RESUMO
OBJECTIVE: To investigate the prevalence and predictors of hereditary hemorrhagic telangiectasia (HHT) and capillary-malformation arteriovenous malformation (CM-AVM) syndrome among children with no prior personal or family history of these diseases who presented with an arteriovenous shunt lesion. STUDY DESIGN: A retrospective chart review was completed on patients aged 0 through 21 years with arteriovenous shunt lesions evaluated at our Cerebrovascular Center. Diagnosis of definite or suspected HHT or CM-AVM was based on clinical features and genetic testing. Associations between final diagnosis and type and number of lesions, epistaxis, telangiectasias, CM, and pulmonary AVMs were assessed. RESULTS: Eighty-nine patients were included. Thirteen (14.6%) had definite HHT, 11 (12.4%) suspected HHT, and 4 (4.5%) definite CM-AVM. Having ≥2 episodes of epistaxis/year and ≥ 2 sites with telangiectasias were each associated with definite HHT (P < .001). Having ≥ 2 CM was associated with definite CM-AVM (P < .001). Pulmonary AVM was associated with increased odds of having definite HHT (OR = 6.3, 95% CI: 1.2-33.4). Multiple lesions (OR = 24.5, 95% CI: 4.5-134.8) and arteriovenous fistulas (OR = 6.2, 95% CI: 1.9-20.3) each increased the likelihood of having definite HHT or CM-AVM. Genetic testing was positive in 31% of patients tested. CONCLUSIONS: We recommend that children with neurovascular shunt lesions be offered genetic testing and undergo further evaluation for HHT and CM-AVM. Awareness and early diagnosis of these conditions is a critical step toward improving long-term outcomes and preventing disease-associated complications.
Assuntos
Fístula Arteriovenosa , Malformações Arteriovenosas Intracranianas , Telangiectasia Hemorrágica Hereditária , Criança , Humanos , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/epidemiologia , Prevalência , Estudos Retrospectivos , Epistaxe , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/epidemiologia , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/epidemiologiaRESUMO
BACKGROUND: US government child labor policies allow children as young as age 10 to be hired as workers on farms not operated by family members. Children may face substantial health risks in an industry known for high worker morbidity and mortality rates, due to high demands for productivity, and low control and little support because of the organization of the workplace. This paper examines how child farmworkers in North Carolina experience their work situation. METHODS: In-depth interviews conducted in 2016 with 30 Latinx child farmworkers, ages 10 to 17, were analyzed using concepts from the demand-control-support model. All had worked as either migrant or seasonal hired farmworkers within the past year. RESULTS: Children reported planting, cultivating, and harvesting crops including fruits, vegetables, and tobacco. The crew leader supervisory system, piece-rate pay, and coworker pressure produced significant demands to work quickly and take risks including lifting heavy loads, operating mechanical equipment, and working in excessive heat. Children had little control over work to counter demands they experienced; and they labored in a state of fear of firing, wage theft, and other sanctions. Support was variable, with younger children more likely to experience family and coworker support than older children. CONCLUSIONS: The high demands with limited control and, for some, little support, that these children experience place them at risk and show the possibility of injury and exploitation. Future research should systematically document the occupational injury and illness of hired child farmworkers, and consider whether changes in labor policy are warranted.
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Agricultura , Trabalho Infantil , Fazendeiros , Carga de Trabalho , Adolescente , Agricultura/economia , Agricultura/métodos , Criança , Feminino , Guatemala/etnologia , Hispânico ou Latino , Humanos , Entrevistas como Assunto , Masculino , México/etnologia , North Carolina , Migrantes , Populações VulneráveisRESUMO
Obesity is related to increased oxidative stress. Although low-intensity physical exercise reduces oxidative stress, obese subjects may show exercise intolerance. For these subjects, inspiratory threshold loading could be an alternative tool to reduce oxidative stress. We investigated the effects of inspiratory threshold loading on biomarkers of oxidative stress in obese and normal-weight subjects. Twenty obese (31.4 ± 6 years old, 10 men and 10 women, 37.5 ± 4.7 kg/m2) and 20 normal-weight (29.4 ± 8 years old, 10 men and 10 women, 23.2 ± 1.5 kg/m2) subjects matched for age and gender participated in the study. Maximal inspiratory pressure (MIP) was assessed by a pressure transducer. Blood sampling was performed before and after loading and control protocols to assess thiobarbituric acid reactive substances (TBARS), protein carbonylation, and reduced glutathione. Inspiratory threshold loading was performed at 60% MIP and maintained until task failure. The 30-min control protocol was performed at 0 cmH2O. Our results demonstrated that inspiratory threshold loading reduced TBARS across time in obese (6.21 ± 2.03 to 4.91 ± 2.14 nmol MDA/ml) and normal-weight subjects (5.60 ± 3.58 to 4.69 ± 2.80 nmol MDA/ml; p = 0.007), but no change was observed in protein carbonyls and glutathione in both groups. The control protocol showed no significant changes in TBARS and protein carbonyls. However, reduced glutathione was increased across time in both groups (obese: from 0.50 ± 0.37 to 0.56 ± 0.35 µmol GSH/ml; normal-weight: from 0.61 ± 0.11 to 0.81 ± 0.23 µmol GSH/ml; p = 0.002). These findings suggest that inspiratory threshold loading could be potentially used as an alternative tool to reduce oxidative stress in both normal-weight and obese individuals.
