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BACKGROUND: White matter (WM) microstructure may vary significantly in pediatric-onset (PO) and adult-onset (AO) patients with multiple sclerosis (MS), a difference that could be explained by the effects of an inherent plasticity in the affected pediatric brains early in the disease, and a phenomenon that does not occur later in life. This hypothesis would support the observation that disease progression is much slower in POMS compared to AOMS patients. OBJECTIVES: To examine WM microstructure in the brain of adults with POMS and AOMS, using tract based spatial statistics (TBSS) analysis of diffusion-tensor imaging (DTI). METHODS: Adults with relapsing-remitting (RR) POMS, who were diagnosed before age of 18 years (n = 16), were compared with age-matched (AOA, n = 23) and disease duration-matched (AOD, n = 22) RR patients who developed MS after the age of 18 years. Scans were analyzed using the FSL software package (Oxford, UK) and statistics were performed using TBSS to evaluate WM microstructure between groups based on the mean fractional anisotropy (FA) values obtained from the DTI. RESULTS: Widespread cortical and deep WM area differences characterized by increased FA values were seen in the AOAMS compared with POMS group (P < 0.05, TFCE corrected). Significantly increased FA values of posterior WM areas were detected in the AODMS compared with POMS group (P < 0.05, TFCE corrected). CONCLUSION: Increased FA values in WM areas of the AOMS compared with the POMS patients suggest that diffuse WM microstructure changes are more attributable to age of onset than a simple function of disease duration and age.
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Encéfalo/patología , Imagen de Difusión Tensora/métodos , Interpretación de Imagen Asistida por Computador/métodos , Esclerosis Múltiple Recurrente-Remitente/patología , Adulto , Edad de Inicio , Humanos , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/patologíaRESUMEN
BACKGROUND: The microbiology component of Australian undergraduate nursing programmes varies considerably. Any actual or potential impact of this variation on infection control practice, as a nursing graduate, is relatively unknown. AIMS: The aim of this study was to explore infection control professionals' perceptions of the importance of microbiology and infection control training in undergraduate nursing curricula and the perceived retention of that knowledge and its transferability to practice. METHOD: Semi-structured interviews were conducted with eight infection control professionals from a range of hospital settings in Australia. FINDINGS: Four main themes emerged: Theory versus practice, importance of role modelling, disjunction between university curricula and 'the real world,' and learning in context. CONCLUSION: As the underpinning element of infection control practice, the role of microbiology education and training in nursing education will benefit from review. Further discussions about the nature and timing of theoretical microbiology content and assessment of undergraduate students' microbiology knowledge to ensure retention and appropriate application of that knowledge in practice are urgently needed.
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Bachillerato en Enfermería/organización & administración , Control de Infecciones , Conocimiento , Personal de Enfermería/psicología , Curriculum , Humanos , Nueva Gales del SurRESUMEN
PURPOSE: To compare functional magnetic resonance imaging (fMRI) activation patterns during a cognitive task, exercise capacity, and symptoms in postconcussion syndrome (PCS) patients who received exercise treatment (n = 4) with a PCS placebo stretching group (n = 4) and a healthy control group (n = 4). METHODS: Subjects completed a math processing task during fMRI and an exercise treadmill test before (time 1) and after approximately 12 weeks (time 2). Exercise subjects performed aerobic exercise at 80% of the heart rate (HR) attained on the treadmill test, 20 minutes per day with an HR monitor at home, 6 days per week. The program was modified as the HR for symptom exacerbation increased. RESULTS: At time 1, there was no difference in fMRI activation between the 2 PCS groups but healthy controls had significantly greater activation in the posterior cingulate gyrus, lingual gyrus, and cerebellum versus all PCS subjects (P < .05, corrected for multiple comparisons). At time 2, exercise PCS did not differ from healthy controls whereas placebo stretching PCS had significantly less activity in the cerebellum (P < .05 corrected) and in the anterior cingulate gyrus and thalamus (P < .001, uncorrected) versus healthy controls. At time 2, exercise PCS achieved a significantly greater exercise HR (P < .001) and had fewer symptoms (P < .0004) than placebo stretching PCS. Cognitive performance did not differ by group or time. CONCLUSIONS: Controlled aerobic exercise rehabilitation may help restore normal cerebral blood flow regulation, as indicated by fMRI activation, in PCS patients. The PCS symptoms may be related to abnormal cerebral blood flow regulation.
