RESUMO
Pain is an experience of a subjective nature, interpreted in a personal way and according to an extensive palette of factors unique to each individual. Orofacial pain can be acute or chronic and it is usually the main reason for the patient to seek dental care. Pain perception varies widely among individuals. This variability is considered a mosaic of factors, which include biopsychosocial factors and genetic factors. Understanding these differences can be extremely beneficial for pain management in a personalized and more efficient way. We performed association studies to investigate phenotypes associated with genetic markers in pain-related genes in two groups of patients who received more or less anesthesia during dental treatment. The study group was comprised of 1289 individuals participating in the Dental Registry and DNA Repository Project (DRDR) of the University of Pittsburgh, with 900 participants in the group that received the most anesthesia and 389 constituting the comparison group that received less anesthesia. We tested 58 phenotypes and genotypic data of seven SNPs in genes that are associated with pain perception, pain modulation and response to drugs used in pain treatment: COMT (rs4818 and rs6269), GCH1 (rs3783641), DRD2 (rs6276), OPRM1 (rs1799971), SCN9A (rs6746030) and SCN10A (rs6795970). The analysis revealed a protective effect of rs1799971 on asthma in the total sample. rs3783641 was associated with salivary secretion disorders in females who received more anesthesia. rs1799971 was also associated with periodontitis in Whites who received less anesthesia. rs4818 was associated with disease and other tongue conditions in the group composed of Blacks who received less anesthesia. In conclusion, our study implicated variants in pain-related genes in asthma and oral phenotypes.
Assuntos
Asma , Catecol O-Metiltransferase , Feminino , Humanos , Catecol O-Metiltransferase/genética , Saúde Bucal , Genética Reversa , Percepção da Dor , Dor/genética , Asma/genética , Canal de Sódio Disparado por Voltagem NAV1.7/genéticaRESUMO
When standing, intrinsic ankle stiffness is smaller when measured using large perturbations, when sway size is large, and when background torque is low. However, there is a large variation in individual intrinsic ankle stiffness. Here we determine if individual variation has consequences for postural control. We examined the relationship between ankle stiffness, ankle torque and body sway across different individuals. Ankle stiffness was estimated in 19 standing participants by measuring torque responses to small, brief perturbations. Perturbation sizes of 0.2 & 0.9 degrees (both lasting 140 ms) measured short- and long-range stiffness respectively, while participants either stood quietly on a fixed platform or were imperceptibly tilted to reduce stability (0.1 Hz sinusoid; 0.2 & 0.4 deg). The spontaneous body sway component (natural random relatively rapid postural adjustments) and background ankle torque were averaged from sections immediately before perturbations. The results show that, first, intrinsic ankle stiffness is positively associated with ankle torque, and that this relationship is stronger for long-range stiffness. Second, intrinsic ankle stiffness is negatively associated with body sway, but, in contrast to the relationship with torque, this relationship is stronger for short-range stiffness. We conclude that high short-range intrinsic ankle stiffness is associated with reduced spontaneous sway, although the causal relationship between these two parameters is unknown. These results suggest that, in normal quiet standing where sway is very small, the most important determinant of intrinsic ankle stiffness may be stillness. In less stable conditions, intrinsic ankle stiffness may be more dependent on ankle torque.
Assuntos
Articulação do Tornozelo/fisiologia , Tornozelo/fisiologia , Individualidade , Equilíbrio Postural/fisiologia , Postura/fisiologia , Amplitude de Movimento Articular/fisiologia , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Posição Ortostática , Torque , Adulto JovemRESUMO
Zika virus (ZIKV) has gained a lot of attention in the past few years due to its rapid spread worldwide and its close association to severe neurological outcomes, such as microcephaly and Guillain-Barre syndrome. In this study, the in vitro and in vivo anti-ZIKV activity of 7-deaza-7-fluoro-2'-C-methyl-adenosine (DFMA) was evaluated. In vitro, using primary mouse neuronal cells and human neural stem cells infected by ZIKV, treatment with DFMA resulted in impaired viral replication and protection against virus-induced cell death. In vivo, when administrated prior to infection, DFMA prevented lethality and markedly reduced viral loads and neuroinflammation, including microgliosis and overall brain damage. Additionally, as an early therapeutic treatment, DFMA increased survival rates in mice. Collectively, these findings demonstrate that the nucleoside analog DFMA inhibits ZIKV infection and viral-induced neuroinflammation in vitro and in vivo without apparent untoward effects, suggesting it may be useful in individuals infected with ZIKV.
