Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 183
Filtrar
1.
G3 (Bethesda) ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781440

RESUMO

Neurexins and their canonical binding partners, neuroligins, are localized to neuronal pre-, and post-synapses, respectively, but less is known about their role in driving behaviors. Here, we use the nematode C. elegans to show that neurexin, but not neuroligin, is required for avoiding specific chemorepellents. We find that adults with knockouts of the entire neurexin locus exhibit a strong avoidance deficit in response to glycerol and a weaker defect in response to copper. Notably, the C. elegans neurexin (nrx-1) locus, like its mammalian homologs, encodes multiple isoforms, α and γ. Using isoform-specific mutations, we find that the γ isoform is selectively required for glycerol avoidance. Next, we used transgenic rescue experiments to show that this isoform functions at least partially in the nervous system. We also confirm that the transgenes are expressed in the neurons and observe protein accumulation in neurites. Furthermore, we tested whether these mutants affect the behavioral responses of juveniles. We find that juveniles (4th larval stages) of mutants knocking out the entire locus or the α-isoforms, but not γ-isoform, are defective in avoiding glycerol. These results suggest that the different neurexin isoforms affect chemosensory avoidance behavior in juveniles and adults, providing a general principle of how isoforms of this conserved gene affect behavior across species.

2.
iScience ; 27(4): 109477, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38551003

RESUMO

Structural neuroplasticity (changes in the size, strength, number, and targets of synaptic connections) can be modified by sleep and sleep disruption. However, the causal relationships between genetic perturbations, sleep loss, neuroplasticity, and behavior remain unclear. The C. elegans GABAergic DVB neuron undergoes structural plasticity in adult males in response to adolescent stress, which rewires synaptic connections, alters behavior, and is dependent on conserved autism-associated genes NRXN1/nrx-1 and NLGN3/nlg-1. We find that four methods of sleep deprivation transiently induce DVB neurite extension in day 1 adults and increase the time to spicule protraction, which is the functional and behavioral output of the DVB neuron. Loss of nrx-1 and nlg-1 prevent DVB structural plasticity and behavioral changes at day 1 caused by adolescent sleep loss. Therefore, nrx-1 and nlg-1 mediate the morphologic and behavioral consequences of sleep loss, providing insight into the relationship between sleep, neuroplasticity, behavior, and neurologic disease.

3.
Sci Rep ; 14(1): 5646, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454017

RESUMO

Brain tumour microstructure is potentially predictive of changes following treatment to cognitive functions subserved by the functional networks in which they are embedded. To test this hypothesis, intra-tumoural microstructure was quantified from diffusion-weighted MRI to identify which tumour subregions (if any) had a greater impact on participants' cognitive recovery after surgical resection. Additionally, we studied the role of tumour microstructure in the functional interaction between the tumour and the rest of the brain. Sixteen patients (22-56 years, 7 females) with brain tumours located in or near speech-eloquent areas of the brain were included in the analyses. Two different approaches were adopted for tumour segmentation from a multishell diffusion MRI acquisition: the first used a two-dimensional four group partition of feature space, whilst the second used data-driven clustering with Gaussian mixture modelling. For each approach, we assessed the capability of tumour microstructure to predict participants' cognitive outcomes after surgery and the strength of association between the BOLD signal of individual tumour subregions and the global BOLD signal. With both methodologies, the volumes of partially overlapped subregions within the tumour significantly predicted cognitive decline in verbal skills after surgery. We also found that these particular subregions were among those that showed greater functional interaction with the unaffected cortex. Our results indicate that tumour microstructure measured by MRI multishell diffusion is associated with cognitive recovery after surgery.


