ABSTRACT
Resumo: Introdução Estudos apontam que adolescentes têm apresentado maior vulnerabilidade para o desenvolvimento de problemas relacionados à saúde mental. Observa-se, no entanto, uma escassez de pesquisas que tratam da experiência do sofrimento psíquico nessa população, bem como da atenção à saúde mental direcionada aos adolescentes e seus familiares, incluindo a vivência da crise. Objetivo O objetivo do estudo foi identificar a compreensão de familiares de adolescentes usuários de um Centro de Atenção Psicossocial Infantojuvenil (CAPSij) sobre as situações de crise vivenciadas pelos adolescentes e sobre a trajetória percorrida em busca de cuidados. Método Participaram cinco familiares de adolescentes vinculados a um CAPSij, que concederam entrevistas abertas com base no método de história oral, cujos produtos foram posteriormente trabalhados por meio de análise temática. Resultados Os resultados indicam que a vivência da crise do adolescente faz emergir sentimentos de medo, perplexidade e culpa nos familiares. Entretanto, tal experiência também é apontada como motivo de maior vínculo entre ambos. Observou-se relatos que relacionam a crise do adolescente à vivência de adversidades familiares e, além disso, embora indiquem a ausência de internações psiquiátricas no processo de cuidado, revelam dificuldades nas trocas com os profissionais e serviços, que facilitem a compreensão da situação, ainda que reconheçam como positivo o apoio dos mesmos nos momentos críticos. Conclusão O estudo contribui apresentando a compreensão da crise pela voz dos familiares de adolescentes e identifica as percepções da experiência de cuidado nos serviços, reforçando a importância do lugar da família na atenção à saúde mental de adolescentes.
Abstract: Introduction Several studies indicate that adolescents are more vulnerable to the development of mental health problems. However, there is a lack of researches on the experience of psychic suffering and attention to mental health for adolescents and their families, including the experience of the mental health crisis. Objective The objective of this study was to identify the understanding of family members of adolescents of a Center for Psychosocial Child and Adolescent Care (CAPSij) about the crisis situations experienced by adolescents and the trajectory covered in the search for care. Method Five family members of adolescents linked to a CAPSij interviewed gave open interviews based on oral history, whose products were later worked through thematic analysis. Results The results indicate that the experience of the adolescent crisis causes feelings of fear, perplexity and guilt to the family. However, this experience is also pointed out as a reason for greater bonding between them. There were reports that relate the adolescent's crisis to the experience of family adversities and, besides, although they indicate the absence of psychiatric hospitalizations in the care process, they reveal difficulties in the exchanges with professionals and services, which could facilitate the understanding of the situation, even though they recognize their support in critical moments as positive. Conclusion The study contributes presenting the crisis understanding by the voice of the relatives of adolescents, and it also identifies the perceptions of care experience in the services, reinforcing the family importance in the attention to the mental health of adolescents.
ABSTRACT
This study investigates the participation of PI3Kγ in the development of joint inflammation and dysfunction in an experimental model of acute gout in mice. Acute gout was induced by injection of monosodium urate (MSU) crystals into the tibiofemoral joint of mice. The involvement of PI3Kγ was evaluated using a selective inhibitor and mice deficient for PI3Kγ (PI3Kγ-/- ) or with loss of kinase activity. Neutrophils recovered from the inflamed joint were quantified and stained for phosphorylated Akt (pAkt) and production of reactive oxygen species (ROS). The adherence of leukocytes to the joint microvasculature was assessed by intravital microscopy and cleaved caspase-1 by Western blot. Injection of MSU crystals induced massive accumulation of neutrophils expressing phosphorylated Akt. In the absence of PI3Kγ, there was reduction of pAkt expression, chemokine production, and neutrophil recruitment. Genetic or pharmacological inhibition of PI3Kγ reduced the adherence of leukocytes to the joint microvasculature, even in joints with established inflammation. Neutrophils from PI3Kγ-/- mice produced less ROS than wild-type neutrophils. There was decreased joint damage and dysfunction in the absence of PI3Kγ. In addition, in the absence of PI3Kγ activity, there was reduction of cleaved caspase-1 and IL-1ß production in synovial tissue after injection of MSU crystals and leukotriene B4 . Our studies suggest that PI3Kγ is crucial for MSU crystal-induced acute joint inflammation. It is necessary for regulating caspase-1 activation and for mediating neutrophil migration and activation. Drugs that impair PI3Kγ function may be useful to control acute gout inflammation.
