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1.
Sci Rep ; 9(1): 17060, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745159

RESUMO

Humans can anticipate music and derive pleasure from it. Expectations facilitate the learning of movements associated with anticipated events, and they are also linked with reward, which may further facilitate learning of the anticipated rewarding events. The present study investigates the synergistic effects of predictability and hedonic responses to music on arousal and motor-learning in a naïve population. Novel melodies were manipulated in their overall predictability (predictable/unpredictable) as objectively defined by a model of music expectation, and ranked as high/medium/low liked based on participants' self-reports collected during an initial listening session. During this session, we also recorded ocular pupil size as an implicit measure of listeners' arousal. During the following motor task, participants learned to play target notes of the melodies on a keyboard (notes were of similar motor and musical complexity across melodies). Pupil dilation was greater for liked melodies, particularly when predictable. Motor performance was facilitated in predictable rather than unpredictable melodies, but liked melodies were learned even in the unpredictable condition. Low-liked melodies also showed learning but mostly in participants with higher scores of task perceived competence. Taken together, these results highlight  the effects of stimuli predictability on learning, which can be however overshadowed by the effects of stimulus liking or task-related intrinsic motivation.


Assuntos
Percepção Auditiva/fisiologia , Música/psicologia , Desempenho Psicomotor/fisiologia , Reconhecimento Psicológico/fisiologia , Adulto , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Memória/fisiologia , Prazer/fisiologia , Pupila/fisiologia , Adulto Jovem
2.
Phys Rev Lett ; 122(8): 088001, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932610

RESUMO

A key ingredient within theories focusing on the rheology of entangled polymers is the way how the topological constraints of an entangled chain are lifted by unconstrained segments, i.e., how the constraining tube is dilated. This important question has been addressed by directly measuring the tube diameter d at the scale of the tube by neutron spin echo spectroscopy. The tube diameter d and plateau modulus G_{N}^{0} of highly entangled polyethylene oxide (PEO) chains of volume fraction c that are diluted by low molecular PEO show a concentration dependence d∝c^{a/2} and G_{N}^{0}∝c^{1+a} with an exponent a close to 4/3. This result allows the clear discrimination between different theoretical models that predict 4/3 or other values between 1 and 2 and provides an important ingredient to tube model theories.

3.
J Nutr Health Aging ; 22(7): 837-846, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30080229

RESUMO

OBJECTIVES: To assess the effects of a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides on cognition and brain functioning in healthy older adults. DESIGN: Double-blind, placebo-controlled, crossover design randomized controlled trial with 26-day intervention phases and a 30-day washout period. SETTING: The Institute for Dementia Research and Prevention at the Pennington Biomedical Research Center. PARTICIPANTS: Ten independently-living, cognitively-healthy older adults (mean age: 67.3 + 2.01 years). INTERVENTION: Daily consumption of an investigational product (trade name "Cerbella TM") consisting of an emulsified liquid combination of standardized fish oil, panax ginseng extract, and green tea catechins in a flavored base of lecithin phospholipids optimized to maximize bioavailability of the active ingredients. MEASUREMENTS: Before and after supplementation with the investigational product or placebo, participants completed cognitive tests including the Mini Mental State Exam (MMSE), Stroop test, Digit Symbol Substitution Test (DSST), and Immediate and Delayed Recall tests, as well as functional magnetic resonance imaging (fMRI) during a standard cognitive task switching paradigm. RESULTS: Performance on the MMSE, Stroop test, and DSST increased significantly over one month of supplementation with the investigational product (one-sample t tests, p<.05) although differences between these changes and corresponding changes during supplementation with placebo were not significant (two-sample t tests, p>.05). During supplementation with the investigational product, brain activation during task performance increased significantly more than during supplementation with placebo in brain regions known to be activated by this task (anterior and posterior cingulate cortex). Functional connectivity during task execution between task regions (middle frontal gyrus and anterior cingulate cortex) increased significantly during supplementation with the investigational product, relative to placebo. Functional connectivity during rest between task regions (precentral gyrus and middle frontal gyrus) and default mode network regions (medial frontal gyrus and precuneus) decreased during supplementation with the investigational product relative to placebo, suggesting greater segregation of task and rest related brain activity. CONCLUSION: One-month supplementation with a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides was associated with suggestive changes in cognitive functioning as well as modification of brain activation and brain functional connectivity in cognitively healthy older adults.


