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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.
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Trastornos Psicóticos , Calidad de Vida , Adolescente , Humanos , Adulto , Trastornos Psicóticos/terapia , Trastornos Psicóticos/diagnóstico , Resultado del Tratamiento , Terapia Conductista , Factores de TiempoRESUMEN
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.
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Vigilancia de Guardia , Infección por el Virus Zika/epidemiología , Virus Zika/aislamiento & purificación , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/estadística & datos numéricos , Vietnam/epidemiología , Adulto JovenRESUMEN
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.
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Ritmo Circadiano/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Pez Cebra/fisiología , Animales , Animales Modificados Genéticamente/fisiología , Antiinflamatorios no Esteroideos/farmacología , Quinasa de la Caseína I/antagonistas & inhibidores , Quinasa de la Caseína I/metabolismo , Larva/efectos de los fármacos , Larva/fisiología , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Glicina/agonistas , Receptores de Glicina/metabolismo , Taurina/farmacología , Pez Cebra/crecimiento & desarrollo , Proteínas de Pez Cebra/antagonistas & inhibidores , Proteínas de Pez Cebra/metabolismoRESUMEN
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.
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Personal de Salud/organización & administración , Salud Laboral , Sistemas de Socorro/organización & administración , Medidas de Seguridad/tendencias , Violencia/estadística & datos numéricos , Exposición a la Guerra/efectos adversos , Altruismo , Bases de Datos Factuales , Atención a la Salud/organización & administración , Femenino , Humanos , Masculino , Estudios Retrospectivos , Medidas de Seguridad/normas , Violencia/prevención & controlRESUMEN
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.
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Diarrhoeal disease is the second leading cause of death in children under age 5 worldwide, with rotavirus being the main etiology. In the Lao People's Democratic Republic, acute watery diarrhoea (AWD) was introduced as one of the national notifiable diseases in 2004. We retrospectively reviewed the aggregate (n = 117 277) and case-based (n = 67 755) AWD surveillance data from 2009 to 2013 reported weekly from 1115 health facilities nationwide. Rotavirus rapid test data from all eight sentinel sites in Vientiane Capital in 2013 were also collected for analysis. The incidence of AWD ranged between 215 and 476 cases per 100 000 population and increased from 2009 to 2012 when it levelled off. The most affected age group was children under 5 who were about seven to nine times more likely to have AWD than the rest of the population (P < 0.0001). In children under 5, 74.8% of the cases were aged 0-24 months and AWD was 1.28 times more common in males (P < 0.0001). Among the 230 stool specimens tested in children under 5 in 2013, 109 (47.4%) tested positive for rotavirus. The increased AWD incidence over the study period may reflect a true increase in AWD or an improved sensitivity of the system. We recommend new mothers breastfeed up to two years after birth, which is known to reduce AWD morbidity and mortality in young children. We also recommend conducting rotavirus disease burden and cost-effectiveness studies to explore the benefits of introduction of rotavirus vaccine.
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Diarrea/epidemiología , Vigilancia de la Población , Infecciones por Rotavirus/epidemiología , Lactancia Materna/métodos , Lactancia Materna/tendencias , Preescolar , Diarrea/mortalidad , Diarrea/virología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Laos/epidemiología , Masculino , Madres , Estudios Retrospectivos , Rotavirus/aislamiento & purificaciónRESUMEN
BACKGROUND: In January 2015, the Lao People's Democratic Republic Ministry of Health received a report of 34 cases of fever and rash with one laboratory-confirmed measles case in Houitone village, Pakseng District of Luang Prabang Province. Between 21 and 27 January, we conducted a field investigation to determine the etiology, magnitude and severity of this outbreak. METHODS: We conducted active case findings in Houitone and neighbouring villages and collected information on age, location, date of rash onset, symptoms and measles vaccination status. We collected serum samples from cases with rash onset of less than 28 days and tested for measles and rubella IgM using enzyme-linked immunosorbent assay. RESULTS: Between 22 December 2014 and 23 January 2015, 190 fever and rash cases were identified in seven villages in Pakseng District with the majority of the cases in Houitone village. The most affected age group was between 1 and 9 years. The majority of the rashes were vesicular. Of the additional 43 serum samples collected, no samples tested positive for measles or rubella IgM. The clinical manifestation and epidemiology of the disease suggested a varicella outbreak. CONCLUSION: The rapid response to a single laboratory-confirmed measles case did not identify a measles outbreak but suggested a varicella outbreak. Low measles vaccination coverage led us to recommend a routine catch-up vaccination campaign. We also recommend collecting information of rash types and photos of rashes in future fever and rash outbreaks to better differentiate potential etiologies.
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Sarampión/epidemiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Laos/epidemiología , Masculino , Sarampión/diagnóstico , Rubéola (Sarampión Alemán)/diagnóstico , Rubéola (Sarampión Alemán)/epidemiología , Encuestas y CuestionariosRESUMEN
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.
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Grano Comestible/toxicidad , Contaminación de Alimentos/análisis , Hepatopatías , Alcaloides de Pirrolicidina/toxicidad , Estudios de Casos y Controles , Enfermedad Crónica , Brotes de Enfermedades , Etiopía/epidemiología , Femenino , Necesidades y Demandas de Servicios de Salud , Humanos , Hepatopatías/diagnóstico , Hepatopatías/epidemiología , Hepatopatías/etiología , Masculino , Salud Pública/métodos , Población Rural/estadística & datos numéricos , Organización Mundial de la SaludRESUMEN
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 â¼10 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.
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Actividad Motora/fisiología , Péptidos/fisiología , Sueño/fisiología , Pez Cebra/fisiología , Secuencia de Aminoácidos , Animales , Ritmo Circadiano/fisiología , Secuencia Conservada , Hipotálamo/metabolismo , Hipotálamo/fisiología , Péptidos y Proteínas de Señalización Intercelular , Larva , Datos de Secuencia Molecular , Neuronas/metabolismo , Péptidos/genética , Péptidos/metabolismo , Receptores de Péptidos/genética , Receptores de Péptidos/metabolismo , Receptores de Péptidos/fisiología , Rombencéfalo/metabolismo , Rombencéfalo/fisiología , Transducción de Señal/fisiología , Médula Espinal/metabolismo , Médula Espinal/fisiologíaRESUMEN
Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotropin releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather probably acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway.
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Regulación de la Expresión Génica/genética , Neuropéptidos/genética , Neuropéptidos/metabolismo , Sueño/genética , Vigilia/genética , Factores de Edad , Compuestos de Anilina/farmacología , Animales , Tronco Encefálico/citología , Tronco Encefálico/crecimiento & desarrollo , Tronco Encefálico/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Larva , Ratones Transgénicos , Actividad Motora/genética , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Pirimidinas/farmacología , Receptores de Complemento 3b/metabolismo , Receptores de Neurotransmisores/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
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.
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Regulación de la Expresión Génica/fisiología , Células Receptoras Sensoriales/fisiología , Canales de Potencial de Receptor Transitorio/fisiología , Animales , Embrión no Mamífero , Pez CebraRESUMEN
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.
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Evaluación de Resultado en la Atención de Salud , Edad Paterna , Esquizofrenia/terapia , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Recurrencia , Riesgo , Factores Sexuales , Adulto JovenRESUMEN
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.
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Separación Celular/métodos , Regulación de la Expresión Génica/fisiología , Hipotálamo/embriología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuronas/metabolismo , Neuropéptidos/metabolismo , Factores de Transcripción/metabolismo , Proteínas de Pez Cebra/metabolismo , Animales , Animales Modificados Genéticamente , Clonación Molecular , Cartilla de ADN/genética , Ensayo de Cambio de Movilidad Electroforética , Técnicas de Silenciamiento del Gen , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Ensayos Analíticos de Alto Rendimiento/métodos , Hipotálamo/metabolismo , Inmunohistoquímica , Ratones , Análisis por Micromatrices , Orexinas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/genética , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
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.
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Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales , Gases/análisis , Conocimientos, Actitudes y Práctica en Salud , Sulfuro de Hidrógeno/análisis , Metano/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , California , Niño , Preescolar , Ciudades , Estudios Transversales , Monitoreo del Ambiente , Energía Geotérmica , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Medición de Riesgo , Adulto JovenRESUMEN
Pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation (AF). Histone deacetylases (HDACs) are vital to calcium homeostasis and AF genesis. However, the electrophysiological effects of HDAC inhibition were unclear. This study evaluated whether HDAC inhibition can regulate PV electrical activity through calcium modulation. Whole-cell patch-clamp, confocal microscopic with fluorescence, and Western blot were used to evaluate electrophysiological characteristics and Ca(2+) dynamics in isolated rabbit PV cardiomyocytes with and without MPT0E014 (a pan HDAC inhibitor), MS-275 (HDAC1 and 3 inhibitor), and MC-1568 (HDAC4 and 6 inhibitor) for 5~8h. Atrial electrical activity and induced-AF (rapid atrial pacing and acetylcholine infusion) were measured in rabbits with and without MPT0E014 (10mg/kg treated for 5 hours) in vivo. MPT0E014 (1 µM)-treated PV cardiomyocytes (n=12) had slower beating rates (2.1 ± 0.2 vs. 2.8 ± 0.1 Hz, p < 0.05) than control PV cardiomyocytes. However, control (n=11) and MPT0E014 (1 µM)-treated (n = 12) SAN cardiomyocytes had similar beating rates (3.2 ± 0.2 vs. 2.9 ± 0.3 Hz). MS-275-treated PV cardiomyocytes (n = 12, 2.3 ± 0.2 Hz), but not MC-1568-treated PV cardiomyocytes (n=14, 3.1 ± 0.3 Hz) had slower beating rates than control PV cardiomocytes. MPT0E014-treated PV cardiomyocytes (n=14) had a lower frequency (2.4 ± 0.6 vs. 0.3 ± 0.1 spark/mm/s, p < 0.05) of Ca(2+) sparks than control PV (n=17) cardiomyocytes. As compared to control, MPT0E014-treated PV cardiomyocytes had reduced Ca(2+) transient amplitudes, sodium-calcium exchanger currents, and ryanodine receptor expressions. Moreover, MPT0E014-treated rabbits had less AF and shorter AF duration than control rabbits. In conclusions, HDAC inhibition reduced PV arrhythmogenesis and AF inducibility with modulation on calcium homeostasis.