Subject(s)
Arthritis, Gouty/enzymology , Arthritis, Gouty/immunology , Caspase 1/metabolism , Class Ib Phosphatidylinositol 3-Kinase/metabolism , Neutrophil Infiltration , Acute Disease , Animals , Cell Adhesion , Cell Movement , Class Ib Phosphatidylinositol 3-Kinase/deficiency , Cytoplasm/metabolism , Enzyme Activation , Inflammasomes/metabolism , Inflammation/pathology , Interleukin-1beta/metabolism , Joints/pathology , Leukotriene B4/metabolism , Male , Mice, Inbred C57BL , Microvessels/pathology , Neutrophils/metabolism , Nociception , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Synovial Membrane/blood supply , Uric AcidABSTRACT
This study sought to identify adolescents' perception regarding the mental health crises they experienced, as well as their trajectory when seeking care. The participants were five adolescents aged between 16 and 17 years who frequent a Center for Child and Adolescent Psychosocial Care (CAPSij, in Portuguese) who gave interviews following open-ended scripts based on oral history methods. The narratives were recorded, transcribed, rendered into text and analyzed through a thematic analysis. Results indicate: (a) the crisis experience connected, in particular, with intense feelings of anguish, sadness and worthlessness, suicide ideation and attempt - experienced as an individual problem; (b) relationships with peers and family members triggering crisis processes when permeated by different types of violence; and as emotional and social support when immersed in relationships of trust; (c) the predominant trajectory for accessing care was centered in points of the Psychosocial Care Network and there were no reports of hospital admissions; (d) difficulties in care are centered on treatment adhesion, participation in collective care spaces and resistance to medication. This study is an advancement, presenting the understanding of mental health crisis and factors involved in this experience, through the perspective of the adolescents who experienced it, as well as identifying the paths they followed when searching for treatment and the perceptions that emerged from the experience of care in the services.
Este estudo objetivou identificar a percepção de adolescentes que vivenciaram a crise em saúde mental sobre tal experiência, bem como sobre a trajetória percorrida em busca de cuidados. Participaram cinco adolescentes de 16 e 17 anos, usuários(as) de um Centro de Atenção Psicossocial Infantojuvenil (CAPSij), que concederam entrevistas valendo-se de roteiros abertos baseados no método de história oral. As narrativas foram gravadas, transcritas, textualizadas e trabalhadas por meio de análise temática. Os resultados indicaram: (a) a vivência da crise atrelada, principalmente, a sentimentos intensos de angústia, tristeza e desvalia, ideação e tentativa de suicídio - vivenciados como um problema individual; (b) as relações entre pares e familiares desencadeadoras dos processos de crise quando permeadas por diferentes tipos de violência, e como suporte emocional e social, quando imersas em relações de confiança; (c) a trajetória predominante de acesso ao cuidado aconteceu centrada em pontos da Rede de Atenção Psicossocial e não houve relato de internação; (d) as dificuldades no cuidado assentaram-se na adesão ao tratamento, participação em espaços coletivos de cuidado e resistências à medicação. O estudo avança, apresentando a compreensão da crise em saúde mental e dos fatores envolvidos nesta experiência, pela voz dos(das) próprios(as) adolescentes que a vivenciaram, bem como identifica os caminhos trilhados em busca de tratamento e as percepções emergidas da experiência de cuidado nos serviços.
El objetivo de este estudio fue identificar la percepción de adolescentes sobre la experiencia de vivir crisis de salud mental, así como sobre la trayectoria recorrida en búsqueda de cuidados. Participaron cinco adolescentes de 16 y 17 años, usuarios(as) de un Centro de Atención Psicosocial Infantojuvenil (CAPSij), que concedieron entrevistas a partir de guiones abiertos, basados en el método de historia oral. Las narraciones fueron grabadas, transcritas, textualizadas y trabajadas mediante un análisis temático. Los resultados indicaron: (a) la vivencia de la crisis asociada, principalmente, a sentimientos intensos de angustia, tristeza y desprotección, ideación y tentativa de suicidio -vividos como un problema individual; (b) las relaciones entre pares y familiares desencadenantes de procesos de crisis, cuando son permeables a diferentes tipos de violencia; y como apoyo emocional y social, cuando están inmersas en relaciones de confianza; (c) la trayectoria predominante de acceso al cuidado se produjo centrada en puntos de la Red de Atención Psicosocial y no hubo narración de internamiento; (d) las dificultades en el cuidado se asentaron en la adhesión al tratamiento, participación en espacios colectivos de cuidado y resistencias a la medicación. El estudio avanza, presentando la comprensión de la crisis en salud mental y de los factores involucrados en esta experiencia, a través de la voz de los(las) propios(as) adolescentes que la vivieron, así como identifica los caminos recorridos en búsqueda de tratamiento y las percepciones surgidas de la experiencia de cuidado en los servicios.
Subject(s)
Mental Disorders/psychology , Suicide, Attempted/psychology , Adolescent , Brazil , Family , Female , Humans , Interviews as Topic , Male , Mental Disorders/diagnosis , Mental Health , Peer Group , Qualitative Research , Self-Assessment , Socioeconomic Factors , Suicidal Ideation , ViolenceABSTRACT
BACKGROUND: Hepatitis C virus (HCV) infection is associated with chronic liver disease, resulting in cirrhosis and hepatocellular carcinoma. Approximately 20% of HCV infections are spontaneously resolved. Here, we assessed the hierarchical relevance of host factors contributing to viral clearance. METHODS: DNA samples from 40 resolved infections and 40 chronic HCV patients paired by age were analyzed. Bivariate analysis was performed to rank the importance of each contributing factor in spontaneous HCV clearance. RESULTS: Interestingly, 63.6% of patients with resolved infections exhibited the protective genotype CC for SNP rs12979860. Additionally, 59.3% of patients with resolved infections displayed the protective genotype TT/TT for SNP ss469415590. Moreover, a ranking of clearance factors was estimated. In order of importance, the IL28B CC genotype (OR 0.197, 95% CI 0.072-0.541) followed by the INFL4 TT/TT genotype (OR 0.237, 95% CI 0.083-0.679), and female gender (OR 0.394, 95% CI 0.159-0.977) were the main predictors for clearance of HCV infection. CONCLUSIONS: HCV clearance is multifactorial and the contributing factors display a hierarchical order. Identifying all elements playing role in HCV clearance is of the most importance for HCV-related disease management. Dissecting the relevance of each contributing factor will certainly improve our understanding of the pathogenesis of HCV infection.
Subject(s)
Hepacivirus/isolation & purification , Hepatitis C/virology , Adult , Antibodies, Viral/immunology , Female , Genetic Predisposition to Disease , Genotype , Hepacivirus/classification , Hepacivirus/genetics , Hepatitis C/genetics , Hepatitis C/immunology , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Sex FactorsABSTRACT
Resumo: Este estudo objetivou identificar a percepção de adolescentes que vivenciaram a crise em saúde mental sobre tal experiência, bem como sobre a trajetória percorrida em busca de cuidados. Participaram cinco adolescentes de 16 e 17 anos, usuários(as) de um Centro de Atenção Psicossocial Infantojuvenil (CAPSij), que concederam entrevistas valendo-se de roteiros abertos baseados no método de história oral. As narrativas foram gravadas, transcritas, textualizadas e trabalhadas por meio de análise temática. Os resultados indicaram: (a) a vivência da crise atrelada, principalmente, a sentimentos intensos de angústia, tristeza e desvalia, ideação e tentativa de suicídio - vivenciados como um problema individual; (b) as relações entre pares e familiares desencadeadoras dos processos de crise quando permeadas por diferentes tipos de violência, e como suporte emocional e social, quando imersas em relações de confiança; (c) a trajetória predominante de acesso ao cuidado aconteceu centrada em pontos da Rede de Atenção Psicossocial e não houve relato de internação; (d) as dificuldades no cuidado assentaram-se na adesão ao tratamento, participação em espaços coletivos de cuidado e resistências à medicação. O estudo avança, apresentando a compreensão da crise em saúde mental e dos fatores envolvidos nesta experiência, pela voz dos(das) próprios(as) adolescentes que a vivenciaram, bem como identifica os caminhos trilhados em busca de tratamento e as percepções emergidas da experiência de cuidado nos serviços.
Abstract: This study sought to identify adolescents' perception regarding the mental health crises they experienced, as well as their trajectory when seeking care. The participants were five adolescents aged between 16 and 17 years who frequent a Center for Child and Adolescent Psychosocial Care (CAPSij, in Portuguese) who gave interviews following open-ended scripts based on oral history methods. The narratives were recorded, transcribed, rendered into text and analyzed through a thematic analysis. Results indicate: (a) the crisis experience connected, in particular, with intense feelings of anguish, sadness and worthlessness, suicide ideation and attempt - experienced as an individual problem; (b) relationships with peers and family members triggering crisis processes when permeated by different types of violence; and as emotional and social support when immersed in relationships of trust; (c) the predominant trajectory for accessing care was centered in points of the Psychosocial Care Network and there were no reports of hospital admissions; (d) difficulties in care are centered on treatment adhesion, participation in collective care spaces and resistance to medication. This study is an advancement, presenting the understanding of mental health crisis and factors involved in this experience, through the perspective of the adolescents who experienced it, as well as identifying the paths they followed when searching for treatment and the perceptions that emerged from the experience of care in the services.
Resumen: El objetivo de este estudio fue identificar la percepción de adolescentes sobre la experiencia de vivir crisis de salud mental, así como sobre la trayectoria recorrida en búsqueda de cuidados. Participaron cinco adolescentes de 16 y 17 años, usuarios(as) de un Centro de Atención Psicosocial Infantojuvenil (CAPSij), que concedieron entrevistas a partir de guiones abiertos, basados en el método de historia oral. Las narraciones fueron grabadas, transcritas, textualizadas y trabajadas mediante un análisis temático. Los resultados indicaron: (a) la vivencia de la crisis asociada, principalmente, a sentimientos intensos de angustia, tristeza y desprotección, ideación y tentativa de suicidio -vividos como un problema individual; (b) las relaciones entre pares y familiares desencadenantes de procesos de crisis, cuando son permeables a diferentes tipos de violencia; y como apoyo emocional y social, cuando están inmersas en relaciones de confianza; (c) la trayectoria predominante de acceso al cuidado se produjo centrada en puntos de la Red de Atención Psicosocial y no hubo narración de internamiento; (d) las dificultades en el cuidado se asentaron en la adhesión al tratamiento, participación en espacios colectivos de cuidado y resistencias a la medicación. El estudio avanza, presentando la comprensión de la crisis en salud mental y de los factores involucrados en esta experiencia, a través de la voz de los(las) propios(as) adolescentes que la vivieron, así como identifica los caminos recorridos en búsqueda de tratamiento y las percepciones surgidas de la experiencia de cuidado en los servicios.
