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1.
Nutrition ; 122: 112389, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38428220

RESUMO

PURPOSE: Nutrient timing is a concept that emphasizes the intentional ingestion of whole or fortified foods, and dietary supplements, to adequately fuel for, and recover from, acute and chronic exercise. The nutrition strategies used by powerlifters around training sessions have not, to our knowledge, been previously investigated. This study explored the self-reported periworkout (before, during, and after) nutrition practices of competitive powerlifters, including what, why, and information source that informed practice, with comparison to current sport nutrition guidelines. METHODS: Actively competing male (n = 240) and female (n = 65) powerlifters completed a cross-sectional online survey of self-reported periworkout nutrition practices in the pre-, intra-, and postexercise periods, fasted training, and supplementation. Data are presented as the number (n) and percentage (%) of all powerlifters practicing a given strategy followed by a % of responses reporting various practices or beliefs within this strategy. Categorical subgroups (sex, age, and weight class; and competitive caliber) were analyzed with a chi-square test or Fisher's exact test and denoted where significant (P ≤ 0.05). RESULTS: Most powerlifters reported paying specific attention to nutrition practices in the pre-exercise period (n = 261; 85.6%) by ingesting more carbohydrate (CHO) rich foods (n = 234; 89.6%) for the purpose of assisting in training performance (n = 222; 85.1%). Most powerlifters reported intraexercise nutrition strategies (n = 211; 69.2%), of which most included ingesting more CHO rich foods (n = 159; 74.5%) for the purpose of feeling less hungry and/or boosting energy levels during training (n = 129; 61.1%). Most powerlifters reported paying attention to postexercise nutrition (n = 244; 80%), by ingesting more protein rich foods (n = 182; 74.6%) for the purpose of recovering better for the whole day (n = 152; 62.3%) and enhancing the benefits of training (n = 149; 61.1%). Most powerlifters did not complete training sessions in the fasted state (n = 262; 85.9%). Most powerlifters reported paying attention to supplementation before training (n = 237; 77.7%), of which preworkout formulas (n = 137; 57.8%), energy drinks (n = 101; 42.6%), creatine (n = 88; 37.1%), and caffeine pills (n = 70; 29.5%) were most reported. Supplementation was used to assist in training performance (n = 197; 83.1%) and increase wakefulness/alertness (n = 183; 77.2%). Males reported more often than females that they informed multiple elements of their nutrition practices with the information they read or watched somewhere (P = 0.002-0.012). CONCLUSION: The periworkout nutrition practices used by competitive powerlifters followed current sport nutrition guidelines, by using CHO sources to fuel for training and ensuring the provision of protein postexercise. Competitive powerlifters may wish to exert caution with supplementation, as there is a risk of harm or inadvertent doping.


Assuntos
Treinamento Resistido , Humanos , Masculino , Feminino , Estudos Transversais , Exercício Físico , Suplementos Nutricionais , Estado Nutricional
2.
Front Physiol ; 14: 1054401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998987

RESUMO

Background: Radiofrequency catheter ablation (RFCA) therapy is the first-line treatment for atrial fibrillation (AF), the most common type of cardiac arrhythmia globally. However, the procedure currently has low success rates in dealing with persistent AF, with a reoccurrence rate of ∼50% post-ablation. Therefore, deep learning (DL) has increasingly been applied to improve RFCA treatment for AF. However, for a clinician to trust the prediction of a DL model, its decision process needs to be interpretable and have biomedical relevance. Aim: This study explores interpretability in DL prediction of successful RFCA therapy for AF and evaluates if pro-arrhythmogenic regions in the left atrium (LA) were used in its decision process. Methods: AF and its termination by RFCA have been simulated in MRI-derived 2D LA tissue models with segmented fibrotic regions (n = 187). Three ablation strategies were applied for each LA model: pulmonary vein isolation (PVI), fibrosis-based ablation (FIBRO) and a rotor-based ablation (ROTOR). The DL model was trained to predict the success of each RFCA strategy for each LA model. Three feature attribution (FA) map methods were then used to investigate interpretability of the DL model: GradCAM, Occlusions and LIME. Results: The developed DL model had an AUC (area under the receiver operating characteristic curve) of 0.78 ± 0.04 for predicting the success of the PVI strategy, 0.92 ± 0.02 for FIBRO and 0.77 ± 0.02 for ROTOR. GradCAM had the highest percentage of informative regions in the FA maps (62% for FIBRO and 71% for ROTOR) that coincided with the successful RFCA lesions known from the 2D LA simulations, but unseen by the DL model. Moreover, GradCAM had the smallest coincidence of informative regions of the FA maps with non-arrhythmogenic regions (25% for FIBRO and 27% for ROTOR). Conclusion: The most informative regions of the FA maps coincided with pro-arrhythmogenic regions, suggesting that the DL model leveraged structural features of MRI images to identify such regions and make its prediction. In the future, this technique could provide a clinician with a trustworthy decision support tool.

