cocaine use highlights the importance of ascertaining whether there is a compounding effect of cocaine use in individuals with HIV. Among neuropsychological domains impacted by HIV, verbal memory deficits have received substantial attention partly because they have been associated with declines in functional status in HIV positive individuals. We collected California Verbal Learning Test-II data from HIV participants who met lifetime diagnostic criteria of cocaine abuse and/or dependence (HIV/CocDx+, N = 80 & HIV/CocDx-, N = 30, respectively) and those with and without recent cocaine use, which was confirmed by toxicology analysis (HIV/Coc+, N = 56 & HIV/Coc-, N = 57, respectively). The Item Specific Deficit Approach (ISDA) was employed to determine any additional cocaine-associated deficits in encoding, consolidation, and retrieval, which attempts to control for potential confounding factors of memory such as attention. Using conventional methods of evaluating memory profiles, we found that the HIV/Coc + group demonstrated worse learning, immediate and delayed free recall, and recognition in contrast to the HIV/Coc - group; although using the ISDA, we found that encoding was the only significant difference between HIV/Coc + and HIV/Coc-participant, with HIV/Coc - performing better. Our data suggest that for individuals with HIV, cocaine use is associated with a temporary decline in verbal memory, is characterized by greater encoding deficits, and these effects may reduce with abstinence. Clinically, our findings suggest that reduced encoding is the likely contributor to verbal memory decline in HIV/Coc + and these effects are partially reversible-at least to the level of their HIV/Coc - counterparts.


Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína , Infecciones por VIH , Cocaína/efectos adversos , Trastornos Relacionados con Cocaína/complicaciones , Infecciones por VIH/complicaciones , Humanos , Trastornos de la Memoria/etiología , Pruebas Neuropsicológicas
12.
Elife ; 102021 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-34280087

RESUMEN

In Heliconius butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis-regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.


Heliconius butterflies have bright patterns on their wings that tell potential predators that they are toxic. As a result, predators learn to avoid eating them. Over time, unrelated species of butterflies have evolved similar patterns to avoid predation through a process known as Müllerian mimicry. Worldwide, there are over 180,000 species of butterflies and moths, most of which have different wing patterns. How do genes create this pattern diversity? And do butterflies use similar genes to create similar wing patterns? One of the genes involved in creating wing patterns is called cortex. This gene has a large region of DNA around it that does not code for proteins, but instead, controls whether cortex is on or off in different parts of the wing. Changes in this non-coding region can act like switches, turning regions of the wing into different colours and creating complex patterns, but it is unclear how these switches have evolved. Butterfly wings get their colour from tiny structures called scales, which each have their own unique set of pigments. In Heliconius butterflies, there are three types of scales: yellow/white scales, black scales, and red/orange/brown scales. Livraghi et al. used a DNA editing technique called CRISPR to find out whether the cortex gene affects scale type. First, Livraghi et al. confirmed that deleting cortex turned black and red scales yellow. Next, they used the same technique to manipulate the non-coding DNA around the cortex gene to see the effect on the wing pattern. This manipulation turned a black-winged butterfly into a butterfly with a yellow wing band, a pattern that occurs naturally in Heliconius butterflies. The next step was to find the mutation responsible for the appearance of yellow wing bands in nature. It turns out that a bit of extra genetic code, derived from so-called 'jumping genes', had inserted itself into the non-coding DNA around the cortex gene, 'flipping' the switch and leading to the appearance of the yellow scales. Genetic information contains the instructions to generate shape and form in most organisms. These instructions evolve over millions of years, creating everything from bacteria to blue whales. Butterfly wings are visual evidence of evolution, but the way their genes create new patterns isn't specific to butterflies. Understanding wing patterns can help researchers to learn how genetic switches control diversity across other species too.


Asunto(s)
Mariposas Diurnas/genética , Pigmentos Biológicos/genética , Alas de Animales/fisiología , Animales , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Color , Fenotipo
13.
J Card Surg ; 25(2): 156-60, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20149006

RESUMEN

OBJECTIVES: A new device has been developed for occlusion of the left atrial appendage (LAA). Previous investigations have been in the canine model. The canine atrial appendage does not vary in size and shape as much as the human. The goal of this study was to investigate band occlusion of right atrial appendages in the pig model, which are more broad based. METHODS: The right atrial appendages of six pigs were approached through a right thoracotomy. An expandable polyester fabric-covered silicone band was placed on the appendage. The animals were evaluated at the time of band placement with fluoroscopy, contrast injection, and in three animals, echocardiography. After one week, the animals were again evaluated with fluoroscopy. The animals were sacrificed at 12 weeks. RESULTS: Bands were placed without complication at the base of all six appendages. All appendages were effectively occluded and all bands remained at the appendage base. The healed atrial surface was consistently smooth and devoid of thrombus. CONCLUSIONS: Occlusion of a broad-based appendage as seen with human LAA is feasible with this novel band technique.


