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1.
Sci Rep ; 9(1): 11171, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371748

RESUMO

Nipah virus (NiV) has emerged as a highly lethal zoonotic paramyxovirus that is capable of causing a febrile encephalitis and/or respiratory disease in humans for which no vaccines or licensed treatments are currently available. There are two genetically and geographically distinct lineages of NiV: NiV-Malaysia (NiV-M), the strain that caused the initial outbreak in Malaysia, and NiV-Bangladesh (NiV-B), the strain that has been implicated in subsequent outbreaks in India and Bangladesh. NiV-B appears to be both more lethal and have a greater propensity for person-to-person transmission than NiV-M. Here we describe the generation and characterization of stable RNA polymerase II-driven infectious cDNA clones of NiV-M and NiV-B. In vitro, reverse genetics-derived NiV-M and NiV-B were indistinguishable from a wildtype isolate of NiV-M, and both viruses were pathogenic in the Syrian hamster model of NiV infection. We also describe recombinant NiV-M and NiV-B with enhanced green fluorescent protein (EGFP) inserted between the G and L genes that enable rapid and sensitive detection of NiV infection in vitro. This panel of molecular clones will enable studies to investigate the virologic determinants of henipavirus pathogenesis, including the pathogenic differences between NiV-M and NiV-B, and the high-throughput screening of candidate therapeutics.

2.
PLoS Pathog ; 15(2): e1007564, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30817809

RESUMO

There are a number of vaccine candidates under development against a small number of the most common outbreak filoviruses all employing the virus glycoprotein (GP) as the vaccine immunogen. However, antibodies induced by such GP vaccines are typically autologous and limited to the other members of the same species. In contrast, T-cell vaccines offer a possibility to design a single pan-filovirus vaccine protecting against all known and even likely existing, but as yet unencountered members of the family. Here, we used a cross-filovirus immunogen based on conserved regions of the filovirus nucleoprotein, matrix and polymerase to construct simian adenovirus- and poxvirus MVA-vectored vaccines, and in a proof-of-concept study demonstrated a protection of the BALB/c and C57BL/6J mice against high, lethal challenges with Ebola and Marburg viruses, two distant members of the family, by vaccine-elicited T cells in the absence of GP antibodies.


Assuntos
Filoviridae/imunologia , Linfócitos T/imunologia , Vacinas Virais/farmacologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra Ebola , Ebolavirus/patogenicidade , Feminino , Filoviridae/metabolismo , Filoviridae/patogenicidade , Doença pelo Vírus Ebola , Imunidade Celular/imunologia , Masculino , Marburgvirus/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Estudo de Prova de Conceito , Linfócitos T/metabolismo
3.
Viruses ; 11(2)2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795592

RESUMO

In North America, Sin Nombre virus (SNV) is the main cause of hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with a fatality rate of 35⁻40%. SNV is a zoonotic pathogen carried by deer mice (Peromyscus maniculatus), and few studies have been performed examining its transmission in deer mouse populations. Studying SNV and other hantaviruses can be difficult due to the need to propagate the virus in vivo for subsequent experiments. We show that when compared with standard intramuscular infection, the intraperitoneal infection of deer mice can be as effective in producing SNV stocks with a high viral RNA copy number, and this method of infection provides a more reproducible infection model. Furthermore, the age and sex of the infected deer mice have little effect on viral replication and shedding. We also describe a reliable model of direct experimental SNV transmission. We examined the transmission of SNV between deer mice and found that direct contact between deer mice is the main driver of SNV transmission rather than exposure to contaminated excreta/secreta, which is thought to be the main driver of transmission of the virus to humans. Furthermore, increases in heat shock responses or testosterone levels in SNV-infected deer mice do not increase the replication, shedding, or rate of transmission. Here, we have demonstrated a model for the transmission of SNV between deer mice, the natural rodent reservoir for the virus. The use of this model will have important implications for further examining SNV transmission and in developing strategies for the prevention of SNV infection in deer mouse populations.