Assuntos
Encéfalo/fisiologia , Catequina/farmacologia , Cognição/efeitos dos fármacos , Ácidos Graxos Essenciais/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Extratos Vegetais/farmacologia , Idoso , Encéfalo/efeitos dos fármacos , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Panax/química , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Descanso , Teste de Stroop , Análise e Desempenho de Tarefas , Chá/química
4.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-948131

RESUMO

BACKGROUND: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.


Assuntos
Humanos , Criança , Adolescente , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Metronidazol/uso terapêutico , Antibacterianos/uso terapêutico , Infecções por Helicobacter/diagnóstico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Amoxicilina/uso terapêutico
5.
ACS Macro Lett ; 6(2): 73-77, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35632894

RESUMO

Controlling the mechanical behavior of novel supramolecular materials is of the utmost importance and requires a fundamental understanding of the underlying physical processes. We present a multimethods approach to the dynamics of entangled transient polyisoprene networks. Small-angle neutron scattering (SANS) on randomly functionalized chains shows homogeneous supramolecular melts with Gaussian chain conformations. The H-bond lifetimes (dielectric α*-process) and the rheological response in terms of the loss modulus G″ differ by 2 orders of magnitude in time. Within the concept of a compact random walk (RW), where the random walker (urazole group acting as a sticker) undergoes multiple returns to its starting point and following the concept of theoretical proposed renormalized sticky bond lifetimes, we quantitatively solve this longstanding and unexplained large discrepancy: While the bond opening gives rise to the dielectric response, for rheological relaxation the association with a new partner is relevant. This takes place only after multiple returns to the original binding partner.

6.
Neuroimage Clin ; 11: 728-735, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27330972

RESUMO

To determine if proton magnetic resonance spectroscopy ((1)H-MRS) detect differences in dementia status in adults with Down syndrome (DS), we used (1)H-MRS to measure neuronal and glial metabolites in the posterior cingulate cortex in 22 adults with DS and in 15 age- and gender-matched healthy controls. We evaluated associations between (1)H-MRS results and cognition among DS participants. Neuronal biomarkers, including N-acetylaspartate (NAA) and glutamate-glutamine complex (Glx), were significantly lower in DS patients with Alzheimer's should probably be changed to Alzheimer (without ' or s) through ms as per the new naming standard disease (DSAD) when compared to non-demented DS (DS) and healthy controls (CTL). Neuronal biomarkers therefore appear to reflect dementia status in DS. In contrast, all DS participants had significantly higher myo-inositol (MI), a putative glial biomarker, compared to CTL. Our data indicate that there may be an overall higher glial inflammatory component in DS compared to CTL prior to and possibly independent of developing dementia. When computing the NAA to MI ratio, we found that presence or absence of dementia could be distinguished in DS. NAA, Glx, and NAA/MI in all DS participants were correlated with scores from the Brief Praxis Test and the Severe Impairment Battery. (1)H-MRS may be a useful diagnostic tool in future longitudinal studies to measure AD progression in persons with DS. In particular, NAA and the NAA/MI ratio is sensitive to the functional status of adults with DS, including prior to dementia.


Assuntos
Ácido Aspártico/análogos & derivados , Demência/etiologia , Demência/metabolismo , Síndrome de Down/complicações , Giro do Cíngulo/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Atividades Cotidianas , Adulto , Análise de Variância , Ácido Aspártico/metabolismo , Demência/psicologia , Síndrome de Down/patologia , Feminino , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Giro do Cíngulo/patologia , Humanos , Inositol/metabolismo , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários
7.
Neuroscience ; 278: 51-61, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25130561

RESUMO

Age-related increases in right frontal cortex activation are a common finding in the neuroimaging literature. However, neurocognitive factors contributing to right frontal over-recruitment remain poorly understood. Here we investigated the influence of age-related reaction time (RT) slowing and white matter (WM) microstructure reductions as potential explanatory factors for age-related increases in right frontal activation during task switching. Groups of younger (N=32) and older (N=33) participants completed a task switching paradigm while functional magnetic resonance imaging (fMRI) was performed, and rested while diffusion tensor imaging (DTI) was performed. Two right frontal regions of interest (ROIs), the dorsolateral prefrontal cortex (DLPFC) and insula, were selected for further analyses from a common network of regions recruited by both age groups during task switching. Results demonstrated age-related activation increases in both ROIs. In addition, the older adult group showed longer RT and decreased fractional anisotropy in regions of the corpus callosum with direct connections to the fMRI ROIs. Subsequent mediation analyses indicated that age-related increases in right insula activation were mediated by RT slowing and age-related increases in right DLPFC activation were mediated by WM microstructure. Our results suggest that age-related RT slowing and WM microstructure declines contribute to age-related increases in right frontal activation during cognitive task performance.