Asunto(s)
Apéndice Atrial/cirugía , Cateterismo Cardíaco/instrumentación , Dispositivo Oclusor Septal , Animales , Puente de Arteria Coronaria , Trombosis Coronaria/prevención & control , Modelos Animales de Enfermedad , Elasticidad , Poliésteres , Siliconas , Porcinos
14.
Clin Neuropsychol ; 34(1): 204-216, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-30931816

RESUMEN

Objective: The relative importance of various mechanisms supporting declarative verbal memory among older adults remains uncertain. The present study examined the impact of strategy use (specifically semantic clustering) versus other variables known to impact memory performance (age, sex, education, FSIQ, processing speed, and executive functioning) on verbal memory functioning among healthy older adults.Methods: Healthy older adults from the California Verbal Learning Test, Second Edition standardization sample were selected (N = 242). Relationships between verbal memory, demographics variables, and neuropsychological factors were established, and a hierarchical regression analysis was conducted to examine the individual contributions of these variables in predicting memory performance.Results: Bivariate correlations suggested that memory was significantly related to demographic factors, IQ, executive functioning, and semantic clustering. Importantly, hierarchical regression analysis revealed that semantic clustering significantly and independently contributed to recall performance beyond the demonstrated impacts of FSIQ, speed, executive functioning, and demographic variables. Furthermore, FSIQ did not moderate the relationship between semantic clustering and memory indicating that this strategy is an important factor in bolstering recall, independent of FSIQ.Conclusions: Our results highlight the critical importance of semantic clustering utilization in enhancing memory performance among healthy older adults.


Asunto(s)
Inteligencia/fisiología , Memoria/fisiología , Pruebas Neuropsicológicas/normas , Semántica , Aprendizaje Verbal/fisiología , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Función Ejecutiva , Femenino , Humanos , Masculino
15.
Front Neurol ; 11: 446, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32547476

RESUMEN

Background: During early stages, patients with neurodegenerative diseases (NDG) often present with depressive symptoms. However, because depression is a heterogeneous disorder, more precise delineation of the specific depressive symptom profiles that arise early in distinct NDG syndromes is necessary to enhance patient diagnosis and care. Methods and Findings: Five-hundred and sixty four participants self-reported their depressive symptoms using the Geriatric Depression Scale (GDS), including 111 healthy older control subjects (NC) and 453 patients diagnosed with one of six NDGs who were at the mild stage of disease (CDR® Dementia Staging Instrument ≤ 1) [186 Alzheimer's disease (AD), 76 behavioral variant frontotemporal dementia (bvFTD), 52 semantic variant primary progressive aphasia (svPPA), 46 non-fluent variant PPA (nfvPPA), 49 progressive supranuclear palsy syndrome (PSPS), 44 corticobasal syndrome (CBS)]. The GDS was divided into subscales based on a previously published factor analysis, representing five symptoms (dysphoria, hopelessness, withdrawal, worry, and cognitive concerns). Mixed models were created to examine differences in depression subscale by group, and logistic regression analyses were performed to determine if patterns of depressive symptoms could predict a patient's NDG syndrome. PSPS patients presented with a hopeless, dysphoric, and withdrawn pattern, while patients with CBS presented with a similar but less severe pattern. Worry was a key symptom in the profile of patients with svPPA, while ADs only had abnormally elevated cognitive concerns. Depressive profile accurately predicted NDG diagnosis at a rate of between 70 and 84% accuracy. Conclusions: These results suggest that attention to specific depressive symptom profile can improve diagnostic sensitivity and can be used to provide more individualized patient care.

16.
Neuropsychol Rev ; 19(2): 186-203, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19472057

RESUMEN

This review focuses on the "real world" implications of infection with HIV/AIDS from a neuropsychological perspective. Relevant literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment, driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical, cognitive, psychosocial, and psychiatric issues on whether someone with HIV/AIDS will be able to return to work, adhere to a complicated medication regimen, or safely drive a vehicle will be discussed. Methodological issues that arise in the context of measuring medication adherence or driving capacity are also explored. Finally, the impact of HIV/AIDS on mood state, fatigue, and interpersonal relationships are addressed, with particular emphasis on how these variables interact with cognition and independent functioning. The purpose of this review is to integrate neuropsychological findings with their real world correlates of functional behavior in the HIV/AIDS population.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/psicología , Enfermedades del Sistema Nervioso Central/psicología , Trastornos del Conocimiento/psicología , Costo de Enfermedad , Infecciones por VIH/psicología , Complejo SIDA Demencia/psicología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Enfermedades del Sistema Nervioso Central/etiología , Enfermedades del Sistema Nervioso Central/virología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/virología , Infecciones por VIH/complicaciones , Humanos , Pruebas Neuropsicológicas , Calidad de Vida
17.
Am J Geriatr Psychiatry ; 17(4): 281-90, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19307857