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Inalação/fisiologia , Peroxidação de Lipídeos/fisiologia , Obesidade/fisiopatologia , Adulto , Biomarcadores/metabolismo , Exercício Físico/fisiologia , Feminino , Glutationa/metabolismo , Humanos , Masculino , Obesidade/metabolismo , Estresse Oxidativo/fisiologia , Carbonilação Proteica/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Pesos e MedidasRESUMO
Aerobic exercise has received increasing attention in the scientific literature as a component of management for individuals who sustain a concussion. Because exercise training has been reported to reduce symptoms and improve function for those experiencing persistent postconcussion symptoms, it represents a potentially useful and clinically pragmatic rehabilitation technique. However, the specific exercise parameters that best facilitate recovery from concussion remain poorly defined and unclear. This review will provide a summary of the current understanding of the role of subsymptom exercise to improve outcomes after a concussion and will describe the exercise parameters that appear to be important. The latter will take into account the three pillars of exercise dose-frequency, duration, and intensity-to examine what is currently known. In addition, we identify important gaps in our knowledge of exercise as a treatment for those who develop persistent symptoms of concussion.
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Terapia por Exercício , Exercício Físico , Síndrome Pós-Concussão/reabilitação , Terapia por Exercício/métodos , Humanos , Fatores de TempoRESUMO
Urban slum environments in the tropics are conducive to the proliferation and the spread of rodent-borne zoonotic pathogens to humans. Calodium hepaticum (Brancroft, 1893) is a zoonotic nematode known to infect a variety of mammalian hosts, including humans. Norway rats (Rattus norvegicus) are considered the most important mammalian host of C. hepaticum and are therefore a potentially useful species to inform estimates of the risk to humans living in urban slum environments. There is a lack of studies systematically evaluating the role of demographic and environmental factors that influence both carriage and intensity of infection of C. hepaticum in rodents from urban slum areas within tropical regions. Carriage and the intensity of infection of C. hepaticum were studied in 402 Norway rats over a 2-year period in an urban slum in Salvador, Brazil. Overall, prevalence in Norway rats was 83% (337/402). Independent risk factors for C. hepaticum carriage in R. norvegicus were age and valley of capture. Of those infected the proportion with gross liver involvement (i.e. >75% of the liver affected, a proxy for a high level intensity of infection), was low (8%, 26/337). Sixty soil samples were collected from ten locations to estimate levels of environmental contamination and provide information on the potential risk to humans of contracting C. hepaticum from the environment. Sixty percent (6/10) of the sites were contaminated with C. hepaticum. High carriage levels of C. hepaticum within Norway rats and sub-standard living conditions within slum areas may increase the risk to humans of exposure to the infective eggs of C. hepaticum. This study supports the need for further studies to assess whether humans are becoming infected within this community and whether C. hepaticum is posing a significant risk to human health.
Assuntos
Capillaria/isolamento & purificação , Portador Sadio/veterinária , Infecções por Enoplida/veterinária , Carga Parasitária , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/parasitologia , Animais , Brasil/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/parasitologia , Infecções por Enoplida/epidemiologia , Infecções por Enoplida/parasitologia , Infecções por Enoplida/patologia , Áreas de Pobreza , Prevalência , Ratos , Fatores de Risco , Doenças dos Roedores/patologiaRESUMO
BACKGROUND/OBJECTIVES: The relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study. SUBJECTS/METHODS: The Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing. RESULTS: Four CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases. CONCLUSIONS: Our findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease.
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Índice de Massa Corporal , Neoplasias da Mama/genética , Metilação de DNA , Epigênese Genética , Obesidade/genética , Irmãos , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Ilhas de CpG/genética , Feminino , Estudo de Associação Genômica Ampla , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estudos Prospectivos , Porto Rico/epidemiologia , Estados Unidos/epidemiologiaRESUMO
ABSTRACT BACKGROUND AND OBJECTIVES: Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. CONTENT: Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects. Titration (or trial) during opioid initiation is a way of starting low and going slow (and assessing the appropriateness of a specific opioid and formulation). Recognizing that multiple factors contribute to an individual's personal experience of pain, the physical, psychological, social, cultural, spiritual, pharmacogenomic, and behavioral factors of the individual patient should be taken into account (tweaking, or tailoring). Finally, for those patients for whom transition (tapering) from opioid is desired, doing so too rapidly can have negative consequences and minimization of problems during this step can be achieved by proper tapering. CONCLUSION: We conclude that a simultaneously aggressive, yet conservative, approach is advocated in the literature in which opioid therapy is divided into three key steps (the 3 T's): titration (or trial), tweaking (or tailoring), and transition (or tapering). Establishment of the 3 T's along with the application of other appropriate good medical practice and clinical experience/judgment, including non-pharmacologic approaches, can assist healthcare providers in the effort to achieve optimal management of pain.
RESUMO JUSTIFICATIVA E OBJETIVOS: Uma boa prática clínica com o uso de opioides como parte de um regime abrangente de tratamento da dor pode enfrentar desafios significativos. Apesar das diretrizes provenientes de sociedades/organizações não governamentais para o manejo da dor, ainda existem obstáculos significativos. A revisão de alguns princípios básicos da analgesia com opioide com base na experiência e no conhecimento das publicações atuais sobre esse cuidado importante da saúde é justificável. CONTEÚDO: De acordo com as diretrizes, a literatura apoia o uso da dose total mais baixa de opioides que forneça o controle adequado da dor com menos efeitos adversos. A titulação (teste), ao iniciar a administração de um opioide, é uma maneira de começar com uma concentração baixa e ir devagar (avaliar a adequação da fórmula específica de um opioide). O ajuste (individualização) é reconhecer que vários fatores contribuem para a experiência pessoal da dor de um indivíduo, tais como fatores físicos, psicológicos, sociais, culturais, espirituais, farmacogenômicos e comportamentais. Finalmente, para aqueles pacientes nos quais a transição (redução gradual) do opioide é desejada, fazer essa transição muito rapidamente pode ter consequências negativas e é possível minimizar os problemas durante essa etapa por meio de uma redução gradual. CONCLUSÃO: Uma abordagem simultânea, agressiva, porém conservadora, é defendida na literatura em que a terapia com opioides é dividida em três etapas principais (os 3 Ts - em inglês: titration, tailoring, tapering): titulação (teste), ajuste (individualização) e transição (redução gradual). Estabelecer os três Ts, juntamente com a aplicação de outra boa prática médica e experiência/julgamento clínico, incluindo abordagens não farmacológicas, pode ajudar os profissionais de saúde no esforço para alcançar o tratamento ideal da dor.
Assuntos
Humanos , Guias de Prática Clínica como Assunto , Dor Crônica/tratamento farmacológico , Manejo da Dor/métodos , Analgésicos Opioides/uso terapêutico , Protocolos ClínicosRESUMO
GS-9857, an inhibitor of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A, demonstrates potent activity against HCV genotypes 1-6 and improved coverage against commonly encountered NS3 resistance-associated variants (RAVs). In this study, the safety, tolerability, antiviral activity and pharmacokinetics (PK) of GS-9857 were evaluated in patients with chronic HCV genotype 1-4 infection. Patients with genotype 1-4 infection received placebo or once-daily GS-9857 at doses ranging from 50 to 300 mg for 3 days under fasting conditions. GS-9857 was well tolerated; all reported adverse events (AEs) were mild or moderate in severity. Diarrhoea and headache were the most commonly reported AEs. Grade 3 or 4 laboratory abnormalities were observed in 17% of patients receiving GS-9857; there were no Grade 3 or 4 abnormalities in alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase levels. GS-9857 demonstrated potent antiviral activity in patients with chronic HCV infection, achieving mean and median maximum reductions in HCV RNA of ≥3 log10 IU/mL following administration of a 100-mg dose in patients with HCV genotype 1a, 1b, 2, 3 or 4 infection. The antiviral activity of GS-9857 was unaffected by the presence of pretreatment NS3 RAVs. In patients with genotype 1-4 infection, GS-9857 exhibited linear PK and was associated with a median half-life of 29-42 h, supporting once-daily dosing. Thus, the tolerability, efficacy and pharmacokinetic profile of GS-9857 support its further evaluation for treatment of patients with chronic HCV infection.
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Antivirais/administração & dosagem , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Compostos Macrocíclicos/administração & dosagem , Sulfonamidas/administração & dosagem , Adolescente , Adulto , Idoso , Ácidos Aminoisobutíricos , Antivirais/efeitos adversos , Antivirais/farmacocinética , Antivirais/farmacologia , Ciclopropanos , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Hepacivirus/isolamento & purificação , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Compostos Macrocíclicos/efeitos adversos , Compostos Macrocíclicos/farmacocinética , Compostos Macrocíclicos/farmacologia , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Prolina/análogos & derivados , Quinoxalinas , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacocinética , Sulfonamidas/farmacologia , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
The myogenic differentiation 1 gene (MYOD1) has a key role in skeletal muscle differentiation and composition through its regulation of the expression of several muscle-specific genes. We first used a general linear mixed model approach to evaluate the association of MYOD1 expression levels on individual beef tenderness phenotypes. MYOD1mRNA levels measured by quantitative polymerase chain reactions in 136 Nelore steers were significantly associated (P ≤ 0.01) with Warner-Bratzler shear force, measured on the longissimus dorsi muscle after 7 and 14 days of beef aging. Transcript abundance for the muscle regulatory gene MYOD1 was lower in animals with more tender beef. We also performed a co-expression network analysis using whole transcriptome sequence data generated from 30 samples of longissimus muscle tissue to identify genes that are potentially regulated by MYOD1. The effect of MYOD1 gene expression on beef tenderness may emerge from its function as an activator of muscle-specific gene transcription such as for the serum response factor (C-fos serum response element-binding transcription factor) gene (SRF), which determines muscle tissue development, composition, growth and maturation.