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Encéfalo/patología , Encéfalo/fisiopatología , Terapia por Ejercicio/métodos , Imagen por Resonancia Magnética/métodos , Síndrome Posconmocional/diagnóstico , Síndrome Posconmocional/rehabilitación , Adolescente , Adulto , Mapeo Encefálico , Estudios de Casos y Controles , Circulación Cerebrovascular/fisiología , Cognición/fisiología , Prueba de Esfuerzo/métodos , Femenino , Estudios de Seguimiento , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valores de Referencia , Resultado del Tratamiento , Adulto JovenRESUMEN
This was a case of an 81-year-old female, an amputee, who presented at hospital with a fractured neck of femur after a fall in the nursing home. The patient was being treated for several complex chronic conditions for which 30 regular medicines were prescribed and 100 tablets were being taken per day. The patient was fluid limited to 1500 mL per day but the need to swallow such a high number of tablets meant that there was no fluid allowance available for any other drinks, not even a cup of tea. In the nursing home, the patient had multiple prescribers, not all from the one surgery. The pharmacist conducted a multifaceted review of the patient's medication and lifestyle factors. Working collaboratively with the wider health care team, the intervention was able to reduce the number of medications and improve the patient's quality of life through improving the effectiveness of other lifestyle factors. This case not only showcases pharmacist interventions but also the synergistic benefit of interprofessional working with patients with chronic and complex conditions. This is arguably more critical in rural or remote areas where there is commonly a paucity of most health practitioners, health assistants and technicians.
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Research shows the critical value of teacher affirmation of LGBTQIA+ identities in improving social and academic outcomes for youth, and in rural areas this need is significant as students often experience discrimination with limited community resources. When provided, professional development is often concerned with safety and bullying with less focus on disrupting heteronormative and transphobic belief systems. Educators experience difficulty discussing these topics, however drawing upon a theory of a pedagogy of discomfort can help facilitators to foster critical thinking and engage learners in emotional labor leading to positive transformation. This article uses survey data to examine the impacts of pedagogical approaches of facilitators that invite and navigate discomfort in a workshop for educators on supporting LGBTQIA+ students in a rural district. Findings show that participants engage in challenging discussions, leading to deeper understandings, compassion, and the potential for positive action in school settings.
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Acoso Escolar , Minorías Sexuales y de Género , Adolescente , Humanos , Instituciones Académicas , Estudiantes/psicologíaRESUMEN
We aimed to investigate whether mild cognitive impairment (MCI) in Parkinson's disease (PD) is characterized by region-specific gray matter (GM) atrophy and to explore correlations between GM and cognition in PD. Magnetic resonance images of 42 newly diagnosed PD patients (of which 11 had MCI) and 37 normal controls were analyzed using voxel-based morphometry. Analyses comparing groups showed no regional atrophy, and in patients there were no significant correlations between cognitive domain test performance and GM loss. In conclusion, GM atrophy does not seem to be a major feature of cognitive dysfunction in incident PD.
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Mapeo Encefálico , Encéfalo/patología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Enfermedad de Parkinson/complicaciones , Anciano , Planificación en Salud Comunitaria , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios ProspectivosRESUMEN
Continuing professional development (CPD) is an essential component of professional practice for registered health practitioners to maintain and enhance knowledge, skills and abilities. There are many topics that practitioners may pursue relevant to their practice environment, and, in recent years, providing culturally safe and respectful practice is an emerging area of need. Unfortunately, many health professionals, whilst willing to offer cultural safe healthcare, may be uncertain of how to enact that practice. The World Health Organisation recognises attainment of the highest possible standard of health as a basic human right, and cultural safety is increasingly becoming an expectation of health professionals. To address this need and the insufficiency of support in the literature, the authors have presented a discussion paper on various aspects of cultural safety and the underlying constructs, such as cultures, that support it. The discussion takes into account core constructs that signpost the path to cultural safety and recognises the role and accountability of all levels of the healthcare system, not merely the practitioner. Finally, we propose a model program for a cultural humility CPD activity incorporating pre-work, online modules, interactive workshop, reflection on professional practice and a post-workshop evaluation.
