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1.
PLoS Comput Biol ; 20(4): e1011516, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38626219

RESUMO

When facing an unfamiliar environment, animals need to explore to gain new knowledge about which actions provide reward, but also put the newly acquired knowledge to use as quickly as possible. Optimal reinforcement learning strategies should therefore assess the uncertainties of these action-reward associations and utilise them to inform decision making. We propose a novel model whereby direct and indirect striatal pathways act together to estimate both the mean and variance of reward distributions, and mesolimbic dopaminergic neurons provide transient novelty signals, facilitating effective uncertainty-driven exploration. We utilised electrophysiological recording data to verify our model of the basal ganglia, and we fitted exploration strategies derived from the neural model to data from behavioural experiments. We also compared the performance of directed exploration strategies inspired by our basal ganglia model with other exploration algorithms including classic variants of upper confidence bound (UCB) strategy in simulation. The exploration strategies inspired by the basal ganglia model can achieve overall superior performance in simulation, and we found qualitatively similar results in fitting model to behavioural data compared with the fitting of more idealised normative models with less implementation level detail. Overall, our results suggest that transient dopamine levels in the basal ganglia that encode novelty could contribute to an uncertainty representation which efficiently drives exploration in reinforcement learning.


Assuntos
Gânglios da Base , Dopamina , Modelos Neurológicos , Recompensa , Dopamina/metabolismo , Dopamina/fisiologia , Incerteza , Animais , Gânglios da Base/fisiologia , Comportamento Exploratório/fisiologia , Reforço Psicológico , Neurônios Dopaminérgicos/fisiologia , Biologia Computacional , Simulação por Computador , Masculino , Algoritmos , Tomada de Decisões/fisiologia , Comportamento Animal/fisiologia , Ratos
2.
Proc Natl Acad Sci U S A ; 119(40): e2200400119, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36161948

RESUMO

The ability of prefrontal cortex to quickly encode novel associations is crucial for adaptive behavior and central to working memory. Fast Hebbian changes in synaptic strength permit forming new associations, but neuronal signatures of this have been elusive. We devised a trialwise index of pattern similarity to look for rapid changes in population codes. Based on a computational model of working memory, we hypothesized that synaptic strength-and consequently, the tuning of neurons-could change if features of a subsequent stimulus need to be "reassociated," i.e., if bindings between features need to be broken to encode the new item. As a result, identical stimuli might elicit different neural responses. As predicted, neural response similarity dropped following rebinding, but only in prefrontal cortex. The history-dependent changes were expressed on top of traditional, fixed selectivity and were not explainable by carryover of previous firing into the current trial or by neural adaptation.


Assuntos
Memória de Curto Prazo , Modelos Neurológicos , Córtex Pré-Frontal , Sinapses , Memória de Curto Prazo/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Sinapses/fisiologia
3.
Brain ; 146(6): 2502-2511, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36395092

RESUMO

Idiopathic rapid eye movement sleep behaviour disorder (iRBD) has now been established as an important marker of the prodromal stage of Parkinson's disease and related synucleinopathies. However, although dopamine transporter single photon emission computed tomography (SPECT) has been used to demonstrate the presence of nigro-striatal deficit in iRBD, quantifiable correlates of this are currently lacking. Sensitivity to rewarding stimuli is reduced in some people with Parkinson's disease, potentially contributing to aspects of the neuropsychiatric phenotype in these individuals. Furthermore, a role for dopaminergic degeneration is suggested by the fact that reward insensitivity can be improved by dopaminergic medications. Patients with iRBD present a unique opportunity to study the relationship between reward sensitivity and early dopaminergic deficit in the unmedicated state. Here, we investigate whether a non-invasive, objective measure of reward sensitivity might be a marker of dopaminergic status in prodromal Parkinson's disease by comparing with SPECT/CT measurement of dopaminergic loss in the basal ganglia. Striatal dopaminergic deficits in iRBD are associated with progression to Parkinsonian disorders. Therefore, identification of a clinically measurable correlate of this degenerative process might provide a basis for the development of novel risk stratification tools. Using a recently developed incentivized eye-tracking task, we quantified reward sensitivity in a cohort of 41 patients with iRBD and compared this with data from 40 patients with Parkinson's disease and 41 healthy controls. Patients with iRBD also underwent neuroimaging with dopamine transporter SPECT/CT. Overall, reward sensitivity, indexed by pupillary response to monetary incentives, was reduced in iRBD cases compared with controls and was not significantly different to that in patients with Parkinson's disease. However, in iRBD patients with normal dopamine transporter SPECT/CT imaging, reward sensitivity was not significantly different from healthy controls. Across all iRBD cases, a positive association was observed between reward sensitivity and dopaminergic SPECT/CT signal in the putamen. These findings demonstrate a direct relationship between dopaminergic deficit and reward sensitivity in patients with iRBD and suggest that measurement of pupillary responses could be of value in models of risk stratification and disease progression in these individuals.


