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1.
Alzheimers Dement ; 19(9): 4174-4186, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37356069

RESUMO

INTRODUCTION: We developed demographically-adjusted normative data for Spanish- and English-speaking Latinos on the Version 3.0 of the National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS3-NB). METHODS: Healthy Latino adults (N = 437) age 50-94 (191 Spanish- and 246 English-speaking) enrolled in Alzheimer's Disease Research Centers completed the UDS3-NB in their preferred language. Normative data were developed via multiple linear regression models on UDS3-NB raw scores stratified by language group with terms for demographic characteristics (age, years of formal education, and sex). RESULTS: Younger age and more years of education were associated with better performance on most tests in both language groups, with education being particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and language groups. DISCUSSION: These normative data are a crucial step toward improving diagnostic accuracy of the UDS3-NB for neurocognitive disorders among Latinos in the United States and addressing disparities in Alzheimer's disease and related dementias. HIGHLIGHTS: We developed normative data on the UDS3-NB for Latinos in the US ages 50-94. Younger age and more years of education were linked to better raw scores in several cognitive tests. Education was particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and between English- and Spanish-speaking Latinos. These normative data might improve diagnostic accuracy of the UDS3-NB among Latinos.


Assuntos
Doença de Alzheimer , Humanos , Estados Unidos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Idioma , Testes Neuropsicológicos , Escolaridade , Hispânico ou Latino
2.
Int J Mol Sci ; 24(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37958529

RESUMO

Umbilical cord blood (UCB) serves as a source of hematopoietic stem and progenitor cells (HSPCs) utilized in the regeneration of hematopoietic and immune systems, forming a crucial part of the treatment for various benign and malignant hematological diseases. UCB has been utilized as an alternative HSPC source to bone marrow (BM). Although the use of UCB has extended transplantation access to many individuals, it still encounters significant challenges in selecting a histocompatible UCB unit with an adequate cell dose for a substantial proportion of adults with malignant hematological diseases. Consequently, recent research has focused on developing ex vivo expansion strategies for UCB HSPCs. Our results demonstrate that co-cultures with the investigated mesenchymal stromal cells (MSCs) enable a 10- to 15-fold increase in the cellular dose of UCB HSPCs while partially regulating the proliferation capacity when compared to HSPCs expanded with early acting cytokines. Furthermore, the secretory profile of UCB-derived MSCs closely resembles that of BM-derived MSCs. Moreover, both co-cultures exhibit alterations in cytokine secretion, which could potentially impact HSPC proliferation during the expansion process. This study underscores the fact that UCB-derived MSCs possess a remarkably similar supportive capacity to BM-derived MSCs, implying their potential use as feeder layers in the ex vivo expansion process of HSPCs.


Assuntos
Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Gravidez , Feminino , Adulto , Humanos , Antígenos CD34 , Sangue Fetal , Células-Tronco Hematopoéticas , Técnicas de Cocultura , Transplante de Células-Tronco Hematopoéticas/métodos , Proliferação de Células
3.
Alzheimer Dis Assoc Disord ; 36(3): 238-243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35380552

RESUMO

OBJECTIVE: The aim was to set syndrome stage-specific (eg, cognitively unimpaired, severe dementia) metrics for functional change. METHODS: We selected 18,097 individuals who participated in 2 National Alzheimer's Coordinating Center visits between June 2005 and May 2020, with completed collateral rating of functioning on activities of daily living assessed by the Functional Activities Questionnaire.Both distribution-based (ie, regression-based reliable change indices) and anchor-based (ie, typical change associated with advancing a syndromal stage for clinically meaningful difference) methods were applied for individuals classified as: unimpaired cognition, mild cognitive impairment, mild dementia, moderate dementia, or severe dementia. RESULTS: There were marked differences in the distribution of functional ratings depending on their syndromal stage. There were also differences in the functional change associated with advancing across different syndromal stages. These informed stage-specific metrics for reliable change indices and clinically meaningful differences. CONCLUSIONS: Our indices provide a hitherto unavailable method that allows clinicians to determine whether observed functional change is reliable or meaningful based on syndromal stage.