Assuntos
Cognição/fisiologia , Lobo Frontal/citologia , Lobo Frontal/fisiologia , Tempo de Reação/fisiologia , Substância Branca/citologia , Substância Branca/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Imagem de Tensor de Difusão , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
8.
Epidemiol Infect ; 141(3): 472-80, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22595455

RESUMO

We investigated a possible outbreak of H. pylori in a rural Northern Plains community. In a cross-sectional survey, we randomly sampled 244 households from a geocoded emergency medical system database. We used a complex survey design and global positioning system units to locate houses and randomly selected one eligible household member to administer a questionnaire and a 13C-urea breath test for active H. pylori infection (n = 166). In weighted analyses, active H. pylori infection was detected in 55·0% of the sample. Factors associated with infection on multivariate analysis included using a public drinking-water supply [odds ratio (OR) 12·2, 95% confidence interval (CI) 2·9-50·7] and current cigarette smoking (OR 4·1, 95% CI 1·7-9·6). People who lived in houses with more rooms, a possible indicator of decreased crowding in the home, were less likely to have active H. pylori infections (OR 0·7, 95% CI 0·5-0·9 for each additional room).


Assuntos
Surtos de Doenças , Inquéritos Epidemiológicos/métodos , Infecções por Helicobacter/etnologia , Helicobacter pylori , Indígenas Norte-Americanos , População Rural/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Respiratórios , Criança , Pré-Escolar , Estudos Transversais , Água Potável , Feminino , Sistemas de Informação Geográfica , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos de Amostragem , Estados Unidos/epidemiologia , Adulto Jovem
9.
Biochemistry ; 50(41): 8957-69, 2011 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-21899261

RESUMO

Monothiol glutaredoxins (mono-Grx) represent a highly evolutionarily conserved class of proteins present in organisms ranging from prokaryotes to humans. Mono-Grxs have been implicated in iron sulfur (FeS) cluster biosynthesis as potential scaffold proteins and in iron homeostasis via an FeS-containing complex with Fra2p (homologue of E. coli BolA) in yeast and are linked to signal transduction in mammalian systems. However, the function of the mono-Grx in prokaryotes and the nature of an interaction with BolA-like proteins have not been established. Recent genome-wide screens for E. coli genetic interactions reported the synthetic lethality (combination of mutations leading to cell death; mutation of only one of these genes does not) of a grxD mutation when combined with strains defective in FeS cluster biosynthesis (isc operon) functions [Butland, G., et al. (2008) Nature Methods 5, 789-795]. These data connected the only E. coli mono-Grx, GrxD to a potential role in FeS cluster biosynthesis. We investigated GrxD to uncover the molecular basis of this synthetic lethality and observed that GrxD can form FeS-bound homodimeric and BolA containing heterodimeric complexes. These complexes display substantially different spectroscopic and functional properties, including the ability to act as scaffold proteins for intact FeS cluster transfer to the model [2Fe-2S] acceptor protein E. coli apo-ferredoxin (Fdx), with the homodimer being significantly more efficient. In this work, we functionally dissect the potential cellular roles of GrxD as a component of both homodimeric and heterodimeric complexes to ultimately uncover if either of these complexes performs functions linked to FeS cluster biosynthesis.


Assuntos
Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Glutarredoxinas/química , Cromatografia em Gel/métodos , Dicroísmo Circular/métodos , Dimerização , Humanos , Ferro/química , Proteínas Ferro-Enxofre/química , Espectrometria de Massas/métodos , Modelos Genéticos , Mutação , Plasmídeos/metabolismo , Espectrofotometria/métodos , Espectrofotometria Ultravioleta/métodos
10.
Appl Environ Microbiol ; 77(21): 7595-604, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21908633

RESUMO

The ability to conduct advanced functional genomic studies of the thousands of sequenced bacteria has been hampered by the lack of available tools for making high-throughput chromosomal manipulations in a systematic manner that can be applied across diverse species. In this work, we highlight the use of synthetic biological tools to assemble custom suicide vectors with reusable and interchangeable DNA "parts" to facilitate chromosomal modification at designated loci. These constructs enable an array of downstream applications, including gene replacement and the creation of gene fusions with affinity purification or localization tags. We employed this approach to engineer chromosomal modifications in a bacterium that has previously proven difficult to manipulate genetically, Desulfovibrio vulgaris Hildenborough, to generate a library of over 700 strains. Furthermore, we demonstrate how these modifications can be used for examining metabolic pathways, protein-protein interactions, and protein localization. The ubiquity of suicide constructs in gene replacement throughout biology suggests that this approach can be applied to engineer a broad range of species for a diverse array of systems biological applications and is amenable to high-throughput implementation.


Assuntos
DNA Bacteriano/genética , Desulfovibrio vulgaris/genética , Genética Microbiana/métodos , Genoma Bacteriano , Genômica/métodos , Ensaios de Triagem em Larga Escala/métodos , Fusão Gênica Artificial , Deleção de Genes , Vetores Genéticos , Mutagênese Insercional/métodos , Recombinação Genética
11.
J Org Chem ; 76(21): 8737-48, 2011 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-21910478

RESUMO

The nature of products in the diazotization of 1-amino-2-acetylenyl-9,10-anthraquinones strongly depends on the nature of substituents at both the alkyne and at the anthraquinone core. Donor substitution (NHAr, OH) at the fourth position stabilizes the diazonium salt at C1, decelerating electrophilic cyclization at the arylethynyl substituent at C2. This effect allows the replacement of the diazonium with azide group and subsequent closure into isoxazole ring with preservation of the alkyne. In contrast, electrophilic 5-exo-dig cyclizations to condensed pyrazoles is observed for the combination of donor substituents at the aryl alkyne moiety and an OAc substituent at C4. The latter process provides a new synthetic route to 3-ethynyl-[1,9-cd]isoxazol-6-ones that are difficult to access otherwise. DFT calculations suggest that donor substituents have only a minor effect on alkyne and diazonium polarization in the reactant but provide specific transition state stabilization by stabilizing the incipient vinyl cation. This analysis provides the first computational data on electrophilic 5-exo-dig cyclization in its parent form and the nucleophile-promoted version. This cyclization is a relatively fast but endothermic process that is rendered thermodynamically feasible by the enol-keto tautomerization with concomitant aromatization in the five-membered heteroaromatic ring. Computations suggest that the importance of nucleophilic assistance in the transition state for a relatively weak nucleophile such as water is minor because the energy gain due to the Lewis base coordination to the carbocationic center is more than compensated for by the unfavorable entropic term for the bimolecular proces.


Assuntos
Antraquinonas/química , Compostos de Diazônio/química , Compostos Heterocíclicos/química , Catálise , Estrutura Molecular , Sais
13.
Curr Cancer Drug Targets ; 10(4): 368-83, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20464779

