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1.
Sci Adv ; 8(24): eabn1104, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35704574

RESUMO

Miniaturization has evolved repeatedly in frogs in the moist leaf litter environments of rainforests worldwide. Miniaturized frogs are among the world's smallest vertebrates and exhibit an array of enigmatic features. One area where miniaturization has predictable consequences is the vestibular system, which acts as a gyroscope, providing sensory information about movement and orientation. We investigated the vestibular system of pumpkin toadlets, Brachycephalus (Anura: Brachycephalidae), a clade of miniaturized frogs from Brazil. The semicircular canals of miniaturized frogs are the smallest recorded for adult vertebrates, resulting in low sensitivity to angular acceleration due to insufficient displacement of endolymph. This translates into a lack of postural control during jumping in Brachycephalus and represents a physical constraint resulting from Poiseuille's law, which governs movement of fluids within tubes.

2.
MMWR Morb Mortal Wkly Rep ; 71(20): 686-689, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35587914

RESUMO

On June 16, 2021, rabies virus infection was confirmed in a dog included in a shipment of rescue animals imported into the United States from Azerbaijan. A multistate investigation was conducted to prevent secondary rabies cases, avoid reintroduction of a dog-maintained rabies virus variant (DMRVV), identify persons who might have been exposed and would be recommended to receive rabies postexposure prophylaxis, and investigate the cause of importation control failures. Results of a prospective serologic monitoring (PSM) protocol suggested that seven of 32 (22%) animals from the same shipment as the dog with confirmed rabies virus infection and who had available titer results after rabies vaccine booster had not been adequately vaccinated against rabies before importation. A requirement for rabies vaccination certificates alone will not adequately identify improper vaccination practices or fraudulent paperwork and are insufficient as a stand-alone rabies importation prevention measure. Serologic titers before importation would mitigate the risk for importing DMRVV.


Assuntos
Doenças do Cão , Vacina Antirrábica , Vírus da Raiva , Raiva , Animais , Azerbaijão , Doenças do Cão/prevenção & controle , Cães , Humanos , Pennsylvania , Estudos Prospectivos , Raiva/epidemiologia , Raiva/prevenção & controle , Raiva/veterinária , Estados Unidos , Vacinação/veterinária
3.
Prev Vet Med ; 198: 105530, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34798304

RESUMO

A cluster of five human Salmonella Guinea cases was identified among Ohio residents through core genome multilocus sequence typing of clinical isolates. An investigation was conducted to characterize illnesses and identify common exposures. Four patients were aged ≤5 years and three of four patients with information available regarding exposure to animals reported prior exposure to bearded dragons. Practices that potentially increased the risk for Salmonella transmission from reptiles to humans included allowing pet reptiles to roam freely in the home, cleaning reptile habitats indoors, and kissing reptiles. These findings prompted a multistate investigation that resulted in the identification of additional closely related Salmonella Guinea isolates from patients across multiple states. The investigation of cases in Ohio and information shared by other states indicated the potential association between human Salmonella Guinea infections and reptiles, particularly bearded dragons. To prevent Salmonella transmission from reptiles, continued educational efforts should address pet owners and focus on specific reptile ownership practices.


Assuntos
Zoonoses Bacterianas/epidemiologia , Lagartos , Salmonelose Animal , Animais , Humanos , Lagartos/microbiologia , Ohio/epidemiologia , Salmonella , Salmonelose Animal/epidemiologia , Salmonelose Animal/prevenção & controle
4.
JAMA Netw Open ; 4(9): e2125203, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524434

