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Embolia/diagnóstico por imagem , Varizes Esofágicas e Gástricas/terapia , Hematemese/terapia , Fígado/diagnóstico por imagem , Adesivos Teciduais , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/diagnóstico , Feminino , Hematemese/etiologia , Humanos , Fígado/irrigação sanguínea , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Estômago/irrigação sanguínea , Estômago/diagnóstico por imagem , Adesivos Teciduais/administração & dosagem , Adesivos Teciduais/efeitos adversosRESUMO
An elevation in reactive oxygen species (ROS) is widely accepted to be a key mechanism that drives chronic obstructive pulmonary disease (COPD) and its major co-morbidity, skeletal muscle wasting. However, it will be perhaps a surprise to many that an elevation in ROS in skeletal muscle is also a critical process for normal skeletal muscle function and in the adaptations to physical exercise. The key message here is that ROS are not solely detrimental. This duality of ROS suggests that the mere use of a broad-acting antioxidant is destined to fail in alleviating skeletal muscle wasting in COPD because it will also be influencing critical physiological ROS-dependent processes. Here, we take a close look at this duality of ROS in skeletal muscle physiology and pathophysiology pertaining to COPD and will aim to gain critical insights from other skeletal muscle wasting conditions due to aging such as sarcopenia.
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Achalasia is a rare primary motility disorder of esophagus; treatments include endoscopic balloon dilatation (EBD) and laparoscopic Heller's cardiomyotomy (LC). This study compared EBD versus LC for treatment of achalasia with focus on quality of life (QoL) and prevalence of post-treatment gastroesophageal reflux disease. This was a retrospective cohort study of all patients diagnosed with achalasia older than 16 treated with either EBD or LC from January 1998 to April 2008. Patients' demographic data, comorbidities, postintervention GERD symptoms, QoL, recurrence of dysphagia, reintervention rate, hospital stay, and time to resumption of diet were collected. Sixty-eight patients were recruited into the study (EBD n= 50; LC n= 18). A significant improvement in QoL was found in patients undergoing LC (0.917 vs. 0.807, P= 0.006). A higher proportion of patients treated with EBD developed post-treatment gastroesophageal reflux symptoms (60.5% vs. 43.8%) when compared with LC, although statistically insignificant (P= 0.34). Patients treated with balloon dilatation had a greater percentage of recurrence of dysphagia (55.1% vs. 26.7%; P= 0.235) and need of reintervention (42.1% vs. 9.1%; P= 0.045). However, these patients had a shorter median hospital stay (1d [range 0-4]) and earlier resumption of diet (0d [range 0-3]). Although EBD is associated with a quicker perioperative recovery, LC accomplished a better QoL, lower incidence of recurrence of dysphagia, and need of reintervention after treatment for achalasia.
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Cárdia/cirurgia , Cateterismo/métodos , Transtornos de Deglutição/prevenção & controle , Acalasia Esofágica/cirurgia , Esofagoscopia/métodos , Laparoscopia/métodos , Qualidade de Vida , Adulto , Estudos de Coortes , Dieta , Dilatação/métodos , Acalasia Esofágica/psicologia , Acalasia Esofágica/terapia , Feminino , Seguimentos , Refluxo Gastroesofágico/etiologia , Hospitalização , Humanos , Tempo de Internação , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Recidiva , Retratamento , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Shyness in late childhood is related to social and psychological problems. The present study examined the relations among shyness, attributional styles and self-esteem. It was hypothesized that self-esteem mediated the effects of attributional styles on shyness. METHODS: Self-reported data on degree of shyness, attributional styles and self-esteem were obtained from 326 Chinese children with mean age of 10.85 years. RESULTS: It was found that positive attributional styles predicted shyness in the negative direction and the effects were fully mediated by self-esteem, and negative attributional styles predicted shyness in the positive direction both directly and through self-esteem. CONCLUSION: The results imply that how children attribute positive and negative outcomes affect both self-esteem and shyness. It is suggested that practitioners should conduct attribution-retraining workshops for shy children and help teachers and parents learn how to mitigate negative attributional style and foster positive attributional styles in children.