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Previous studies in patients with multiple sclerosis (MS) revealed increased lesion count and volume on 3 T compared to 1.5 T. Morphological and spatial lesion characteristics between 1.5 T and 3 T have not been examined. The aim of this study was to investigate the effect of changing from a 1.5 T to a 3 T MRI scanner on the number, volume and spatial distribution of signal abnormalities (SA) on brain MRI in a sample of MS patients and normal controls (NC), using pair- and voxel-wise comparison procedures. Forty-one (41) MS patients (32 relapsing-remitting and 9 secondary-progressive) and 38 NC were examined on both 1.5 T and 3 T within one week in random order. T2-weighted hyperintensities (T2H) and T1-weighted hypointensities (T1H) were outlined semiautomatically by two operators in a blinded fashion on 1.5 T and 3 T images. Spatial lesion distribution was assessed using T2 and T1 voxel-wise SA probability maps (SAPM). Pair-wise analysis examined the proportion of SA not simultaneously outlined on 1.5 T and 3 T. A posteriori unblinded analysis was conducted to examine the non-overlapping identifications of SA between the 1.5 T and 3 T. For pair-wise T2- and T1-analyses, a higher number and individual volume of SA were detected on 3 T compared to 1.5 T (p<0.0001) in both MS and NC. Logistic regression analysis showed that the likelihood of missing SA on 1.5 T was significantly higher for smaller SA in both MS and NC groups. SA probability map (SAPM) analysis revealed significantly more regionally distinct spatial SA differences on 3 T compared to 1.5 T in both groups (p<0.05); these were most pronounced in the occipital, periventricular and cortical regions for T2H. This study provides important information regarding morphological and spatial differences between data acquired using 1.5 T and 3 T protocols at the two scanner field strengths.
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Algoritmos , Encéfalo/patología , Interpretación de Imagen Asistida por Computador/métodos , Esclerosis Múltiple/patología , Adolescente , Adulto , Anciano , Humanos , Aumento de la Imagen/métodos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Patients with ischemic stroke are at risk for developing vascular cognitive impairment ranging from mild impairments to dementia. MRI findings of infarction, white matter hyperintensities, and global cerebral atrophy have been implicated in the development of vascular cognitive impairment. The present study investigated regional gray matter volume differences between patients with ischemic stroke with no cognitive impairment and those with impairment in at least one domain of cognitive function. METHODS: Ninety-one patients with ischemic stroke participated. Detailed neuropsychological testing was used to characterize cognitive functioning in 7 domains: orientation, attention, working memory, language, visuospatial ability, psychomotor speed, and memory. High-resolution T1-weighted 3-dimensional fast-spoiled gradient recalled structural MRIs were processed using optimized voxel-based morphometry techniques while controlling for lesions. Whole brain voxelwise regional differences in gray matter volume were assessed between patients with stroke with no impaired cognitive domains and patients with stroke with at least one impaired cognitive domain. Logistic regression models were used to assess the contribution of demographic variables, stroke-related variables, and voxel-based morphometry results to classification of cognitive impairment group membership. RESULTS: Fifty-one patients had no impairments in any cognitive domain and 40 patients were impaired in at least one cognitive domain. Logistic regression identified significant contributions to cognitive impairment groups for demographic variables, stroke-related variables, and cognitive domain performance. Voxel-based morphology results demonstrated significant gray matter volume reductions in patients with stroke with one or more cognitive domain impairment compared with patients with stroke without cognitive impairment that was seen mostly in the thalamus with smaller reductions found in the cingulate gyrus and frontal, temporal, parietal, and occipital lobes. These reductions were present after controlling for group differences in age, education, stroke volume, and laterality of stroke. The addition of voxel-based morphometry-derived thalamic volume significantly improved a logistic regression model predicting cognitive impairment group membership when added to demographic variables, stroke-related variables, and cognitive domain performance. CONCLUSIONS: These results suggest a central role for the thalamus and lesser roles for other cortical regions in the development of cognitive impairment after ischemic stroke. Indeed, consideration of thalamic volumes adds significant information to the classification of cognitive impaired versus nonimpaired groups beyond information provided by demographic, stroke-related, and cognitive performance measures.