RESUMO

We recently demonstrated that poly(ADP-ribose) polymerase (PARP)-1 is involved in angiogenesis and tumour aggressiveness. In this study we have compared the influence of abrogation of PARP-1 expression by stable gene silencing to that of the pharmacological inhibition of cellular PARP activity using PARP-1/-2 inhibitors on the chemosensitivity of tumour cells to the wide spectrum methylating agent temozolomide (TMZ) and to the N3-adenine selective methylating agent {1-methyl-4-[1-methyl-4-(3-methoxysulfonylpropanamido)pyrrole-2-carboxamido]-pyrrole-2-carboxamido}propane (Me-Lex). Silencing of PARP-1 in melanoma or cervical carcinoma lines enhanced in vitro sensitivity to TMZ and Me- Lex, and induced a higher level of cell accumulation at the G2/M phase of cell cycle with respect to controls. GPI 15427, which inhibits both PARP-1 and PARP-2, increased sensitivity to TMZ and Me-Lex both in PARP-1-proficient and - deficient cells. However, it induced different cell cycle modulations depending on PARP-1 expression, provoking a G2/M arrest only in PARP-1 silenced cells. Treatment of PARP-1 silenced cells with TMZ or Me-Lex resulted in a more extensive phosphorylation of Chk-1 and p53 as compared to PARP-1 proficient cells. The combination of the methylating agents with GPI 15427 increased Chk-1 and p53 phosphorylation both in PARP-1 proficient or deficient cells. When mice challenged with PARP-1 silenced melanoma cells were treated with the TMZ and PARP inhibitor combination there was an additional reduction in tumour growth with respect to treatment with TMZ alone. These results suggest the involvement of PARP-2 or other PARPs, in the repair of DNA damage provoked by methylating agents, highlighting the importance of targeting both PARP-1 and PARP-2 for cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Dacarbazina/análogos & derivados , Inibidores Enzimáticos/farmacologia , Netropsina/análogos & derivados , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Western Blotting , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dacarbazina/farmacologia , Sinergismo Farmacológico , Citometria de Fluxo , Fase G2/efeitos dos fármacos , Células HeLa , Humanos , Melanoma Experimental/patologia , Metilação , Camundongos , Netropsina/farmacologia , Poli(ADP-Ribose) Polimerases/genética , Temozolomida
14.
Trop Med Int Health ; 14(2): 204-12, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19236666

RESUMO

OBJECTIVES: To describe a family-focused approach to HIV care and treatment and report on the first 2 years experience of implementing the mother-to-child transmission (MTCT)-plus program in Abidjan, Côte d'Ivoire. PROGRAM: The MTCT-plus initiative aims to enroll HIV-infected pregnant and postpartum women in comprehensive HIV care and treatment for themselves and their families. MAIN OUTCOMES: Between August 2003 and August 2005, 605 HIV-infected pregnant or postpartum women and 582 HIV-exposed infants enrolled. Of their 568 male partners reported alive, 52% were aware of their wife's HIV status and 30% were tested for HIV; 53% of these tested partners were found to be HIV-infected and 78% enrolled into the program. Overall only 10% of the women enrolled together with their infected partner. On the other hand, the program involved half of the seronegative men who came for voluntary counselling and testing (VCT) in the care of their families. Of 1624 children <15 years reported alive by their mothers (excluding the last newborn infants of the most recent pregnancy systematically screened for HIV), only 10.8% were brought in for HIV testing, of whom 12.3% were found to be HIV-infected. LESSONS LEARNED AND CHALLENGES: The family-focused model of HIV care pays attention to the needs of families and household members. The program was successful in enrolling HIV women, their partners and infants in continuous follow-up. However engaging partners and family members of newly enrolled women into care involves numerous challenges such as disclosure of HIV status by women to their partners and family members. Further efforts are required to understand barriers for families accessing HIV services as strategies to improve partner involvement and provide access to care for other children in the households are needed in this West African urban setting.


Assuntos
Aconselhamento , Família , Infecções por HIV/prevenção & controle , Parceiros Sexuais , Adolescente , Adulto , Criança , Pré-Escolar , Côte d'Ivoire/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Soroprevalência de HIV , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Gravidez , Avaliação de Programas e Projetos de Saúde , Adulto Jovem
15.
Mol Psychiatry ; 14(10): 968-75, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18490926

RESUMO

In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder.


Assuntos
Tonsila do Cerebelo/fisiologia , Arginina Vasopressina/genética , Transtorno Autístico/genética , Variação Genética , Personalidade/genética , Receptores de Vasopressinas/genética , Adulto , Expressão Facial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Repetições de Microssatélites
16.
Haemophilia ; 13(3): 279-86, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17498077