Assuntos
Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina , Dopamina , Recompensa
4.
Brain ; 145(5): 1610-1623, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35348621

RESUMO

The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role of the claustrum remains unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications. Claustral lesions are associated with an array of signs and symptoms, including changes in cognitive, perceptual and motor abilities; electrical activity; mental state; and sleep. The wide range of symptoms observed following claustral lesions do not provide compelling evidence to support prominent current theories of claustrum function such as multisensory integration or salience computation. Conversely, the lesions studies support the hypothesis that the claustrum regulates cortical excitability. We argue that the claustrum is connected to, or part of, multiple brain networks that perform both fundamental and higher cognitive functions. As a multifunctional node in numerous networks, this may explain the manifold effects of claustrum damage on brain and behaviour.


Assuntos
Claustrum , Animais , Gânglios da Base , Humanos , Dor , Percepção , Sono
5.
J Cogn Neurosci ; 34(9): 1681-1701, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704549

RESUMO

Attention can be allocated in working memory (WM) to select and privilege relevant content. It is unclear whether attention selects individual features or whole objects in WM. Here, we used behavioral measures, eye-tracking, and EEG to test the hypothesis that attention spreads between an object's features in WM. Twenty-six participants completed a WM task that asked them to recall the angle of one of two oriented, colored bars after a delay while EEG and eye-tracking data were collected. During the delay, an orthogonal "incidental task" cued the color of one item for a match/mismatch judgment. On congruent trials (50%), the cued item was probed for subsequent orientation recall; on incongruent trials (50%), the other memory item was probed. As predicted, selecting the color of an object in WM brought other features of the cued object into an attended state as revealed by EEG decoding, oscillatory α-power, gaze bias, and improved orientation recall performance. Together, the results show that attentional selection spreads between an object's features in WM, consistent with object-based attentional selection. Analyses of neural processing at recall revealed that the selected object was automatically compared with the probe, whether it was the target for recall or not. This provides a potential mechanism for the observed benefits of nonpredictive cueing in WM, where a selected item is prioritized for subsequent decision-making.


Assuntos
Atenção , Memória de Curto Prazo , Sinais (Psicologia) , Humanos , Rememoração Mental
6.
Clin Infect Dis ; 75(5): 849-856, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34950944

RESUMO

BACKGROUND: Household contact tracing for tuberculosis (TB) may facilitate diagnosis and access to TB preventive treatment (TPT). We investigated whether household contact tracing and intensive TB/human immunodeficiency virus (HIV) screening would improve TB-free survival. METHODS: Household contacts of index TB patients in 2 South African provinces were randomized to home tracing and intensive HIV/TB screening or standard of care (SOC; clinic referral letters). The primary outcome was incident TB or death at 15 months. Secondary outcomes included tuberculin skin test (TST) positivity in children ≤14 years and undiagnosed HIV. RESULTS: From December 2016 through March 2019, 1032 index patients (4459 contacts) and 1030 (4129 contacts) were randomized to the intervention and SOC arms. Of intervention arm contacts, 3.2% (69 of 2166) had prevalent microbiologically confirmed TB. At 15 months, the cumulative incidence of TB or death did not differ between the intensive screening (93 of 3230, 2.9%) and SOC (80 of 2600, 3.1%) arms (hazard ratio, 0.90; 95% confidence interval [CI], .66-1.24). TST positivity was higher in the intensive screening arm (38 of 845, 4.5%) compared with the SOC arm (15 of 800, 1.9%; odds ratio, 2.25; 95% CI, 1.07-4.72). Undiagnosed HIV was similar between arms (41 of 3185, 1.3% vs 32 of 2543, 1.3%; odds ratio, 1.02; 95% CI, .64-1.64). CONCLUSIONS: Household contact tracing with intensive screening and referral did not reduce incident TB or death. Providing referral letters to household contacts of index patients is an alternative strategy to home visits. CLINICAL TRIALS REGISTRATION: ISRCTN16006202.