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Isquemia Encefálica/complicaciones , Trastornos del Conocimiento/etiología , Imagen por Resonancia Magnética , Sustancia Gris Periacueductal/patología , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/psicología , Corteza Cerebral/patología , Trastornos del Conocimiento/diagnóstico , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Logísticos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Accidente Cerebrovascular/etiología , Tálamo/patologíaRESUMEN
Magnetic resonance imaging (MRI) is the most important paraclinical measure for assessing and monitoring the pathologic changes implicated in the onset and progression of multiple sclerosis (MS). Conventional MRI sequences, such as T1-weighted gadolinium (Gd) enhanced and spin-echo T2-weighted imaging, only provide an incomplete picture of the degree of inflammation and underlying neurodegenerative changes in this disease. Two- and three-dimensional fluid-attenuated inversion recovery and double inversion recovery sequences allow better identification of cortical, periventricular and infratentorial lesions. Ultra-high field strength MRI has the potential to detect subpial cortical and deep gray matter lesions. Unenhanced T1-weighted imaging can reveal hypointense black holes, a measure of chronic neurodegeneration. Magnetization transfer imaging (MTI) is increasingly used to characterize the evolution of MS lesions and normal-appearing brain tissue. Evidence suggests that the dynamics of magnetization transfer changes correlate with the extent of demyelination and remyelination. Magnetic resonance spectroscopy, which provides details on tissue biochemistry, metabolism, and function, also has the capacity to reveal neuroprotective mechanisms. By measuring the motion of water, diffusion imaging can provide information about the orientation, size, and geometry of tissue damage in white and gray matter. These advanced non-conventional MRI techniques relate better to clinical impairment, disease progression, accumulation of disability, and have the potential to detect neuroprotective effects of treatment. Although detecting the status of neuronal integrity using MRI techniques continues to improve, a "gold standard" model remains to be established.
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Imagen por Resonancia Magnética , Esclerosis Múltiple/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/clasificación , Esclerosis Múltiple/tratamiento farmacológico , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Although the cognitive disorder of multiple sclerosis (MS) is well characterized, little is known about personality changes that may occur in this disease. There are reliable personality tests available for research in neurological disease, based on the well-known Five Factor Model. Preliminary research suggests that cognitively impaired MS patients exhibit elevation in Neuroticism, and diminution in Extraversion, Agreeableness, and Conscientiousness, as do patients with Alzheimer's disease. We predicted that these characteristics would be associated with lower neocortical volume. We studied 44 patients using brain MRI and the NEO Five-Factor Inventory. Regression models controlling for T2 lesion volume, depression, and cognitive dysfunction revealed significant correlation between cortical atrophy and reduction in Extraversion and Conscientiousness. Discrepancies between patient- and informant-reports were found, and overreporting of high Openness and Conscientiousness among patients was associated with lower neocortical volume. A final regression model accounting for depression, cognitive function, and personality accounted for 38% of the variance in neocortical volume. These findings suggest that cortical atrophy in MS is associated with adverse impact on personality, although longitudinal research is needed to test this hypothesis.