Assuntos
Disfunção Cognitiva , Demência , Atividades Cotidianas , Idoso , Disfunção Cognitiva/psicologia , Demência/psicologia , Humanos , Inquéritos e Questionários
4.
Epilepsia ; 60(11): e110-e114, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31592545

RESUMO

The epileptic baboon provides a natural model of idiopathic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). This retrospective, case-controlled study aims to evaluate cardiac biomarkers of epilepsy, specifically QT-interval prolongation and heart rate variability (HRV), in pedigreed, captive baboons undergoing scalp electroencephalography (EEG). We retrospectively identified 21 epileptic (nine females, mean age = 11.4 ± 5.4 years) and 19 asymptomatic control (12 females, mean age = 10.5 ± 6.3 years) baboons, who had undergone scalp EEG studies with an artifact-free, 10-beat electrocardiogram sample. All baboons were sedated with subanesthetic doses of ketamine prior to electrode placement. PR, QT, and RR intervals were measured, and Fridericia-corrected QT duration (QTcF) and root mean square of successive differences between RR intervals (RMSSD; representative of HRV) values were compared between the groups. The epilepsy group had significantly prolonged QT and QTcF intervals (P = .005) compared to controls. RMSSD values were nonsignificantly decreased in epileptic baboons compared to the control group. This study demonstrates cardiac repolarization anomalies and reduction of HRV in epileptic baboons, providing new cardiac biomarkers in pedigreed baboons and potential risk factors for SUDEP.


Assuntos
Eletrocardiografia/métodos , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Frequência Cardíaca/fisiologia , Animais , Estudos de Casos e Controles , Epilepsia/diagnóstico , Epilepsia/genética , Feminino , Masculino , Papio , Linhagem , Estudos Retrospectivos
5.
Exp Brain Res ; 236(8): 2347-2362, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29947955

RESUMO

Healthy aging affects manual asymmetries in simple motor tasks, such as unilateral reaching and aiming. The effects of aging on manual asymmetries in the performance of a complex, naturalistic task are unknown, but are relevant for investigating the praxis system. This study examined how aging influences manual asymmetry in different contexts in a tool manipulation task. Fifty healthy, right-hand-dominant young (N = 29; 21.41 ± 2.87 years), and elderly (N = 21; mean: 74.14 ± 6.64 years) participants performed a 'slicing' gesture in response to a verbal command in two contexts: with (tool) and without the tool (pantomime). For interjoint relationships between shoulder plane of elevation and elbow flexion, a HAND × AGE × CONTEXT interaction existed (F1,43 = 4.746, p = 0.035). In pantomime, interjoint control deviated more in the left (non-dominant) than the right (dominant) limb in the elderly adult group (Wilcoxon, p = 0.010). No such differences existed in the young adult group (Wilcoxon, p = 0.471). Furthermore, contextual information reduced interjoint deviation in young adults when the task was performed with the right (dominant) hand (Wilcoxon, p = 0.001) and in the elderly adults when the task was performed with the left (non-dominant) hand (Wilcoxon, p = 0.012). The presence of the tool did not reduce interjoint deviation for the right hand in the elderly group (Wilcoxon, p = 0.064) or the left hand in the young group (Wilcoxon, p = 0.044). Deviation within trials (i.e., intrasubject deviation) in elbow flexion was higher in the elderly relative to the young adult group (p = 0.003). Finally, resultant peak velocities were smaller (p = 0.002) and cycle duration longer (p < 0.0001) in the elderly adult group. This study provides novel evidence that aging affects manual asymmetries and sensorimotor control in a naturalistic task and warrants that aging research considers the context in which the task is performed.