Assuntos
Infecções por HIV , Tuberculose , Criança , Busca de Comunicante , HIV , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , África do Sul/epidemiologia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
7.
Clin Infect Dis ; 74(Suppl_1): S5-S13, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34725706

RESUMO

BACKGROUND: Invasive group B Streptococcus (iGBS) sepsis and meningitis are important causes of child mortality, but studies on neurodevelopmental impairment (NDI) after iGBS are limited. Using Griffiths Mental Development Scales-Extended Revised (GMDS-ER), we described NDI in iGBS survivors and non-iGBS children from South Africa, as part of a 5-country study. METHODS: We identified children aged 5-8 years with a history of iGBS and children with no history of iGBS between October 2019 and January 2021. Children were matched on sex, and birth data (month, year) (matched cohort study). Moderate or Severe NDI was the primary outcome as a composite of GMDS-ER motor, GMDS-ER cognition, hearing, and vision. Secondary outcomes included mild NDI, any emotional-behavioral problems, and GMDS-ER developmental quotients (DQ) calculated by dividing the age equivalent GMDS-ER score by the chronological age. RESULTS: In total, 160 children (iGBS survivors, 43; non-iGBS, 117) were assessed. Among iGBS survivors 13 (30.2%) had meningitis, and 30 (69.8%) had sepsis. Six (13.9%) iGBS survivors, and 5 (4.3%) non-iGBS children had moderate or severe NDI. Children who survived iGBS were 5.56 (95% confidence interval [CI]: 1.07-28.93; P = .041) times more likely to have moderate or severe NDI at 5-8 years than non-iGBS children. Compared to the non-iGBS children, iGBS meningitis survivors had a significantly lower global median DQ (P < .05), as well as a lower median DQ for the language GMDS-ER subscale and performance GMDS-ER subscale (P < .05). CONCLUSIONS: Children surviving iGBS, particularly meningitis, are more likely to have NDI at 5-8 years compared to non-iGBS children. Further research is required to improve detection and care for at-risk newborns.


Assuntos
Deficiências do Desenvolvimento , Meningites Bacterianas , Criança , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/epidemiologia , Humanos , Recém-Nascido , Meningites Bacterianas/complicações , Meningites Bacterianas/epidemiologia , Fatores de Risco , Streptococcus agalactiae , Sobreviventes
8.
Cogn Psychol ; 135: 101472, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35364511

RESUMO

Motivation can improve performance when the potential rewards outweigh the cost of effort expended. In working memory (WM), people can prioritise rewarded items at the expense of unrewarded items, suggesting a fixed memory capacity. But can capacity itself change with motivation? Across four experiments (N = 30-34) we demonstrate motivational improvements in WM even when all items were rewarded. However, this was not due to better memory precision, but rather better selection of the probed item within memory. Motivational improvements operated independently of encoding, maintenance, or attention shifts between items in memory. Moreover, motivation slowed responses. This contrasted with the benefits of rewarding items unequally, which allowed prioritisation of one item over another. We conclude that motivation can improve memory recall, not via precision or capacity, but via speed-accuracy trade-offs when selecting the item to retrieve.


Assuntos
Memória de Curto Prazo , Motivação , Atenção , Humanos , Memória de Curto Prazo/fisiologia , Rememoração Mental , Recompensa
9.
Exp Brain Res ; 240(12): 3351-3360, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36350356

RESUMO

Dopamine is crucially involved in decision-making and overstimulation within dopaminergic pathways can lead to impulsive behaviour, including a desire to take risks and reduced deliberation before acting. These behavioural changes are side effects of treatment with dopaminergic drugs in Parkinson disease, but their likelihood of occurrence is difficult to predict and may be influenced by the individual's baseline endogenous dopamine state, and indeed correlate with sensation-seeking personality traits. We here collected data on a standard gambling task in healthy volunteers given either placebo, 2.5 mg of the dopamine antagonist haloperidol or 100/25 mg of the dopamine precursor levodopa in a within-subject design. We found an increase in risky choices on levodopa. Choices were, however, made faster on haloperidol with no effect of levodopa on deliberation time. Shortened deliberation times on haloperidol occurred in low sensation-seekers only, suggesting a correlation between sensation-seeking personality trait and baseline dopamine levels. We hypothesise that levodopa increases risk-taking behaviour via overstimulation at both D1 and D2 receptor level, while a single low dose of haloperidol, as previously reported (Frank and O'Reilly 2006), may block D2 receptors pre- and post-synaptically and may paradoxically lead to higher striatal dopamine acting on remaining striatal D1 receptors, causing speedier decision without influencing risk tolerance. These effects could also fit with a recently proposed computational model of the basal ganglia (Moeller and Bogacz 2019; Moeller et al. 2021). Furthermore, our data suggest that the actual dopaminergic drug effect may be dependent on the individual's baseline dopamine state, which may influence our therapeutic decision as clinicians in the future.


Assuntos
Dopamina , Haloperidol , Humanos , Dopamina/farmacologia , Haloperidol/farmacologia , Levodopa/efeitos adversos , Tomada de Decisões/fisiologia , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Dopaminérgicos/farmacologia
10.
J Phys Chem A ; 126(20): 3135-3144, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35580328

RESUMO

Neutral lanthanum clusters are studied by photoionization time-of-flight mass spectroscopy, laser threshold photoionization spectroscopy, and density functional theory (DFT). Mass abundance spectra (MS) registered at multiple photoionization wavelengths in the range of 195-230 nm by single photon ionization reveal the production of all sizes, Lan (n ≥ 50), in good abundance, nullifying previously predicted low abundances for certain sizes in the 3-14 size range. Also, the MS do not reveal the extraordinary stability of any specific size, as one would expect, from previous theoretical predictions of 7- and 13-atom clusters as magic. Ionization energies (IEs) are measured for Lan (n = 2-14) clusters. DFT has been used to determine the stable geometric isomers for 2- to 10-atom clusters and to calculate their IEs. The theoretical IEs of 2-7 atom clusters are in decent agreement with their experimental values; however, the theoretical IEs are somewhat lower by ∼0.4 eV for n ≥ 8 than their experimental IEs.

11.
Proc Natl Acad Sci U S A ; 116(45): 22802-22810, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31636213

RESUMO

Studies of selective attention during perception have revealed modulation of the pupillary response according to the brightness of task-relevant (attended) vs. -irrelevant (unattended) stimuli within a visual display. As a strong test of top-down modulation of the pupil response by selective attention, we asked whether changes in pupil diameter follow internal shifts of attention to memoranda of visual stimuli of different brightness maintained in working memory, in the absence of any visual stimulation. Across 3 studies, we reveal dilation of the pupil when participants orient attention to the memorandum of a dark grating relative to that of a bright grating. The effect occurs even when the attention-orienting cue is independent of stimulus brightness, and even when stimulus brightness is merely incidental and not required for the working-memory task of judging stimulus orientation. Furthermore, relative dilation and constriction of the pupil occurred dynamically and followed the changing temporal expectation that 1 or the other stimulus would be probed across the retention delay. The results provide surprising and consistent evidence that pupil responses are under top-down control by cognitive factors, even when there is no direct adaptive gain for such modulation, since no visual stimuli were presented or anticipated. The results also strengthen the view of sensory recruitment during working memory, suggesting even activation of sensory receptors. The thought-provoking corollary to our findings is that the pupils provide a reliable measure of what is in the focus of mind, thus giving a different meaning to old proverbs about the eyes being a window to the mind.


Assuntos
Memória de Curto Prazo , Pupila/fisiologia , Visão Ocular/fisiologia , Atenção/fisiologia , Humanos
12.
J Neurosci ; 40(18): 3604-3620, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32234779

RESUMO

Reward has a remarkable ability to invigorate motor behavior, enabling individuals to select and execute actions with greater precision and speed. However, if reward is to be exploited in applied settings, such as rehabilitation, a thorough understanding of its underlying mechanisms is required. In a series of experiments, we first demonstrate that reward simultaneously improves the selection and execution components of a reaching movement. Specifically, reward promoted the selection of the correct action in the presence of distractors, while also improving execution through increased speed and maintenance of accuracy. These results led to a shift in the speed-accuracy functions for both selection and execution. In addition, punishment had a similar impact on action selection and execution, although it enhanced execution performance across all trials within a block, that is, its impact was noncontingent to trial value. Although the reward-driven enhancement of movement execution has been proposed to occur through enhanced feedback control, an untested possibility is that it is also driven by increased arm stiffness, an energy-consuming process that enhances limb stability. Computational analysis revealed that reward led to both an increase in feedback correction in the middle of the movement and a reduction in motor noise near the target. In line with our hypothesis, we provide novel evidence that this noise reduction is driven by a reward-dependent increase in arm stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate motor performance without compromising accuracy.SIGNIFICANCE STATEMENT While reward is well-known for enhancing motor performance, how the nervous system generates these improvements is unclear. Despite recent work indicating that reward leads to enhanced feedback control, an untested possibility is that it also increases arm stiffness. We demonstrate that reward simultaneously improves the selection and execution components of a reaching movement. Furthermore, we show that punishment has a similar positive impact on performance. Importantly, by combining computational and biomechanical approaches, we show that reward leads to both improved feedback correction and an increase in stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate performance without compromising accuracy. This work suggests that stiffness control plays a vital, and underappreciated, role in the reward-based imporvemenets in motor control.


Assuntos
Movimento/fisiologia , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Punição/psicologia , Recompensa , Adolescente , Adulto , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Adulto Jovem
13.
Cogn Affect Behav Neurosci ; 21(6): 1196-1206, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34652602

RESUMO

Human decisions can be reflexive or planned, being governed respectively by model-free and model-based learning systems. These two systems might differ in their responsiveness to our needs. Hunger drives us to specifically seek food rewards, but here we ask whether it might have more general effects on these two decision systems. On one hand, the model-based system is often considered flexible and context-sensitive, and might therefore be modulated by metabolic needs. On the other hand, the model-free system's primitive reinforcement mechanisms may have closer ties to biological drives. Here, we tested participants on a well-established two-stage sequential decision-making task that dissociates the contribution of model-based and model-free control. Hunger enhanced overall performance by increasing model-free control, without affecting model-based control. These results demonstrate a generalized effect of hunger on decision-making that enhances reliance on primitive reinforcement learning, which in some situations translates into adaptive benefits.


Assuntos
Tomada de Decisões , Fome , Humanos , Aprendizagem , Reforço Psicológico , Recompensa
14.
Molecules ; 26(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209338

RESUMO

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine, etc. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. Moreover, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidence of antioxidant effects supports the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. One study suggests that daily intake of 100 mg of flavonoids through the diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological, and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/therapeutic molecules.


Assuntos
Antioxidantes , Cardiotônicos , Doenças Cardiovasculares , Flavonoides , Frutas/química , Verduras/química , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Disponibilidade Biológica , Cardiotônicos/química , Cardiotônicos/farmacocinética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/prevenção & controle , Flavonoides/química , Flavonoides/farmacocinética , Flavonoides/uso terapêutico , Humanos
15.
Br J Sociol ; 72(1): 8-25, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33764513

RESUMO

Capital and Ideology represents a significant further statement from Thomas Piketty. The arguments made by the "New Piketty" are largely compatible with those of his previous Capital in the Twenty-First Century, but reflect broadening of scope and deepening of causal analysis, most markedly through the adoption of a world historical perspective. The result is a fuller offering for understanding inequality's pattern in the world, why it exists and how we can best respond to it. The book presents a wide range of arguments, which do not on first glance appear unified. This review essay distills these into six propositions, describes and evaluates each in turn, and identifies some threads that link them. In the process, it provides a critical assessment of Capital and Ideology.


Assuntos
Dissidências e Disputas , Política , Livros , Humanos , Fatores Socioeconômicos
16.
J Contemp Dent Pract ; 22(8): 882-889, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34753839

RESUMO

AIM AND OBJECTIVE: The study was conducted to evaluate the effects of N-acetylcysteine (NAC) on the propagation and differentiation of stem cells from human exfoliated deciduous teeth(SHED). MATERIALS AND METHODS: SHEDs were isolated by explant culture method and characterized for stem cell properties using flow cytometry method. MTT assay and Cell Counting Kit-8 (CCK-8) assay were used to examine the viability and proliferation of the SHEDs. The effects of NAC-induced osteo/odontoblastic differentiation of SHEDs were determined by functional staining for mineralization, and the gene expression of osteo/odontoblastic transcription factors and proteins was evaluated by real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR) analyses. Protein levels of collagen type 1 (COL1), dentin sialophosphoprotein (DSPP), and dentin matrix acidic phosphoprotein 1(DMP-1) were calculated by the Western blot method to assess the osteo/odontogenic differentiation. RESULTS: SHEDs presented mesenchymal stem cell (MSC)-like characteristics on flow cytometric analysis. The cell viability and metabolic activity of SHEDs were increased with an increase in the concentrations of NAC from 0.5 to 10 nM. However, the concentrations of NAC from 0.5 to 2.5 mM did not affect cell proliferation. NAC incorporated at a concentration of 2.5 mM showed higher mineralization and considerably increased gene expression levels of runt-related transcription factor 2 (RUNX2), COL1A1, DSPP, and DMP-1. It significantly increased the protein expression of odontoblast-related matrix proteins like COL1, DSPP, and DMP-1. CONCLUSION: NAC regulates the healthy propagation of dental stem cells in vitro. Its effects on the differentiation of dental pulp SHEDs remain unidentified. This study explores that NAC can encourage the mineralization of SHEDs and differentiate them into the odontoblastic lineage. CLINICAL SIGNIFICANCE: The results propose that NAC could have a significant pharmacological role in activating and enhancing odontogenic differentiation of dental stem cells and possibly a prospect in regenerative dentistry.


Assuntos
Acetilcisteína , Polpa Dentária , Acetilcisteína/farmacologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Humanos , Odontoblastos , Células-Tronco , Dente Decíduo
17.
Clin Infect Dis ; 70(6): 1110-1114, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-31056692

RESUMO

BACKGROUND: Animal-model studies have demonstrated less group B streptococcal (GBS) invasive disease and gastrointestinal colonization after enteral administration of serotype-specific capsular antibodies. There is, however, a paucity of information on the association of breast milk GBS serotype-specific capsular antibodies and risks for invasive disease in infants. The aim of this study was to explore the association between natural secretory immunoglobulin A (sIgA) capsular antibodies in breast milk and the occurrence of late-onset disease (LOD) in young infants. METHODS: A matched case-control study was undertaken in infants <3 months of age in Johannesburg, South Africa. Breast milk samples were collected on cases and controls matched for gestational age, maternal age, and human immunodeficiency virus status at time of enrollment. Capsular serotype Ia, Ib, III, and V sIgA antibody concentrations were measured using the fluorescence-based micro-bead immunosorbent assay. RESULTS: Breast milk samples were available for 31 LOD cases (8 serotype Ia and 23 serotype III), 21 recto-vaginally colonized matched controls (10 serotype Ia and 11 serotype III), and 84 serotype Ia and 105 serotype III noncolonized matched controls. Using a Bayesian model to estimate the probability of disease, there were 90% reductions in the risks of developing serotypes Ia and III LOD with sIgA concentrations ≥0.14 µg/mL and ≥2.52 µg/mL, respectively. CONCLUSIONS: Breast milk sIgA capsular antibodies were associated with lower risks for LOD in young infants. The ability of GBS polysaccharide-protein conjugate vaccines currently under development to induce sIgA responses warrant investigation as potential mediators of protection against LOD.


Assuntos
Leite Humano , Infecções Estreptocócicas , Animais , Anticorpos Antibacterianos , Teorema de Bayes , Estudos de Casos e Controles , Feminino , Humanos , Lactente , África do Sul/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae
18.
Semin Respir Crit Care Med ; 41(1): 131-140, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32000289

RESUMO

Phaeohyphomycosis refers to infections due to a large group of heterogenous organisms called "dematiaceous" or "melanized" fungi. These fungi are distinguished by the predominance of melanin in their cell walls, which likely acts as a virulence factor. Virtually, everyone is exposed to dematiaceous fungi through inhalation, as they are ubiquitous in the environment, although the development of infection is extremely uncommon. Invasive disease is rare but remains important due to the ability to cause serious disease in immunocompetent and immunocompromised hosts, unlike other fungal infections such as aspergillosis. A large variety of invasive manifestations can be caused by these organisms, including deep local infections, pulmonary infection, cerebral infection, and disseminated disease, which is associated with high mortality. While advances in molecular techniques are promising, they have still not replaced histology and culture as the primary diagnostic tools. Therapy is not standardized and is based primarily on clinical experience from descriptive case reports.


Assuntos
Antifúngicos/uso terapêutico , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Feoifomicose/microbiologia , Fungos/classificação , Fungos/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido
19.
J Vis ; 20(13): 6, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33289797

RESUMO

Studying the sources of errors in memory recall has proven invaluable for understanding the mechanisms of working memory (WM). While one-dimensional memory features (e.g., color, orientation) can be analyzed using existing mixture modeling toolboxes to separate the influence of imprecision, guessing, and misbinding (the tendency to confuse features that belong to different memoranda), such toolboxes are not currently available for two-dimensional spatial WM tasks. Here we present a method to isolate sources of spatial error in tasks where participants have to report the spatial location of an item in memory, using two-dimensional mixture models. The method recovers simulated parameters well and is robust to the influence of response distributions and biases, as well as number of nontargets and trials. To demonstrate the model, we fit data from a complex spatial WM task and show the recovered parameters correspond well with previous spatial WM findings and with recovered parameters on a one-dimensional analogue of this task, suggesting convergent validity for this two-dimensional modeling approach. Because the extra dimension allows greater separation of memoranda and responses, spatial tasks turn out to be much better for separating misbinding from imprecision and guessing than one-dimensional tasks. Code for these models is freely available in the MemToolbox2D package and is integrated to work with the commonly used MATLAB package MemToolbox.


Assuntos
Memória de Curto Prazo/fisiologia , Memória Espacial/fisiologia , Idoso , Feminino , Percepção de Forma/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Testes Neuropsicológicos , Orientação Espacial/fisiologia
20.
J Contemp Dent Pract ; 21(10): 1113-1116, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33686031

RESUMO

AIMS: To assess the staining efficacy of the innovative "Pravara" stain on ground sections of human teeth under a stereomicroscope. In this study, the ground sections were stained with the innovative stain. The stain is obtained from a leafless tree called Terminalia chebula. Terminalia chebula, commonly known as Harad, is found in South Asia from India. Few species are found in the Pravara region of Maharashtra, India. MATERIALS AND METHODS: A total of 40 extracted teeth were collected and ground sections of each tooth were prepared. The samples were randomly divided into two groups: group I-control (without stain), group II-study group (the samples in this group were stained with the help of innovative "Pravara" stain). The sections were graded from I to III according to the differentiation and contrast of tissues. RESULTS: The ground sections in group II stained with Pravara stain demonstrated better contrast for structures within sections under a microscope in comparison with group I (control group). CONCLUSION: The study demonstrates the efficacy of a new innovative Pravara stain, which is a simple, economical, quick, and effective staining method for the ground sections of the teeth. CLINICAL SIGNIFICANCE: This innovative Pravara stain is cost-effective, saves time, ecofriendly, and highlights the anatomical structures more effectively and does not fade easily with time.


Assuntos
Corantes , Dente , Técnicas Histológicas , Humanos , Índia , Coloração e Rotulagem
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