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1.
Psychol Med ; 53(6): 2339-2351, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35144700

RESUMO

BACKGROUND: Contrasting the well-described effects of early intervention (EI) services for youth-onset psychosis, the potential benefits of the intervention for adult-onset psychosis are uncertain. This paper aims to examine the effectiveness of EI on functioning and symptomatic improvement in adult-onset psychosis, and the optimal duration of the intervention. METHODS: 360 psychosis patients aged 26-55 years were randomized to receive either standard care (SC, n = 120), or case management for two (2-year EI, n = 120) or 4 years (4-year EI, n = 120) in a 4-year rater-masked, parallel-group, superiority, randomized controlled trial of treatment effectiveness (Clinicaltrials.gov: NCT00919620). Primary (i.e. social and occupational functioning) and secondary outcomes (i.e. positive and negative symptoms, and quality of life) were assessed at baseline, 6-month, and yearly for 4 years. RESULTS: Compared with SC, patients with 4-year EI had better Role Functioning Scale (RFS) immediate [interaction estimate = 0.008, 95% confidence interval (CI) = 0.001-0.014, p = 0.02] and extended social network (interaction estimate = 0.011, 95% CI = 0.004-0.018, p = 0.003) scores. Specifically, these improvements were observed in the first 2 years. Compared with the 2-year EI group, the 4-year EI group had better RFS total (p = 0.01), immediate (p = 0.01), and extended social network (p = 0.05) scores at the fourth year. Meanwhile, the 4-year (p = 0.02) and 2-year EI (p = 0.004) group had less severe symptoms than the SC group at the first year. CONCLUSIONS: Specialized EI treatment for psychosis patients aged 26-55 should be provided for at least the initial 2 years of illness. Further treatment up to 4 years confers little benefits in this age range over the course of the study.


Assuntos
Transtornos Psicóticos , Qualidade de Vida , Adolescente , Humanos , Adulto , Transtornos Psicóticos/terapia , Transtornos Psicóticos/diagnóstico , Resultado do Tratamento , Terapia Comportamental , Fatores de Tempo
2.
Nat Methods ; 13(2): 147-50, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26657556

RESUMO

The zebrafish (Danio rerio) is a useful vertebrate model system in which to study neural circuits and behavior, but tools to modulate neurons in freely behaving animals are limited. As poikilotherms that live in water, zebrafish are amenable to thermal and pharmacological perturbations. We exploit these properties by using transient receptor potential (TRP) channels to activate or ablate specific neuronal populations using the chemical and thermal agonists of heterologously expressed TRPV1, TRPM8 and TRPA1.


Assuntos
Regulação da Expressão Gênica/fisiologia , Células Receptoras Sensoriais/fisiologia , Canais de Potencial de Receptor Transitório/fisiologia , Animais , Embrião não Mamífero , Peixe-Zebra
3.
Development ; 142(6): 1113-24, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25725064

RESUMO

Loss of neurons that express the neuropeptide hypocretin (Hcrt) has been implicated in narcolepsy, a debilitating disorder characterized by excessive daytime sleepiness and cataplexy. Cell replacement therapy, using Hcrt-expressing neurons generated in vitro, is a potentially useful therapeutic approach, but factors sufficient to specify Hcrt neurons are unknown. Using zebrafish as a high-throughput system to screen for factors that can specify Hcrt neurons in vivo, we identified the LIM homeobox transcription factor Lhx9 as necessary and sufficient to specify Hcrt neurons. We found that Lhx9 can directly induce hcrt expression and we identified two potential Lhx9 binding sites in the zebrafish hcrt promoter. Akin to its function in zebrafish, we found that Lhx9 is sufficient to specify Hcrt-expressing neurons in the developing mouse hypothalamus. Our results elucidate an evolutionarily conserved role for Lhx9 in Hcrt neuron specification that improves our understanding of Hcrt neuron development.


Assuntos
Separação Celular/métodos , Regulação da Expressão Gênica/fisiologia , Hipotálamo/embriologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Clonagem Molecular , Primers do DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Técnicas de Silenciamento de Genes , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Hipotálamo/metabolismo , Imuno-Histoquímica , Camundongos , Análise em Microsséries , Orexinas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
4.
J Neurosci ; 36(6): 1823-40, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26865608

RESUMO

The hypothalamus plays an important role in regulating sleep, but few hypothalamic sleep-promoting signaling pathways have been identified. Here we demonstrate a role for the neuropeptide QRFP (also known as P518 and 26RFa) and its receptors in regulating sleep in zebrafish, a diurnal vertebrate. We show that QRFP is expressed in ∼10 hypothalamic neurons in zebrafish larvae, which project to the hypothalamus, hindbrain, and spinal cord, including regions that express the two zebrafish QRFP receptor paralogs. We find that the overexpression of QRFP inhibits locomotor activity during the day, whereas mutation of qrfp or its receptors results in increased locomotor activity and decreased sleep during the day. Despite the restriction of these phenotypes to the day, the circadian clock does not regulate qrfp expression, and entrained circadian rhythms are not required for QRFP-induced rest. Instead, we find that QRFP overexpression decreases locomotor activity largely in a light-specific manner. Our results suggest that QRFP signaling plays an important role in promoting sleep and may underlie some aspects of hypothalamic sleep control. SIGNIFICANCE STATEMENT: The hypothalamus is thought to play a key role in regulating sleep in vertebrate animals, but few sleep-promoting signaling pathways that function in the hypothalamus have been identified. Here we use the zebrafish, a diurnal vertebrate, to functionally and anatomically characterize the neuropeptide QRFP. We show that QRFP is exclusively expressed in a small number of neurons in the larval zebrafish hypothalamus that project widely in the brain. We also show that QRFP overexpression reduces locomotor activity, whereas animals that lack QRFP signaling are more active and sleep less. These results suggest that QRFP signaling participates in the hypothalamic regulation of sleep.


Assuntos
Atividade Motora/fisiologia , Peptídeos/fisiologia , Sono/fisiologia , Peixe-Zebra/fisiologia , Sequência de Aminoácidos , Animais , Ritmo Circadiano/fisiologia , Sequência Conservada , Hipotálamo/metabolismo , Hipotálamo/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular , Larva , Dados de Sequência Molecular , Neurônios/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Receptores de Peptídeos/fisiologia , Rombencéfalo/metabolismo , Rombencéfalo/fisiologia , Transdução de Sinais/fisiologia , Medula Espinal/metabolismo , Medula Espinal/fisiologia
5.
Langmuir ; 33(12): 3000-3013, 2017 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-28215075

RESUMO

The excellent performance of functionalized iron oxide nanoparticles (IONPs) in nanomaterial and biomedical applications often relies on achieving the attachment of ligands to the iron oxide surface both in sufficient number and with proper orientation. Toward this end, we determine relationships between the ligand chemical structure and surface binding on magnetic IONPs for a series of related benzoic acid and catechol derivatives. Ligand exchange was used to introduce the model ligands, and the resultant nanoparticles were characterized using Fourier transform infrared-attenuated internal reflectance spectroscopy, transmission electron microscopy, and nanoparticle solubility behavior. An in-depth analysis of ligand electronic effects and reaction conditions reveals that the nature of ligand binding does not solely depend on the presence of functional groups known to bind to IONPs. The structure of the resultant ligand-surface complex was primarily influenced by the relative positioning of hydroxyl and carboxylic acid groups within the ligand and whether or not HCl(aq) was added to the ligand-exchange reaction. Overall, this study will help guide future ligand-design and ligand-exchange strategies toward realizing truly custom-built IONPs.

6.
Ethiop Med J ; 54(1): 27-32, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27069276

RESUMO

BACKGROUND: An outbreak of a chronic liver disease of unidentified cause, known as "Unidentified Liver Disease (ULD)" by local communities was first observed in a rural village in Tigray, northern-Ethiopia in 2001. Little was known about the geographical extent, trend, and epidemiology of the disease. METHODS: The Ethiopian Public Health Institute (EPHI) by then Ethiopian Health and Nutrition Research Institute (EHNRI), Centers for Disease Control and Prevention, World Health Organization, and Tigray Regional Health Bureaue established the ULD surveillance system in 2009 to characterize and monitor trends for this emerging disease and to identify cases for treatment and follow up. A large-scale official training was provided to the surveillance staff on case identification, management and reporting. In absence of a confirmatory test, the system used simple case definitions that could be applied by frontline staff with varying clinical training. To maximize resources, health extension workers already conducting household visits in affected communities identified cases and increased community awareness about the disease. A team was placed in Shire, in close proximity to the outbreak region, to provide support and collect reports from health facilities and district health offices. RESULTS: As of September 2011, a total of 1,033 cases, including 314 deaths were identified. Contamination of locally produced grains with several pyrrolizidine alkaloid producing plants was identified cause of the disease. Staff interviews identified that shortage and turnover of trained staff were major challenges. LESSONS LEARNED: Long term dedication by frontline staff, using simple case definitions to identify cases, and active collection of missing reports were critical for surveillance of this chronic non-infectious disease of unknown cause in a rural, resource-limited setting.


Assuntos
Grão Comestível/toxicidade , Contaminação de Alimentos/análise , Hepatopatias , Alcaloides de Pirrolizidina/toxicidade , Estudos de Casos e Controles , Doença Crônica , Surtos de Doenças , Etiópia/epidemiologia , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Masculino , Saúde Pública/métodos , População Rural/estatística & dados numéricos , Organização Mundial da Saúde
7.
Can J Psychiatry ; 60(8): 346-53, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26454556

RESUMO

OBJECTIVE: Multiple etiological and prognostic factors have been implied in schizophrenia and its outcome. Advanced paternal age has been reported as a risk factor in schizophrenia. Whether this may affect schizophrenia outcome was not previously studied. We hypothesized that advanced paternal age may have a negative effect on the outcome of relapse in schizophrenia. METHOD: We interviewed 191 patients with first-episode schizophrenia and their relatives for parental ages, sociodemographic factors at birth, birth rank, family history of psychotic disorders, and obstetric complications. The outcome measure was the presence of relapse at the end of the first year of treatment. RESULTS: In the 1-year follow-up period, 42 (22%) patients experienced 1 or more relapses. The mean paternal age was 34.62 years (SD 7.69). Patients who relapsed had significantly higher paternal age, poorer medication adherence, were female, and were hospitalized at onset, compared with patients who did not relapse. A multivariate regression analysis showed that advanced paternal age (OR 1.05, 95% CI 1.01 to 1.10), medication nonadherence (OR 2.37, 95% CI 1.12 to 4.99), and female sex (OR 2.44, 95% CI 1.14 to 5.24) independently contributed to a higher risk of relapse. Analysis between different paternal age groups found a significantly higher relapse rate with paternal age over 40. CONCLUSIONS: Advanced paternal age is found to be modestly but significantly related to more relapses, and such an effect is the strongest at a cut-off of paternal age of 40 years or older. The effect is less likely to be mediated through less effective parental supervision or nonadherence to medication. Other possible biological mechanisms need further explorations.


Assuntos
Avaliação de Resultados em Cuidados de Saúde , Idade Paterna , Esquizofrenia/terapia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Recidiva , Risco , Fatores Sexuais , Adulto Jovem
8.
Nucleic Acids Res ; 41(4): 2769-78, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23303782

RESUMO

Zinc-finger nucleases (ZFNs) and TAL effector nucleases (TALENs) have been shown to induce targeted mutations, but they have not been extensively tested in any animal model. Here, we describe a large-scale comparison of ZFN and TALEN mutagenicity in zebrafish. Using deep sequencing, we found that TALENs are significantly more likely to be mutagenic and induce an average of 10-fold more mutations than ZFNs. We observed a strong correlation between somatic and germ-line mutagenicity, and identified germ line mutations using ZFNs whose somatic mutations rates are well below the commonly used threshold of 1%. Guidelines that have previously been proposed to predict optimal ZFN and TALEN target sites did not predict mutagenicity in vivo. However, we observed a significant negative correlation between TALEN mutagenicity and the number of CpG repeats in TALEN target sites, suggesting that target site methylation may explain the poor mutagenicity of some TALENs in vivo. The higher mutation rates and ability to target essentially any sequence make TALENs the superior technology for targeted mutagenesis in zebrafish, and likely other animal models.


Assuntos
Desoxirribonucleases/metabolismo , Mutagênese , Dedos de Zinco , Animais , Ilhas de CpG , Mutação em Linhagem Germinativa , Mutação INDEL , Mutação , Peixe-Zebra/embriologia , Peixe-Zebra/genética
9.
J Environ Health ; 78(5): 14-21, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26738314

RESUMO

Lake County, California, is in a high geothermal-activity area. Over the past 30 years, the city of Clearlake has reported health effects and building evacuations related to geothermal venting. Previous investigations in Clearlake revealed hydrogen sulfide at levels known to cause health effects and methane at levels that can cause explosion risks. The authors conducted an investigation in multiple cities and towns in Lake County to understand better the risk of geothermal venting to the community. They conducted household surveys and outdoor air sampling of hydrogen sulfide and methane and found community members were aware of geothermal venting and some expressed concerns. The authors did not, however, find hydrogen sulfide above the California Environmental Protection Agency air quality standard of 30 parts per billion over one hour or methane above explosive thresholds. The authors recommend improving risk communication, continuing to monitor geothermal gas effects on the community, and using community reports and complaints to monitor and document geothermal venting incidents.


Assuntos
Poluentes Atmosféricos/análise , Exposição Ambiental , Gases/análise , Conhecimentos, Atitudes e Prática em Saúde , Sulfeto de Hidrogênio/análise , Metano/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , California , Criança , Pré-Escolar , Cidades , Estudos Transversais , Monitoramento Ambiental , Energia Geotérmica , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Medição de Risco , Adulto Jovem
10.
Neuropsychobiology ; 69(4): 243-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24993979

RESUMO

BACKGROUND/AIMS: The Remission in Schizophrenia Working Group has defined remission as 'a low-mild symptom intensity level, maintained for a minimum of 6 months, where such symptoms do not affect an individual's behaviour' [Andreasen et al.: Am J Psychiatry 2005;162:441-449]. Since brain morphology relates to symptomatology, treatment and illness progression, MRI may assist in predicting remission. METHODS: Thirty-nine patients newly diagnosed with DSM-IV schizophrenia underwent MRI brain scan prior to antipsychotic exposure. The Global Assessment of Functioning (GAF) score was entered into a voxel-based analysis to evaluate its relationship with cerebral grey matter volume from the baseline MRI. We entered age, total intracranial volume and intake GAF score as co-variates. Males and females were analysed separately because gender is a potent determinant of outcome. RESULTS: Males had lower GAF scores than females, both at intake and at 1 year. Males comprised only 40% (12 out of 39) of the early remission group. For females only, early remission was strongly and positively correlated with bilateral lentiform and striatal volumes. For males, there was no such relationship. CONCLUSION: Larger striato-thalamic volume correlated with early remission in females only. These baseline MRI findings were unlikely to be confounded by antipsychotic treatment and chronicity. These brain morphological markers show gender dimorphism and may assist in the prediction of early remission in newly diagnosed schizophrenia.


Assuntos
Corpo Estriado/patologia , Esquizofrenia/diagnóstico , Esquizofrenia/patologia , Tálamo/patologia , Adulto , Antipsicóticos/uso terapêutico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Prognóstico , Esquizofrenia/tratamento farmacológico , Caracteres Sexuais
11.
Am J Public Health ; 103(8): e52-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23763401

RESUMO

OBJECTIVES: We describe the demographics of the decedents from the tornado outbreak in Alabama on April 27, 2011; examine the circumstances of death surrounding these fatalities; and identify measures to prevent future tornado-related fatalities. METHODS: We collected information about the decedents from death certificates, disaster-related mortality surveillance, and interview data collected by American Red Cross volunteers from the decedent's families. We describe demographic characteristics, circumstances and causes of death, and sheltering behaviors before death. RESULTS: Of the 247 fatalities, females and older adults were at highest risk for tornado-related deaths. Most deaths were directly related to the tornadoes, on scene, and trauma-related. The majority of the deceased were indoors in single-family homes. Word of mouth was the most common warning mechanism. CONCLUSIONS: This tornado event was the third deadliest in recent US history. Our findings support the need for local community shelters, enhanced messaging to inform the public of shelter locations, and encouragement of word-of-mouth warnings and personal and family preparedness planning, with a special focus on assisting vulnerable individuals in taking shelter.


Assuntos
Desastres/estatística & dados numéricos , Tornados , Ferimentos e Lesões/mortalidade , Distribuição por Idade , Fatores Etários , Alabama/epidemiologia , Feminino , Humanos , Masculino , Vigilância da População , Fatores de Risco , Fatores Sexuais
12.
Aust N Z J Psychiatry ; 46(2): 100-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22311526

RESUMO

OBJECTIVE: The aim of the current study was to investigate the rates and predictors of symptomatic remission and recovery in patients presenting with first-episode psychosis 3 years after treatment initiation. METHODS: Seven hundred participants aged 15-25 years consecutively enrolled in a territory-wide early intervention programme in Hong Kong from July 2001 to August 2003 fulfilled study inclusion criteria, with 539 completing 3-year follow-up. Baseline and follow-up variables were collected via systematic medical file review. The operational criteria for recovery were based on clinical definition incorporating both symptom and functional dimensions. RESULTS: By the end of 3-year follow-up, 58.8% (n = 317) and 17.4% (n = 94) of participants met criteria for symptomatic remission and recovery, respectively. Around half (51.2%, n = 276) were not remitted either symptomatically or functionally in the last 12 months of follow-up. Of those who achieved sustained symptomatic remission, only 43.1% were also in functional remission. Patients in symptomatic remission had lower rate of admissions, shorter duration of hospitalisations and more favourable psychosocial functioning than non-remitted counterparts. Logistic regression analysis revealed that female sex, older age of onset of psychosis, shorter duration of untreated psychosis (DUP) and early symptom resolution predicted symptomatic remission at the end of follow-up. Higher educational attainment, superior baseline occupational status and shorter DUP were found to be predictive of recovery. CONCLUSION: In a large representative cohort of Chinese young people presenting with first-episode psychosis, although more than half achieved symptomatic remission 3 years after service entry, the rates of functional remission and recovery were low. More intensive psychosocial interventions may be required to further improve patients' functional outcome.


Assuntos
Transtornos Psicóticos/diagnóstico , Indução de Remissão , Adolescente , Adulto , Fatores Etários , Feminino , Seguimentos , Hong Kong , Humanos , Masculino , Prognóstico , Recidiva , Fatores de Risco , Fatores Sexuais , Fatores de Tempo
13.
Neuron ; 54(5): 771-85, 2007 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-17553425

RESUMO

Enduring forms of synaptic plasticity are thought to require ongoing regulation of adhesion molecules, such as N-cadherin, at synaptic junctions. Little is known about the activity-regulated trafficking of adhesion molecules. Here we demonstrate that surface N-cadherin undergoes a surprisingly high basal rate of internalization. Upon activation of NMDA receptors (NMDAR), the rate of N-cadherin endocytosis is significantly reduced, resulting in an accumulation of N-cadherin in the plasma membrane. Beta-catenin, an N-cadherin binding partner, is a primary regulator of N-cadherin endocytosis. Following NMDAR stimulation, beta-catenin accumulates in spines and exhibits increased binding to N-cadherin. Overexpression of a mutant form of beta-catenin, Y654F, prevents the NMDAR-dependent regulation of N-cadherin internalization, resulting in stabilization of surface N-cadherin molecules. Furthermore, the stabilization of surface N-cadherin blocks NMDAR-dependent synaptic plasticity. These results indicate that NMDAR activity regulates N-cadherin endocytosis, providing a mechanistic link between structural plasticity and persistent changes in synaptic efficacy.