Assuntos
Envelhecimento/fisiologia , Fenômenos Biomecânicos/fisiologia , Lateralidade Funcional/fisiologia , Mãos/fisiologia , Atividade Motora/fisiologia , Adulto , Idoso , Cotovelo/fisiologia , Feminino , Humanos , Masculino , Adulto Jovem
6.
PLoS Comput Biol ; 12(4): e1004786, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27096600

RESUMO

Multifunctionality is a common trait of many natural proteins and peptides, yet the rules to generate such multifunctionality remain unclear. We propose that the rules defining some protein/peptide functions are compatible. To explore this hypothesis, we trained a computational method to predict cell-penetrating peptides at the sequence level and learned that antimicrobial peptides and DNA-binding proteins are compatible with the rules of our predictor. Based on this finding, we expected that designing peptides for CPP activity may render AMP and DNA-binding activities. To test this prediction, we designed peptides that embedded two independent functional domains (nuclear localization and yeast pheromone activity), linked by optimizing their composition to fit the rules characterizing cell-penetrating peptides. These peptides presented effective cell penetration, DNA-binding, pheromone and antimicrobial activities, thus confirming the effectiveness of our computational approach to design multifunctional peptides with potential therapeutic uses. Our computational implementation is available at http://bis.ifc.unam.mx/en/software/dcf.


Assuntos
Desenho de Fármacos , Peptídeos/química , Engenharia de Proteínas/métodos , Algoritmos , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/fisiologia , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/genética , Peptídeos Penetradores de Células/fisiologia , Células Cultivadas , Biologia Computacional , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Aprendizado de Máquina , Camundongos , Modelos Estatísticos , Dados de Sequência Molecular , Sinais de Localização Nuclear , Peptídeos/genética , Peptídeos/fisiologia , Ligação Proteica , Engenharia de Proteínas/estatística & dados numéricos , Estrutura Secundária de Proteína
7.
Exp Brain Res ; 235(5): 1519-1529, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28251336

RESUMO

Visuospatial working memory (VSWM) is a set of cognitive processes used to encode, maintain and manipulate spatial information. One important feature of VSWM is that it has a limited capacity such that only few items can be actively stored and manipulated simultaneously. Given the limited capacity, it is important to determine the conditions that affect memory performance as this will improve our understanding of the architecture and function of VSWM. Previous studies have shown that VSWM is disrupted when task-irrelevant eye movements are performed during the maintenance phase; however, relatively fewer studies examined the role of eye movements performed during the encoding phase. On one hand, performing eye movements during the encoding phase could result in a stronger memory trace because the memory formation is reinforced by the activation of the motor system. On the other hand, performing eye movements to each target could disrupt the configural processing of the spatial array because the spatial representation has to be updated with each movement to maintain perceptual stability. Therefore, this work was conducted to examine whether task-relevant saccadic eye movements performed during the encoding phase of a visuospatial working memory task affect the recall of serially presented targets. Results from two experiments showed that average recall accuracy was significantly higher when the spatial array (set size ≥ 7) was encoded using a covert strategy-that is, while participants fixated on a central target, in comparison to an overt strategy-that is, while participants moved their eyes to fixate on each target. Furthermore, the improvement in accuracy was evident only for targets presented in the first half of the sequence, suggesting that the primacy effect is modulated by the presence of eye movements. We propose that executing saccades during encoding could interfere with the ability to use a chunking strategy or disrupt active visualization of the configuration. In conclusion, this is the first study to show that task-relevant saccadic eye movements performed during encoding may actually reduce the spatial span of VSWM. These results extend the current knowledge about the role of eye movements in VSWM, and have implications for future studies investigating the VSWM.