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Corteza Cerebral/patología , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/patología , Personalidad , Adulto , Atrofia/etiología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Examen Neurológico , Pruebas Neuropsicológicas , Trastornos de la Personalidad/etiología , Pruebas de Personalidad , Análisis de RegresiónRESUMEN
Multiple sclerosis is characterized by the dual pathological processes of inflammation and neurodegeneration. Conventional MRI techniques are considered the best tools for assessing and monitoring lesion burden and inflammation but are limited in their ability to assess axonal loss. Optical coherence tomography (OCT) is a simple high-resolution technique that uses near infrared light to quantify the thickness of the retinal nerve fiber layer (RNFL), which contains only non-myelinated axons. RNFL thickness (RNFLT) was measured using OCT on thirty consecutive MS patients (60 eyes). Eighteen patients underwent quantitative MRI analysis including T1- and T2-lesion volumes (LV), normalized brain volume (NBV), normalized cortical, white and gray matter volumes (NCV, NWMV, and NGMV), and mean whole brain diffusivity (MD). There was a strong association between NBV and average RNFL thickness (p<0.001, partial rp=0.77). The T2-LV and NWMV were significantly associated with average RNFL thickness (p=0.002, partial rp= -0.76 and p=0.005, partial rp=0.68, respectively) and there were trends toward association with T1-LV (p=0.041) and NGMV (p=0.067). There was negative correlation between average RNFL thickness (average of both eyes) and disability as assessed by EDSS (p=0.02). The results support potential usefulness of OCT for MS patient monitoring and research applications.
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Encéfalo/patología , Esclerosis Múltiple/patología , Fibras Nerviosas/patología , Retina/patología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodosRESUMEN
Healthcare-associated infections (HAIs) have become a significant and costly problem for healthcare institutions worldwide. Despite the crucial role of infection prevention and control (IC) procedures, there is a substantial body of evidence to indicate that IC knowledge and practices of health professional graduates is, however, sub-optimal. This paper presents a discussion of the critical role microbiology plays in infection control education and practice, arguing that without an ability to apply microbiology knowledge to IC decision-making, there is an inherent risk of incorrect application of IC practices and thus a risk to patient (and nurse) safety. The authors propose a re-conceptualization of infection control competency, using nursing as an exemplar profession, to reflect practice that is not based on simple memorization of protocols but rather on a sound understanding of microbiology and informed decision-making. The proposal for re-conceptualizing the definition and assessment of IC competence, if adopted, would potentially enhance students' understanding and synthesis of microbiology knowledge and help build students' capacity to apply that knowledge to practice.
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Alterations of auditory feedback during piano performance can be profoundly disruptive. Furthermore, different alterations can yield different types of disruptive effects. Whereas alterations of feedback synchrony disrupt performed timing, alterations of feedback pitch contents can disrupt accuracy. The current research tested whether these behavioral dissociations correlate with differences in brain activity. Twenty pianists performed simple piano keyboard melodies while being scanned in a 3-T magnetic resonance imaging (MRI) scanner. In different conditions they experienced normal auditory feedback, altered auditory feedback (asynchronous delays or altered pitches), or control conditions that excluded movement or sound. Behavioral results replicated past findings. Neuroimaging data suggested that asynchronous delays led to increased activity in Broca's area and its right homologue, whereas disruptive alterations of pitch elevated activations in the cerebellum, area Spt, inferior parietal lobule, and the anterior cingulate cortex. Both disruptive conditions increased activations in the supplementary motor area. These results provide the first evidence of neural responses associated with perception/action mismatch during keyboard production.