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Controle Interno-Externo , Autoimagem , Timidez , Criança , Comportamento Infantil , Feminino , Humanos , Masculino , Modelos Psicológicos , PsicometriaRESUMO
BACKGROUND: It is unclear whether the initial route of allergen exposure in early life could influence the subsequent development of allergy, with cutaneous sensitization leading to peanut allergy (PA), and tolerance induced by oral exposure. The skin- and gastrointestinal (GI)-homing markers, cutaneous lymphocyte antigen (CLA) and α4ß7 integrin, are used to determine whether the state of PA correlates with peanut-specific CLA responses, with tolerance associated with predominant α4ß7 responses. METHODS: CLA+ and α4ß7+ memory T cells were isolated and cultured with peanut extract to assess their proliferation. Stimulation indices were compared in peanut allergic and non-allergic (NA) groups, and peanut-specific cytokine production was measured. RESULTS: In peanut allergic patients, peanut-specific proliferation predominates in the skin-homing CLA+ subset, whilst peanut-tolerant groups have a mixed CLA/α4ß7 response (P = 0.008). Comparison with a control food antigen (ovalbumin) showed that these differences are allergen specific. Cytokine responses showed trends towards Th1 skewing in the GI-homing α4ß7+ cells of peanut-tolerant groups and Th2 skewing in the skin-homing CLA+ cells of peanut allergic patients. CONCLUSION: The predominance of the CLA+ response to peanut in peanut allergic patients is consistent with the hypothesis that allergic sensitization occurs through the skin. The predominant α4ß7+ response in peanut-tolerant groups suggests that allergen exposure through the GI tract induces tolerance.
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Antígenos de Diferenciação de Linfócitos T/metabolismo , Tolerância Imunológica/imunologia , Memória Imunológica/imunologia , Integrinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Hipersensibilidade a Amendoim/imunologia , Linfócitos T/imunologia , Arachis/imunologia , Células Cultivadas , Criança , Pré-Escolar , Citocinas/metabolismo , Feminino , Trato Gastrointestinal/imunologia , Humanos , Ativação Linfocitária , Masculino , Extratos Vegetais/imunologia , Estudos Prospectivos , Receptores de Retorno de Linfócitos/metabolismo , Pele/imunologiaRESUMO
Vaccines against COVID-19 are now available for adolescents in Hong Kong but vaccine hesitancy is a major barrier to herd immunity. This survey study explores Hong Kong adolescents' attitudes towards the COVID-19 vaccination. 2609 adolescents from across Hong Kong completed an online survey focused on the intent to vaccinate and the reasons for their choice. 39% of adolescents intended to take the COVID-19 vaccination and significant factors for this decision include: having at least one parent vaccinated, knowing somebody diagnosed with COVID-19 and receiving the influenza vaccine. Adolescents' major concerns were either the safety and efficacy of the vaccine or the risk of infection. This study has proved that even in adolescents the vaccine hesitancy model is prominent with adolescents' intentions highly related to confidence in the vaccine and perception of disease risk. Future interventions should target these specific concerns to ensure adolescents are well educated to overcome vaccine hesitancy.
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COVID-19 , Vacinas contra Influenza , Adolescente , Atitude , Vacinas contra COVID-19 , Estudos Transversais , Humanos , SARS-CoV-2 , VacinaçãoRESUMO
OBJECTIVE: Superficial Zone Protein (SZP) is expressed by the superficial zone chondrocytes and is involved in boundary lubrication of the articular cartilage surface. SZP protein expression is dependent on anatomical location and is regulated by the transforming growth factor-ß (TGF-ß) pathway. The hypothesis of this study was that between load-bearing, and non-load-bearing locations, of the femoral medial condyle alternative splice isoforms of SZP are different, and regulated by TGF-ß1. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) we identified differentially expressed SZP alternative splicing. Using recombinant proteins of the N-terminal region produced from these isoforms, we identified differences in binding to heparin and the extracellular matrix. RESULTS: We identified a novel splice form of SZP (isoform E), lacking exons 2-5. Differences in alternative splicing were observed between anterior load-bearing locations of the femoral medial condyle (M1) compared to the posterior non-load-bearing location (M4). TGF-ß1 increased splicing out of exons 4 and 5 encoding a heparin binding domain. The minimal induction time for changes in splicing by TGF-ß1 at the M1 location was 1h, although this did change total SZP mRNA levels. Inhibition of Smad3 phosphorylation inhibited TGF-ß1 induced splicing, and SZP protein expression. Recombinant proteins corresponding to isoforms upregulated by TGF-ß1 had reduced binding. The SZP dimerization domain is located within exon 3. CONCLUSIONS: In conclusion, alternative splicing of SZP is regulated by TGF-ß1 signaling and may regulate SZP interaction with heparin/heparan sulfate or other components in the extracellular matrix of articular cartilage by splicing out of the heparin binding domain.
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Processamento Alternativo/genética , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Glicoproteínas/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática , Éxons/genética , Glicoproteínas/genética , Immunoblotting , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Proteínas de Membrana/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Suporte de CargaRESUMO
BACKGROUND: Although the influences of parenting on children's development of social competence have been well established, research on the underlying mechanisms of this link is relatively limited. The present study examined children's coping strategies as a mediator of the effects of maternal authoritativeness and maternal inductive responses on their social competence. METHOD: The mothers of 183 Hong Kong Chinese children aged 6 to 8 years (89 girls and 94 boys) reported on their adoption of authoritative parenting and their responses to their children's expressions of emotion, and rated their children's adoption of constructive coping strategies. The children's teachers reported on the children's prosocial behaviour, and rated their level of peer acceptance at school. RESULTS: A model of maternal authoritativeness and supportive maternal responses affecting children's social competence is presented. The study results show that the effects of authoritative parenting on children's adoption of constructive coping strategies were mediated by supportive maternal responses to children's expression of emotion, and that the effects of maternal authoritativeness and maternal responses on children's social competence were mediated by children's coping strategies. These results suggest that school personnel should organize training programmes on emotion-coping strategies for both parents and children. CONCLUSION: The findings imply that positive parenting facilitates children's acquisition of constructive emotion-coping strategies. Programmes on emotion-coping strategies should be introduced for both parents and school children.
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Adaptação Psicológica , Autoritarismo , Mães/psicologia , Poder Familiar/psicologia , Comportamento Social , Criança , Emoções , Feminino , Hong Kong , Humanos , Masculino , Relações Mãe-Filho , Ajustamento SocialRESUMO
OBJECTIVE: To determine the internal consistency, construct validity, and scaling properties of the traditional Chinese version of the Child and Adolescent Needs and Strengths-Trauma Comprehensive (TC-CANS-Trauma). METHODS: 66 male and 62 female children, adolescents, and young adults aged 3 to 22 years who were referred to trauma treatment service were selected by convenience sampling. The original English version of the CANS-Trauma was translated to traditional Chinese by a medical professional, back-translated to English by a clinical psychologist, and then cross-checked by another psychologist to ensure consistency. Chinese wordings were adjusted to maintain the conceptual rather than literal meaning. Participants were assessed using the TC-CANS-Trauma as well as the traditional Chinese version of the Life Events Checklist (LEC), the Children's Impact of Event Scale-Revised (CHIES-R), the Strengths and Difficulties Questionnaire-Impact Component (SDQ-Impact), and the Parenting Sense of Competence (PSOC). Internal consistency of eight primary domains of the TC-CANS-Trauma was evaluated by Cronbach's alpha. Construct (convergent and divergent) validity of five of these domains with the LEC, the CHIES-R, the SDQ-Impact, and the PSOC was assessed. Rasch modelling was used to evaluate the scaling properties of the eight primary domains of the TC-CANS-Trauma. RESULTS: Internal consistency of the eight primary domains of the TC-CANS-Trauma was satisfactory, with Cronbach's alpha ranging from 0.63 to 0.90. Construct (convergent and divergent) validity of five of these domains with the LEC, the CHIES-R, the SDQ-Impact, and the PSOC was good. In Rasch modelling, most TC-CANS-Trauma domains showed good item separation values. Infit and outfit statistics of most domain items were <2 indicating good item fitness in their respective domains. For person separation, all domains of the TC-CANS-Trauma did not have a sufficient discriminability to identify high and low performers. CONCLUSIONS: The TC-CANS-Trauma is valid for comprehensive assessment of trauma-related domains among Hong Kong children and adolescents. Its ratings can be used to guide the levels of clinical intervention required. Clinicians are recommended to implement the TC-CANS-Trauma to facilitate trauma-informed practice in Hong Kong.
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Tradução , Adolescente , Criança , Feminino , Hong Kong , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate (sgACC) may serve as a biomarker for transcranial magnetic stimulation (rTMS) treatment response. The first aim was to establish whether this finding is veridical or artifactually induced by the pre-processing method. Furthermore, alternative biomarkers were identified and the clinical utility for personalized medicine was examined. METHODS: Resting-state fMRI data were collected in medication-refractory depressed patients (n = 70, 16 males) before undergoing neuronavigated left DLPFC rTMS. Seed-based analyses were performed with and without global signal regression pre-processing to identify biomarkers of short-term and long-term treatment response. Receiver Operating Characteristic curve and supervised machine learning analyses were applied to assess the clinical utility of these biomarkers for the classification of categorical rTMS response. RESULTS: Regardless of the pre-processing method, DLPFC-sgACC connectivity was not associated with treatment outcome. Instead, poorer connectivity between the sgACC and three clusters (peak locations: frontal pole, superior parietal lobule, occipital cortex) and DLPFC-central opercular cortex were observed in long-term nonresponders. The identified connections could serve as acceptable to excellent markers. Combining the features using supervised machine learning reached accuracy rates of 95.35% (CI=82.94-100.00) and 88.89% (CI=63.96-100.00) in the cross-validation and test dataset, respectively. LIMITATIONS: The sample size was moderate, and features for machine learning were based on group differences. CONCLUSIONS: Long-term nonresponders showed greater disrupted connectivity in regions involving the central executive network. Our findings may aid the development of personalized medicine for medication-refractory depression.
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Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Biomarcadores , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/terapia , Giro do Cíngulo , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Córtex Pré-Frontal/diagnóstico por imagem , Estimulação Magnética TranscranianaRESUMO
The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic beta-islet cells together with T cells expressing an LCMV-gp-specific T cell receptor to assess the requirements for the induction of autoimmunity. Our studies have shown that administration of the gp peptide gp33 leads to the activation of P14-transgenic T cells, as measured by the upregulation of activation markers and the induction of effector cytotoxic activity. This treatment also leads to expansion and deletion of P14 T cells. Despite the induction of cytotoxic T lymphocyte activity, peptide administration is not sufficient to induce diabetes. However, the administration of gp peptide together with an activating anti-CD40 antibody rapidly induces diabetes. These findings suggest that the induction of tolerance versus autoimmunity is determined by resting versus activated antigen-presenting cells.