Assuntos
Memória de Curto Prazo/fisiologia , Movimentos Sacádicos/fisiologia , Aprendizagem Seriada/fisiologia , Percepção Espacial/fisiologia , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Rememoração Mental/fisiologia , Testes Neuropsicológicos , Estimulação Luminosa , Adulto Jovem
8.
EMBO J ; 30(19): 4059-70, 2011 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-21873977

RESUMO

The transcription factor RUNX1 is essential to establish the haematopoietic gene expression programme; however, the mechanism of how it activates transcription of haematopoietic stem cell (HSC) genes is still elusive. Here, we obtained novel insights into RUNX1 function by studying regulation of the human CD34 gene, which is expressed in HSCs. Using transgenic mice carrying human CD34 PAC constructs, we identified a novel downstream regulatory element (DRE), which is bound by RUNX1 and is necessary for human CD34 expression in long-term (LT)-HSCs. Conditional deletion of Runx1 in mice harbouring human CD34 promoter-DRE constructs abrogates human CD34 expression. We demonstrate by chromosome conformation capture assays in LT-HSCs that the DRE physically interacts with the human CD34 promoter. Targeted mutagenesis of RUNX binding sites leads to perturbation of this interaction and decreased human CD34 expression in LT-HSCs. Overall, our in vivo data provide novel evidence about the role of RUNX1 in mediating interactions between distal and proximal elements of the HSC gene CD34.


Assuntos
Antígenos CD34/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Animais , Transplante de Medula Óssea , Cromatina/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Sangue Fetal/citologia , Genótipo , Células HL-60 , Humanos , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Sequências Reguladoras de Ácido Nucleico/genética
9.
Artigo em Inglês | MEDLINE | ID: mdl-38747154

RESUMO

BACKGROUND: Anxiety may precede motor symptoms in cervical dystonia (CD) and is associated with an earlier onset of dystonia. Our understanding of anxiety in CD is inadequate. OBJECTIVE: To investigate brain networks associated with anxiety in CD. METHODS: Twenty-six subjects with idiopathic CD underwent MRI Brain without contrast. Correlational tractography was derived using Diffusion MRI connectometry. Quantitative Anisotropy (QA) was used in deterministic diffusion fiber tracking. Correlational tractography was then used to correlate QA with State-Trait Anxiety Inventory (STAI) state (STAI-S) and trait (STAI-T) subscales. RESULTS: Connectometry analysis showed direct correlation between state anxiety and QA in tracts from amygdala to thalamus/ pulvinar bilaterally, and trait anxiety and QA in tracts from amygdala to motor cortex, sensorimotor cortex and parietal association area bilaterally (FDR ≤0.05). CONCLUSION: Our efforts to map anxiety to brain networks in CD highlight the role of the amygdala in the pathophysiology of anxiety in CD.

10.
medRxiv ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38464267

RESUMO

Retrotransposons are viral-like DNA sequences that constitute approximately 41% of the human genome. Studies in Drosophila, mice, cultured cells, and human brain indicate that retrotransposons are activated in settings of tauopathy, including Alzheimer's disease, and causally drive neurodegeneration. The anti-retroviral medication 3TC (lamivudine), a nucleoside analog reverse transcriptase inhibitor, limits retrotransposon activation and suppresses neurodegeneration in tau transgenic Drosophila, two mouse models of tauopathy, and in brain assembloids derived from patients with sporadic Alzheimer's disease. We performed a 24-week phase 2a open-label clinical trial of 300 mg daily oral 3TC (NCT04552795) in 12 participants aged 52-83 years with a diagnosis of mild cognitive impairment due to suspected Alzheimer's disease. Primary outcomes included feasibility, blood brain barrier penetration, effects of 3TC on reverse transcriptase activity in the periphery, and safety. Secondary outcomes included changes in cognition and fluid-based biomarkers of neurodegeneration and neuroinflammation. All participants completed the six-month trial; one event of gastrointestinal bleeding due to a peptic ulcer was reported. 3TC was detected in blood and cerebrospinal fluid (CSF) of all participants, suggestive of adherence to study drug and effective brain penetration. Cognitive measures remained stable throughout the study. Glial fibrillary acidic protein (GFAP) (P=0.03) and Flt1 (P=0.05) were significantly reduced in CSF over the treatment period; Aß42/40 (P=0.009) and IL-15 (P=0.006) were significantly elevated in plasma. While this is an open label study of small sample size, the significant decrease of some neurodegeneration- and neuroinflammation-related biomarkers in CSF, significantly elevated levels of plasma Aß42/40, and a trending decrease of CSF NfL after six months of 3TC exposure suggest a beneficial effect on subjects with mild cognitive impairment due to suspected Alzheimer's disease. Feasibility, safety, tolerability, and central nervous system (CNS) penetration assessments further support clinical evaluation of 3TC in a larger placebo-controlled, multi-dose clinical trial.

11.
Percept Mot Skills ; 117(2): 578-96, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24611258

RESUMO

Previous researchers have found that participants associate higher frequencies with locations that are higher in space and lower frequencies with lower locations, creating a phenomenological-spatial association for the frequency of auditory tones. With such an association, the frequency of an auditory tone could potentially bias movements along multiple axes. This hypothesis was tested. In four experiments, nine frequencies (250-1,250 Hz) were binaurally presented to blindfolded participants (n = 10, 12, 20, & 9; M age = 22 yr.) who indicated the perceived location of the stimuli on a measurement scale oriented in the vertical, the horizontal (Experiment 1), or depth dimension (Experiment 2). In Experiment 3, participants were asked to indicate the perceived location of the frequencies on a two-dimensional vertical board located in front of them. In Experiment 4, participants indicated the perceived location in three-dimensional space. An optoelectronic device recorded at all locations. Analyses of constant error indicated a spatial association in the vertical, horizontal, and depth dimensions when responses were restricted to only one dimension (Experiments 1 & 2). Higher frequencies were perceived to be located higher, farther to the right, and farther away from the body than lower frequencies. However, this spatial association was only exhibited in the vertical dimension when the responses were unconstrained in two dimensions (vertical and horizontal; Experiment 3) and all three dimensions (Experiment 4). Although this spatial association is a robust phenomenon, it appears that the association only biases actions when indicating perceived locations in the vertical dimension during unconstrained responses.


Assuntos
Percepção da Altura Sonora/fisiologia , Localização de Som/fisiologia , Percepção Espacial/fisiologia , Adolescente , Adulto , Percepção Auditiva/fisiologia , Feminino , Humanos , Masculino , Adulto Jovem
12.
Mov Disord Clin Pract ; 10(11): 1666-1670, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37982111

RESUMO

Background: Sensory tricks (STs) are voluntary maneuvers that dampen the abnormal movement in cervical dystonia (CD). Objectives: To investigate the effect of ST on CD severity and treatment. Methods: Data on 1039 individuals with a modified Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score were extracted from the CD Patient Registry for Observation of OnabotulinumtoxinA (onabotA) Efficacy study. Univariate and multivariate models evaluated the direct and indirect impact of ST on CD severity and treatment, while controlling for confounds. Results: Complete ST was associated with a 10% lower mean onabotA dose. Absence of complete ST was associated with a higher onabotA dose after controlling for dystonia severity (OR = 1.37, P = 0.04). ST moderated the relationship between dystonia severity and toxin dose (ß = -0.16, P = 0.02). Conclusions: ST is related to lower CD severity and toxin dose. It may have a direct effect on lowering toxin dose, independent of CD severity.

13.
Parkinsonism Relat Disord ; 114: 105792, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37540934

RESUMO

INTRODUCTION: Anxiety is present in 30-40% of patients with cervical dystonia (CD). It has been ascribed to a direct effect of the state of motor symptoms on related pain, disability, and disfigurement. Accordingly, any reported benefit of botulinum toxin (BoNT) on anxiety is thought to be secondary to its effect on the same. We sought to evaluate the distinctive impact of botulinum toxin (BoNT) on anxiety in cervical dystonia (CD). METHODS: In this prospective observational study, 60 participants with idiopathic isolated CD were recruited from clinic. We assessed motor and anxiety burden using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) parts I-III and State-Trait Anxiety Inventory (STAI). Assessments were done at time of BoNT (baseline) and at 6 weeks post-injection. RESULTS: STAI and motor severity TWSTRS scores poorly correlated at the baseline visit (rho = -0.30, p = 0.411). Both, motor TWSTRS (Mdifference = -1.46, p < 0.024) and STAI (Mdifference = -10.37, p = 0.007) improved from baseline to 6 weeks (peak effect). The change in motor TWSTRS poorly correlated with change in anxiety scores from baseline visit to 6 weeks (rho = -0.14, p > 0.999). Of these measures of anxiety, improvement in STAI-T had the largest effect size (rank biserial = 0.52). CONCLUSION: BoNT improves both motor severity and anxiety in CD. Poor correlation between motor severity and anxiety at both the time of injection and during the time of peak effect, and improvement in trait anxiety suggests that BoNT has a direct beneficial effect on anxiety.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Torcicolo , Humanos , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/uso terapêutico , Torcicolo/complicações , Estudos Prospectivos , Fármacos Neuromusculares/farmacologia , Fármacos Neuromusculares/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Resultado do Tratamento
14.
BMC Med Res Methodol ; 12: 65, 2012 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-22559914

RESUMO

BACKGROUND: Large epidemiological studies in DNA biobanks have increasingly used less invasive methods for obtaining DNA samples, such as saliva collection. Although lower amounts of DNA are obtained as compared with blood collection, this method has been widely used because of its more simple logistics and increased response rate. The present study aimed to verify whether a storage time of 8 months decreases the quality of DNA from collected samples. METHODS: Saliva samples were collected with an OrageneTM DNA Self-Collection Kit from 4,110 subjects aged 14-15 years. The samples were processed in two aliquots with an 8-month interval between them. Quantitative and qualitative evaluations were carried out in 20% of the samples by spectrophotometry and genotyping. Descriptive analyses and paired t-tests were performed. RESULTS: The mean volume of saliva collected was 2.2 mL per subject, yielding on average 184.8 µg DNA per kit. Most samples showed a Ratio of OD differences (RAT) between 1.6 and 1.8 in the qualitative evaluation. The evaluation of DNA quality by TaqMan®, High Resolution Melting (HRM), and restriction fragment length polymorphism-PCR (RFLP-PCR) showed a rate of success of up to 98% of the samples. The sample store time did not reduce either the quantity or quality of DNA extracted with the Oragene kit. CONCLUSION: The study results showed that a storage period of 8 months at room temperature did not reduce the quality of the DNA obtained. In addition, the use of the Oragene kit during fieldwork in large population-based studies allows for DNA of high quantity and high quality.


Assuntos
DNA/análise , Controle de Qualidade , Kit de Reagentes para Diagnóstico , Saliva/química , Manejo de Espécimes/normas , Adolescente , Brasil , Estudos de Coortes , DNA/isolamento & purificação , Interpretação Estatística de Dados , Jejum , Feminino , Técnicas de Genotipagem , Humanos , Técnicas de Diluição do Indicador , Masculino , Reprodutibilidade dos Testes , Espectrofotometria , Fatores de Tempo
15.
Addict Neurosci ; 32022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36059430

RESUMO

The central nucleus of the amygdala (CeA) is a critical brain region in the integration of emotional behaviors and is one of the major output areas of the amygdaloid complex. The CeA is composed of GABAergic interneurons and projection neurons which co-express a range of peptides including neuropeptide Y (NPY). Importantly, GABA and NPY signaling, via the NPY Y1 receptor (Y1R), in the CeA modulate binge-like ethanol intake in rodents and these systems undergo neuroplastic alterations following a history of ethanol consumption. Here we assessed the roles of GABAergic and Y1R+ circuits arising from the CeA and innervating the lateral habenula (LHb), a brain region that modulates the aversive properties of ethanol, in modulating binge-like ethanol intake in mice using "drinking in the dark" (DID) procedures. Using an anterograde cre-inducible reporter virus we established the CeA → LHb circuit in male and female vgat-ires-cre and NPY1r-cre mice. Next, we found that chemogenetic silencing of both the GABAergic or Y1R+ CeA → LHb circuit significantly blunted binge-like intake of a 20% ethanol solution but this same procedure failed to alter the consumption of a 3% sucrose solution. Finally, one, 4-day cycle of DID failed to alter basal or effects of ethanol or NPY on inhibitory transmission in Y1R+ CeA → LHb neurons. The present results suggest that blunting GABAergic tone in LHb-projecting CeA neurons may represent a new approach to preventing the development of AUDs. Drugs that target NPY Y1Rs are potential attractive targets.

16.
Pharmaceutics ; 13(8)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34452080

RESUMO

Cell penetrating peptides (CPPs) are molecules capable of passing through biological membranes. This capacity has been used to deliver impermeable molecules into cells, such as drugs and DNA probes, among others. However, the internalization of these peptides lacks specificity: CPPs internalize indistinctly on different cell types. Two major approaches have been described to address this problem: (i) targeting, in which a receptor-recognizing sequence is added to a CPP, and (ii) activation, where a non-active form of the CPP is activated once it interacts with cell target components. These strategies result in multifunctional peptides (i.e., penetrate and target recognition) that increase the CPP's length, the cost of synthesis and the likelihood to be degraded or become antigenic. In this work we describe the use of machine-learning methods to design short selective CPP; the reduction in size is accomplished by embedding two or more activities within a single CPP domain, hence we referred to these as moonlighting CPPs. We provide experimental evidence that these designed moonlighting peptides penetrate selectively in targeted cells and discuss areas of opportunity to improve in the design of these peptides.

17.
Paediatr Perinat Epidemiol ; 24(1): 12-23, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20078825

RESUMO

We investigated the association between breast feeding, economic factors and conviction for violent delinquency by age 25 years among subjects of the 1982 Birth Cohort from Pelotas, Southern Brazil. Information on breast-feeding pattern and duration was collected in childhood, during the 1983, 1984 and 1986 follow-ups. Information on socio-economic and family characteristics was also obtained between 1982 and 1996. Of the 5914 livebirths enrolled in the cohort, 5228 had obtained an identification document within the state of Rio Grande do Sul, and could thus be identified in judiciary databases. The outcome studied was conviction due to a violent act between ages 12 and 25 years. A total of 106 young people had been convicted at least once (3.0% of men and 1.0% of women). Subjects born to black or mixed mothers and coming from low-income families were at higher risk of having been convicted. Neither crude nor adjusted analyses showed any association between breast feeding and conviction for violent delinquency. Violent delinquency apparently depends more on social factors than on individual factors such as breast feeding.


Assuntos
Aleitamento Materno , Delinquência Juvenil/estatística & dados numéricos , Fatores Socioeconômicos , Violência/estatística & dados numéricos , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Escolaridade , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Pobreza , Gravidez , Fatores de Risco , Fatores Sexuais , Adulto Jovem
18.
Rev Panam Salud Publica ; 28(2): 71-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20963272

RESUMO

OBJECTIVE: To examine associations between certain aspects of self-reported Quality of Life (QoL) in early adolescence, and gender, skin color, maternal education at birth, and changes in socioeconomic position (SEP) occurring from 0-11 years of age. METHODS: A longitudinal study of a birth cohort composed of 5 249 individuals born in 1993 in Pelotas, Brazil, who were followed periodically from birth to age 11. Socioeconomic variables were collected at birth in 1993, and again, in 2004. The following eight variables were analyzed: relationship with mother, relationship with father, family conflicts, physical punishment by parents, family relationship problems, discrimination, academic failure, and fear of neighborhood of residence. Adjustments were made using a hierarchical model. RESULTS: Skin color was related to all the variables (more so for nonwhites than for whites), except in family conflicts. Physical punishment and academic failure were more frequent in males. Discrimination and fear of neighborhood were more prevalent in females. Maternal education at birth was inversely associated, especially with failing/repeating a grade in school(19.5 times more frequent in the lower maternal education group than in the highest). A similar pattern was found with the SEP change: worse QoL in the group that was always poor (at birth and at 11 years of age) than in the group that was never poor. Fear of neighborhood was not related to maternal education or SEP change. CONCLUSIONS: Gender, skin color, maternal education, and SEP change were related to various measured aspects of QoL. These results should be considered in policymaking that seeks to minimize inequities at birth, across the life-course, and for future generations.


Assuntos
Psicologia do Adolescente , Qualidade de Vida , Fatores Socioeconômicos , Adolescente , Adulto , Brasil , Estudos de Coortes , Escolaridade , Etnicidade/psicologia , Conflito Familiar/psicologia , Medo , Feminino , Humanos , Masculino , Relações Pais-Filho , Pais/psicologia , Pobreza/psicologia , Preconceito , Punição/psicologia , Características de Residência , População Urbana
19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5045-5048, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019120

RESUMO

The Thulium fiber laser (TFL) is being explored as a potential alternative to the gold standard Holmium:YAG laser for infrared laser ablation of kidney stones. Laser-induced vapor bubbles contribute to both the ablation mechanism and stone retropulsion. In this preliminary study, a biocompatible surfactant with concentrations of 1-5% was used to enhance the vapor bubble dimensions during the laser pulse. Bubble dimensions using surfactant increased on average by 25% compared with water only (control). With further development, introduction of the surfactant into the saline irrigation flow typically delivered through the working channel of the ureteroscope during laser lithotripsy, may contribute to more efficient stone ablation.Clinical Relevance-This preliminary study demonstrates that the dimensions of laser-induced vapor bubbles created during infrared laser lithotripsy can be enhanced by up to 25%, for potential clinical translation into more efficient lithotripsy and use in the "popcorn" ablation method.


Assuntos
Lasers de Estado Sólido , Litotripsia a Laser , Surfactantes Pulmonares , Tensoativos , Túlio
20.
Public Health Nutr ; 12(11): 2225-35, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19656435

RESUMO

OBJECTIVE: Obesity is an increasingly prevalent nutritional disorder throughout the world. In particular, abdominal obesity is associated with cardiovascular and metabolic risk. The present study aimed to evaluate the effects of skin colour and life-course socio-economic indicators on waist circumference (WC), hip circumference (HC) and waist:hip ratio (WHR) in young adults. DESIGN: Population-based birth cohort study. Individuals born in 1982 in Pelotas (southern Brazil) were visited on a number of occasions from birth to age 23-24 years. A sample of the cohort was sought in 2006 and 972 individuals were located. The analysis was restricted to individuals with complete data available (442 males, 414 females). RESULTS: In men, family income at birth and in 2004-5 were positively associated with WC and HC, but not with WHR. Regardless of current income, men born to wealthier families had larger WC and HC as adults. Skin colour was not associated with any of the outcomes. In women, early poverty was associated with smaller HC, and current poverty with larger WC. Poverty at any age thus led to higher WHR. Black women had larger WC and HC than white women, but there were no differences in WHR. All the associations were partially mediated by education and behavioural variables. CONCLUSIONS: The effects of early socio-economic position on WC and HC persist even after adjustment for adult socio-economic position, highlighting the importance of interventions during the first years of life.


Assuntos
Renda , Obesidade Abdominal/economia , Obesidade Abdominal/etnologia , Grupos Raciais , Circunferência da Cintura , Relação Cintura-Quadril , Adulto , Brasil/epidemiologia , Feminino , Quadril , Humanos , Masculino , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos , Circunferência da Cintura/etnologia , Adulto Jovem
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