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Encéfalo/irrigación sanguínea , Imagen por Resonancia Magnética , Música , Desempeño Psicomotor/fisiología , Estimulación Acústica , Adulto , Encéfalo/fisiología , Retroalimentación Sensorial , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Oxígeno/sangre , Adulto JovenRESUMEN
OBJECTIVE: To investigate differences in region-specific gray matter (GM) damage between adults with pediatric-onset (PO) multiple sclerosis (MS) and adult-onset (AO) MS. METHODS: Twenty-four relapsing-remitting (RR) adults with POMS (mean age = 35 years, mean disease duration = 18.4 years) were compared to 23 age-matched (AOA, mean age = 33.9 years, mean disease duration = 2.4 years) and 24 disease-duration matched (AOD, mean age = 45.9 years, mean disease duration = 18.5 years) RRMS adults who developed MS after the age of 18. Three-dimensional-T1-weighted images were acquired on a 1.5 T MRI. Image analysis was conducted using voxel-based morphometry (Statistical Parametric Mapping 8). RESULTS: There were no regional GM atrophy differences between POMS and AODMS groups. No regional GM atrophy differences were found between POMS and AOAMS patients when disease duration was included as a covariate. CONCLUSIONS: Regional GM differences were not found between POMS adults and MS controls matched for age or disease duration. Although of limited sample size, these findings suggest that there are no regional GM atrophy differences between RR POMS and AOMS.
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Envejecimiento/patología , Encéfalo/patología , Sustancia Gris/patología , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple Recurrente-Remitente/patología , Adulto , Atrofia/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Remisión Espontánea , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenAsunto(s)
Honorarios y Precios , Registros Médicos/economía , Acceso de los Pacientes a los Registros/economía , Registros Electrónicos de Salud/economía , Registros Electrónicos de Salud/legislación & jurisprudencia , Humanos , Registros Médicos/legislación & jurisprudencia , Acceso de los Pacientes a los Registros/legislación & jurisprudenciaRESUMEN
INTRODUCTION: Masking level differences (MLDs) are differences in the hearing threshold for the detection of a signal presented in a noise background, where either the phase of the signal or noise is reversed between ears. We use N0/Nπ to denote noise presented in-phase/out-of-phase between ears and S0/Sπ to denote a 500 Hz sine wave signal as in/out-of-phase. Signal detection level for the noise/signal combinations N0Sπ and NπS0 is typically 10-20 dB better than for N0S0. All combinations have the same spectrum, level, and duration of both the signal and the noise. METHODS: Ten participants (5 female), age: 22-43, with N0Sπ-N0S0 MLDs greater than 10 dB, were imaged using a sparse BOLD fMRI sequence, with a 9 second gap (1 second quiet preceding stimuli). Band-pass (400-600 Hz) noise and an enveloped signal (.25 second tone burst, 50% duty-cycle) were used to create the stimuli. Brain maps of statistically significant regions were formed from a second-level analysis using SPM5. RESULTS: The contrast NπS0- N0Sπ had significant regions of activation in the right pulvinar, corpus callosum, and insula bilaterally. The left inferior frontal gyrus had significant activation for contrasts N0Sπ-N0S0 and NπS0-N0S0. The contrast N0S0-N0Sπ revealed a region in the right insula, and the contrast N0S0-NπS0 had a region of significance in the left insula. CONCLUSION: Our results extend the view that the thalamus acts as a gating mechanism to enable dichotic listening, and suggest that MLD processing is accomplished through thalamic communication with the insula, which communicate across the corpus callosum to either enhance or diminish the binaural signal (depending on the MLD condition). The audibility improvement of the signal with both MLD conditions is likely reflected by activation in the left inferior frontal gyrus, a late stage in the what/where model of auditory processing.