Assuntos
Adenosina/análogos & derivados , Antivirais/farmacologia , Inflamação/virologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/complicações , Adenosina/farmacologia , Adenosina/uso terapêutico , Animais , Antivirais/uso terapêutico , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Culicidae/citologia , Humanos , Inflamação/tratamento farmacológico , Camundongos , Doenças do Sistema Nervoso/tratamento farmacológico , Células-Tronco Neurais , Células Vero , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Zika virus , Infecção por Zika virus/tratamento farmacológicoRESUMO
BACKGROUND: Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long-term virological and adherence outcomes to antiviral treatment in CHB patients. METHODS: A prospective 183 Brazilian CHB patient cohort treated with monotherapy or combination adefovir dipivoxil, entecavir, lamivudine and/or tenofovir disoproxil fumarate was studied in a reference tertiary centre. Treatment adherence was evaluated by a validated questionnaire named 'Assessment of Adherence to Antiviral Therapy Questionnaire' (CEAT-HBV) within three yearly periods (2010/2011, 2013/2014 and 2014/2015). RESULTS: CEAT-HBV identified 43% (79/183) patients with non-adherence to antiviral treatment and among them, 67% (53/79) were viral load positive. The main causes associated with non-response to antiviral treatment were drug resistance variants followed by non-adherence, insufficient treatment duration and other causes. Single-dose pharmacokinetics demonstrated 35% (23/65) antiviral non-adherence. 2 years after the first assessment, the CEAT-HBV indicated that 71% (101/143) of subjects adhered to treatment (per-protocol population). However, 21% (40/183) of the patients could not be evaluated and were excluded. The main reasons for exclusion were death (20/183), 11 out 20 deaths due to hepatocellular carcinoma. HBV booklet was used for medical education. The third CEAT-HBV assessment (2014/2015) showed that 83% (112/135) patients were compliant with treatment adherence (per-protocol population). Long-term evaluation showed that adherence rate based on CEAT-HBV continue to increase after 4-years (P<0.001). CONCLUSIONS: The results highlight the importance of CHB therapy adherence assessment monitoring. Long-term adherence outcomes were dynamic and it is possible to increase the migration rate to adherence/HBV-DNA-negative group.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Cooperação do Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Brasil/epidemiologia , Estudos de Coortes , DNA Viral , Feminino , Genótipo , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
Yellow fever virus (YFV) is a human Flavivirus reemerging in parts of the world. While a vaccine is available, large outbreaks have recently occurred in Brazil and certain African countries. Development of an effective antiviral against YFV is crucial, as there is no available effective drug against YFV. We have identified several novel nucleoside analogs with potent antiviral activity against YFV with 50% effective concentration (EC50) values between 0.25 and 1 µM with selectivity indices over 100 in culture.