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Fibrilación Atrial/prevención & control , Fibrilación Atrial/fisiopatología , Calcio/fisiología , Inhibidores de Histona Desacetilasas/farmacología , Miocitos Cardíacos/fisiología , Venas Pulmonares/fisiología , Animales , Inhibidores de Histona Desacetilasas/uso terapéutico , Masculino , Miocitos Cardíacos/efectos de los fármacos , Venas Pulmonares/efectos de los fármacos , ConejosRESUMEN
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.
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Cuerpo Estriado/patología , Esquizofrenia/diagnóstico , Esquizofrenia/patología , Tálamo/patología , Adulto , Antipsicóticos/uso terapéutico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Pronóstico , Esquizofrenia/tratamiento farmacológico , Caracteres SexualesRESUMEN
Dangerously cold weather threatens life and property. During periods of extreme cold due to wind chill, the National Weather Service (NWS) issues wind chill warnings to prompt the public to take action to mitigate risks. Wind chill warnings are based on ambient temperatures and wind speeds. Since 2010, NWS has piloted a new extreme cold warning issued for cold temperatures in wind and nonwind conditions. The North Dakota Department of Health, NWS, and the Centers for Disease Control and Prevention collaborated in conducting household surveys in Burleigh County, North Dakota, to evaluate this new warning. The objectives of the evaluation were to assess whether residents heard the new warning and to determine if protective behaviors were prompted by the warning. This was a cross-sectional survey design using the Community Assessment for Public Health Emergency Response (CASPER) methodology to select a statistically representative sample of households from Burleigh County. From 10 to 11 April 2012, 188 door-to-door household interviews were completed. The CASPER methodology uses probability sampling with weighted analysis to estimate the number and percentage of households with a specific response within Burleigh County. The majority of households reported having heard both the extreme cold and wind chill warnings, and both warnings prompted protective behaviors. These results suggest this community heard the new warning and took protective actions after hearing the warning.
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OBJECTIVE: Relapse is common among patients with psychotic disorders. Identification of relapse predictors is important for decision regarding maintenance medication. Naturalistic studies often identify medication non-adherence as a dominant predictor. There are relatively few studies for predictors where adherence is already known. It is this situation i.e., discontinuation of medication that predictors will be most useful. We identify predictors for relapse in situations of (i) discontinuation and (ii) continuation of maintenance medication. METHOD: Analysis of relapse predictors is based on a randomized controlled study (n=178) comparing relapse rates between patients who discontinued or continued medication for at least 1 year following first-episode psychosis. Demographic, clinical and neurocognitive variables were assessed at baseline as predictors of relapse within 1 year. RESULTS: Risk of relapse was 79% in the discontinuation group and 41% in the maintenance group. Predictors in the discontinuation group were diagnosis of schizophrenia, poorer semantic fluency performance, and higher blink rate. Predictors in the continuation group were disinhibition soft signs and more general psychopathology symptoms. CONCLUSION: Different predictors of relapse were identified for first episode psychosis patients who discontinued and continued maintenance medication. Neurocognitive dysfunctions are important predictors for both groups. While signs of frontal dysfunction and dopamine hyperactivity predict relapse in the discontinuation group, sign of cognitive disinhibition predicts relapse in the continuation group.
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Antipsicóticos/administración & dosificación , Dibenzotiazepinas/administración & dosificación , Trastornos Psicóticos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Fumarato de Quetiapina , Prevención Secundaria , Resultado del Tratamiento , Adulto JovenRESUMEN
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.