RESUMEN

OBJECTIVE: To evaluate the hypothesis that poor adherence to highly active antiretroviral treatment (HAART) would be more strongly related to cognitive impairment among older than among younger HIV-seropositive adults. SETTING AND PARTICIPANTS: A volunteer sample of 431 HIV-infected adult patients prescribed self-administered HAART was recruited from community agencies and university-affiliated infectious disease clinics in the Los Angeles area. MEASUREMENTS: Neurocognitive measures included tests of attention, information processing speed, learning/memory, verbal fluency, motor functioning, and executive functioning. Medication adherence was measured using microchip-embedded pill bottle caps (Medication Event Monitoring System) and self-report. Latent/structural analysis techniques were used to evaluate factor models of cognition and adherence. RESULTS: Mean adherence rates were higher among older (>or=50 years) than younger (<50 years) HIV-positive adults. However, latent/structural modeling demonstrated that neurocognitive impairment was associated with poorer medication adherence among older participants only. When cognitive subdomains were examined individually, executive functioning, motor functioning, and processing speed were most strongly related to adherence in this age group. CD4 count and drug problems were also more strongly associated with adherence among older than younger adults. CONCLUSIONS: Older HIV-positive individuals with neurocognitive impairment or drug problems are at increased risk of suboptimal adherence to medication. Likewise, older adults may be especially vulnerable to immunological and neurocognitive dysfunction under conditions of suboptimal HAART adherence. These findings highlight the importance of optimizing medication adherence rates and evaluating neurocognition in the growing population of older HIV-infected patients.


Asunto(s)
Envejecimiento/psicología , Terapia Antirretroviral Altamente Activa , Trastornos del Conocimiento/psicología , Infecciones por VIH/psicología , Cumplimiento de la Medicación/psicología , Adulto , Trastornos del Conocimiento/complicaciones , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Autoadministración
18.
Int J Neurosci ; 119(10): 1830-47, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19922389

RESUMEN

INTRODUCTION: This study examined whether IQ predicts neuropsychological performance among children with varying ability levels. METHOD: 177 children/adolescents were subdivided as Below Average (BA; N = 71; IQ = 60-85), Average (A; N = 72; IQ = 90-110), or Above Average (AA; N = 34; IQ = 115-140) in IQ. Assessments included intelligence, achievement, memory, and executive functioning measures. RESULTS: Group differences were found on all tests (p < .001). Planned comparisons revealed differences between BA and A on seven variables, and between A and AA on five variables with small-to-medium effect sizes. Correlations were found between IQ and neuropsychological functioning and varied by group membership. DISCUSSION: In children, IQ predicts neuropsychological performance differentially based upon ability level, with stronger relationships shown in lower IQ ranges.


Asunto(s)
Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/fisiopatología , Inteligencia/fisiología , Pruebas Neuropsicológicas , Adolescente , Atención , Niño , Desarrollo Infantil , Preescolar , Trastornos del Conocimiento/psicología , Escolaridad , Femenino , Humanos , Aprendizaje/fisiología , Masculino , Destreza Motora , Análisis Multivariante , Valor Predictivo de las Pruebas , Solución de Problemas , Escalas de Valoración Psiquiátrica , Estadística como Asunto
19.
Int J Neurosci ; 119(10): 1779-803, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19922386

RESUMEN

OBJECTIVE: To examine the hypothesis of subcortical pathologic impairment in HIV/AIDS. METHOD: The study included 22 HIV+, 22 HIV- controls, 22 learning disordered (LD) HIV-, and 22 depressive HIV-. The groups were compared on eight WMS-III Indices. RESULTS: Analyses revealed significantly lower scores (p < .05) in HIV+ on visual immediate memory, immediate memory, visual delayed memory, auditory delayed memory, working memory, and general memory. For all cases, HIV+ participants scored below the control group only. CONCLUSIONS: WMS-III indices discriminated HIV+ participants from normal comparisons. Inability to find differences between HIV+ and depressive and LD groups reflects the isolation of the subcortical effect to the HIV+ group.


Asunto(s)
Depresión/complicaciones , Infecciones por VIH/complicaciones , Trastornos de la Memoria/complicaciones , Trastornos de la Memoria/diagnóstico , Adulto , Análisis de Varianza , Depresión/virología , Femenino , Humanos , Inteligencia , Discapacidades para el Aprendizaje/fisiopatología , Discapacidades para el Aprendizaje/virología , Masculino , Trastornos de la Memoria/virología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Reproducibilidad de los Resultados
20.
Int J Neurosci ; 119(10): 1810-29, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19922388

RESUMEN

OBJECTIVE: This article addresses whether measures for assessing premorbid intellectual functioning are adequate for geriatric schizophrenia. METHOD: We included geriatric schizophrenia-spectrum disorders (SSD; n = 37), frontotemporal dementia (FTD; n = 41), and geriatric controls (n = 107), and employed measures of verbal ability. RESULTS: Pearson's correlations and ANOVAs for discrepancy comparisons showed unique patterns of spared function in SSD when compared to FTD and controls. CONCLUSIONS: Findings lend support to the specificity of cognitive processes in SSD, even when accounting for processes common to the theoretically similar FTD. SSD showed a distinct pattern of spared ability which supports clinical utilization of discrepant measures of premorbid intellectual estimation for SSD.


Asunto(s)
Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Evaluación Geriátrica , Esquizofrenia/complicaciones , Psicología del Esquizofrénico , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Electroencefalografía/métodos , Femenino , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/psicología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones/métodos , Escalas de Valoración Psiquiátrica , Estadística como Asunto
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