Subject(s)
Humans , Male , Female , Adolescent , Suicide, Attempted/psychology , Mental Disorders/psychology , Peer Group , Self-Assessment , Socioeconomic Factors , Violence , Brazil , Family , Mental Health , Interviews as Topic , Qualitative Research , Suicidal Ideation , Mental Disorders/diagnosisABSTRACT
The prevalence of Autism Spectrum Disorder in the world population and in Brazil is increasing. The Internet has become an important source of information regarding access to health services, including mental health. It remains to be seen if the virtual paths in search of information are related to the outcomes of the line of care for mental disorders advocated by the SUS, such as Autism. Therefore, this article sets out to analyze the virtual network of access to information about care for Autism in the municipality of Rio de Janeiro in 2017 through the perspective of Social Network Analysis. In this regard, virtual data were collected, such as: virtual information sources; care services cited by the virtual sources and type of service (Public, Private or NGOs). Through the use of Gephi software, a sociogram was generated and analyzed. The results point to a predominance of NGO services in the network, greater centrality of degree and power of intermediation in NGO services, in addition to the isolation of public health services. The result implies that the information system about access to public health services for the treatment of ASD is expanded to the general population by contributing to improved access to these services.
Constata-se o aumento da prevalência do Transtorno do Espectro Autista na população mundial e no Brasil. A internet tem se constituído importante fonte de informação ao acesso aos serviços de saúde, incluindo a saúde mental. Cabe sabermos se os caminhos virtuais em busca de informação se relacionam aos desfechos da linha de cuidado para transtornos mentais preconizada pelo SUS, como para o Autismo. Portanto, o presente artigo tem como objetivo analisar a rede virtual de acesso a informações sobre atendimento para Autismo no município do Rio de Janeiro em 2017, através da perspectiva da Análise de Rede Sociais. Para isso, foram coletados dados virtuais como: fontes virtuais de informação, serviços de atendimento citados pelas fontes virtuais e tipo de serviço (Público, privado ou ONGs). Através do uso do software Gephi, foi gerado e analisado um sociograma. Os resultados apontam para uma predominância de serviços de ONGs na rede, maior centralidade de grau e poder de intermediação desses serviços, além do isolamento dos serviços públicos de saúde. O resultado pressupõe que o sistema de informações acerca do acesso aos serviços de saúde pública para o tratamento do TEA seja expandido para a população em geral, contribuindo com a melhoria do acesso a esses serviços.
Subject(s)
Autism Spectrum Disorder/therapy , Delivery of Health Care/organization & administration , Health Services Accessibility , User-Computer Interface , Brazil , Humans , Internet , Mental Health Services/organization & administration , National Health Programs/organization & administration , Prevalence , Social Networking , SoftwareABSTRACT
Resumo Constata-se o aumento da prevalência do Transtorno do Espectro Autista na população mundial e no Brasil. A internet tem se constituído importante fonte de informação ao acesso aos serviços de saúde, incluindo a saúde mental. Cabe sabermos se os caminhos virtuais em busca de informação se relacionam aos desfechos da linha de cuidado para transtornos mentais preconizada pelo SUS, como para o Autismo. Portanto, o presente artigo tem como objetivo analisar a rede virtual de acesso a informações sobre atendimento para Autismo no município do Rio de Janeiro em 2017, através da perspectiva da Análise de Rede Sociais. Para isso, foram coletados dados virtuais como: fontes virtuais de informação, serviços de atendimento citados pelas fontes virtuais e tipo de serviço (Público, privado ou ONGs). Através do uso do software Gephi, foi gerado e analisado um sociograma. Os resultados apontam para uma predominância de serviços de ONGs na rede, maior centralidade de grau e poder de intermediação desses serviços, além do isolamento dos serviços públicos de saúde. O resultado pressupõe que o sistema de informações acerca do acesso aos serviços de saúde pública para o tratamento do TEA seja expandido para a população em geral, contribuindo com a melhoria do acesso a esses serviços.