RESUMO

This multicentre study sought to estimate the incidence of upper gastrointestinal (UGI) bleeding in haemophiliacs and its relationship to use of non-steroidal anti-inflammatory drugs (NSAIDs). Cox models were used to estimate relative hazards (RH) with 95% confidence intervals (CI) for postulated risk factors. Conditional logistic regression and stored sera were used to assess UGI bleeding risk with Heliobacter pylori seropositivity in cases compared with closely matched controls. During a mean of 17.4 months (range 2-34), 2285 participants, ages 13-89 (mean 36.5) were followed for 3309 person-years (py). Forty-two experienced a UGI bleeding event (incidence 1.3 per 100 py), most from ulcer (11), gastritis (four), varices (five) and Mallory Weiss tears (eight). RH was significantly increased with traditional NSAID use for <1 month (OR: 3.66; 95% CI: 1.1-11.9), but not with coxibs use. RH was significantly and independently increased with age >46 years (3.5; 95% CI: 1.1-10.6) and hepatic decompensation (4.4; 95% CI: 1.7-11.6). Likelihood of bleeding was substantially but not significantly increased (OR: 4.6; 95% CI: 0.3-83.9) with H. pylori seropositivity. These findings suggest that coxibs are a safer alternative than traditional NSAIDs in the treatment of haemophilic arthropathy.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Helicobacter pylori , Hemartrose/complicações , Hemofilia A/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Hemorragia Gastrointestinal/etiologia , Hemartrose/tratamento farmacológico , Hemofilia A/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Fatores de Risco
17.
Aliment Pharmacol Ther ; 25(5): 523-36, 2007 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-17305754

RESUMO

BACKGROUND: Several meta-analyses assessing the efficacy of anti-Helicobacter pylori treatment in adults have been published but a comparable meta-analysis in children is lacking. AIMS: To summarize the efficacy of treatments aimed at eradicating H. pylori in children and to identify sources of variation in treatment efficacy across studies. METHODS: We searched Medline, reference lists from published study reports, and conference proceedings for anti-H. pylori treatment trials in children. Weighted meta-regression models were used to find sources of variation in efficacy. RESULTS: Eighty studies (127 treatment arms) with 4436 children were included. Overall, methodological quality of these studies was poor with small sample sizes and few randomized-controlled trials. The efficacy of therapies varied across treatment arms, treatment duration, method of post-treatment assessment and geographic location. Among the regimens tested, 2-6 weeks of nitroimidazole and amoxicillin, 1-2 weeks of clarithromycin, amoxicillin and a proton pump inhibitor, and 2 weeks of a macrolide, a nitroimidazole and a proton pump inhibitor or bismuth, amoxicillin and metronidazole were the most efficacious in developed countries. CONCLUSIONS: Before worldwide treatment recommendations are given for eradication of H. pylori, additional well-designed randomized placebo-controlled paediatric trials are needed, especially in developing countries where both drug resistance and disease burden is high.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adolescente , Adulto , Criança , Pré-Escolar , Quimioterapia Combinada , Humanos , Lactente , Recém-Nascido , Resultado do Tratamento
18.
DNA Repair (Amst) ; 3(6): 617-27, 2004 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-15135729

RESUMO

Base-excision (BER) and nucleotide-excision (NER) repair play pivotal roles in protecting the genomes of dividing cells from damage by endogenous and exogenous agents (i.e. environmental genotoxins). However, their role in protecting the genome of post-mitotic neuronal cells from genotoxin-induced damage is less clear. The present study examines the role of the BER enzyme 3-alkyladenine DNA glycosylase (AAG) and the NER protein xeroderma pigmentosum group A (XPA) in protecting cerebellar neurons and astrocytes from chloroacetaldehyde (CAA) or the alkylating agent 3-methyllexitropsin (Me-Lex), which produce ethenobases or 3-methyladenine (3-MeA), respectively. Neuronal and astrocyte cell cultures prepared from the cerebellum of wild type (C57BL/6) mice or Aag(-/-) or Xpa(-/-) mice were treated with 0.1-50 microM CAA for 24h to 7 days and examined for cell viability, DNA fragmentation (TUNEL labeling), nuclear changes, and glutathione levels. Aag(-/-) neurons were more sensitive to the acute (>20 microM) and long-term (>5 microM) effects of CAA than comparably treated wild type neurons and this sensitivity correlated with the extent of DNA fragmentation and nuclear changes. Aag(-/-) neurons were also sensitive to Me-Lex at comparable concentrations of CAA. In contrast, Xpa(-/-) neurons were more sensitive than either wild type or Aag(-/-) neurons to CAA (>10 microM), but less sensitive than Aag(-/-) neurons to Me-Lex. Astrocytes from the cerebellum of wild type, Aag(-/-) or Xpa(-/-) mice were essentially insensitive to CAA at the concentrations tested. These studies demonstrate that BER and NER are required to protect neurons from genotoxin-induced cell death.