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Células Apresentadoras de Antígenos/imunologia , Antígenos Virais , Autoimunidade/imunologia , Tolerância Imunológica/imunologia , Proteínas Virais , Animais , Antígenos CD28/imunologia , Antígenos CD40/imunologia , Glicoproteínas/genética , Glicoproteínas/imunologia , Interferon gama/imunologia , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Ratos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T/imunologiaRESUMO
OBJECTIVE: To determine the roles of superficial zone protein (SZP), hyaluronan (HA), and surface-active phospholipids (SAPL) in boundary lubrication of articular cartilage through systematic enzyme digestion using trypsin, hyaluronidase, and phospolipase-C (PLC) surface treatments. METHODS: The friction coefficient of articular cartilage surfaces was measured with an atomic force microscope (AFM) before and after enzyme digestion. Surface roughness, adhesion, and stiffness of the articular surface were also measured to determine the mechanism of friction in the boundary lubrication regime. Histology and transmission electron microscopy were used to visualize the surface changes of treatment groups that showed significant friction changes after enzyme digestion. RESULTS: A significant increase in the friction coefficient of both load-bearing and non load-bearing regions of the joint was observed after proteolysis by trypsin. Treatment with trypsin, hyaluronidase, or PLC did not affect the surface roughness. However, trypsin treatment decreased the adhesion significantly. Results indicate that the protein component at the articular cartilage surface is the main boundary lubricant, with SZP being a primary candidate. The prevailing nanoscale deformation processes are likely plastic and/or viscoelastic in nature, suggesting that plowing is the dominant friction mechanism. CONCLUSIONS: The findings of this study indicate that SZP plays an intrinsic and critical role in boundary lubrication at the articular surface of cartilage, whereas the effects of HA and SAPL on the tribological behavior are marginal.
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Cartilagem Articular/ultraestrutura , Substâncias de Crescimento/metabolismo , Proteoglicanas/metabolismo , Líquido Sinovial/fisiologia , Análise de Variância , Animais , Fenômenos Biomecânicos , Cartilagem Articular/metabolismo , Cartilagem Articular/fisiologia , Bovinos , Fricção , Lubrificação , Microscopia de Força Atômica , Líquido Sinovial/metabolismoRESUMO
BACKGROUND: Peanut allergy poses significant healthcare problems, because its prevalence is increasing in many countries, and it is rarely outgrown. To explore the immunological mechanisms that underlie peanut allergy and tolerance, we compared the peanut-specific responses of peanut-allergic (PA) and nonallergic (NA) individuals. METHODS: We measured peanut-specific peripheral blood mononuclear cells (PBMC) proliferation using tritiated thymidine. The frequency of peanut-specific T cells amongst PBMC was determined by carboxyfluorescein succinimidyl ester labelling. The role of IgE-dependent facilitated antigen presentation (FAP) in modulating proliferation was investigated by depleting IgE from plasma with anti-IgE-coated beads and then assessing PBMC proliferation in the presence of IgE-depleted or nondepleted plasma. RESULTS: We found that peanut-specific PBMC proliferation is higher and peaks earlier in PA than in NA donors. We investigated the immunological mechanisms that could underlie these differences. We found that both PA and NA have memory responses to peanut, but the frequency of peanut-specific T cells is higher in PA than in NA. Facilitated antigen presentation could cause both the higher proliferation and precursor frequency in PA. Facilitated antigen presentation activity in vitro was confirmed by showing that IgE depletion decreases proliferation, while adding IgE back restores it. CONCLUSION: Our results identify FAP as a mechanism that underlies higher responses to peanut in PA. In these individuals, high levels of peanut-specific IgE could furthermore maintain long-term allergic T-cell responses. We raise the question whether, in the future, therapies targeting IgE such as anti-IgE antibodies may be used to suppress these T-cell responses.