Assuntos
Caderinas/metabolismo , Espinhas Dendríticas/metabolismo , Endocitose/fisiologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Sinapses/metabolismo , Animais , Animais Recém-Nascidos , Células COS , Membrana Celular/metabolismo , Chlorocebus aethiops , Espinhas Dendríticas/ultraestrutura , Hipocampo/citologia , Humanos , Camundongos , Microscopia Confocal , Mutação/genética , Plasticidade Neuronal/fisiologia , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Ligação Proteica/fisiologia , Transporte Proteico/fisiologia , Ratos , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/fisiologia , beta Catenina/genética , beta Catenina/metabolismo
14.
Aust N Z J Psychiatry ; 45(3): 199-205, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21261552

RESUMO

OBJECTIVE: The aim of the current study was to investigate gender differences with respect to pre-treatment characteristics, clinical presentation, service utilization and functional outcome in patients presenting with first-episode psychosis. METHODS: A total of 700 participants (men, n = 360; women, n = 340) aged 15 to 25 years consecutively enrolled in a territory-wide first-episode psychosis treatment programme in Hong Kong from July 2001 to August 2003 were studied. Baseline and three-year follow up variables were collected via systematic medical file review. RESULTS: At service entry, men had significantly lower educational attainment (p < 0.01), longer median duration of untreated psychosis (p < 0.001), fewer past suicidal attempts (p < 0.01), more severe negative symptoms (p < 0.05) and fewer affective symptoms (p < 0.01) than women. There was no significant gender difference in age of onset. In three-year follow up, men had more prominent negative symptoms (p < 0.001), fewer affective symptoms (p < 0.01), more violent behaviour and forensic records (p < 0.01), and higher rate of substance abuse (p < 0.01). Women achieved higher levels of functioning than men (Social Occupational Functioning Assessment Scale (SOFAS), p < 0.001) and a significantly higher proportion of women than men engaged in full-time employment or study for at least 12 consecutive months (p < 0.001) in the initial three years after psychiatric treatment. CONCLUSION: Notable gender differences in clinical profiles, illness trajectory and functional outcome were demonstrated in Chinese young people suffering from first-episode psychosis. Differential needs between men and women and hence gender-specific therapeutic strategies should be considered in early intervention service.


Assuntos
Transtornos Psicóticos/diagnóstico , Caracteres Sexuais , Adolescente , Adulto , Feminino , Seguimentos , Hong Kong , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/psicologia , Tentativa de Suicídio/psicologia
15.
Percept Mot Skills ; 112(1): 91-103, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21466082

RESUMO

Random number generation with a written response mode provides a potentially appealing marker for executive processes. Impaired performance on written random number generation tasks has been reported in chronic schizophrenic patients. However, no study has investigated whether such a deficit occurs in early schizophrenia and whether its profile and severity are similar to those in patients with chronic illness. This study investigated the ability to generate random numbers in patients with early schizophrenia (n = 44) and a healthy control group (n = 48). Patients were less able to maintain several production strategies and generated more stereotyped response sequences, whereas their abilities to identify randomness with an even-handed treatment of digits and to monitor the equality of occurrence of single digits appeared to remain intact. These results provide evidence that some aspects of the deficits in random number generation among chronic schizophrenic patients are also present at early psychotic episode, while some other aspects are relatively less affected in the early years.


Assuntos
Transtornos Cognitivos/psicologia , Função Executiva/fisiologia , Psicologia do Esquizofrênico , Adulto , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Esquizofrenia , Índice de Gravidade de Doença
16.
Ann Neurol ; 64(3): 284-93, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18825662

RESUMO

OBJECTIVE: A major goal of epilepsy research is to understand the molecular and functional basis of seizure genesis. A human GABA(A) gamma2 gene mutation (R43Q) is associated with generalized epilepsy. Introduction of this mutation into a mouse by gene targeting recapitulates the human phenotype demonstrating a strong genotype to phenotype link. GABA(A) receptors play a role in the moment-to-moment control of brain function and also on the long-term wiring of the brain by directing neuronal development. Our objective was to determine whether developmental expression of the mutation alters seizure susceptibility later in life. METHODS: A tetracycline-based conditional model for activation of a hypomorphic Q43 disease allele was created and validated. Seizure susceptibility was assessed using the subcutaneous pentylenetetrazole model. RESULTS: Seizure susceptibility was significantly reduced in mice where the Q43 allele was suppressed during development. INTERPRETATION: These results demonstrate that a human epilepsy-causing mutation impacts network stability during a critical developmental period. These data suggest that identification of presymptomatic children may provide a window for therapeutic intervention before overt symptoms are observed, potentially altering the course of epileptogenesis.


Assuntos
Encéfalo/metabolismo , Epilepsia/genética , Epilepsia/metabolismo , Predisposição Genética para Doença/genética , Mutação/genética , Receptores de GABA-A/genética , Animais , Encéfalo/fisiopatologia , Química Encefálica/genética , Convulsivantes , Modelos Animais de Doenças , Epilepsia/fisiopatologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Rede Nervosa/fisiopatologia , Inibição Neural/genética , Pentilenotetrazol , Tetraciclina/farmacologia , Ácido gama-Aminobutírico/metabolismo
17.
Cogn Neuropsychiatry ; 14(4-5): 451-72, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19634039

RESUMO

INTRODUCTION: The endophenotype research strategy aims at reducing complex clinical phenomena to reveal a more tractable mapping to underlying genes. Cognitive dysfunctions have been widely pursued as target endophenotype in schizophrenia. We critically discuss the promise and limitations of this approach. METHODS: Relevant theoretical and empirical issues on genes and behaviour, neurocognitive structure and psychopathology were selectively reviewed and discussed. RESULTS: Some important inherent limitations of the current cognitive endophenotype approach were identified. These include reliance on (1) classic neuropsychology; (2) deficit measures; and (3) a general information processing approach with the use of content-independent, neutral stimuli. As a result, many current cognitive endophenotypes are likely to overlap and converge with general cognitive impairments, which may be shared with other disorders. CONCLUSIONS: We propose three novel directions for further psychosis endophenotype research: (1) in addition to such content-independent computational processes, which operate in a similar way regardless of the stimuli, it is important to consider the potential roles of "content-dependent endophenotypes", which operate on different stimuli in consistently different manners. Advances in cognitive studies suggest there may be evolutionarily important aspects of cognition which are content-dependent. We propose that both content-independent and content-dependent processes should be addressed in psychosis research. (2) In line with the emphasis on content, close attention should be paid to the study of "psychopathological endophenotypes" in addition to cognitive endophenotypes. (3) "Neurocomputational endophenotypes" may be defined by parsing cognitive processes into "subsystems" with specific computational processing algorithms and considering key computational parameters suggested from these models. These potential "neurocomputational endophenotypes" (such as neuronal noise, synaptic learning algorithms) are potentially intermediate variables located between the levels of cognition and neurobiology.


Assuntos
Cognição/fisiologia , Biologia Computacional , Neurologia , Fenótipo , Transtornos Psicóticos/psicologia , Genótipo , Humanos , Transtornos Mentais/psicologia
18.
Prehosp Disaster Med ; 34(3): 265-273, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31204639