Assuntos
Neoplasias Encefálicas , Disfunção Cognitiva , Feminino , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Cognição , Imagem de Difusão por Ressonância Magnética/métodos , Córtex Cerebral/patologia , Encéfalo/patologia
4.
Cortex ; 173: 1-15, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38354669

RESUMO

The extent to which tumour-infiltrated brain tissue contributes to cognitive function remains unclear. We tested the hypothesis that cortical tissue infiltrated by diffuse gliomas participates in large-scale cognitive circuits using a unique combination of intracranial electrocorticography (ECoG) and resting-state functional magnetic resonance (fMRI) imaging in four patients. We also assessed the relationship between functional connectivity with tumour-infiltrated tissue and long-term cognitive outcomes in a larger, overlapping cohort of 17 patients. We observed significant task-related high gamma (70-250 Hz) power modulations in tumour-infiltrated cortex in response to increased cognitive effort (i.e., switch counting compared to simple counting), implying preserved functionality of neoplastic tissue for complex tasks probing executive function. We found that tumour locations corresponding to task-responsive electrodes exhibited functional connectivity patterns that significantly co-localised with canonical brain networks implicated in executive function. Specifically, we discovered that tumour-infiltrated cortex with larger task-related high gamma power modulations tended to be more functionally connected to the dorsal attention network (DAN). Finally, we demonstrated that tumour-DAN connectivity is evident across a larger cohort of patients with gliomas and that it relates to long-term postsurgical outcomes in goal-directed attention. Overall, this study contributes convergent fMRI-ECoG evidence that tumour-infiltrated cortex participates in large-scale neurocognitive circuits that support executive function in health. These findings underscore the potential clinical utility of mapping large-scale connectivity of tumour-infiltrated tissue in the care of patients with diffuse gliomas.


Assuntos
Encéfalo , Glioma , Humanos , Encéfalo/fisiologia , Função Executiva/fisiologia , Cognição/fisiologia , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Vias Neurais/fisiologia
5.
Neurosurgery ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38251897

RESUMO

BACKGROUND AND OBJECTIVES: Spasmodic dysphonia is a dystonia of the vocal chords producing difficulty with speech. Current hypotheses are that this is a condition of dysregulated thalamic sensory motor integration. A recent randomized controlled trial of thalamic deep brain stimulation (DBS) demonstrated its safety and efficacy. Our objective was to determine whether the outcome could be predicted by stimulation of thalamic sensorimotor areas and adjacent white matter connectivity as assessed by diffusion tractography. METHODS: A cohort of 6 participants undergoing thalamic DBS for adductor spasmodic dysphonia was studied. Electrodes were localized with the Lead-DBS toolbox. Group-based analyses were performed with atlases, coordinates, and using voxel-based symptom mapping. Diffusion tensor imaging (3 T, 64 directions, 2-mm isotropic) was used to perform individual probabilistic tractography (cerebellothalamic tract and pallidothalamic tract) and segmentation of the thalamus. Monopolar review was performed at 0.5 V and binarised as effective or ineffective. RESULTS: Effective contacts stimulated more of thalamic sensorimotor areas than ineffective contacts (P < .05, false discovery rate corrected). This effect was consistent across analytical and statistical techniques. Group-level and tractography analyses did not identify a specific "sweet spot" suggesting the benefit of DBS is derived from modulating individual thalamic sensorimotor areas. Stimulations at 1 year involved predicted thalamic sensorimotor regions with additional cerebellothalamic tract involvement. CONCLUSION: Stimulation of thalamic sensorimotor areas was associated with improvement in symptoms of spasmodic dysphonia. These data are consistent with DBS acting on pathophysiologically dysregulated thalamic sensorimotor integration in spasmodic dysphonia.

6.
Brain Commun ; 5(6): fcad329, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075945

RESUMO

Radiofrequency thalamotomy is a neurosurgical management option for medically-refractory tremor. In this observational study, we evaluate the MRI features of the resultant lesion, their temporal dynamics, and how they vary depending on surgical factors. We report on lesion characteristics including size and location, as well as how these vary over time and across different MRI sequences. Data from 12 patients (2 essential tremor, 10 Parkinson's disease) who underwent unilateral radiofrequency thalamotomy for tremor were analysed. Lesion characteristics were compared across five structural sequences. Volumetric analysis of lesion features was performed at early (<5 weeks) and late (>5 months) timepoints by manual segmentation. Lesion location was determined after registration of lesions to standard space. All patients showed tremor improvement (clinical global impressions scale) postoperatively. Chronic side-effects included balance disturbances (n = 4) and worsening mobility due to parkinsonism progression (n = 1). Early lesion features including a necrotic core, cytotoxic oedema and perilesional oedema were best demarcated on T2-weighted sequences. Multiple lesions were associated with greater cytotoxic oedema compared with single lesions (T2-weighted mean volume: 537 ± 112 mm³ versus 302 ± 146 mm³, P = 0.028). Total lesion volume reduced on average by 90% between the early and late scans (T2-weighted mean volume: 918 ± 517 versus 75 ± 50 mm³, t = 3.592, P = 0.023, n = 5), with comparable volumes demonstrated at ∼6 months after surgery. Lesion volumes on susceptibility-weighted images were larger than those of T2-weighted images at later timepoints. Radiofrequency thalamotomy produces focused and predictable lesion imaging characteristics over time. T2-weighted scans distinguish between the early lesion core and oedema characteristics, while lesions may remain more visible on susceptibility-weighted images in the months following surgery. Scanning patients in the immediate postoperative period and then at 6 months is clinically meaningful for understanding the anatomical basis of the transient and permanent effects of thalamotomy.

7.
bioRxiv ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38106124

RESUMO

Animal foraging is an essential and evolutionarily conserved behavior that occurs in social and solitary contexts, but the underlying molecular pathways are not well defined. We discover that conserved autism-associated genes (NRXN1(nrx-1), NLGN3(nlg-1), GRIA1,2,3(glr-1), GRIA2(glr-2), and GLRA2,GABRA3(avr-15)) regulate aggregate feeding in C. elegans, a simple social behavior. NRX-1 functions in chemosensory neurons (ADL and ASH) independently of its postsynaptic partner NLG-1 to regulate social feeding. Glutamate from these neurons is also crucial for aggregate feeding, acting independently of NRX-1 and NLG-1. Compared to solitary counterparts, social animals show faster presynaptic release and more presynaptic release sites in ASH neurons, with only the latter requiring nrx-1. Disruption of these distinct signaling components additively converts behavior from social to solitary. Aggregation induced by circuit activation is also dependent on nrx-1. Collectively, we find that aggregate feeding is tuned by conserved autism-associated genes through complementary synaptic mechanisms, revealing molecular principles driving social feeding.

8.
Transl Psychiatry ; 13(1): 367, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036526

RESUMO

Neurexins are synaptic adhesion molecules that play diverse roles in synaptic development, function, maintenance, and plasticity. Neurexin genes have been associated with changes in human behavior, where variants in NRXN1 are associated with autism, schizophrenia, and Tourette syndrome. While NRXN1, NRXN2, and NRXN3 all encode major α and ß isoforms, NRXN1 uniquely encodes a γ isoform, for which mechanistic roles in behavior have yet to be defined. Here, we show that both α and γ isoforms of neurexin/nrx-1 are required for the C. elegans behavioral response to food deprivation, a sustained period of hyperactivity upon food loss. We find that the γ isoform regulates initiation and the α isoform regulates maintenance of the behavioral response to food deprivation, demonstrating cooperative function of multiple nrx-1 isoforms in regulating a sustained behavior. The γ isoform alters monoamine signaling via octopamine, relies on specific expression of NRX-1 isoforms throughout the relevant circuit, and is independent of neuroligin/nlg-1, the canonical trans-synaptic partner of nrx-1. The α isoform regulates the pre-synaptic structure of the octopamine producing RIC neuron and its maintenance role is conditional on neuroligin/nlg-1. Collectively, these results demonstrate that neurexin isoforms can have separate behavioral roles and act cooperatively across neuronal circuits to modify behavior, highlighting the need to directly analyze and consider all isoforms when defining the contribution of neurexins to behavior.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Octopamina/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Neurônios/metabolismo , Sinapses/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo
9.
J Am Assoc Lab Anim Sci ; 62(4): 336-348, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37758479

RESUMO

To assess the impact of the COVID-19 pandemic on facility oversight and animal care at 2 y after declaration of the pandemic, we distributed a comprehensive survey to targeted groups within the broader animal research community in early 2022. A total of 265 surveys were returned (161 responses to IACUC questions, 193 responses to animal resource program [ARP] questions, and 89 responses to both). IACUC questions focused on the use of virtual interactions for IACUC activities and on remote work for IACUC support staff during and after the pandemic. ARP questions focused on remote work arrangements, altered work schedules, personnel shortages, and operational changes made during and after the pandemic. Results indicate that IACUCs readily adopted remote work options for staff and virtual meetings, changes that are now largely viewed as permanent, and are using modified methods for postapproval monitoring (PAM), while largely rejecting virtual semiannual facility inspections. This pattern reflects available guidance for virtual IACUC meetings, whereas new guidance for virtual semiannual facility inspections might have caused confusion and regulatory compliance concerns. Remote work options were available for some ARP staff, depending on job responsibilities, but were mostly eliminated by 2 y after the start of the pandemic. ARP staff expressed a strong desire for continued in-person presence of supervisors; this preference was not expressed by IACUC staff. Based on the timing of the survey (April 2022), substantial disruptions in the labor market had resulted in a considerable number of job openings and lack of entry level staff. Long-term assessment of effects on compliance and IACUC engagement would be useful given the widespread use of virtual IACUC meetings and other changes related to institutional and programmatic adoption of remote work options in ARPs.


Assuntos
Comitês de Cuidado Animal , Experimentação Animal , COVID-19 , Animais , Bem-Estar do Animal , Animais de Laboratório , Pandemias
10.
Brain ; 146(12): 5015-5030, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37433037

RESUMO

Subthalamic nucleus (STN) beta-triggered adaptive deep brain stimulation (ADBS) has been shown to provide clinical improvement comparable to conventional continuous DBS (CDBS) with less energy delivered to the brain and less stimulation induced side effects. However, several questions remain unanswered. First, there is a normal physiological reduction of STN beta band power just prior to and during voluntary movement. ADBS systems will therefore reduce or cease stimulation during movement in people with Parkinson's disease and could therefore compromise motor performance compared to CDBS. Second, beta power was smoothed and estimated over a time period of 400 ms in most previous ADBS studies, but a shorter smoothing period could have the advantage of being more sensitive to changes in beta power, which could enhance motor performance. In this study, we addressed these two questions by evaluating the effectiveness of STN beta-triggered ADBS using a standard 400 ms and a shorter 200 ms smoothing window during reaching movements. Results from 13 people with Parkinson's disease showed that reducing the smoothing window for quantifying beta did lead to shortened beta burst durations by increasing the number of beta bursts shorter than 200 ms and more frequent switching on/off of the stimulator but had no behavioural effects. Both ADBS and CDBS improved motor performance to an equivalent extent compared to no DBS. Secondary analysis revealed that there were independent effects of a decrease in beta power and an increase in gamma power in predicting faster movement speed, while a decrease in beta event related desynchronization (ERD) predicted quicker movement initiation. CDBS suppressed both beta and gamma more than ADBS, whereas beta ERD was reduced to a similar level during CDBS and ADBS compared with no DBS, which together explained the achieved similar performance improvement in reaching movements during CDBS and ADBS. In addition, ADBS significantly improved tremor compared with no DBS but was not as effective as CDBS. These results suggest that STN beta-triggered ADBS is effective in improving motor performance during reaching movements in people with Parkinson's disease, and that shortening of the smoothing window does not result in any additional behavioural benefit. When developing ADBS systems for Parkinson's disease, it might not be necessary to track very fast beta dynamics; combining beta, gamma, and information from motor decoding might be more beneficial with additional biomarkers needed for optimal treatment of tremor.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Estimulação Encefálica Profunda/métodos , Tremor/terapia , Movimento/fisiologia , Núcleo Subtalâmico/fisiologia
12.
Nat Commun ; 14(1): 3672, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37339989

RESUMO

High-resolution imaging has revolutionized the study of single cells in their spatial context. However, summarizing the great diversity of complex cell shapes found in tissues and inferring associations with other single-cell data remains a challenge. Here, we present CAJAL, a general computational framework for the analysis and integration of single-cell morphological data. By building upon metric geometry, CAJAL infers cell morphology latent spaces where distances between points indicate the amount of physical deformation required to change the morphology of one cell into that of another. We show that cell morphology spaces facilitate the integration of single-cell morphological data across technologies and the inference of relations with other data, such as single-cell transcriptomic data. We demonstrate the utility of CAJAL with several morphological datasets of neurons and glia and identify genes associated with neuronal plasticity in C. elegans. Our approach provides an effective strategy for integrating cell morphology data into single-cell omics analyses.