Assuntos
Modelos Animais de Doenças , Infecções por Hantavirus/transmissão , Síndrome Pulmonar por Hantavirus/transmissão , Peromyscus/virologia , Vírus Sin Nombre/fisiologia , Animais , Reservatórios de Doenças/virologia , Feminino , Masculino , Peromyscus/fisiologia , Doenças dos Roedores/transmissão , Doenças dos Roedores/virologia , Eliminação de Partículas Virais , Zoonoses/transmissão , Zoonoses/virologia
4.
Nat Commun ; 10(1): 105, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30631063

RESUMO

The 2013-2016 Ebola virus (EBOV) disease epidemic demonstrated the grave consequences of filovirus epidemics in the absence of effective therapeutics. Besides EBOV, two additional ebolaviruses, Sudan (SUDV) and Bundibugyo (BDBV) viruses, as well as multiple variants of Marburg virus (MARV), have also caused high fatality epidemics. Current experimental EBOV monoclonal antibodies (mAbs) are ineffective against SUDV, BDBV, or MARV. Here, we report that a cocktail of two broadly neutralizing ebolavirus mAbs, FVM04 and CA45, protects nonhuman primates (NHPs) against EBOV and SUDV infection when delivered four days post infection. This cocktail when supplemented by the anti-MARV mAb MR191 exhibited 100% efficacy in MARV-infected NHPs. These findings provide a solid foundation for clinical development of broadly protective immunotherapeutics for use in future filovirus epidemics.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Ebolavirus/imunologia , Infecções por Filoviridae/imunologia , Marburgvirus/imunologia , Doenças dos Primatas/imunologia , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Ebolavirus/classificação , Ebolavirus/efeitos dos fármacos , Ebolavirus/fisiologia , Infecções por Filoviridae/terapia , Infecções por Filoviridae/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Imunoterapia/métodos , Marburgvirus/efeitos dos fármacos , Marburgvirus/fisiologia , Doenças dos Primatas/terapia , Doenças dos Primatas/virologia , Primatas , Resultado do Tratamento
5.
Cell Host Microbe ; 25(1): 49-58.e5, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30629918

RESUMO

Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134AF, a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134AF could fully protect ferrets against lethal EBOV, SUDV, and BDBV infection, and a single 25-mg/kg dose was sufficient to protect NHPs against all three viruses. The development of MBP134AF provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Ebolavirus/patogenicidade , Furões/virologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Bem-Estar do Animal , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/administração & dosagem , Linhagem Celular , Cercopithecus aethiops , Modelos Animais de Doenças , Feminino , Filoviridae/imunologia , Infecções por Filoviridae/imunologia , Infecções por Filoviridae/prevenção & controle , Infecções por Filoviridae/virologia , Glicoproteínas/imunologia , Cobaias , Células HEK293 , Doença pelo Vírus Ebola/virologia , Humanos , Células Matadoras Naturais , Macaca , Macaca fascicularis , Masculino , Primatas , Análise de Sobrevida , Resultado do Tratamento , Proteínas Virais/imunologia
6.
Cell Rep ; 25(7): 1982-1993.e4, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30428362

RESUMO

Synthetically engineered DNA-encoded monoclonal antibodies (DMAbs) are an in vivo platform for evaluation and delivery of human mAb to control against infectious disease. Here, we engineer DMAbs encoding potent anti-Zaire ebolavirus (EBOV) glycoprotein (GP) mAbs isolated from Ebola virus disease survivors. We demonstrate the development of a human IgG1 DMAb platform for in vivo EBOV-GP mAb delivery and evaluation in a mouse model. Using this approach, we show that DMAb-11 and DMAb-34 exhibit functional and molecular profiles comparable to recombinant mAb, have a wide window of expression, and provide rapid protection against lethal mouse-adapted EBOV challenge. The DMAb platform represents a simple, rapid, and reproducible approach for evaluating the activity of mAb during clinical development. DMAbs have the potential to be a mAb delivery system, which may be advantageous for protection against highly pathogenic infectious diseases, like EBOV, in resource-limited and other challenging settings.