Abstract The prevalence of Autism Spectrum Disorder in the world population and in Brazil is increasing. The Internet has become an important source of information regarding access to health services, including mental health. It remains to be seen if the virtual paths in search of information are related to the outcomes of the line of care for mental disorders advocated by the SUS, such as Autism. Therefore, this article sets out to analyze the virtual network of access to information about care for Autism in the municipality of Rio de Janeiro in 2017 through the perspective of Social Network Analysis. In this regard, virtual data were collected, such as: virtual information sources; care services cited by the virtual sources and type of service (Public, Private or NGOs). Through the use of Gephi software, a sociogram was generated and analyzed. The results point to a predominance of NGO services in the network, greater centrality of degree and power of intermediation in NGO services, in addition to the isolation of public health services. The result implies that the information system about access to public health services for the treatment of ASD is expanded to the general population by contributing to improved access to these services.
Subject(s)
Humans , Delivery of Health Care/organization & administration , Autism Spectrum Disorder/therapy , Health Services Accessibility , User-Computer Interface , Software , Brazil , Prevalence , Internet , Social Networking , Mental Health Services/organization & administration , National Health Programs/organization & administrationABSTRACT
AIM: The purpose of this retrospective multicenter study was to evaluate the use and the self-perceived efficacy and tolerability of pharmacological and non-pharmacological treatments in children and adolescents with primary headaches. METHODS: Study of a cohort of children and adolescents diagnosed with primary headache, consecutively referred to 13 juvenile Italian Headache Centers. An ad hoc questionnaire was used for clinical data collection. RESULTS: Among 706 patients with primary headaches included in the study, 637 cases with a single type of headache (migraine 76% - with and without aura in 10% and 67% respectively; tension-type headache 24%) were selected (mean age at clinical interview: 12 years). Acetaminophen and non-steroidal anti-inflammatory drugs (in particular ibuprofen) were commonly used to treat attacks, by 76% and 46% of cases respectively. Triptans were used overall by 6% of migraineurs and by 13% of adolescents with migraine, with better efficacy than acetaminophen and non-steroidal anti-inflammatory drugs. Preventive drugs were used by 19% of migraineurs and by 3% of subjects with tension-type headache. In migraineurs, flunarizine was the most frequently used drug (18%), followed by antiepileptic drugs (7%) and pizotifen (6%), while cyproheptadine, propanolol and amitriptyline were rarely used. Pizotifen showed the best perceived efficacy and tolerability. Melatonin and nutraceuticals were used by 10% and 32% of subjects, respectively, both for migraine and tension-type headache, with good results in terms of perceived efficacy and tolerability. Non-pharmacological preventive treatments (i.e. relaxation techniques, biofeedback, cognitive-behavioral therapy, acupuncture) were used only by 10% of cases (migraine 9%, tension-type headache 15%). DISCUSSION: Non-steroidal anti-inflammatory drugs, especially ibuprofen, should be preferred to acetaminophen for acute attacks of migraine or tension-type headache, because they were usually more effective and well tolerated. Triptans could be used more frequently as first or almost second choice for treating migraine attack in adolescents. Non-pharmacological preventive treatments are recommended by some pediatric guidelines as first-line interventions for primary headaches and their use should be implemented in clinical practice. Prospective multicenter studies based on larger series are warranted to better understand the best treatment strategies for young people with primary headaches.
Subject(s)
Migraine Disorders/therapy , Pediatrics/methods , Tension-Type Headache/therapy , Adolescent , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Behavior Therapy , Child , Female , Humans , Italy , Male , Migraine Disorders/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Retrospective Studies , Surveys and Questionnaires , Tension-Type Headache/drug therapyABSTRACT
Hepatitis C virus (HCV) is a major public health problem that affects more than 180 million people worldwide. Identification of HCV transmission networks is of critical importance for disease control. HCV related cases are often difficult to identify due to the characteristic long incubation period and lack of symptoms during the acute phase of the disease, making it challenging to link related cases to a common source of infection. Additionally, HCV transmission chains are difficult to trace back since viral variants from epidemiologically linked cases are genetically related but rarely identical. Genetic relatedness studies primarily rely on information obtained from the rapidly evolving HCV hypervariable region 1 (HVR1). However, in some instances, the rapid divergence of this region can lead to loss of genetic links between related isolates, which represents an important challenge for outbreak investigations and genetic relatedness studies. Sequencing of multiple and longer sub-genomic regions has been proposed as an alternative to overcome the limitations imposed by the rapid molecular evolution of the HCV HVR1. Additionally, conventional molecular approaches required to characterize the HCV intra-host genetic variation are laborious, time-consuming, and expensive while providing limited information about the composition of the viral population. Next generation sequencing (NGS) approaches enormously facilitate the characterization of the HCV intra-host population by detecting rare variants at much lower frequencies. Thus, NGS approaches using multiple sub-genomic regions should improve the characterization of the HCV intra-host population. Here, we explore the usefulness of multiregion sequencing using a NGS platform for genetic relatedness studies among HCV cases.