Assuntos
Caenorhabditis elegans , Neurônios , Animais , Caenorhabditis elegans/genética , Perfilação da Expressão Gênica , Transcriptoma
13.
J Opt Soc Am A Opt Image Sci Vis ; 40(3): 573-582, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37133040

RESUMO

Wide-field image correction in systems that look through the atmosphere generally requires a tomographic reconstruction of the turbulence volume to compensate for anisoplanatism. The reconstruction is conditioned by estimating the turbulence volume as a profile of thin homogeneous layers. We present the signal to noise ratio (SNR) of a layer, which quantifies how difficult a single layer of homogeneous turbulence is to detect with wavefront slope measurements. The signal is the sum of wavefront tip and tilt variances at the signal layer, and the noise is the sum of wavefront tip and tilt auto-correlations given the aperture shape and projected aperture separations at all non-signal layers. An analytic expression for layer SNR is found for Kolmogorov and von Kármán turbulence models, then verified with a Monte Carlo simulation. We show that the Kolmogorov layer SNR is a function of only layer Fried length, the spatio-angular sampling of the system, and normalized aperture separation at the layer. In addition to these parameters, the von Kármán layer SNR also depends on aperture size, and layer inner and outer scales. Due to the infinite outer scale, layers of Kolmogorov turbulence tend to have lower SNR than von Kármán layers. We conclude that the layer SNR is a statistically valid performance metric to be used when designing, simulating, operating, and quantifying the performance of any system that measures properties of layers of turbulence in the atmosphere from slope data.

14.
Cortex ; 159: 286-298, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36645968

RESUMO

Though the lateral frontal cortex is broadly implicated in cognitive control, functional MRI (fMRI) studies suggest fine-grained distinctions within this region. To examine this question electrophysiologically, we placed electrodes on the lateral frontal cortex in patients undergoing awake craniotomy for tumor resection. Patients performed verbal tasks with a manipulation of attentional switching, a canonical control demand. Power in the high gamma range (70-250 Hz) distinguished electrodes based on their location within a high-resolution fMRI network parcellation of the frontal lobe. Electrodes within the canonical fronto-parietal control network showed increased power in the switching condition, a result absent in electrodes within default mode, language and somato-motor networks. High gamma results contrasted with spatially distributed power decreases in the beta range (12-30 Hz). These results confirm the importance of fine-scale functional distinctions within the human frontal lobe, and pave the way for increased precision of functional mapping in tumor surgeries.


Assuntos
Mapeamento Encefálico , Neoplasias , Humanos , Mapeamento Encefálico/métodos , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiologia , Vigília , Imageamento por Ressonância Magnética , Cognição/fisiologia
15.
Mov Disord ; 38(3): 423-434, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36562479

RESUMO

BACKGROUND: Subthalamic nucleus (STN) stimulation is an effective treatment for Parkinson's disease and induced local field potential (LFP) changes that have been linked with clinical improvement. STN stimulation has also been used in dystonia although the internal globus pallidus is the standard target where theta power has been suggested as a physiomarker for adaptive stimulation. OBJECTIVE: We aimed to explore if enhanced theta power was also present in STN and if stimulation-induced spectral changes that were previously reported for Parkinson's disease would occur in dystonia. METHODS: We recorded LFPs from 7 patients (12 hemispheres) with isolated craniocervical dystonia whose electrodes were placed such that inferior, middle, and superior contacts covered STN, zona incerta, and thalamus. RESULTS: We did not observe prominent theta power in STN at rest. STN stimulation induced similar spectral changes in dystonia as in Parkinson's disease, such as broadband power suppression, evoked resonant neural activity (ERNA), finely-tuned gamma oscillations, and an increase in aperiodic exponents in STN-LFPs. Both power suppression and ERNA localize to STN. Based on this, single-pulse STN stimulation elicits evoked neural activities with largest amplitudes in STN, which are relayed to the zona incerta and thalamus with changing characteristics as the distance from STN increases. CONCLUSIONS: Our results show that STN stimulation-induced spectral changes are a nondisease-specific response to high-frequency stimulation, which can serve as placement markers for STN. This broadens the scope of STN stimulation and makes it an option for other disorders with excessive oscillatory peaks in STN. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Estimulação Encefálica Profunda , Distonia , Distúrbios Distônicos , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Núcleo Subtalâmico/fisiologia , Distonia/terapia , Doença de Parkinson/terapia , Estimulação Encefálica Profunda/métodos , Globo Pálido , Distúrbios Distônicos/terapia
16.
Brain ; 146(3): 1200-1211, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256589