Assuntos
Acetaldeído/análogos & derivados , Adenina/análogos & derivados , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , DNA Glicosilases/fisiologia , Reparo do DNA , Proteínas de Ligação a DNA/fisiologia , Mutagênicos/toxicidade , Netropsina/análogos & derivados , Acetaldeído/toxicidade , Adenina/metabolismo , Alquilantes/toxicidade , Animais , Astrócitos/citologia , Técnicas de Cultura de Células , DNA Glicosilases/genética , Proteínas de Ligação a DNA/genética , Feminino , Glutationa/metabolismo , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Netropsina/toxicidade , Neurônios/efeitos dos fármacos , Oxirredução , Proteína de Xeroderma Pigmentoso Grupo A
19.
Aliment Pharmacol Ther ; 19 Suppl 1: 22-7, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14725575

RESUMO

The management of gastro-oesophageal reflux disease (GERD) continues to garner vast amounts of attention among physicians who care for adults. However, there is an increasing awareness of the fact that this disease, as well as several other lifelong digestive diseases (i.e. Crohn's disease) may actually have their origins in childhood. Paediatric gastro-oesophageal reflux (GER) is likely to share a similar pathophysiology to adult GER, and mounting evidence from published preliminary data suggests a genetic susceptibility to GERD. However, further studies will be necessary to confirm this hypothesis. In children, GER has a distinct presentation from that in adults, with the diagnostic work-up based upon the patient's age as well as their presenting signs and symptoms. Like their adult counterparts, the early detection and treatment of GER in children may result in a better long-term outcome, improved quality-of-life, and a reduction in overall healthcare burden. While the treatment of GER in infants tends to be conservative (i.e. positioning during feeding, smaller feedings), its management in older children parallels that of adults and includes lifestyle changes and pharmacological therapy. However, with persistent symptoms, acid suppression is the mainstay of GERD management in both children and adults. Several studies in children have verified that acid suppression with a proton pump inhibitor is superior to histamine-2 receptor antagonists. Among the proton pump inhibitors, both lansoprazole and omeprazole have been the subject of published adult and paediatric studies demonstrating their short and long-term safety, in addition to their efficacy in a variety of oesophageal and supra-oesophageal GERD related conditions. These two proton pump inhibitors are manufactured as capsules containing enteric-coated granules that can be emptied into soft foods or liquids without compromising their pharmacological effects or pharmacokinetic properties. Lansoprazole is also available as a strawberry-flavoured suspension that is acceptable to children and as an oral disintegrating tablet.


Assuntos
Refluxo Gastroesofágico/epidemiologia , Criança , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/terapia , Fármacos Gastrointestinais/uso terapêutico , Humanos , Meio-Oeste dos Estados Unidos/epidemiologia , Prevalência , Inibidores da Bomba de Prótons
20.
Health Phys ; 84(6): 756-63, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12822585

RESUMO

Radiation workers undergo routine monitoring for the evaluation of external and internal radiation exposures. The monitoring of internal exposures involves gamma spectrometry of the whole body (whole body counting) and measurements of excreta samples. Medical procedures involving internal administration of radioactive radionuclides are widely and commonly used. Medical radionuclides are typically short-lived, but high activities are generally administered, whereas occupational radionuclides are mostly long-lived and, if present, are found generally in relatively smaller quantities. The aim of the present work was to study the interference of some common medical radionuclides (201Tl, 9mTc, 57Co, and 131I) with the detection of internal occupational exposures to natural uranium and to 137Cs. Workers having undergone a medical procedure with one of the radionuclides mentioned above were asked to give frequent urine samples and to undergo whole body and thyroid counting with phoswich detectors operated at the Nuclear Research Center Negev. Urine and whole body counting monitoring were continued as long as radioactivity was detectable by gamma spectrometry. The results indicate that the activity of medical radionuclides may interfere with interpretation of occupational intakes for months after administration.


Assuntos
Exposição Ocupacional/análise , Radioisótopos/análise , Radiometria/métodos , Espectrometria gama/métodos , Contagem Corporal Total/métodos , Artefatos , Radioisótopos de Césio/análise , Análise de Falha de Equipamento/métodos , Reações Falso-Positivas , Raios gama , Humanos , Controle de Qualidade , Radioisótopos/urina , Compostos Radiofarmacêuticos/análise , Compostos Radiofarmacêuticos/urina , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Urânio/análise
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