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Apresentação de Antígeno/imunologia , Imunoglobulina E/imunologia , Hipersensibilidade a Amendoim/imunologia , Estudos de Casos e Controles , Proliferação de Células , Humanos , Tolerância Imunológica , Imunidade , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Ativação Linfocitária , Especificidade do Receptor de Antígeno de Linfócitos TRESUMO
OBJECTIVE: To review the first 8-month outcome of the Common Mental Disorder Clinic model in Hong Kong in terms of patient exit status and improvement in depressive and anxiety symptoms. METHODS: During the first appointment, patients were interviewed by a multidisciplinary team comprising a psychiatrist, a psychiatric nurse, and an occupational therapist. A multidisciplinary case conference was conducted to discuss clinical observations, diagnosis, issues of concern, and the optimal individualised treatment plan. Low-intensity interventions by nurses and/or occupational therapists were provided, as were optional, time-limited, protocol-based interventions by clinical psychologists for those with mild to moderate depressive and anxiety symptoms. Pharmacological intervention may be used when indicated. Upon completion of the treatment plan, patients were reassessed by the treating psychiatrist. Discharge options included discharge without psychiatric follow-up, step-up to psychiatric outpatient clinics, and step-down services. The self-administered Patient Health Questionnaire-9 (PHQ-9) and Generalised Anxiety Disorder 7-item scale (GAD-7) were used to assess the past 2 weeks' depressive and anxiety symptoms, respectively, at baseline and at each session. RESULTS: From July 2015 to February 2016, 1325 Chinese patients received the new service. Of them, 170 men and 363 women (mean age, 52.6 years) completed the treatment plan. After treatment, their mean PHQ-9 score decreased from 11.06 to 7.55 (p < 0.001), and the mean GAD-7 score decreased from 9.94 to 6.54 (p < 0.001). After treatment, 42.4% and 48.2% of the patients were within the normal range of PHQ-9 and GAD-7 scores, respectively, compared with 16.9% and 20.8% before treatment. The mean time to implementation of the individualised treatment plan was 82.33 days. Of the patients, 54.4% were discharged without any need for medical or psychiatric follow-up; 28% were stepped up to psychiatric outpatient clinics; and 17.3% were stepped down. The predictors of exit status were whether psychiatric medication was prescribed during initial intake (p = 0.011), whether psychiatric medication was prescribed at last follow-up (p < 0.001), the service period (p = 0.010), and the GAD-7 final score (p = 0.005). CONCLUSIONS: The first 8-month outcome of the new service model was encouraging, with shortened waiting time, reduced severity of symptoms, and better exit status (high recovery and step-down rates).
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Avaliação de Resultados em Cuidados de Saúde , Equipe de Assistência ao Paciente , Ansiedade/terapia , Povo Asiático , Depressão/terapia , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Psicoterapia , Estudos Retrospectivos , Fatores de TempoRESUMO
Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (also called the 'citric acid' or Krebs) cycle. Both IDH2 and IDH1 (localized in the cytoplasm) proteins catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). Mutant IDH enzymes have neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked differentiation of hematopoietic progenitor cells. The prognostic significance of mutant IDH (mIDH) is controversial but appears to be influenced by co-mutational status and the specific location of the mutation (IDH1-R132, IDH2-R140, IDH2-R172). Treatments specifically or indirectly targeted to mIDH are currently under clinical investigation; these therapies have been generally well tolerated and, when used as single agents, have shown promise for inducing responses in some mIDH patients when used as first-line treatment or in relapsed or refractory AML or MDS. Use of mIDH inhibitors in combination with drugs with non-overlapping mechanisms of action is especially promising, as such regimens may address the clonal heterogeneity and the multifactorial pathogenic processes involved in mIDH myeloid malignancies. Advances in mutational analysis have made testing more rapid and convenient, and less expensive; such testing should become part of routine diagnostic workup and repeated at relapse to identify patients who may benefit from treatments that target mIDH.
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Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Mutação , Animais , Biomarcadores Tumorais , Análise Mutacional de DNA , Frequência do Gene , Humanos , Isocitrato Desidrogenase/metabolismo , Isoenzimas , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/mortalidade , Síndromes Mielodisplásicas/enzimologia , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/genética , PrognósticoRESUMO
A "stone in the pond" strategy is a practical approach to investigating large-scale nosocomial tuberculosis (TB) exposures. Here, we describe such a risk-stratified approach to contact tracing after a TB exposure that occurred over 5 months in a pediatric inpatient ward in a country with a moderate TB burden. Infect Control Hosp Epidemiol 2017;38:1509-1511.