RESUMO

INTRODUCTION: In recent years, several high-profile attacks on hospitals providing medical aid in conflict settings have raised international concern. The International Humanitarian Law prohibits the deliberate targeting of health care settings. Violation of this law is considered a war crime and impacts both those delivering and receiving medical aid. PROBLEM: While it has been demonstrated that both aid workers and health care settings are increasingly being targeted, little is known about the trends and characteristics of security incidents involving aid workers in health care compared to non-health care settings. METHODS: Data from the publicly available Aid Worker Security Database (AWSD) containing security incidents involving humanitarian aid workers world-wide were used in this study. The security incidents occurring from January 1, 1997 through December 31, 2016 were classified by two independent reviewers as having occurred in health care and non-health care settings, and those in health care settings were further classified into five categories (hospital, health clinic, mobile clinic, ambulance, and vaccination visit) for the analysis. A stratified descriptive analysis, χ2 Goodness of Fit test, and Cochran-Armitage test for trend were used to examine and compare security incidents occurring in health care and non-health care settings. RESULTS: Among the 2,139 security incidents involving 4,112 aid workers listed in the AWSD during the study period, 74 and 2,065 incidents were in health care settings and non-health care settings, respectively. There was a nine-fold increase from five to 45 incidents in health care settings (χ2 = 56.27; P < .001), and a five-fold increase from 159 to 852 incidents in non-health care settings (χ2 = 591.55; P < .001), from Period 1 (1997-2001) to Period 4 (2012-2016). Of the 74 incidents in health care settings, 23 (31.1%) occurred in ambulances, 15 (20.3%) in hospitals, 13 (17.6%) in health clinics, 13 (17.6%) during vaccination visits, and six (8.1%) in mobile clinics. Bombings were the most common means of attack in hospitals (N = 9; 60.0%), followed by gun attacks (N = 3; 20.0%). In health care settings, 184 (95.3%) were national staff and nine (4.7%) were international staff. CONCLUSION: Security threats are a growing occupational health hazard for aid workers, especially those working in health care settings. There is a need for high-quality data from the field to better monitor the rapidly changing security situation and improve counter-strategies so aid workers can serve those in need without having to sacrifice their lives.


Assuntos
Pessoal de Saúde/organização & administração , Saúde Ocupacional , Socorro em Desastres/organização & administração , Medidas de Segurança/tendências , Violência/estatística & dados numéricos , Exposição à Guerra/efeitos adversos , Altruísmo , Bases de Dados Factuais , Atenção à Saúde/organização & administração , Feminino , Humanos , Masculino , Estudos Retrospectivos , Medidas de Segurança/normas , Violência/prevenção & controle
19.
Sci Rep ; 9(1): 12405, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455847

RESUMO

The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Peixe-Zebra/fisiologia , Animais , Animais Geneticamente Modificados/fisiologia , Anti-Inflamatórios não Esteroides/farmacologia , Caseína Quinase I/antagonistas & inibidores , Caseína Quinase I/metabolismo , Larva/efeitos dos fármacos , Larva/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Receptores de Glicina/agonistas , Receptores de Glicina/metabolismo , Taurina/farmacologia , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/metabolismo
20.
Western Pac Surveill Response J ; 10(2): 22-30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31720051

RESUMO

OBJECTIVE: To document the evolution and optimization of the Zika virus (ZIKV) disease surveillance system in southern Viet Nam in 2016 and to describe the characteristics of the identified ZIKV-positive cases. METHODS: We established a sentinel surveillance system to monitor ZIKV transmission in eight sites in eight provinces and expanded the system to 71 sites in 20 provinces in southern Viet Nam in 2016. Blood and urine samples from patients who met the case definition at the sentinel sites were tested for ZIKV using real-time reverse transcription polymerase chain reaction at the Pasteur Institute in Ho Chi Minh City (PI-HCMC). We conducted descriptive analysis and mapped the ZIKV-positive cases. RESULTS: In 2016, 2190 specimens from 20 provinces in southern Viet Nam were tested for ZIKV at PI-HCMC; 626 (28.6%), 484 (22.1%), 35 (1.6%) and 1045 (47.7%) tests were conducted in the first, second, third and fourth quarters of the year, respectively. Of these tested specimens, 214 (9.8%) were ZIKV positive with 212 (99.1%) identified in the fourth quarter. In the fourth quarter, the highest positivity rate was those in age groups 30-39 years (30.0%) and 40-59 years (31.6%). Of the 214 ZIKV-positive patients, 210 (98.1%) presented with rash, 194 (90.7%) with fever, 149 (69.6%) with muscle pain, 123 (57.5%) with joint pain and 66 (30.8%) with conjunctivitis. DISCUSSION: The surveillance system for ZIKV disease underwent several phases of optimization in 2016, guided by the most up-to-date local data. Here we demonstrate an adaptable surveillance system that detected ZIKV-positive cases in southern Viet Nam.


Assuntos
Vigilância de Evento Sentinela , Infecção por Zika virus/epidemiologia , Zika virus/isolamento & purificação , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos , Vietnã/epidemiologia , Adulto Jovem
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