RESUMO

Unravelling the complex events driving grade-specific spatial distribution of brain tumour occurrence requires rich datasets from both healthy individuals and patients. Here, we combined open-access data from The Cancer Genome Atlas, the UK Biobank and the Allen Brain Human Atlas to disentangle how the different spatial occurrences of glioblastoma multiforme and low-grade gliomas are linked to brain network features and the normative transcriptional profiles of brain regions. From MRI of brain tumour patients, we first constructed a grade-related frequency map of the regional occurrence of low-grade gliomas and the more aggressive glioblastoma multiforme. Using associated mRNA transcription data, we derived a set of differential gene expressions from glioblastoma multiforme and low-grade gliomas tissues of the same patients. By combining the resulting values with normative gene expressions from post-mortem brain tissue, we constructed a grade-related expression map indicating which brain regions express genes dysregulated in aggressive gliomas. Additionally, we derived an expression map of genes previously associated with tumour subtypes in a genome-wide association study (tumour-related genes). There were significant associations between grade-related frequency, grade-related expression and tumour-related expression maps, as well as functional brain network features (specifically, nodal strength and participation coefficient) that are implicated in neurological and psychiatric disorders. These findings identify brain network dynamics and transcriptomic signatures as key factors in regional vulnerability for glioblastoma multiforme and low-grade glioma occurrence, placing primary brain tumours within a well established framework of neurological and psychiatric cortical alterations.


Assuntos
Neoplasias Encefálicas , Conectoma , Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Transcriptoma , Estudo de Associação Genômica Ampla , Glioma/genética , Neoplasias Encefálicas/metabolismo
17.
Br J Nutr ; 130(1): 83-92, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-36128619

RESUMO

Changes between diet quality and health-related quality of life (HR-QoL) over 12 years were examined in men and women, in 2844 adults (46 % males; mean age 47·3 (sd 9·7) years) from the Australian Diabetes, Obesity and Lifestyle study with data at baseline, 5 and 12 years. Dietary intake was assessed with a seventy-four-item FFQ. Diet quality was estimated with the Dietary Guideline Index, Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurological Delay Index (MIND) and Dietary Inflammatory Index. HR-QoL in terms of global, physical component summary (PCS) and mental component summary (MCS) was assessed with the Short-Form Health Survey-36. Fixed effects regression models adjusted for confounders were performed. Mean MCS increased from baseline (49·0, sd 9·3) to year 12 (50·7, sd 9·1), whereas mean PCS decreased from baseline (51·7, sd 7·4) to year 12 (49·5, sd 8·6). For the total sample, an improvement in MIND was associated with an improvement in global QoL (ß = 0·28, 95 % CI (0·007, 0·55)). In men, an improvement in MIND was associated with an improvement in global QoL (ß = 0·28, 95 % CI (0·0004, 0·55)). In women, improvement in MIND was associated with improvements in global QoL (ß = 0·62 95 % CI (0·38, 0·85)), MCS (ß = 0·75, 95 % CI (0·29, 1·22)) and PCS (ß = 0·75, 95 % CI (0·29, 1·22)). Positive changes in diet quality were associated with broad improvements in HR-QoL, and most benefits were observed in women when compared to men. These findings support the need for strategies to assist the population in consuming healthy dietary patterns to lead to improvements in HR-QoL.


Assuntos
Diabetes Mellitus , Qualidade de Vida , Masculino , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Austrália , Estilo de Vida , Dieta , Obesidade
18.
Stereotact Funct Neurosurg ; 100(4): 253-258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35820403

RESUMO

Magnetic resonance imaging (MRI) in patients with implanted deep brain stimulation (DBS) systems is subject to strict guidelines in order to ensure patient safety. Criteria include limits on the number of implanted leads. Here, we describe the case of a 29-year-old patient with generalized dystonia implanted with 4 DBS electrodes and 2 implantable pulse generators, who had an off-label spinal MRI without regard for manufacturer guidance yet suffered no adverse effects. This suggests that manufacturer guidelines might be overly restrictive with regards to limits on implanted DBS hardware. Further research in this area is needed to widen access to this fundamental imaging modality for patients with DBS.