3.
J Int Assoc Provid AIDS Care ; 22: 23259582221144448, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594233

RESUMO

This paper highlights experiences and perceptions of older gay males living with Human Immunodeficiency Virus (HIV) in relation to age, sexual orientation, HIV status and how they perceive health. Participants were gay males aged 50 and over living in England, diagnosed with HIV for longer than 2 years. In total, 19 interviews were conducted between March 2020 and March 2021. Data were analysed using thematic analysis. Three major themes were generated: 1.) Health as holistic and as a balance; 2.) The impact of HIV on people's lives; 3.) The Intersectionality of stigma: a lifetime of discrimination. Participants highlighted the changing nature of the concept of health through their lifespan while the intersectionality of stigma in different contexts is examined considering the personal journey of living with HIV. The implications of health as a complex concept and intersectional stigma on the planning and delivering of care in this population are discussed.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , HIV , Homossexualidade Masculina , Envelhecimento , Pesquisa Qualitativa , Estigma Social , Inglaterra
4.
Europace ; 25(2): 469-477, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36369980

RESUMO

AIMS: Existing strategies that identify post-infarct ventricular tachycardia (VT) ablation target either employ invasive electrophysiological (EP) mapping or non-invasive modalities utilizing the electrocardiogram (ECG). Their success relies on localizing sites critical to the maintenance of the clinical arrhythmia, not always recorded on the 12-lead ECG. Targeting the clinical VT by utilizing electrograms (EGM) recordings stored in implanted devices may aid ablation planning, enhancing safety and speed and potentially reducing the need of VT induction. In this context, we aim to develop a non-invasive computational-deep learning (DL) platform to localize VT exit sites from surface ECGs and implanted device intracardiac EGMs. METHODS AND RESULTS: A library of ECGs and EGMs from simulated paced beats and representative post-infarct VTs was generated across five torso models. Traces were used to train DL algorithms to localize VT sites of earliest systolic activation; first tested on simulated data and then on a clinically induced VT to show applicability of our platform in clinical settings. Localization performance was estimated via localization errors (LEs) against known VT exit sites from simulations or clinical ablation targets. Surface ECGs successfully localized post-infarct VTs from simulated data with mean LE = 9.61 ± 2.61 mm across torsos. VT localization was successfully achieved from implanted device intracardiac EGMs with mean LE = 13.10 ± 2.36 mm. Finally, the clinically induced VT localization was in agreement with the clinical ablation volume. CONCLUSION: The proposed framework may be utilized for direct localization of post-infarct VTs from surface ECGs and/or implanted device EGMs, or in conjunction with efficient, patient-specific modelling, enhancing safety and speed of ablation planning.


Assuntos
Ablação por Cateter , Aprendizado Profundo , Taquicardia Ventricular , Humanos , Técnicas Eletrofisiológicas Cardíacas , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/cirurgia , Eletrocardiografia/métodos , Infarto/cirurgia
5.
J Microencapsul ; 40(1): 1-14, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36533609

RESUMO

The aim is to prepare, characterise, and evaluate the biological activities and key molecular interactions of L-ascorbic acid and phosphatidylcholine (PC-AA) complex vesicles. PC-AA complexes were prepared and characterised using DLS, TEM, FTIR, UV-Vis, in-vitro release, bioactivities, and cytotoxicity. The key interactions of the AA with the PC were studied with MD simulations. PC-AA complex provides improved stability towards the degradation of AA in aqueous solutions while also slowing its release profile. The PC-AA complexes with an optimal molar ratio of PC: AA = 2.5:1 was shown to have a hydrodynamic diameter of 368.67 ± 4.65 nm and an EE of 68.16 ± 0.23%. At low concentration, the PC-AA complexes have no toxicity towards human dermal fibroblast cells over 48 h. Importantly, MD suggests that AA only forms the PC-AA complex when in its neutral form which is the desired active form. PC-AA complex could be a potential active to use in medicinal and cosmeceutical applications.


Assuntos
Ácido Ascórbico , Lecitinas , Humanos , Ácido Ascórbico/farmacologia
6.
Chemosphere ; 310: 136873, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36252896

RESUMO

To address climate change concerns, and reduce the carbon footprint caused by fossil fuel use, it is likely that blend ratios of renewable biodiesel with commercial mineral diesel fuel will steadily increase, resulting in biodiesel use becoming more widespread. Exhaust toxicity of unblended biodiesels changes depending on feedstock type, however the effect of feedstock on blended fuels is less well known. The aim of this study was to assess the impact of biodiesel feedstock on exhaust toxicity of 20% blended biodiesel fuels (B20). Primary human airway epithelial cells were exposed to exhaust diluted 1/15 with air from an engine running on conventional ultra-low sulfur diesel (ULSD) or 20% blends of soy, canola, waste cooking oil (WCO), tallow, palm or cottonseed biodiesel in diesel. Physico-chemical exhaust properties were compared between fuels and the post-exposure effect of exhaust on cellular viability and media release was assessed 24 h later. Exhaust properties changed significantly between all fuels with cottonseed B20 being the most different to both ULSD and its respective unblended biodiesel. Exposure to palm B20 resulted in significantly decreased cellular viability (96.3 ± 1.7%; p < 0.01) whereas exposure to soy B20 generated the greatest number of changes in mediator release (including IL-6, IL-8 and TNF-α, p < 0.05) when compared to air exposed controls, with palm B20 and tallow B20 closely following. In contrast, canola B20 and WCO B20 were the least toxic with only mediators G-CSF and TNF-α being significantly increased. Therefore, exposure to palm B20, soy B20 and tallow B20 were found to be the most toxic and exposure to canola B20 and WCO B20 the least. The top three most toxic and the bottom three least toxic B20 fuels are consistent with their unblended counterparts, suggesting that feedstock type greatly impacts exhaust toxicity, even when biodiesel only comprises 20% of the fuel.


Assuntos
Biocombustíveis , Material Particulado , Humanos , Biocombustíveis/toxicidade , Biocombustíveis/análise , Material Particulado/análise , Fator de Necrose Tumoral alfa , Óleo de Sementes de Algodão , Emissões de Veículos/toxicidade , Emissões de Veículos/análise , Gasolina/toxicidade , Minerais
7.
Nat Commun ; 12(1): 6343, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732700

RESUMO

Peptide secondary metabolites are common in nature and have diverse pharmacologically-relevant functions, from antibiotics to cross-kingdom signaling. Here, we present a method to design large libraries of modified peptides in Escherichia coli and screen them in vivo to identify those that bind to a single target-of-interest. Constrained peptide scaffolds were produced using modified enzymes gleaned from microbial RiPP (ribosomally synthesized and post-translationally modified peptide) pathways and diversified to build large libraries. The binding of a RiPP to a protein target leads to the intein-catalyzed release of an RNA polymerase σ factor, which drives the expression of selectable markers. As a proof-of-concept, a selection was performed for binding to the SARS-CoV-2 Spike receptor binding domain. A 1625 Da constrained peptide (AMK-1057) was found that binds with similar affinity (990 ± 5 nM) as an ACE2-derived peptide. This demonstrates a generalizable method to identify constrained peptides that adhere to a single protein target, as a step towards "molecular glues" for therapeutics and diagnostics.


Assuntos
Antivirais/química , Antivirais/farmacologia , Peptídeos/química , Peptídeos/farmacologia , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Cinética , Modelos Moleculares , Peptídeos/genética , Ligação Proteica , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Tratamento Farmacológico da COVID-19
8.
Nat Commun ; 12(1): 3916, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168153

RESUMO

Integration of information across the senses is critical for perception and is a common property of neurons in the cerebral cortex, where it is thought to arise primarily from corticocortical connections. Much less is known about the role of subcortical circuits in shaping the multisensory properties of cortical neurons. We show that stimulation of the whiskers causes widespread suppression of sound-evoked activity in mouse primary auditory cortex (A1). This suppression depends on the primary somatosensory cortex (S1), and is implemented through a descending circuit that links S1, via the auditory midbrain, with thalamic neurons that project to A1. Furthermore, a direct pathway from S1 has a facilitatory effect on auditory responses in higher-order thalamic nuclei that project to other brain areas. Crossmodal corticofugal projections to the auditory midbrain and thalamus therefore play a pivotal role in integrating multisensory signals and in enabling communication between different sensory cortical areas.


Assuntos
Córtex Auditivo/fisiologia , Vias Neurais/fisiologia , Córtex Somatossensorial/fisiologia , Estimulação Acústica , Animais , Eletrofisiologia/métodos , Feminino , Neurônios GABAérgicos/fisiologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Interneurônios/fisiologia , Masculino , Mesencéfalo/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Optogenética , Células Receptoras Sensoriais/fisiologia , Córtex Somatossensorial/citologia , Tálamo/citologia , Tálamo/fisiologia
9.
Am J Physiol Renal Physiol ; 320(1): F133-F144, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33283643

RESUMO

The majority of patients with chronic kidney disease (CKD) receiving dialysis do not achieve target serum phosphorus concentrations, despite treatment with phosphate binders. Tenapanor is a nonbinder, sodium/hydrogen exchanger isoform 3 (NHE3) inhibitor that reduces paracellular intestinal phosphate absorption. This preclinical study evaluated the effect of tenapanor and varying doses of sevelamer carbonate on urinary phosphorus excretion, a direct reflection of intestinal phosphate absorption. We measured 24-h urinary phosphorus excretion in male rats assigned to groups dosed orally with vehicle or tenapanor (0.3 mg/kg/day) and provided a diet containing varying amounts of sevelamer [0-3% (wt/wt)]. We also evaluated the effect of the addition of tenapanor or vehicle on 24-h urinary phosphorus excretion to rats on a stable dose of sevelamer [1.5% (wt/wt)]. When administered together, tenapanor and sevelamer decreased urinary phosphorus excretion significantly more than either tenapanor or sevelamer alone across all sevelamer dose levels. The Bliss statistical model of independence indicated that the combination was synergistic. A stable sevelamer dose [1.5% (wt/wt)] reduced mean ± SE urinary phosphorus excretion by 42 ± 3% compared with vehicle; together, tenapanor and sevelamer reduced residual urinary phosphorus excretion by an additional 37 ± 6% (P < 0.05). Although both tenapanor and sevelamer reduce intestinal phosphate absorption individually, administration of tenapanor and sevelamer together results in more pronounced reductions in intestinal phosphate absorption than if either agent is administered alone. Further evaluation of combination tenapanor plus phosphate binder treatment in patients receiving dialysis with hyperphosphatemia is warranted.


Assuntos
Quelantes/farmacologia , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Isoquinolinas/farmacologia , Rim/efeitos dos fármacos , Fósforo/urina , Eliminação Renal/efeitos dos fármacos , Sevelamer/farmacologia , Trocador 3 de Sódio-Hidrogênio/antagonistas & inibidores , Sulfonamidas/farmacologia , Animais , Sinergismo Farmacológico , Humanos , Mucosa Intestinal/metabolismo , Rim/metabolismo , Masculino , Ratos Sprague-Dawley , Trocador 3 de Sódio-Hidrogênio/metabolismo , Fatores de Tempo
10.
Elife ; 92020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32420865

RESUMO

Primary cortical areas contain maps of sensory features, including sound frequency in primary auditory cortex (A1). Two-photon calcium imaging in mice has confirmed the presence of these global tonotopic maps, while uncovering an unexpected local variability in the stimulus preferences of individual neurons in A1 and other primary regions. Here we show that local heterogeneity of frequency preferences is not unique to rodents. Using two-photon calcium imaging in layers 2/3, we found that local variance in frequency preferences is equivalent in ferrets and mice. Neurons with multipeaked frequency tuning are less spatially organized than those tuned to a single frequency in both species. Furthermore, we show that microelectrode recordings may describe a smoother tonotopic arrangement due to a sampling bias towards neurons with simple frequency tuning. These results help explain previous inconsistencies in cortical topography across species and recording techniques.


Assuntos
Estimulação Acústica/métodos , Córtex Auditivo/fisiologia , Vias Auditivas/fisiologia , Percepção Auditiva/fisiologia , Mapeamento Encefálico/métodos , Animais , Fenômenos Eletrofisiológicos/fisiologia , Feminino , Furões , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia
11.
Nat Commun ; 11(1): 324, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949136

RESUMO

Neural adaptation enables sensory information to be represented optimally in the brain despite large fluctuations over time in the statistics of the environment. Auditory contrast gain control represents an important example, which is thought to arise primarily from cortical processing. Here we show that neurons in the auditory thalamus and midbrain of mice show robust contrast gain control, and that this is implemented independently of cortical activity. Although neurons at each level exhibit contrast gain control to similar degrees, adaptation time constants become longer at later stages of the processing hierarchy, resulting in progressively more stable representations. We also show that auditory discrimination thresholds in human listeners compensate for changes in contrast, and that the strength of this perceptual adaptation can be predicted from physiological measurements. Contrast adaptation is therefore a robust property of both the subcortical and cortical auditory system and accounts for the short-term adaptability of perceptual judgments.


Assuntos
Córtex Auditivo/fisiologia , Vias Auditivas/fisiologia , Percepção Auditiva/fisiologia , Mesencéfalo/fisiologia , Neurônios/fisiologia , Tálamo/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Limiar Auditivo/fisiologia , Discriminação Psicológica , Eletrofisiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Modelos Neurológicos , Ruído , Optogenética , Espectrografia do Som
12.
Acta Neuropathol ; 137(6): 879-899, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30739198

RESUMO

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole-genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (p value = 4.82e - 08, OR = 2.12), and two known loci: UNC13A, led by rs1297319 (p value = 1.27e - 08, OR = 1.50) and HLA-DQA2 led by rs17219281 (p value = 3.22e - 08, OR = 1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole-genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n ≥ 3) as compared to controls (n = 0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g., DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis.


Assuntos
Proteínas do Tecido Nervoso/genética , Proteinopatias TDP-43/genética , Idoso , Expansão das Repetições de DNA , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Feminino , Lobo Frontal/metabolismo , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/imunologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos HLA-DQ/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/fisiologia , Canais de Potássio/genética , Progranulinas/genética , Progranulinas/fisiologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas/genética , Proteínas/fisiologia , RNA Mensageiro/biossíntese , Fatores de Risco , Análise de Sequência de RNA , Sociedades Científicas , Proteinopatias TDP-43/imunologia , População Branca/genética
13.
Eur J Neurosci ; 49(8): 990-1004, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29804304

RESUMO

Ray Guillery was a neuroscientist known primarily for his ground-breaking studies on the development of the visual pathways and subsequently on the nature of thalamocortical processing loops. The legacy of his work, however, extends well beyond the visual system. Thanks to Ray Guillery's pioneering anatomical studies, the ferret has become a widely used animal model for investigating the development and plasticity of sensory processing. This includes our own work on the auditory system, where experiments in ferrets have revealed the role of sensory experience during development in shaping the neural circuits responsible for sound localization, as well as the capacity of the mature brain to adapt to changes in inputs resulting from hearing loss. Our research has also built on Ray Guillery's ideas about the possible functions of the massive descending projections that link sensory areas of the cerebral cortex to the thalamus and other subcortical targets, by demonstrating a role for corticothalamic feedback in the perception of complex sounds and for corticollicular projection neurons in learning to accommodate altered auditory spatial cues. Finally, his insights into the organization and functions of transthalamic corticocortical connections have inspired a raft of research, including by our own laboratory, which has attempted to identify how information flows through the thalamus.


Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Plasticidade Neuronal , Tálamo/fisiologia , Animais , Córtex Auditivo/crescimento & desenvolvimento , Vias Auditivas/crescimento & desenvolvimento , Vias Auditivas/fisiologia , Furões , História do Século XX , História do Século XXI , Neurociências/história , Localização de Som/fisiologia , Tálamo/crescimento & desenvolvimento
14.
Physiother Res Int ; 23(4): e1738, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30126016

RESUMO

BACKGROUND AND PURPOSE: A review to investigate whether there are effective workplace interventions that manage chronic musculoskeletal disorders. METHODS: The literature search included published articles between 2008 and 2017. The databases used in this search were MEDLINE, Scopus, CINAHL, AMED, PsycINFO, Academic Search Complete, Cochrane, and PEDro. A limited search on websites for relevant grey literature was also conducted. RESULTS: The review included 12 studies that investigated effectiveness of a specific strength exercise programme or interventions provided by health professionals at the workplace when compared with controls or interventions not at the workplace. Seven studies were classified as high quality (>85% of criteria met) and five studies were classified as acceptable. Studies were heterogeneous preventing a meta-analysis. No intervention was clearly superior to another. DISCUSSION: There was some consistency in the results of the selected studies, suggesting that workplace interventions such as high-intensity strength exercises and/or integrated health care can decrease pain and symptoms for employees who experience long-term musculoskeletal disorders. However, the current research is limited.


Assuntos
Gerenciamento Clínico , Terapia por Exercício , Doenças Musculoesqueléticas/terapia , Local de Trabalho , Ergonomia , Humanos , Saúde Ocupacional , Resultado do Tratamento
15.
Cereb Cortex ; 28(1): 350-369, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29136122

RESUMO

Despite decades of microelectrode recordings, fundamental questions remain about how auditory cortex represents sound-source location. Here, we used in vivo 2-photon calcium imaging to measure the sensitivity of layer II/III neurons in mouse primary auditory cortex (A1) to interaural level differences (ILDs), the principal spatial cue in this species. Although most ILD-sensitive neurons preferred ILDs favoring the contralateral ear, neurons with either midline or ipsilateral preferences were also present. An opponent-channel decoder accurately classified ILDs using the difference in responses between populations of neurons that preferred contralateral-ear-greater and ipsilateral-ear-greater stimuli. We also examined the spatial organization of binaural tuning properties across the imaged neurons with unprecedented resolution. Neurons driven exclusively by contralateral ear stimuli or by binaural stimulation occasionally formed local clusters, but their binaural categories and ILD preferences were not spatially organized on a more global scale. In contrast, the sound frequency preferences of most neurons within local cortical regions fell within a restricted frequency range, and a tonotopic gradient was observed across the cortical surface of individual mice. These results indicate that the representation of ILDs in mouse A1 is comparable to that of most other mammalian species, and appears to lack systematic or consistent spatial order.


Assuntos
Córtex Auditivo/metabolismo , Cálcio/metabolismo , Neurônios/metabolismo , Localização de Som/fisiologia , Estimulação Acústica/métodos , Potenciais de Ação/fisiologia , Animais , Vias Auditivas/metabolismo , Sinalização do Cálcio/fisiologia , Orelha/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Processamento de Sinais Assistido por Computador , Imagens com Corantes Sensíveis à Voltagem
16.
Eur J Pharmacol ; 815: 219-232, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28899697

RESUMO

Degradation of podocyte structural integrity and function are hallmarks of proteinuric chronic kidney disease. In vivo, injury of podocytes manifests itself in the form of disruption of foot process morphology and associated cytoskeletal architecture, de-differentiation, and loss of adhesion to the glomerular basement membrane. Given the critical role played by this highly specialized cell type in maintaining glomerular filtration, there is a need for improved physiologically relevant cellular models that enable detection of disease-relevant indicators of podocyte perturbation. We have addressed this need by evaluating a subclone of conditionally immortalized human podocytes through quantitative benchmarking against freshly isolated primary human podocytes. Benchmarking was performed by measuring key phenotypic parameters, expression of podocyte specific proteins and multiparametric responses to stressors that model different aspects of podocyte perturbation. We subsequently employed the subcloned cells to profile the protective activity of structurally distinct adenosine kinase inhibitors. Our results support the translatability of our cellular model and set the stage for broader screening of renoprotective compounds with a view to eventually treat proteinuric kidney disease.


Assuntos
Citoproteção/efeitos dos fármacos , Podócitos/efeitos dos fármacos , Insuficiência Renal Crônica/patologia , Avaliação Pré-Clínica de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fenótipo
17.
Elife ; 62017 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-28891466

RESUMO

Topographic representation of the receptor surface is a fundamental feature of sensory cortical organization. This is imparted by the thalamus, which relays information from the periphery to the cortex. To better understand the rules governing thalamocortical connectivity and the origin of cortical maps, we used in vivo two-photon calcium imaging to characterize the properties of thalamic axons innervating different layers of mouse auditory cortex. Although tonotopically organized at a global level, we found that the frequency selectivity of individual thalamocortical axons is surprisingly heterogeneous, even in layers 3b/4 of the primary cortical areas, where the thalamic input is dominated by the lemniscal projection. We also show that thalamocortical input to layer 1 includes collaterals from axons innervating layers 3b/4 and is largely in register with the main input targeting those layers. Such locally varied thalamocortical projections may be useful in enabling rapid contextual modulation of cortical frequency representations.


Assuntos
Córtex Auditivo/anatomia & histologia , Vias Neurais/anatomia & histologia , Tálamo/anatomia & histologia , Animais , Feminino , Camundongos Endogâmicos C57BL , Neuroimagem
18.
J Neurosci ; 37(25): 6149-6161, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28559384

RESUMO

Feedback signals from the primary auditory cortex (A1) can shape the receptive field properties of neurons in the ventral division of the medial geniculate body (MGBv). However, the behavioral significance of corticothalamic modulation is unknown. The aim of this study was to elucidate the role of this descending pathway in the perception of complex sounds. We tested the ability of adult female ferrets to detect the presence of a mistuned harmonic in a complex tone using a positive conditioned go/no-go behavioral paradigm before and after the input from layer VI in A1 to MGBv was bilaterally and selectively eliminated using chromophore-targeted laser photolysis. MGBv neurons were identified by their short latencies and sharp tuning curves. They responded robustly to harmonic complex tones and exhibited an increase in firing rate and temporal pattern changes when one frequency component in the complex tone was mistuned. Injections of fluorescent microbeads conjugated with a light-sensitive chromophore were made in MGBv, and, following retrograde transport to the cortical cell bodies, apoptosis was induced by infrared laser illumination of A1. This resulted in a selective loss of ∼60% of layer VI A1-MGBv neurons. After the lesion, mistuning detection was impaired, as indicated by decreased d' values, a shift of the psychometric curves toward higher mistuning values, and increased thresholds, whereas discrimination performance was unaffected when level cues were also available. Our results suggest that A1-MGBv corticothalamic feedback contributes to the detection of harmonicity, one of the most important grouping cues in the perception of complex sounds.SIGNIFICANCE STATEMENT Perception of a complex auditory scene is based on the ability of the brain to group those sound components that belong to the same source and to segregate them from those belonging to different sources. Because two people talking simultaneously may differ in their voice pitch, perceiving the harmonic structure of sounds is very important for auditory scene analysis. Here we demonstrate mistuning sensitivity in the thalamus and that feedback from the primary auditory cortex is required for the normal ability of ferrets to detect a mistuned harmonic within a complex sound. These results provide novel insight into the function of descending sensory pathways in the brain and suggest that this corticothalamic circuit plays an important role in scene analysis.


Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Retroalimentação Fisiológica/fisiologia , Furões/fisiologia , Tálamo/fisiologia , Estimulação Acústica , Animais , Córtex Auditivo/citologia , Córtex Auditivo/diagnóstico por imagem , Limiar Auditivo/fisiologia , Comportamento Animal/fisiologia , Sinais (Psicologia) , Discriminação Psicológica/fisiologia , Feminino , Corpos Geniculados/fisiologia , Som , Tálamo/citologia , Tálamo/diagnóstico por imagem
19.
J Acoust Soc Am ; 141(4): 2591, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28464637

RESUMO

Old, hearing-impaired listeners generally benefit little from lateral separation of multiple talkers when listening to one of them. This study aimed to determine how spatial release from masking (SRM) in such listeners is affected when the interaural time differences (ITDs) in the temporal fine structure (TFS) are manipulated by tone-vocoding (TVC) at the ears by a master hearing aid system. Word recall was compared, with and without TVC, when target and masker sentences from a closed set were played simultaneously from the front loudspeaker (co-located) and when the maskers were played 45° to the left and right of the listener (separated). For 20 hearing-impaired listeners aged 64 to 86, SRM was 3.7 dB smaller with TVC than without TVC. This difference in SRM correlated with mean audiometric thresholds below 1.5 kHz, even when monaural TFS sensitivity (discrimination of frequency-shifts in identically filtered complexes) was partialed out, suggesting that low-frequency audiometric thresholds may be a good indicator of candidacy for hearing aids that preserve ITDs. The TVC difference in SRM was not correlated with age, pure-tone ITD thresholds, nor fundamental frequency difference limens, and only with monaural TFS sensitivity before control for low-frequency audiometric thresholds.


Assuntos
Envelhecimento/psicologia , Correção de Deficiência Auditiva/instrumentação , Sinais (Psicologia) , Auxiliares de Audição , Perda Auditiva Bilateral/reabilitação , Perda Auditiva Neurossensorial/reabilitação , Mascaramento Perceptivo , Pessoas com Deficiência Auditiva/reabilitação , Localização de Som , Percepção da Fala , Estimulação Acústica , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros , Audiometria da Fala , Limiar Auditivo , Feminino , Audição , Perda Auditiva Bilateral/diagnóstico , Perda Auditiva Bilateral/fisiopatologia , Perda Auditiva Bilateral/psicologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Neurossensorial/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Pessoas com Deficiência Auditiva/psicologia , Discriminação da Altura Tonal , Psicoacústica , Processamento de Sinais Assistido por Computador
20.
J Acoust Soc Am ; 139(6): EL246, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27369180

RESUMO

The harmonic structure of sounds is an important grouping cue in auditory scene analysis. The ability of ferrets to detect mistuned harmonics was measured using a go/no-go task paradigm. Psychometric functions plotting sensitivity as a function of degree of mistuning were used to evaluate behavioral performance using signal detection theory. The mean (± standard error of the mean) threshold for mistuning detection was 0.8 ± 0.1 Hz, with sensitivity indices and reaction times depending on the degree of mistuning. These data provide a basis for investigation of the neural basis for the perception of complex sounds in ferrets, an increasingly used animal model in auditory research.


Assuntos
Percepção Auditiva , Comportamento Animal , Sinais (Psicologia) , Furões/psicologia , Atividade Motora , Detecção de Sinal Psicológico , Estimulação Acústica , Animais , Vias Auditivas/fisiologia , Feminino , Furões/fisiologia , Psicoacústica , Tempo de Reação , Fatores de Tempo
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