7.
mSphere ; 3(5)2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30381349

RESUMO

Ebola virus (EBOV) has been responsible for sporadic outbreaks in Central Africa since 1976 and has the potential of causing social disruption and public panic as illustrated by the 2013-2016 epidemic in West Africa. Transmission of EBOV has been described to occur via contact with infected bodily fluids, supported by data indicating that infectious EBOV could be cultured from blood, semen, saliva, urine, and breast milk. Parameters influencing transmission of EBOV are, however, largely undefined in part due to the lack of an established animal model to study mechanisms of pathogen spread. Here, we investigated EBOV transmissibility in male and female ferrets. After intranasal challenge, an infected animal was placed in direct contact with a naive ferret and in contact with another naive ferret (separated from the infected animal by a metal mesh) that served as the indirect-contact animal. All challenged animals, male direct contacts, and one male indirect contact developed disease and died. The remaining animals were not viremic and remained asymptomatic but developed EBOV-glycoprotein IgM and/or IgG specific antibodies-indicative of virus transmission. EBOV transmission via indirect contact was frequently observed in this model but resulted in less-severe disease compared to direct contact. Interestingly, these observations are consistent with the detection of specific antibodies in humans living in areas of EBOV endemicity.IMPORTANCE Our knowledge regarding transmission of EBOV between individuals is vague and is mostly limited to spreading via direct contact with infectious bodily fluids. Studying transmission parameters such as dose and route of infection is nearly impossible in naturally acquired cases-hence the requirement for a laboratory animal model. Here, we show as a proof of concept that ferrets can be used to study EBOV transmission. We also show that transmission in the absence of direct contact is frequent, as all animals with indirect contact with the infected ferrets had detectable antibodies to the virus, and one succumbed to infection. Our report provides a new small-animal model for studying EBOV transmission that does not require adaptation of the virus, providing insight into virus transmission among humans during epidemics.

8.
J Infect Dis ; 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30304515

RESUMO

Background: There remains an important need for prophylactic anti-Ebola virus vaccine candidates that elicit long-lasting immune responses and can be delivered to vulnerable populations that are unable to receive live-attenuated or viral vector vaccines. Methods: We designed novel synthetic anti-Ebola virus glycoprotein (EBOV-GP) DNA vaccines as a strategy to expand protective breadth against diverse EBOV strains and evaluated the impact of vaccine dosing and route of administration on protection against lethal EBOV-Makona challenge in cynomolgus macaques. Long-term immunogenicity was monitored in nonhuman primates for >1 year, followed by a 12-month boost. Results: Multiple-injection regimens of the EBOV-GP DNA vaccine, delivered by intramuscular administration followed by electroporation, were 100% protective against lethal EBOV-Makona challenge. Impressively, 2 injections of a simple, more tolerable, and dose-sparing intradermal administration followed by electroporation generated strong immunogenicity and was 100% protective against lethal challenge. In parallel, we observed that EBOV-GP DNA vaccination induced long-term immune responses in macaques that were detectable for at least 1 year after final vaccination and generated a strong recall response after the final boost. Conclusions: These data support that this simple intradermal-administered, serology-independent approach is likely important for additional study towards the goal of induction of anti-EBOV immunity in multiple at-risk populations.

9.
J Infect Dis ; 218(suppl_5): S471-S474, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29889278

RESUMO

Ferrets are used for studying infections with wild-type Ebola virus isolates. Here, we investigated whether these animals are also susceptible to wild-type isolates of Marburg virus (MARV). Ferrets were challenged intramuscularly or intranasally with MARV strain Angola and monitored for 3 weeks. Unexpectedly, the animals neither showed observable signs of disease nor died of infection, and viremia was not detected after challenge. All animals were seropositive for MARV-specific immunoglobulin antibodies. Confirmatory studies with MARV strain Musoke and Ravn virus yielded the same outcomes. Therefore, ferrets may be of limited usefulness for studying the pathogenesis of MARV and Ravn virus infections.

10.
Pract Radiat Oncol ; 8(4): 279-286, 2018 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29429922

RESUMO

INTRODUCTION: An electronic checklist has been designed with the intention of reducing errors while minimizing user effort in completing the checklist. We analyze the clinical use and evolution of the checklist over the past 5 years and review data in an incident learning system (ILS) to investigate whether it has contributed to an improvement in patient safety. METHODS AND MATERIALS: The checklist is written as a standalone HTML application using VBScript. User selection of pertinent demographic details limits the display of checklist items only to those necessary for the particular clinical scenario. Ten common clinical scenarios were used to illustrate the difference between the maximum possible number of checklist items available in the code versus the number displayed to the user at any one time. An ILS database of errors and near misses was reviewed to evaluate whether the checklist influenced the occurrence of reported events. RESULTS: Over 5 years, the number of checklist items available in the code nearly doubled, whereas the number displayed to the user at any one time stayed constant. Events reported in our ILS related to the beam energy used with pacemakers, projection of anatomy on digitally reconstructed radiographs, orthogonality of setup fields, and field extension beyond match lines, did not recur after the items were added to the checklist. Other events related to bolus documentation and breakpoints continued to be reported. CONCLUSION: Our checklist is adaptable to the introduction of new technologies, transitions between planning systems, and to errors and near misses recorded in the ILS. The electronic format allows us to restrict user display to a small, relevant, subset of possible checklist items, limiting the planner effort needed to review and complete the checklist.

11.
J Infect Dis ; 217(6): 916-925, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29365142

RESUMO

The 2013-2016 West Africa outbreak demonstrated the epidemic potential of Ebola virus and highlighted the need for counter strategies. Monoclonal antibody (mAb)-based therapies hold promise as treatment options for Ebola virus infections. However, production of clinical-grade mAbs is labor intensive, and immunity is short lived. Conversely, adeno-associated virus (AAV)-mediated mAb gene transfer provides the host with a genetic blueprint to manufacture mAbs in vivo, leading to steady release of antibody over many months. Here we demonstrate that AAV-mediated expression of nonneutralizing mAb 5D2 or 7C9 confers 100% protection against mouse-adapted Ebola virus infection, while neutralizing mAb 2G4 was 83% protective. A 2-component cocktail, AAV-2G4/AAV-5D2, provided complete protection when administered 7 days prior to challenge and was partially protective with a 3-day lead time. Finally, AAV-mAb therapies provided sustained protection from challenge 5 months following AAV administration. AAV-mAb may be a viable alternative strategy for vaccination against emerging infectious diseases.

12.
Sci Rep ; 7(1): 1204, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28446775

RESUMO

Critical care needs have been rising in recent decades as populations age and comorbidities increase. Sepsis-related admissions to critical care contribute up to 50% of volume and septic shock carries a 35-54% fatality rate. Improvements in sepsis-related care and mortality would have a significant impact of a resource-intensive area of health care delivery. Unfortunately, research has been hampered by the lack of an animal model that replicates the complex care provided to humans in an intensive care unit (ICU). We developed a protocol to provide full ICU type supportive care to Rhesus macaques. This included mechanical ventilation, continuous sedation, fluid and electrolyte management and vasopressor support in response to Ebolavirus-induced septic shock. The animals accurately recapitulated human responses to a full range of ICU interventions (e.g. fluid resuscitation). This model can overcome current animal model limitations by accurately emulating the complexity of ICU care and thereby provide a platform for testing new interventions in critical care and sepsis without placing patients at risk.


Assuntos
Cuidados Críticos/métodos , Estado Terminal , Doença pelo Vírus Ebola/complicações , Choque Séptico/terapia , Animais , Modelos Animais de Doenças , Macaca mulatta
13.
J Infect Dis ; 214(suppl 3): S281-S289, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27651412

RESUMO

Enhanced virulence and/or transmission of West African Ebola virus (EBOV) variants, which are divergent from their Central African counterparts, are suspected to have contributed to the sizable toll of the recent Ebola virus disease (EVD) outbreak. This study evaluated the pathogenicity and shedding in rhesus macaques infected with 1 of 2 West African isolates (EBOV-C05 or EBOV-C07) or a Central African isolate (EBOV-K). All animals infected with EBOV-C05 or EBOV-C07 died of EVD, whereas 2 of 3 EBOV-K-infected animals died. The viremia level was elevated 10-fold in EBOV-C05-infected animals, compared with EBOV-C07- or EBOV-K-infected animals. More-severe lung pathology was observed in 2 of 6 EBOV-C05/C07-infected macaques. This is the first detailed analysis of the recently circulating EBOV-C05/C07 in direct comparison to EBOV-K with 6 animals per group, and it showed that EBOV-C05 but not EBOV-C07 can replicate at higher levels and cause more tissue damage in some animals. Increased virus shedding from individuals who are especially susceptible to EBOV replication is possibly one of the many challenges facing the community of healthcare and policy-making responders since the beginning of the outbreak.


Assuntos
Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/virologia , Animais , Ebolavirus/fisiologia , Doença pelo Vírus Ebola/patologia , Humanos , Macaca mulatta , Especificidade da Espécie , Viremia , Virulência , Eliminação de Partículas Virais
14.
J Neurosurg ; 124(2): 538-45, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26406795

RESUMO

OBJECTIVE: The object of this study was to determine the mortality and neurological outcome of patients with mild traumatic brain injury (mTBI) who require neurosurgical intervention (NSI), identify clinical predictors of a poor outcome, and investigate the effect of failed nonoperative management and delayed NSI on outcome. METHODS: A cross-sectional study of 10 years was performed, capturing all adults with mTBI and NSI. Primary outcome variables were mortality and Glasgow Outcome Scale (GOS) score. Patients were divided into an immediate intervention group, which received an NSI after the initial cranial CT scan, and a delayed intervention group, which had failed nonoperative management and received an NSI after 2 or more cranial CT scans. RESULTS: The mortality rate in mTBI patients requiring NSI was 13%, and the mean GOS score was 3.6 ± 1.2. An age > 60 years was independently predictive of a worse outcome, and epidural hematoma was independently predictive of a good outcome. Logistic regression analysis using independent variables was calculated to create a model for predicting poor neurological outcomes in patients with mTBI undergoing NSI and had 74.1% accuracy. Patients in the delayed intervention group had worse mortality (25% vs 9%) and worse mean GOS scores (2.9 ± 1.3 vs 3.7 ± 1.2) than those in the immediate intervention group. CONCLUSIONS: Data in this study demonstrate that patients with mTBI requiring NSI have higher mortality rates and worse neurological outcomes and should therefore be classified separately from mTBI patients not requiring NSI. Additionally, mTBI patients requiring NSI after the failure of nonoperative management have worse outcomes than those receiving immediate intervention and should be considered separately.


Assuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/cirurgia , Doenças do Sistema Nervoso/etiologia , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Lesões Encefálicas/mortalidade , Craniotomia , Estudos Transversais , Feminino , Escala de Coma de Glasgow , Hematoma Epidural Craniano/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
15.
J Emerg Med ; 50(1): 47-50, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26602425

RESUMO

BACKGROUND: Local anesthetics are commonly used in the emergency department (ED). Overdoses can lead to disastrous complications including cardiac toxicity and arrest. Recognition of local anesthetic systemic toxicity (LAST) is important; however, prevention is even more critical. Knowledge of proper lidocaine dosage can prevent LAST. LAST may be effectively treated with lipid emulsion therapy. Although the mechanism is not well understood, its use may have a profound impact on morbidity and mortality. CASE REPORT: Fifty milliliters of 2% lidocaine was infiltrated for local anesthesia in a 35-year-old woman during the incision and drainage of a labial abscess. Following the procedure, the patient complained of vomiting, with rapid progression to an altered mental state and seizure requiring endotracheal intubation for airway protection. Suspecting lidocaine toxicity, intralipids were ordered. While waiting for the intralipids, the patient decompensated and suffered pulseless electrical activity (PEA) cardiac arrest. A 100-mL bolus of 20% intralipids was administered 3 minutes into the resuscitation, after which return of spontaneous circulation occurred. The intralipid bolus was then followed by a continuous infusion of 0.25 mL/kg/minute, for an infusion dose of 930 mL. Despite a complicated hospital course, the patient was discharged home neurologically intact. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We believe this patient's cardiovascular collapse was secondary to an iatrogenic overdose of lidocaine. This is one of the first cases to support the efficacy of intravenous lipids in the treatment of LAST in humans in the ED.


Assuntos
Anestésicos Locais/efeitos adversos , Emulsões Gordurosas Intravenosas/uso terapêutico , Parada Cardíaca/terapia , Lidocaína/efeitos adversos , Adulto , Serviço Hospitalar de Emergência , Feminino , Parada Cardíaca/induzido quimicamente , Humanos , Resultado do Tratamento
16.
Psychiatry Res ; 228(3): 380-5, 2015 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-26163727

RESUMO

While knowledge on service users' perspective on their admissions to psychiatric wards has improved substantially in the last decade, there is a paucity of knowledge of the perspectives of caregivers. This study aimed to determine caregiver's perception of the levels of perceived coercion, perceived pressures and procedural justice experienced by service users during their admission to acute psychiatric in-patient units. The perspective of caregivers were then compared to the perspectives of their related service users, who had been admitted to five psychiatric units in Ireland. Caregivers were interviewed using an adapted version of the MacArthur admission experience interview. Sixty-six caregivers participated in this study and the majority were parents. Seventy one percent of service users were admitted involuntarily and nearly half had a diagnosis of schizophrenia or schizoaffective disorder. Caregivers of involuntarily admitted individuals perceived the service users' admission as less coercive than reported by the service users. Caregivers also perceived a higher level of procedural justice in comparison to the level reported by service users. Reducing the disparity of perceptions between caregivers and service users could result in caregivers having a greater understanding of the admission process and why some service users may be reluctant to be admitted.


Assuntos
Cuidadores/psicologia , Coerção , Internação Compulsória de Doente Mental , Unidade Hospitalar de Psiquiatria , Adulto , Idoso , Hospitais Psiquiátricos , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Pais/psicologia , Admissão do Paciente , Percepção , Transtornos Psicóticos/psicologia , Esquizofrenia
17.
Behav Cogn Psychother ; 42(3): 327-38, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23578588

RESUMO

BACKGROUND: Different theories concerning pathways to insight have been proposed which underpin the numerous assessment measures. Cognitive behavioural therapy (CBT) is one treatment approach that has been used to improve insight. AIMS: The aim of this review was to promote a greater focus on developing effective CBT strategies to ameliorate insight in psychosis through the exploration of the concept of insight in psychosis and evaluation of research in the area. METHOD: A comprehensive search and review of published studies examining the impact of CBT on insight in psychosis was conducted. We searched the databases PubMed, Medline, PsychInfo, the Psychology and Behavioral Sciences Database, and CINAHL with limits set to 10 years, humans, and English language. We hand-searched reference lists of major studies on insight, and theoretical review papers. We filtered our results according to relevance and chose 50 papers for final consideration. RESULTS: The multidimensionality of insight is reflected in the variety of different insight measures in clinical use. Research findings on the impact of CBT on insight are conflicting. Cognitive insight and clinical insight appear to be different concepts that are not fully captured by existing measurement scales. CONCLUSIONS: The conflicting results found in research examining the impact of CBT on insight may be partially explained by the different theories underpinning insight in psychosis communicated through psychoeducation in CBT. Furthermore, the use of more than one insight assessment measure may capture the complexity of insight more effectively. Qualitative research with service users would enrich the knowledge in this area.


Assuntos
Conscientização , Terapia Cognitivo-Comportamental , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/terapia , Humanos , Educação de Pacientes como Assunto , Transtornos Psicóticos/diagnóstico
18.
Am J Med Genet A ; 155A(10): 2560-5, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21910238

RESUMO

In 2006, we reported the cognitive and behavioral phenotype of the seventh case of Roifman syndrome (OMIM 300258). Aged 11 years 6 months, the patient displayed significant intellectual disability with proportionate impairments in attentional-executive, memory, and visuo-spatial abilities despite appearing socially "able." This discrepancy may be explained by good social-emotional skills masking his intellectual disability, by decline in cognitive abilities over time, or by unusual neuroradiological abnormalities not previously examined in Roifman syndrome. Here, we present results from a structural MRI scan, neurocognitive evaluations repeated 2 and 5 years post-baseline and assessments of face and emotional processing. The MRI revealed partial agenesis of the corpus callosum, bilateral hypoplastic hippocampi but bilaterally intact amygdala. No evidence was found for decline in the patient's neurocognitive profile. Emotional processing data indicated an age-appropriate pattern of reactivity to emotional stimuli and preserved facial identity recognition abilities, but impairments in recognition of negative facial expressions. The results confirmed a stable pattern of intellectual disability, and indicated that Roifman syndrome may be associated with major structural neuro-anatomical abnormalities. We suggest that the relative strengths in emotion and face processing are consistent with the patient's apparently able social behavior, and with intact amygdalar function.


Assuntos
Cardiomiopatias/patologia , Síndromes de Imunodeficiência/patologia , Retardo Mental Ligado ao Cromossomo X/patologia , Osteocondrodisplasias/patologia , Doenças Retinianas/patologia , Adolescente , Encéfalo/patologia , Criança , Emoções , Expressão Facial , Humanos , Imagem por Ressonância Magnética , Testes Neuropsicológicos
19.
J Infect Dis ; 204(2): 200-8, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21571728

RESUMO

UNLABELLED: (See the editorial commentary by Bausch, on pages 179-81.) BACKGROUND: Reston ebolavirus was recently detected in pigs in the Philippines. Specific antibodies were found in pig farmers, indicating exposure to the virus. This important observation raises the possibility that pigs may be susceptible to Ebola virus infection, including from other species, such as Zaire ebolavirus (ZEBOV), and can transmit to other susceptible hosts. METHODS: This study investigated whether ZEBOV, a species commonly reemerging in central Africa, can replicate and induce disease in pigs and can be transmitted to naive animals. Domesticated Landrace pigs were challenged through mucosal exposure with a total of 1 ×10(6) plaque-forming units of ZEBOV and monitored for virus replication, shedding, and pathogenesis. Using similar conditions, virus transmission from infected to naive animals was evaluated in a second set of pigs. RESULTS: Following mucosal exposure, pigs replicated ZEBOV to high titers (reaching 10(7) median tissue culture infective doses/mL), mainly in the respiratory tract, and developed severe lung pathology. Shedding from the oronasal mucosa was detected for up to 14 days after infection, and transmission was confirmed in all naive pigs cohabiting with inoculated animals. CONCLUSIONS: These results shed light on the susceptibility of pigs to ZEBOV infection and identify an unexpected site of virus amplification and shedding linked to transmission of infectious virus.


Assuntos
Ebolavirus/crescimento & desenvolvimento , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/veterinária , Doenças dos Suínos/transmissão , Doenças dos Suínos/virologia , Replicação Viral , Eliminação de Partículas Virais , Animais , Doença pelo Vírus Ebola/patologia , Doença pelo Vírus Ebola/transmissão , Doença pelo Vírus Ebola/virologia , Pulmão/patologia , Mucosa Bucal/virologia , Mucosa Nasal/virologia , Sistema Respiratório/virologia , Suínos , Doenças dos Suínos/patologia
20.
Behav Genet ; 41(3): 437-44, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21191642

RESUMO

Tuberous sclerosis complex (TSC) is a genetic disorder associated with mTOR over-activation and disruption of MAPK, PI3K and AMPK signalling. Children with TSC have significant deficits on neuropsychological attention tasks, particularly dual tasking. Here we investigated attentional skills and related behaviours in daily life in normally intelligent adults with TSC and matched controls using the Test of Everyday Attention for Children (TEA-Ch) and the Attention-Deficit Scales for Adults (ADSA). No group differences were demonstrated on selective or sustained attention tasks carried out alone. However, adults with TSC performed significantly worse when these tasks were combined in a cross-modal dual task condition. On the ADSA the TSC group had significantly worse scores on several subscales (attention/concentration, behaviour/disorganization, academic and emotional behaviours) compared to controls and these correlated with dual task performance, indicating a clear impact of dual task deficits on attention-related behaviours in daily life. The presence or absence of epilepsy did not influence dual task performance or attention-deficits in daily life. Taken together with similar findings in children, results suggest that dual task difficulties are a core feature of the neuropsychological phenotype of TSC.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Atenção , Testes Neuropsicológicos/estatística & dados numéricos , Esclerose Tuberosa/genética , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Epilepsia/genética , Feminino , Humanos , Inteligência/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Psicometria , Serina-Treonina Quinases TOR/genética , Esclerose Tuberosa/diagnóstico
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