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Busca de Comunicante , Programas de Rastreamento/métodos , Teste Tuberculínico , Tuberculose Pulmonar/diagnóstico , Adolescente , Criança , Pré-Escolar , Agentes Comunitários de Saúde , Feminino , Humanos , Lactente , Masculino , Singapura , Tuberculose Pulmonar/transmissãoRESUMO
Acute myeloid leukemia (AML) is characterized by accumulation of myeloid cells in the bone marrow because of impaired differentiation and proliferation, resulting in hematopoietic insufficiency. NPM1 is one of the most commonly mutated genes in AML, present in 20-30% of cases. Mutations in NPM1 represent a distinct entity in the World Health Organization (WHO) classification and commonly indicate a better risk prognosis. In this review, we discuss the many functions of NPM1, the consequence of mutations in NPM1 and possible mechanisms through which mutations lead to leukemogenesis. We also discuss clinical consequences of mutations, associated gene expression patterns and the role of NPM1 mutations in informing prognosis and therapeutic decisions and predicting relapse in AML.
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Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Proteínas Nucleares/genética , Biomarcadores Tumorais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Tomada de Decisão Clínica , Epistasia Genética , Regulação Leucêmica da Expressão Gênica , Frequência do Gene , Humanos , Leucemia Mieloide Aguda/terapia , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Neoplasia Residual/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Nucleofosmina , Prognóstico , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Processamento de Proteína Pós-Traducional , RecidivaRESUMO
BACKGROUND: We investigated the effect of multi-domain lifestyle (physical, nutritional, cognitive) interventions among frail and pre-frail community-living older persons on reducing depressive symptoms. METHOD: Participants aged 65 and above were randomly allocated to 24 weeks duration interventions with nutritional supplementation (N=49), physical training (N=48), cognitive training (N=50), combination intervention (N=49) and usual care control (N=50). Depressive symptoms were assessed by the Geriatric Depression Scale (GDS-15) at baseline (0M), 3 month (3M), 6 month (6M) and 12 month (12M). RESULTS: Mean GDS scores in the control group increased from 0.52 (0M) and 0.54 (3M) to 0.74 (6M), and 0.83 (12M). Compared to the control group, interventions showed significant differences (∆=change) at 6M for cognitive versus control (∆=-0.39, p=0.021, group*time interaction p=0.14); physical versus control (∆ =-0.37, p=0.026, group*time interaction p=0.13), and at 12M for nutrition versus control (∆ =-0.46, p=0.016, group*time interaction p=0.15). The effect for combination versus control was significant at 6M (∆ =-0.43, p=0.020) and 12M (∆ =-0.51, p=0.005, group*time interaction p=0.026). Estimated 12-month cumulative incidence of depressive symptoms (GDS≥2) relative to control were OR=0.38, p=0.037 (nutrition); OR=0.71, p=0.40 (cognitive); OR=0.39, p=0.042 (physical training) and OR=0.38, p=0.037 (combination). Changes in gait speed and energy level were significantly associated with changes in GDS scores over time. CONCLUSION: Multi-domain interventions that reverse frailty among community-living older persons also reduce depressive symptomatology. Public health education and programmatic measures combining nutritional, physical and cognitive interventions for at-risk frail older people may likely benefit psychological wellbeing.
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Depressão/psicologia , Idoso Fragilizado/psicologia , Estilo de Vida , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , MasculinoRESUMO
Equine coronaviruses (ECoV) are the only coronavirus known to infect horses. So far, data on ECoV infection in horses remain limited to the USA, France and Japan and its geographic distribution is not well understood. We carried out RT-PCR on 306 nasal and 315 rectal swabs and tested 243 sera for antibodies to detect coronavirus infections in apparently healthy horses in Saudi Arabia and Oman. We document evidence of infection with ECoV and HKU23 coronavirus by RT-PCR. There was no conclusive evidence of Middle East respiratory syndrome coronavirus infection in horses. Serological data suggest that lineage A betacoronavirus infections are commonly infecting horses in Saudi Arabia and Oman but antibody cross-reactivities between these viruses do not permit us to use serological data alone to identify which coronaviruses are causing these infections.