RESUMO

Importance: Extensively drug-resistant Campylobacter jejuni infections cannot be treated with any commonly recommended antibiotics and pose an increasing public health threat. Objectives: To investigate cases of extensively drug-resistant C jejuni associated with pet store puppies and describe the epidemiologic and laboratory characteristics of these infections. Design, Setting, and Participants: In August 2017, health officials identified, via survey, patients with C jejuni infections who reported contact with puppies sold by pet stores. In conjunction with state and federal partners, the Centers for Disease Control and Prevention investigated cases of culture-confirmed C jejuni infections in US patients with an epidemiologic or molecular association with pet store puppies between January 1, 2016, and February 29, 2020. Available records from cases occurring before 2016 with genetically related isolates were also obtained. Main Outcomes and Measures: Patients were interviewed about demographic characteristics, health outcomes, and dog exposure during the 7 days before illness onset. Core genome multilocus sequence typing was used to assess isolate relatedness, and genomes were screened for resistance determinants to predict antibiotic resistance. Isolates resistant to fluoroquinolones, macrolides, and 3 or more additional antibiotic classes were considered to be extensively drug resistant. Cases before 2016 were identified by screening all sequenced isolates submitted for surveillance using core genome multilocus sequence typing. Results: A total of 168 patients (median [interquartile range] age, 37 [19.5-51.0] years; 105 of 163 female [64%]) with an epidemiologic or molecular association with pet store puppies were studied. A total of 137 cases occurred from January 1, 2016, to February 29, 2020, with 31 additional cases dating back to 2011. Overall, 117 of 121 patients (97%) reported contact with a dog in the week before symptom onset, of whom 69 of 78 (88%) with additional information reported contact with a pet store puppy; 168 isolates (88%) were extensively drug resistant. Traceback investigation did not implicate any particular breeder, transporter, distributer, store, or chain. Conclusions and Relevance: Strains of extensively drug-resistant C jejuni have been circulating since at least 2011 and are associated with illness among pet store customers, employees, and others who come into contact with pet store puppies. The results of this study suggest that practitioners should ask about puppy exposure when treating patients with Campylobacter infection, especially when they do not improve with routine antibiotics, and that the commercial dog industry should take action to help prevent the spread of extensively drug-resistant C jejuni from pet store puppies to people.


Assuntos
Zoonoses Bacterianas/epidemiologia , Infecções por Campylobacter/epidemiologia , Campylobacter jejuni , Surtos de Doenças , Doenças do Cão/transmissão , Animais de Estimação , Adulto , Animais , Infecções por Campylobacter/microbiologia , Infecções por Campylobacter/veterinária , Cães , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia
5.
Biol Chem ; 401(2): 249-262, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-31299006

RESUMO

Rickettsial species have independently lost several genes owing to reductive evolution while retaining those predominantly implicated in virulence, survival, and biosynthetic pathways. In this study, we have identified a previously uncharacterized Rickettsia conorii gene RC0497 as an N-acetylmuramoyl-L-alanine amidase constitutively expressed during infection of cultured human microvascular endothelial cells at the levels of both mRNA transcript and encoded protein. A homology-based search of rickettsial genomes reveals that RC0497 homologs, containing amidase_2 family and peptidoglycan binding domains, are highly conserved among the spotted fever group (SFG) rickettsiae. The recombinant RC0497 protein exhibits α-helix secondary structure, undergoes a conformational change in the presence of zinc, and exists as a dimer at higher concentrations. We have further ascertained the enzymatic activity of RC0497 via demonstration of its ability to hydrolyze Escherichia coli peptidoglycan. Confocal microscopy on E. coli expressing RC0497 and transmission immunoelectron microscopy of R. conorii revealed its localization predominantly to the cell wall, septal regions of replicating bacteria, and the membrane of vesicles pinching off the cell wall. In summary, we have identified and functionally characterized RC0497 as a peptidoglycan hydrolase unique to spotted fever rickettsiae, which may potentially serve as a novel moonlighting protein capable of performing multiple functions during host-pathogen interactions.


Assuntos
Amidoidrolases/isolamento & purificação , Amidoidrolases/metabolismo , Peptidoglicano/metabolismo , Rickettsia conorii/enzimologia , Amidoidrolases/química , Peptidoglicano/química , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Especificidade da Espécie
6.
J Am Vet Med Assoc ; 256(1): 66-76, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841088

RESUMO

OBJECTIVE: To evaluate rabies virus (RABV) characterization data obtained from animal specimens submitted to the US public health rabies surveillance system and propose a standardized approach to sample selection for RABV characterization that could enhance early detection of important rabies epizootic events in the United States. SAMPLE: United States public health rabies surveillance system data collected from January 1, 2010, through December 31, 2015. PROCEDURES: Data were reviewed to identify RABV-positive specimens for which virus characterization would likely provide information regarding any of 4 overarching events (discovery of novel variants, translocation of RABV variants, host-shift events, and any unusual rabies-related event) that could substantially alter animal rabies epizootiology in the United States. These specimens were designated as specimens of epizootiological importance (SEIs). Estimates of the additional number of specimens that public health laboratories could expect to process each year if all SEIs underwent RABV characterization were calculated. RESULTS: During the 6-year period, the mean annual number of SEIs was 855 (95% CI, 739 to 971); the mean number of SEIs that underwent virus characterization was 270 (95% CI, 187 to 353). Virus characterization of all SEIs would be expected to increase the public health laboratories' test load by approximately 585 (95% CI, 543 to 625) specimens/y. CONCLUSIONS AND CLINICAL RELEVANCE: Prioritization of RABV characterization of SEIs may improve early detection of rabies events associated with RABV host shifts, variant translocations, and importation. Characterization of SEIs may help refine wildlife rabies management practices. Each public health laboratory should evaluate testing of SEIs to ensure diagnostic laboratory capacity is not overstretched.


Assuntos
Vírus da Raiva , Raiva/veterinária , Animais , Animais Selvagens , Estados Unidos
7.
MMWR Morb Mortal Wkly Rep ; 67(42): 1174-1177, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30359345

RESUMO

On July 24, 2017, the Ohio Department of Health (ODH) was notified of a positive rabies test result from a domestic cat in Summit County, a county considered free from terrestrial rabies. Oral rabies vaccination (ORV) of raccoons, in the form of consumable bait, is conducted each year along the Ohio-Pennsylvania border to prevent the westward expansion of the raccoon rabies virus variant (RVV). In the United States, several distinct rabies virus variants exist; raccoon RVV is enzootic along the eastern parts of the United States (from Florida to Maine), including several counties in northeast Ohio (1). Animal rabies vaccination is protective against all rabies virus variants. The rabid cat (cat A) was located west of the ORV barrier, raising concern that it had acquired the infection from a raccoon and suggesting a possible breach in the ORV barrier (Figure 1). ODH initiated an investigation to identify persons and animals exposed to the rabid cat during its viral shedding period and collaborated with CDC to determine the likely origin of the virus (Figure 2). Public health investigators later discovered that the cat originated in North Carolina. Phylogenetic analysis confirmed that the virus was most similar to the raccoon RVV that circulates in North Carolina (Figure 3); therefore, this ORV breach was likely the result of human-mediated movement of a rabid animal rather than natural expansion of the raccoon rabies virus enzootic area. This report summarizes the investigation and highlights the importance of owner compliance regarding rabies vaccination.


Assuntos
Doenças do Gato/virologia , Raiva/veterinária , Viagem , Administração Oral , Animais , Doenças do Gato/diagnóstico , Gatos , Feminino , Humanos , North Carolina/epidemiologia , Ohio/epidemiologia , Vigilância em Saúde Pública , Raiva/diagnóstico , Raiva/epidemiologia , Raiva/prevenção & controle , Vacina Antirrábica/administração & dosagem , Vírus da Raiva/genética , Vírus da Raiva/isolamento & purificação
8.
MMWR Morb Mortal Wkly Rep ; 67(37): 1032-1035, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30235182

RESUMO

Campylobacter causes an estimated 1.3 million diarrheal illnesses in the United States annually (1). In August 2017, the Florida Department of Health notified CDC of six Campylobacter jejuni infections linked to company A, a national pet store chain based in Ohio. CDC examined whole-genome sequencing (WGS) data and identified six isolates from company A puppies in Florida that were highly related to an isolate from a company A customer in Ohio. This information prompted a multistate investigation by local and state health and agriculture departments and CDC to identify the outbreak source and prevent additional illness. Health officials from six states visited pet stores to collect puppy fecal samples, antibiotic records, and traceback information. Nationally, 118 persons, including 29 pet store employees, in 18 states were identified with illness onset during January 5, 2016-February 4, 2018. In total, six pet store companies were linked to the outbreak. Outbreak isolates were resistant by antibiotic susceptibility testing to all antibiotics commonly used to treat Campylobacter infections, including macrolides and quinolones. Store record reviews revealed that among 149 investigated puppies, 142 (95%) received one or more courses of antibiotics, raising concern that antibiotic use might have led to development of resistance. Public health authorities issued infection prevention recommendations to affected pet stores and recommendations for testing puppies to veterinarians. This outbreak demonstrates that puppies can be a source of multidrug-resistant Campylobacter infections in humans, warranting a closer look at antimicrobial use in the commercial dog industry.


Assuntos
Infecções por Campylobacter/epidemiologia , Campylobacter jejuni/efeitos dos fármacos , Surtos de Doenças , Cães/microbiologia , Farmacorresistência Bacteriana Múltipla , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/prevenção & controle , Campylobacter jejuni/isolamento & purificação , Criança , Pré-Escolar , Busca de Comunicante , Surtos de Doenças/prevenção & controle , Fezes/microbiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem , Zoonoses
9.
PLoS One ; 10(8): e0136316, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26312485

RESUMO

St. Louis encephalitis virus (SLEV) is a re-emerging arbovirus in South America. In 2005, an encephalitis outbreak caused by SLEV was reported in Argentina. The reason for the outbreak remains unknown, but may have been related to virological factors, changes in vectors populations, avian amplifying hosts, and/or environmental conditions. The main goal of this study was to characterize the complete genome of epidemic and non-epidemic SLEV strains from Argentina. Seventeen amino acid changes were detected; ten were non-conservative and located in proteins E, NS1, NS3 and NS5. Phylogenetic analysis showed two major clades based on geography: the North America and northern Central America (NAnCA) clade and the South America and southern Central America (SAsCA) clade. Interestingly, the presence of SAsCA genotype V SLEV strains in the NAnCA clade was reported in California, Florida and Texas, overlapping with known bird migration flyways. This work represents the first step in understanding the molecular mechanisms underlying virulence and biological variation among SLEV strains.


Assuntos
Doenças Transmissíveis Emergentes/genética , Vírus da Encefalite de St. Louis , Encefalite de St. Louis/genética , Genoma Viral , Filogenia , Proteínas Virais/genética , Animais , Argentina , Chlorocebus aethiops , Doenças Transmissíveis Emergentes/epidemiologia , Vírus da Encefalite de St. Louis/genética , Vírus da Encefalite de St. Louis/patogenicidade , Encefalite de St. Louis/epidemiologia , Genótipo , Humanos , Estados Unidos/epidemiologia , Células Vero
10.
PLoS One ; 9(10): e107539, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25295750

RESUMO

INTRODUCTION: In the continental US, four terrestrial mammalian species are reservoirs for seven antigenic rabies virus variants. Cross species transmission (CST) occurs when a rabies virus variant causes disease in non-reservoir species. METHODS: This study analyzed national surveillance data for rabies in terrestrial mammals. The CST rate was defined as: number of rabid non-reservoir animals/number of rabid reservoir animals. CST rates were analyzed for trend. Clusters of high CST rate counties were evaluated using space-time scanning statistics. RESULTS: The number of counties reporting a raccoon variant CST rate >1.0 increased from 75 in 1992 to 187 in 2011; counties with skunk variant CST rates >1.0 remained unchanged during the same period. As of 2011, for every rabid raccoon reported within the raccoon variant region, there were 0.73 cases of this variant reported in non-reservoir animals. Skunks were the most common non-reservoir animal reported with the raccoon rabies variant. Domestic animals were the most common non-reservoir animal diagnosed with a skunk rabies virus variant (n = 1,601). Cross species transmission rates increased fastest among domestic animals. CONCLUSIONS: Cross species transmission of rabies virus variants into non-reservoir animals increases the risk of human exposures and threatens current advances toward rabies control. Cross species transmission in raccoon rabies enzootic regions increased dramatically during the study period. Pet owners should vaccinate their dogs and cats to ensure against CST, particularly in regions with active foci of rabies circulation. Clusters of high CST activity represent areas for further study to better understand interspecies disease transmission dynamics. Each CST event has the potential to result in a rabies virus adapted for sustained transmission in a new species; therefore further understanding of the dynamics of CST may help in early detection or prevention of the emergence of new terrestrial rabies virus variants.


Assuntos
Vírus da Raiva/patogenicidade , Raiva/transmissão , Animais , Animais Domésticos/virologia , Animais Selvagens/virologia , Gatos , Cães , Mephitidae/virologia , Guaxinins/virologia , Estados Unidos
11.
PLoS Negl Trop Dis ; 7(1): e1931, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23359824

RESUMO

O'nyong nyong virus (ONNV) and Chikungunya virus (CHIKV) are two closely related alphaviruses with very different infection patterns in the mosquito, Anopheles gambiae. ONNV is the only alphavirus transmitted by anopheline mosquitoes, but specific molecular determinants of infection of this unique vector specificity remain unidentified. Fifteen distinct chimeric viruses were constructed to evaluate both structural and non-structural regions of the genome and infection patterns were determined through artificial infectious feeds in An. gambiae with each of these chimeras. Only one region, non-structural protein 3 (nsP3), was sufficient to up-regulate infection to rates similar to those seen with parental ONNV. When ONNV non-structural protein 3 (nsP3) replaced nsP3 from CHIKV virus in one of the chimeric viruses, infection rates in An. gambiae went from 0% to 63.5%. No other single gene or viral region addition was able to restore infection rates. Thus, we have shown that a non-structural genome element involved in viral replication is a major element involved in ONNV's unique vector specificity.


Assuntos
Alphavirus/fisiologia , Especificidade de Hospedeiro , Proteínas não Estruturais Virais/genética , Alphavirus/genética , Animais , Anopheles/virologia , Vírus Chikungunya/genética , Vetores de Doenças , Proteínas não Estruturais Virais/metabolismo
12.
PLoS Negl Trop Dis ; 6(11): e1875, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23133685

RESUMO

Venezuelan equine encephalitis virus (VEEV) has been the causative agent for sporadic epidemics and equine epizootics throughout the Americas since the 1930s. In 1969, an outbreak of Venezuelan equine encephalitis (VEE) spread rapidly from Guatemala and through the Gulf Coast region of Mexico, reaching Texas in 1971. Since this outbreak, there have been very few studies to determine the northward extent of endemic VEEV in this region. This study reports the findings of serologic surveillance in the Gulf Coast region of Mexico from 2003-2010. Phylogenetic analysis was also performed on viral isolates from this region to determine whether there have been substantial genetic changes in VEEV since the 1960s. Based on the findings of this study, the Gulf Coast lineage of subtype IE VEEV continues to actively circulate in this region of Mexico and appears to be responsible for infection of humans and animals throughout this region, including the northern State of Tamaulipas, which borders Texas.


Assuntos
Vírus da Encefalite Equina Venezuelana/isolamento & purificação , Encefalomielite Equina Venezuelana/epidemiologia , Doenças Endêmicas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Estudos Soroepidemiológicos , Adulto Jovem
13.
Behav Genet ; 42(5): 787-97, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22692226

RESUMO

A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52 %) and female offspring aged 15.7 ± 2.4 years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression.


Assuntos
Depressão/psicologia , Pais/psicologia , Autoimagem , Adolescente , Adulto , Criança , Depressão/epidemiologia , Família , Feminino , Humanos , Relação entre Gerações , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Suécia/epidemiologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto Jovem
14.
Arch Gen Psychiatry ; 68(2): 181-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21300945

RESUMO

CONTEXT: It is necessary to understand the etiologic structure of child and adolescent psychopathology to advance theory and guide future research. OBJECTIVE: To test alternative models of the higher-order structure of etiologic effects on 11 dimensions of child and adolescent psychopathology using confirmatory factor analyses of genetic and environmental covariances. DESIGN: Representative sample of twins. SETTING: Home interviews. PARTICIPANTS: A total of 1571 pairs of 9- to 17-year-old twins. MAIN OUTCOME MEASURES: Structured assessments of psychopathology using adult caregivers and youth as informants. RESULTS: The best-fitting genetic model revealed that most genetic factors nonspecifically influence risk for either all 11 symptom dimensions or for dimensions of psychopathology within 1 of 2 broad domains. With some notable exceptions, dimension-specific genetic influences accounted for modest amounts of variance. CONCLUSIONS: To inform theory and guide molecular genetic studies, an etiologic model is offered in which 3 patterns of pleiotropy are hypothesized to be the principal modes of genetic risk transmission for common forms of child and adolescent psychopathology. Some common environmental influences were found, but consistent with a "generalist genes, specialist environments" model, there was little sharing of environmental influences. This implies that prevalent dimensions of child and adolescent psychopathology mostly share their genetic liabilities but are differentiated by nonshared experiences.


Assuntos
Doenças em Gêmeos/genética , Doenças em Gêmeos/psicologia , Transtornos Mentais/genética , Transtornos Mentais/psicologia , Meio Social , Adolescente , Agorafobia/epidemiologia , Agorafobia/genética , Agorafobia/psicologia , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/genética , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Criança , Transtorno da Conduta/epidemiologia , Transtorno da Conduta/genética , Transtorno da Conduta/psicologia , Estudos Transversais , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Doenças em Gêmeos/epidemiologia , Análise Fatorial , Feminino , Pleiotropia Genética/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Humanos , Incidência , Controle Interno-Externo , Masculino , Transtornos Mentais/epidemiologia , Modelos Psicológicos , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/psicologia , Fenótipo , Transtornos Fóbicos/epidemiologia , Transtornos Fóbicos/genética , Transtornos Fóbicos/psicologia , Fatores de Risco
15.
J Immunol ; 186(6): 3346-55, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21317386

RESUMO

Chronic inflammation contributes to numerous diseases, and regulation of inflammation is crucial for disease control and resolution. Sex hormones have potent immunoregulatory abilities. Specifically, estrogen influences immune cells and inflammation, which contributes to the sexual dimorphism of autoimmunity and protection against disease seen during pregnancy in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although long thought to act primarily on T cells, recent evidence demonstrated that myeloid cells, such as dendritic cells (DCs), are essential in mediating estrogen's protective effects. Estriol (E3), a pregnancy-specific estrogen, has therapeutic efficacy in MS and EAE, and we evaluated whether E3 could act exclusively through DCs to protect against the inflammatory autoimmune disease EAE. Levels of activation markers (CD80 and CD86) and inhibitory costimulatory markers (PD-L1, PD-L2, B7-H3, and B7-H4) were increased in E3 DCs. E3 DCs had decreased proinflammatory IL-12, IL-23, and IL-6 mRNA expression, increased immunoregulatory IL-10 and TGF-ß mRNA expression, and a decreased ratio of IL-12/IL-10 protein production. Importantly, transfer of E3 DCs to mice prior to active induction of EAE protected them from developing EAE through immune deviation to a Th2 response. This protection was apparent, even in the face of in vitro and in vivo inflammatory challenge. In summary, our results showed that E3 generates tolerogenic DCs, which protect against the inflammatory autoimmune disease EAE. Targeted generation of tolerogenic DCs with immunomodulatory therapeutics, such as E3, has potential applications in the treatment of numerous autoimmune and chronic inflammatory diseases.


Assuntos
Doenças Autoimunes/metabolismo , Doenças Autoimunes/prevenção & controle , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Estriol/fisiologia , Tolerância Imunológica , Animais , Doenças Autoimunes/patologia , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/metabolismo , Células Dendríticas/transplante , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/prevenção & controle , Estriol/farmacologia , Feminino , Inibidores do Crescimento/fisiologia , Mediadores da Inflamação/administração & dosagem , Mediadores da Inflamação/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez , Proteínas da Gravidez/farmacologia , Proteínas da Gravidez/fisiologia , Fase de Repouso do Ciclo Celular/imunologia , Baço/citologia , Baço/imunologia , Baço/transplante
16.
J Abnorm Psychol ; 119(2): 376-88, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20455610

RESUMO

Despite consistent documentation of associations between childhood negative emotionality and externalizing psychopathology, few genetically informative studies have investigated the etiology of that association. The goal of the current study was to delineate the etiology of the covariation of negative emotionality and childhood externalizing problems (e.g., oppositional defiant disorder, conduct disorder, inattention, and hyperactivity/impulsivity). Twin families were recruited from Georgia state birth records and completed parental report questionnaires of negative emotionality and common Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) child psychiatric disorders. Results suggest both genetic and environmental influences underlying negative emotionality and each externalizing symptom dimension, with additional evidence for sibling competition/rater contrast effects for inattention and hyperactivity/impulsivity. Bivariate model-fitting analyses indicated that a portion of the additive (43%-75%) and nonadditive (26%-100%) genetic influences underlying each symptom dimension was accounted for by the genetic influences underlying negative emotionality. Finally, an independent pathways model examining the etiology of the association between negative emotionality and the externalizing dimensions indicated that a substantial portion of the additive genetic, nonadditive genetic, and nonshared environmental influences underlying externalizing behavior is shared with negative emotionality.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/genética , Transtorno da Conduta/genética , Doenças em Gêmeos , Emoções , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Criança , Pré-Escolar , Transtorno da Conduta/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Georgia , Humanos , Masculino , Fatores Sexuais , Meio Social , Inquéritos e Questionários , Gêmeos/genética , Gêmeos/psicologia
17.
Arch Gen Psychiatry ; 67(5): 529-38, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20439834

RESUMO

CONTEXT: The association between maternal smoking during pregnancy (SDP) and offspring disruptive behaviors has been well documented, but it is unclear whether exposure to SDP or the effects of factors correlated with SDP account for the increased risk. OBJECTIVE: To test whether the association between SDP and offspring criminal convictions was consistent with a causal connection or due to familial background factors by controlling for measured covariates and using a quasi-experimental approach. DESIGN: We used a population-based study of children born in Sweden from 1983 to 1989 (N = 609,372) to examine the association between SDP and offspring criminal convictions while controlling for measured traits of both parents. We also compared siblings differentially exposed to SDP (n = 50,339) to account for unmeasured familial factors that could account for the association. SETTING: Population-based study of all children born in Sweden from 1983 to 1989 with information on maternal SDP and offspring criminal convictions based on national registries collected by the Swedish government. PATIENTS OR OTHER PARTICIPANTS: Children born in Sweden from 1983 to 1989 (N = 609,372) and siblings differentially exposed to SDP (n = 50,339). MAIN OUTCOME MEASURES: Violent and nonviolent convictions, based on the Swedish National Crime Register, a register with detailed information on all convictions in the country. RESULTS: Moderate (hazard rate [HR], 2.47; 95% confidence interval [CI], 2.34-2.60) and high (HR, 3.43; 95% CI, 3.25-3.63) levels of maternal SDP were associated with an increased risk for offspring violent convictions, even when controlling for maternal and paternal traits. There was no association between SDP and violent convictions, however, when comparing differentially exposed siblings (HR(moderate), 1.02; 95% CI, 0.79-1.30; HR(high), 1.03; 95% CI, 0.78-1.37). Smoking during pregnancy also was associated with nonviolent convictions in the entire population (HR(moderate), 1.62; 95% CI, 1.58-1.66; HR(high), 1.87; 95% CI, 1.82-1.92) and when controlling for covariates. But, there was no association when comparing siblings who were differentially exposed (HR(moderate), 0.89; 95% CI, 0.78-1.01; HR(high), 0.89; 95% CI, 0.78-1.02). CONCLUSION: The results suggest that familial background factors account for the association between maternal SDP and criminal convictions, not the specific exposure to SDP.


Assuntos
Transtorno da Personalidade Antissocial/epidemiologia , Crime/estatística & dados numéricos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Fatores Socioeconômicos , Logro , Adulto , Transtorno da Personalidade Antissocial/etiologia , Estudos de Casos e Controles , Causalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Meio Social , Suécia , Violência/psicologia , Violência/estatística & dados numéricos , Adulto Jovem
18.
Child Dev ; 81(1): 80-100, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20331655

RESUMO

The current study, based on all births in Sweden from 1983 to 1991 (N = 654,707), explored the processes underlying the association between smoking during pregnancy (SDP) and offspring school grades and mathematic proficiency at age 15. The analyses compared relatives who varied in their exposure to SDP and who varied in their genetic relatedness. Although SDP was statistically associated with academic achievement (AA) when comparing unrelated individuals, the results suggest that SDP does not cause poorer academic performance, as full siblings differentially exposed to SDP did not differ in their academic scores. The pattern of results suggests that genetic factors shared by parents and their offspring help explain why offspring exposed to SDP have lower levels of AA.


Assuntos
Escolaridade , Exposição Materna/efeitos adversos , Mães , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Gravidez , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/etiologia , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Suécia/epidemiologia , Fatores de Tempo
19.
J Gen Virol ; 90(Pt 8): 1848-1858, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19403754

RESUMO

Little is known about viral determinants of virulence associated with western equine encephalitis virus (WEEV). Here, we have analysed six North American WEEV isolates in an outbred CD1 mouse model. Full genome sequence analyses showed < or =2.7 % divergence among the six WEEV isolates. However, the percentage mortality and mean time to death (MTD) varied significantly when mice received subcutaneous injections of 10(3) p.f.u. of each virus. Two WEEV strains, McMillan (McM) and Imperial 181 (IMP), were the most divergent of the six in genome sequence; McM caused 100 % mortality by 5 days post-infection, whereas IMP caused no mortality. McM had significantly higher titres in the brain than IMP. Similar differences in virulence were observed when McM and IMP were administered by aerosol, intranasal or intravenous routes. McM was 100 % lethal with an MTD of 1.9 days when 10(3) p.f.u. of each virus was administered by intracerebral inoculation; in contrast, IMP caused no mortality. The presence of IMP in the brains after infection by different routes and the lack of observed mortality confirmed that IMP is neuroinvasive but not neurovirulent. Based on morbidity, mortality, MTD, severity of brain lesions, virus distribution patterns, routes of infection and differences in infection of cultured cells, McM and IMP were identified as high- and low-virulence isolates, respectively.


Assuntos
Vírus da Encefalite Equina do Oeste/isolamento & purificação , Vírus da Encefalite Equina do Oeste/patogenicidade , Encefalomielite Equina/virologia , Variação Genética , Animais , Encéfalo/patologia , Encéfalo/virologia , Análise por Conglomerados , Vírus da Encefalite Equina do Oeste/genética , Genoma Viral , Histocitoquímica/métodos , Camundongos , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Homologia de Sequência , Análise de Sobrevida , Ensaio de Placa Viral/métodos , Virulência
20.
Vaccine ; 24(4): 485-94, 2006 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-16137802

RESUMO

We conducted a cross sectional survey of 3163 women and men in six Asian countries to examine willingness for children and adults to be vaccinated against shigellosis and other forms of dysentery. The six sites were clustered into three regions for ease of comparison. The regions are: Northeast Asia (China), Southeast Asia (Thailand, Vietnam, and Indonesia) and South Asia (Bangladesh and Pakistan). We used multiple logistic regression to identify region-specific models for vaccination willingness for both adults and children. A vaccine to protect against dysentery, if available would be very much in demand throughout the three Asian regions for children. For adults, the responses indicate that vaccine uptake by adults will vary. A large proportion of respondents in all regions, specifically in China, do not perceive themselves at risk yet still consider a shigellosis vaccine desirable.


Assuntos
Atenção à Saúde/métodos , Disenteria Bacilar/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Vacinas contra Shigella/administração & dosagem , Adulto , Ásia , Criança , Pré-Escolar , Disenteria , Disenteria Bacilar/psicologia , Feminino , Humanos , Programas de Imunização , Lactente , Masculino , Psicologia , Saúde Pública , Vacinas contra Shigella/imunologia
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