Subject(s)
Hepacivirus/genetics , Hepatitis C/virology , High-Throughput Nucleotide Sequencing , Multilocus Sequence Typing , Adult , Evolution, Molecular , Female , Genotype , Hepacivirus/classification , Hepatitis C/epidemiology , Humans , Male , Middle Aged , Phylogeny , Viral Load , Viral Nonstructural Proteins/geneticsABSTRACT
Here, we describe the molecular characterization of six human Mycobacterium bovis clinical isolates, including three multidrug resistant (MDR) strains, collected in Mexico through the National Survey on Tuberculosis Drug Resistance (ENTB-2008), a nationally representative survey conducted during 2008-2009 in nine states with a stratified cluster sampling design. The genetic background of bovine M. bovis strains identified in three different states of Mexico was studied in parallel to assess molecular relatedness of bovine and human strains. Additionally, resistance to first and second line anti-tuberculosis (TB) drugs and molecular identification of mutations conferring drug resistance was also performed. All strains were characterized by spoligotyping and 24-loci MIRU-VNTRs, and analyzed using the SITVIT2 (n = 112,000 strains) and SITVITBovis (n = 25,000 strains) proprietary databases of Institut Pasteur de la Guadeloupe. Furthermore, data from this study (n = 55 isolates), were also compared with genotypes recorded for M. bovis from USA (n = 203), Argentina (n = 726), as well as other isolates from Mexico (independent from the present study; n = 147), to determine any evidence for genetic relatedness between circulating M. bovis strains. The results showed that all human M. bovis cases were not genetically related between them or to any bovine strain. Interestingly, a high degree of genetic variability was observed among bovine strains. Several autochthonous and presumably imported strains were identified. The emergence of drug-resistant M. bovis is an important public health problem that jeopardizes the success of TB control programs in the region.
Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Mutation , Mycobacterium bovis/genetics , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/microbiology , Antitubercular Agents/therapeutic use , Databases, Genetic , Genotype , Humans , Mexico/epidemiology , Microbial Sensitivity Tests , Minisatellite Repeats , Molecular Diagnostic Techniques , Mycobacterium bovis/drug effects , Mycobacterium bovis/isolation & purification , Phenotype , Phylogeny , Predictive Value of Tests , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/transmission , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/transmissionABSTRACT
Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.
Subject(s)
Epidemiological Monitoring , Hepacivirus/classification , Hepacivirus/genetics , Hepatitis C/epidemiology , Hepatitis C/transmission , Computational Biology/methods , Hepacivirus/isolation & purification , Hepatitis C/virology , Humans , Molecular Epidemiology/methodsABSTRACT
Hepatitis C virus (HCV) genotype 3a accounts for â¼80% of HCV infections in Pakistan, where â¼10 million people are HCV-infected. Here, we report analysis of the genetic heterogeneity of HCV NS3 and NS5b subgenomic regions from genotype 3a variants obtained from Pakistan. Phylogenetic analyses showed that Pakistani genotype 3a variants were as genetically diverse as global variants, with extensive intermixing. Bayesian estimates showed that the most recent ancestor for genotype 3a in Pakistan was last extant in â¼1896-1914 C.E. (range: 1851-1932). This genotype experienced a population expansion starting from â¼1905 to â¼1970 after which the effective population leveled. Death/birth models suggest that HCV 3a has reached saturating diversity with decreasing turnover rate and positive extinction. Taken together, these observations are consistent with a long and complex history of HCV 3a infection in Pakistan.
Subject(s)
Genetic Variation , Hepacivirus/genetics , Hepatitis C/virology , Bayes Theorem , Evolution, Molecular , Genotype , Hepatitis C/epidemiology , Humans , Pakistan/epidemiology , Phylogeny , Viral Nonstructural ProteinsABSTRACT
Infection with hepatitis A virus (HAV) is the commonest viral cause of liver disease and presents an important public health problem worldwide. Several unique HAV properties and molecular mechanisms of its interaction with host were recently discovered and should aid in clarifying the pathogenesis of hepatitis A. Genetic characterization of HAV strains have resulted in the identification of different genotypes and subtypes, which exhibit a characteristic worldwide distribution. Shifts in HAV endemicity occurring in different parts of the world, introduction of genetically diverse strains from geographically distant regions, genotype displacement observed in some countries and population expansion detected in the last decades of the 20th century using phylogenetic analysis are important factors contributing to the complex dynamics of HAV infections worldwide. Strong selection pressures, some of which, like usage of deoptimized codons, are unique to HAV, limit genetic variability of the virus. Analysis of subgenomic regions has been proven useful for outbreak investigations. However, sharing short sequences among epidemiologically unrelated strains indicates that specific identification of HAV strains for molecular surveillance can be achieved only using whole-genome sequences. Here, we present up-to-date information on the HAV molecular epidemiology and evolution, and highlight the most relevant features of the HAV-host interactions.
Subject(s)
Hepatitis A virus/classification , Hepatitis A virus/genetics , Hepatitis A/virology , Animals , Disease Outbreaks/prevention & control , Genetic Variation , Hepatitis A/epidemiology , Hepatitis A/transmission , High-Throughput Nucleotide Sequencing , Host-Pathogen Interactions , Humans , Phylogeny , Phylogeography , RNA, ViralABSTRACT
Clinical infection by hepatitis A virus (HAV) is generally self-limited but in some cases can progress to liver failure. Here, an HAV outbreak investigation among children with acute liver failure in a highly endemic country is presented. In addition, a sensitive method for HAV whole genome amplification and sequencing suitable for analysis of clinical samples is described. In this setting, two fatal cases attributed to acute liver failure and two asymptomatic cases living in the same household were identified. In a second household, one HAV case was observed with jaundice which resolved spontaneously. Partial molecular characterization showed that both households were infected by HAV subtype IA; however, the infecting strains in the two households were different. The HAV outbreak strains recovered from all cases grouped together within cluster IA1, which contains closely related HAV strains from the United States commonly associated with international travelers. Full-genome HAV sequences obtained from the household with the acute liver failure cases were related (genetic distances ranging from 0.01% to 0.04%), indicating a common-source infection. Interestingly, the strain recovered from the asymptomatic household contact was nearly identical to the strain causing acute liver failure. The whole genome sequence from the case in the second household was distinctly different from the strains associated with acute liver failure. Thus, infection with almost identical HAV strains resulted in drastically different clinical outcomes.
Subject(s)
Disease Outbreaks , Genome, Viral , Hepatitis A virus/genetics , Hepatitis A/complications , Hepatitis A/epidemiology , Liver Failure, Acute/epidemiology , Adolescent , Child , Cluster Analysis , Female , Hepatitis A/pathology , Hepatitis A/virology , Hepatitis A virus/isolation & purification , Humans , Liver Failure, Acute/pathology , Liver Failure, Acute/virology , Male , Molecular Sequence Data , Phylogeny , RNA, Viral/genetics , Sequence Analysis, DNA , United StatesABSTRACT
The genetic characterization of hepatitis A virus (HAV) strains is commonly accomplished by sequencing subgenomic regions, such as the VP1/P2B junction. HAV genome is not extensively variable, thus presenting opportunity for sharing sequences of subgenomic regions among genetically unrelated isolates. The degree of misrepresentation of phylogenetic relationships by subgenomic regions is especially important for tracking transmissions. Here, we analyzed whole-genome (WG) sequences of 101 HAV strains identified from 4 major multi-state, food-borne outbreaks of hepatitis A in the Unites States and from 14 non-outbreak-related HAV strains that shared identical VP1/P2B sequences with the outbreak strains. Although HAV strains with an identical VP1/P2B sequence were specific to each outbreak, WG were different, with genetic diversity reaching 0.31% (mean 0.09%). Evaluation of different subgenomic regions did not identify any other section of the HAV genome that could accurately represent phylogenetic relationships observed using WG sequences. The identification of 2-3 dominant HAV strains in 3 out of 4 outbreaks indicates contamination of the implicated food items with a heterogeneous HAV population. However, analysis of intra-host HAV variants from eight patients involved in one outbreak showed that only a single sequence variant established infection in each patient. Four non-outbreak strains were found closely related to strains from 2 outbreaks, whereas ten were genetically different from the outbreak strains. Thus, accurate tracking of HAV strains can be accomplished using HAV WG sequences, while short subgenomic regions are useful for identification of transmissions only among cases with known epidemiological association.
Subject(s)
Disease Outbreaks , Genes, Viral , Hepatitis A virus/genetics , Hepatitis A/virology , Food Microbiology , Genetic Variation , Hepatitis A/epidemiology , Humans , Phylogeny , Sequence Analysis, DNAABSTRACT
Asthma has been defined as a disease of chronic airway inflammation in which many cells and cellular products participate with variable degrees of airflow obstruction and hyperresponsiveness that lead to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Prominent among these cellular elements are two cell types referred to as the invariant natural killer T (iNKT) cells and a subpopulation of T cells expressing the molecule CD161, which are both thought to play a role in the pathogenesis of asthma. Although the presence of iNKT and other CD161(+) cells in murine models has been associated with asthma, relatively few studies have been performed in the adult patient with asthma that have been often conflicting and even fewer studies are available in children. The present study was performed to investigate the peripheral blood frequencies of iNKT and CD161(+) T cells in children with asthma. A total of 35 children, 19 stable asthmatic patients, 6 who had experienced an asthmatic attack within 24 hours and had not received any treatment, and 10 healthy controls, aged 6-12 years, were enrolled in the study. iNKT and CD161(+) T-cell frequencies in blood were measured together with quantitative levels of IL-4 and interferon (IFN) γ using a cytofluorimetric approach. The results show that iNKT cells are increased in pediatric asthmatic patients undergoing exacerbations of asthma. These cells also produced less IFN-γ and more IL-4 than children with stable asthma and in healthy control children. These results suggest that iNKT cells might participate in the development of the asthmatic exacerbations. The increased production of IL-4 in conjunction with the decrease of IFN-γ may be mechanistically responsible, at least partially, for the heightening of the immunologic response leading to the asthmatic attack in children. Knowledge of these interactive mechanisms involving the iNKT cell and our understanding of its role in the exacerbation of asthma hold great promise in the development of better diagnostic predictive markers of disease progression as well as new forms of therapeutic interventions.
Subject(s)
Asthma/immunology , Interferon-gamma/metabolism , Interleukin-4/metabolism , Natural Killer T-Cells/immunology , CD4 Antigens/metabolism , Cell Separation , Child , Disease Progression , Female , Flow Cytometry , Humans , Lymphocyte Activation , Lymphocyte Count , Male , NK Cell Lectin-Like Receptor Subfamily B/metabolismABSTRACT
Tuberculosis is an important public health problem in Mexico. However, limited information about the genetic diversity of Mycobacterium tuberculosis strains circulating in the country is available. In this work, 109 multidrug-resistant (MDR) M. tuberculosis isolates collected in 23 different states of Mexico in 2003 were retrospectively characterized by spoligotyping and MIRU-VNTRs. All isolates, except for a single cluster containing two strains (subcluster E1), were split when information from the 12-loci MIRUs and spoligo-pattern was simultaneously analyzed. The discriminative power of 12-loci MIRU-VNTR and spoligotyping, by the Hunter-Gaston index, were 0.9998 and 0.9011, respectively. These findings suggest that almost all cases were epidemiologically unrelated. Instead, the genetic variations observed among these strains are suggestive of emergence of acquired drug-resistance during the course of treatment. The results suggest a high degree of genetic variability and a high frequency of SIT53 (T1 family) spoligotype among the MDR M. tuberculosis isolates included in the study.
Subject(s)
Genetic Variation , Genotype , Mycobacterium tuberculosis/genetics , Tuberculosis, Multidrug-Resistant/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Antibiotics, Antitubercular/pharmacology , Child , Child, Preschool , Cluster Analysis , DNA, Bacterial , Female , Humans , Male , Mexico/epidemiology , Microbial Sensitivity Tests , Middle Aged , Minisatellite Repeats , Molecular Typing , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/drug effects , Topography, Medical , Young AdultABSTRACT
No controlled studies exist regarding the pharmaceutical reduction of ataxia symptoms in ataxia telangiectasia (A-T). In a multicenter, double-blind, randomized, placebo-controlled crossover trial, oral betamethasone (BETA) and placebo were compared in terms of their reduction of ataxia symptoms as assessed with the International Cooperative Ataxia Rating Scale (ICARS). In this study of 13 A-T children, betamethasone reduced the ICARS total score by a median of 13 points in the intent-to-treat population and 16 points in the per-protocol population (ie, median percent decreases of ataxia symptoms of 28% and 31%, respectively). In conclusion, Oral betamethasone could be a promising therapy to relieve ataxia symptoms in A-T patients; however, long-term effectiveness and safety must be established. (Current Controlled Trials, number ISRCTN08774933.)
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Ataxia Telangiectasia/drug therapy , Ataxia Telangiectasia/physiopathology , Betamethasone/administration & dosage , Administration, Oral , Adolescent , Ataxia Telangiectasia/diagnosis , Child , Female , Humans , Male , Treatment OutcomeABSTRACT
BACKGROUND: Next-generation sequencing allows the analysis of an unprecedented number of viral sequence variants from infected patients, presenting a novel opportunity for understanding virus evolution, drug resistance and immune escape. However, sequencing in bulk is error prone. Thus, the generated data require error identification and correction. Most error-correction methods to date are not optimized for amplicon analysis and assume that the error rate is randomly distributed. Recent quality assessment of amplicon sequences obtained using 454-sequencing showed that the error rate is strongly linked to the presence and size of homopolymers, position in the sequence and length of the amplicon. All these parameters are strongly sequence specific and should be incorporated into the calibration of error-correction algorithms designed for amplicon sequencing. RESULTS: In this paper, we present two new efficient error correction algorithms optimized for viral amplicons: (i) k-mer-based error correction (KEC) and (ii) empirical frequency threshold (ET). Both were compared to a previously published clustering algorithm (SHORAH), in order to evaluate their relative performance on 24 experimental datasets obtained by 454-sequencing of amplicons with known sequences. All three algorithms show similar accuracy in finding true haplotypes. However, KEC and ET were significantly more efficient than SHORAH in removing false haplotypes and estimating the frequency of true ones. CONCLUSIONS: Both algorithms, KEC and ET, are highly suitable for rapid recovery of error-free haplotypes obtained by 454-sequencing of amplicons from heterogeneous viruses.The implementations of the algorithms and data sets used for their testing are available at: http://alan.cs.gsu.edu/NGS/?q=content/pyrosequencing-error-correction-algorithm.