Assuntos
Estimulação Encefálica Profunda , Distúrbios Distônicos , Adulto , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/métodos , Distúrbios Distônicos/etiologia , Eletrodos Implantados/efeitos adversos , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Uso Off-Label
19.
Proc Natl Acad Sci U S A ; 119(19): e2121037119, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35512092

RESUMO

Studies from a variety of species indicate that arginine­vasopressin (AVP) and its V1a receptor (Avpr1a) play a critical role in the regulation of a range of social behaviors by their actions in the social behavior neural network. To further investigate the role of AVPRs in social behavior, we performed CRISPR-Cas9­mediated editing at the Avpr1a gene via pronuclear microinjections in Syrian hamsters (Mesocricetus auratus), a species used extensively in behavioral neuroendocrinology because they produce a rich suite of social behaviors. Using this germ-line gene-editing approach, we generated a stable line of hamsters with a frame-shift mutation in the Avpr1a gene resulting in the null expression of functional Avpr1as. Avpr1a knockout (KO) hamsters exhibited a complete lack of Avpr1a-specific autoradiographic binding throughout the brain, behavioral insensitivity to centrally administered AVP, and no pressor response to a peripherally injected Avpr1a-specific agonist, thus confirming the absence of functional Avpr1as in the brain and periphery. Contradictory to expectations, Avpr1a KO hamsters exhibited substantially higher levels of conspecific social communication (i.e., odor-stimulated flank marking) than their wild-type (WT) littermates. Furthermore, sex differences in aggression were absent, as both male and female KOs exhibited more aggression toward same-sex conspecifics than did their WT littermates. Taken together, these data emphasize the importance of comparative studies employing gene-editing approaches and suggest the startling possibility that Avpr1a-specific modulation of the social behavior neural network may be more inhibitory than permissive.


Assuntos
Sistemas CRISPR-Cas , Receptores de Vasopressinas , Agressão/fisiologia , Animais , Arginina/metabolismo , Arginina Vasopressina/genética , Cricetinae , Mesocricetus , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo , Comportamento Social
20.
Acta Neurochir (Wien) ; 164(8): 2021-2034, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35230551

RESUMO

BACKGROUND: Gliomas are typically considered to cause relatively few neurological impairments. However, cognitive difficulties can arise, for example during treatment, with potential detrimental effects on quality of life. Accurate, reproducible, and accessible cognitive assessment is therefore vital in understanding the effects of both tumor and treatments. Our aim is to compare traditional neuropsychological assessment with an app-based cognitive screening tool in patients with glioma before and after surgical resection. Our hypotheses were that cognitive impairments would be apparent, even in a young and high functioning cohort, and that app-based cognitive screening would complement traditional neuropsychological assessment. METHODS: Seventeen patients with diffuse gliomas completed a traditional neuropsychological assessment and an app-based touchscreen tablet assessment pre- and post-operatively. The app assessment was also conducted at 3- and 12-month follow-up. Impairment rates, mean performance, and pre- and post-operative changes were compared using standardized Z-scores. RESULTS: Approximately 2-3 h of traditional assessment indicated an average of 2.88 cognitive impairments per patient, while the 30-min screen indicated 1.18. As might be expected, traditional assessment using multiple items across the difficulty range proved more sensitive than brief screening measures in areas such as memory and attention. However, the capacity of the screening app to capture reaction times enhanced its sensitivity, relative to traditional assessment, in the area of non-verbal function. Where there was overlap between the two assessments, for example digit span tasks, the results were broadly equivalent. CONCLUSIONS: Cognitive impairments were common in this sample and app-based screening complemented traditional neuropsychological assessment. Implications for clinical assessment and follow-up are discussed.


Assuntos
Neoplasias Encefálicas , Transtornos Cognitivos , Glioma , Aplicativos Móveis , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Cognição , Transtornos Cognitivos/etiologia , Glioma/complicações , Glioma/diagnóstico , Glioma/cirurgia , Humanos , Testes Neuropsicológicos , Qualidade de Vida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...