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Cuerpo Calloso , Audición/fisiología , Imagen por Resonancia Magnética/métodos , Ruido , Tálamo , Adulto , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/fisiología , Femenino , Pruebas Auditivas , Humanos , Masculino , Radiografía , Tálamo/diagnóstico por imagen , Tálamo/fisiologíaRESUMEN
Traditional magnetic resonance imaging (MRI) techniques have contributed to the management of multiple sclerosis (MS) but are limited in their ability to detect neuronal damage. Advanced MRI metrics provide assessment of microscopic neuronal changes; however, few studies have examined the effects of MS therapies on these measures. This prospective, open-label, observational study evaluated the effect of subcutaneous glatiramer acetate (GA) 20mg/day on the 1- and 2-year changes in diffusion-weighted imaging (DWI) measures in patients with relapsing-remitting (RR) MS and in age- and sex-matched healthy controls (HC). Inclusion criteria were age 18-65, RR disease course, expanded disability status scale (EDSS) score ≤5.5 and disease duration<20 years. MS patients and HC underwent 1.5T MRI scans and clinical examinations at baseline and at 1- and 2-year follow-up. Nineteen RRMS patients and 16 HC completed the 1-year follow-up and 16 MS patients and 13 HC the 2-year follow-up of the study. In MS patients, treatment with GA promoted recovery of DWI mean parenchymal diffusivity (MPD) at year 1 (-7.1%, p=0.007) and at year 2 (-10.1%, p=0.028). The recovery of DWI MPD was significantly higher in MS patients compared to HC at year 1 (p=0.01) and year 2 (p<0.001). GA promoted recovery of DWI entropy at 2 years (-1.2%, p=0.018). No significant DWI MPD and entropy changes were observed in HC over the follow-up. No significant deterioration in magnetization transfer ratio occurred over the follow-up in MS patients and HC. Patients on GA and HC did not develop significant global or regional atrophy over 2 years. GA significantly improved microscopic tissue damage in the brain, as measured by DWI over the 1- and 2-year follow-up.
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The rs6265 single nucleotide polymorphism (SNP) is a genetic variation in the brain-derived neurotrophic factor (BDNF) gene wherein the presence of the A-allele at rs6265 causes replacement of a valine (Val) at position 66 by methionine (Met). We reported recently that the Met66 allele was associated with lower brain damage as evidenced by measurement of gray matter (GM) volume in multiple sclerosis (MS) patients. The objective of this study was to determine the voxel-wise regional GM differences between the Val66Val and Met66 allele groups in MS patients by using voxel-based morphometry (VBM)-optimized analysis corrected for lesion misclassification in Statistical Parametric Mapping (SPM5). High-resolution 3D-T1-weighted SPGR images from a total of 188 MS patients were acquired on a 1.5T MRI. The Val66Val group included 129 MS patients and the Met66 allele group (comprised of Val66Met or Met66Met genotypes) included 59 MS patients. The SPM analysis of covariance tool was used to assess group differences after controlling for variation in head size, MS disease course and gender. VBM analysis did not yield significant family wise error (FWE) corrected results. This was also confirmed with the non-parametric analysis using threshold-free cluster enhancement (TFCE) method. However, the results from VBM as well as the TFCE analyses (p<0.001, uncorrected) showed higher GM volume in the cingulate of MS patients with Met66 allele than those with Val66Val. Future studies are warranted to investigate longitudinally possible protective role of the Met66 allele of the BDNF rs6265 SNP in relation to specific GM regions.
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BACKGROUND: Mycophenolate mofetil (MMF, CellCept®) has been utilized as an antirejection agent in transplant recipients and in patients with myriad autoimmune disorders including multiple sclerosis (MS). OBJECTIVE: To investigate radiographic and clinical safety involving monotherapy use of daily oral MMF (1 g b.i.d.) versus weekly intramuscular interferon beta 1a (Avonex® at 30 mcg) in relapsing-remitting MS (RRMS). METHODS: We organized a randomized, serial, 6-monthly, MRI-blinded, parallel-group multicenter pilot study to determine the safety of MMF versus interferon beta monotherapy in 35 untreated patients with RRMS, all of whom exhibited evidence of gadolinium (Gd) enhancement on a screening MRI of the brain. The primary outcome was the reduction in the cumulative mean number of combined active lesions (CAL), new Gd-enhancing lesions, and new T2 lesions on MRI analyses. RESULTS: Both interferon beta and MMF appeared safe and well tolerated in the majority of patients. There was no difference between MMF therapy and the standard regimen of interferon beta therapy on the primary safety MRI endpoints of the study. However, the MMF group showed a trend toward a lower accumulation of combined active lesions, CAL, Gd and T2 lesions when compared with interferon beta treated patients. CONCLUSIONS: The results from this pilot study suggest that the application of MMF monotherapy in MS deserves further exploration.