Assuntos
Antivirais/uso terapêutico , Nucleosídeos/análogos & derivados , Nucleosídeos/uso terapêutico , Febre Amarela/tratamento farmacológico , Vírus da Febre Amarela/efeitos dos fármacos , Vírus da Febre Amarela/patogenicidade , África , Animais , Brasil , Linhagem Celular Tumoral , Chlorocebus aethiops , Humanos , Estrutura Molecular , Células Vero , Febre Amarela/virologiaAssuntos
Colecistite Acalculosa/complicações , Infecção por Zika virus/complicações , Colecistite Acalculosa/cirurgia , Doença Aguda , Colecistectomia Laparoscópica/métodos , Vesícula Biliar/patologia , Vesícula Biliar/virologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Ultrassonografia , Zika virus/genética , Infecção por Zika virus/diagnósticoRESUMO
BACKGROUND: The latent variable "δ" has been validated as a dementia phenotype. δ can be extracted from Spearman's general intelligence factor "g" in any data set that contains measures of cognition and instrumental activities of daily living (IADL). We used δ composites ("d-scores") to estimate the prevalence of dementia in the Hispanic Established Population for Epidemiological Studies in the Elderly (H-EPESE). METHOD: δ was constructed from Mini-Mental State Examination, a clock-drawing task (CLOX), and IADL. δ's H-EPESE factor weights were validated in the well-characterized Texas Alzheimer's Research and Care Consortium (TARCC). Optimal thresholds for the discrimination between "Alzheimer's disease" (AD) versus normal controls (NCs) were determined by receiver operating characteristic curve. Those thresholds were used to estimate the prevalence of dementia in H-EPESE. RESULTS: Each δ homolog fits its source's data well. d-scores were strongly associated with Clinical Dementia Rating scale Sum of Boxes (r = .74-.85, all p < .001], and accurately distinguished AD cases from NCs, in both Mexican Americans (MAs) and non-Hispanic Whites (NHWs) [c = 0.94-0.96]. The TARCC MA threshold estimated the prevalence of dementia at 21.4% in H-EPESE. The NHW threshold estimated the prevalence of dementia at 21.0%. CONCLUSIONS: It is possible to export δ composites from populations to well-characterized cohorts for validation.
Assuntos
Atividades Cotidianas/classificação , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/etnologia , Entrevista Psiquiátrica Padronizada/estatística & dados numéricos , Americanos Mexicanos/psicologia , Testes Neuropsicológicos/estatística & dados numéricos , Psicometria/estatística & dados numéricos , População Branca/psicologia , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Estudos de Coortes , Estudos Transversais , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etnologia , Feminino , Humanos , Inteligência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Sudoeste dos Estados Unidos , Estatísticas não ParamétricasRESUMO
OBJECTIVE: Trigeminal neuralgia is a debilitating facial pain disorder, frequently caused by vascular compression of the trigeminal nerve. Vascular compression that results in trigeminal neuralgia occurs along the cisternal segment of the nerve. CONCLUSION: Imaging combined with clinical information is critical to correctly identify patients who are candidates for microvascular decompression. The purpose of this article is to review trigeminal nerve anatomy and to provide strategies for radiologists to recognize important MRI findings in patients with trigeminal neuralgia.
Assuntos
Imageamento por Ressonância Magnética , Síndromes de Compressão Nervosa/etiologia , Nervo Trigêmeo/anatomia & histologia , Neuralgia do Trigêmeo/diagnóstico , Doenças Vasculares/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/cirurgia , Nervo Trigêmeo/patologia , Nervo Trigêmeo/cirurgia , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/cirurgia , Doenças Vasculares/cirurgiaAssuntos
Humanos , Diagnóstico por Imagem/métodos , Ecocardiografia/métodos , Gestão da Qualidade Total , Acreditação/métodos , Ecocardiografia Transesofagiana/métodos , Ecocardiografia sob Estresse/métodos , Equipamentos para Diagnóstico/normas , Ocupações em Saúde/normas , Pacientes , Prova Pericial/métodosRESUMO
Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures such as pesticides, plastics, or medications. The purpose of our study was to determine if organic chemicals previously detected in a sample of typically developing children could be detected in teeth from a sample of children with autism. Eighty-three deciduous teeth from children with autism spectrum disorders (ASD) were chosen from our tooth repository. Organic compounds were assessed using liquid chromatography tandem mass spectrometry and gas chromatography methods. Consistent with a prior report from Camann et al., (2013), we have demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth. This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism.