Dietary nitrate supplementation and cognitive health: the nitric oxide-dependent neurovascular coupling hypothesis.

Diet is currently recognized as a major modifiable agent of human health. In particular, dietary nitrate has been increasingly explored as a strategy to modulate different physiological mechanisms with demonstrated benefits in multiple organs, including gastrointestinal, cardiovascular, metabolic, and endocrine systems. An intriguing exception in this scenario has been the brain, for which the evidence of the nitrate benefits remains controversial. Upon consumption, nitrate can undergo sequential reduction reactions in vivo to produce nitric oxide (•NO), a ubiquitous paracrine messenger that supports multiple physiological events such as vasodilation and neuromodulation. In the brain, •NO plays a key role in neurovascular coupling, a fine process associated with the dynamic regulation of cerebral blood flow matching the metabolic needs of neurons and crucial for sustaining brain function. Neurovascular coupling dysregulation has been associated with neurodegeneration and cognitive dysfunction during different pathological conditions and aging. We discuss the potential biological action of nitrate on brain health, concerning the molecular mechanisms underpinning this association, particularly via modulation of •NO-dependent neurovascular coupling. The impact of nitrate supplementation on cognitive performance was scrutinized through preclinical and clinical data, suggesting that intervention length and the health condition of the participants are determinants of the outcome. Also, it stresses the need for multimodal quantitative studies relating cellular and mechanistic approaches to function coupled with behavior clinical outputs to understand whether a mechanistic relationship between dietary nitrate and cognitive health is operative in the brain. If proven, it supports the exciting hypothesis of cognitive enhancement via diet.

Individual satisfaction with HIV/AIDS care in Belo Horizonte, Brazil.

Individual satisfaction is associated with increased retention in HIV/AIDS care services and adherence to treatment. This study assessed factors associated with individual satisfaction at the initiation of antiretroviral therapy and compared the proportions of satisfaction at the initiation of antiretroviral therapy and after three months of follow-up. Face-to-face interviews were carried out among 398 individuals of three HIV/ AIDS healthcare services in Belo Horizonte, Brazil. Variables included sociodemographic and clinical characteristics, perception about healthcare services, and domains of quality of life. Individuals that rated the quality of healthcare services as good or very good were classified as satisfied. A logistic regression analysis of the association between independent variables and individual satisfaction was performed. The proportion of individual satisfaction with healthcare services was 95.5% at the initiation of antiretroviral therapy and 96.7% after three months and these changes were not statistically significant (p = 0.472). The physical domain of quality of life was found to be associated with satisfaction at the initiation of antiretroviral therapy (OR = 1.38; CI = 1.11-1.71; p = 0.003). Training and supervision of health professionals for addressing the needs of individuals with lower levels of physical domain of quality of life may improve satisfaction with HIV/ AIDS care.

Carbon Monoxide and Cyanide Intoxication: An Association to Remember.

Carbon monoxide and cyanide are toxins that induce cellular hypoxia; both can be produced in the context of domestic fires and may have a synergistic effect. We present the case of a man, victim of a house fire, who was initially diagnosed as having carbon monoxide poisoning, but that afterwards also presented signs and symptoms compatible with cyanide poisoning. He was successfully treated with an antidote. We want to highlight this relatively frequent association of poisonings and the need for urgent empirical treatment.

O monóxido de carbono e o cianeto são toxinas que induzem hipóxia celular; ambos podem ser produzidos em contexto de incêndios domésticos e podem exercer um efeito tóxico sinérgico. Apresentamos o caso de um homem, vítima de incêndio doméstico, que foi inicialmente diagnosticado como intoxicação por monóxido de carbono, mas que posteriormente apresentou também sinais e sintomas compatíveis com intoxicação por cianeto, tendo sido tratado com sucesso com antídotos dirigidos. Pretendemos alertar para esta associação de intoxicações relativamente frequente e para a necessidade de tratamento empírico urgente.

Identification of hospitalized patients with community-acquired infection in whom treatment guidelines do not apply: a validated model.

OBJECTIVES: To develop and validate a clinical model to identify patients admitted to hospital with community-acquired infection (CAI) caused by pathogens resistant to antimicrobials recommended in current CAI treatment guidelines. METHODS: International prospective cohort study of consecutive patients admitted with bacterial infection. Logistic regression was used to associate risk factors with infection by a resistant organism. The final model was validated in an independent cohort. RESULTS: There were 527 patients in the derivation and 89 in the validation cohort. Independent risk factors identified were: atherosclerosis with functional impairment (Karnofsky index <70) [adjusted OR (aOR) (95% CI) = 2.19 (1.41-3.40)]; previous invasive procedures [adjusted OR (95% CI) = 1.98 (1.28-3.05)]; previous colonization with an MDR organism (MDRO) [aOR (95% CI) = 2.67 (1.48-4.81)]; and previous antimicrobial therapy [aOR (95% CI) = 2.81 (1.81-4.38)]. The area under the receiver operating characteristics (AU-ROC) curve (95% CI) for the final model was 0.75 (0.70-0.79). For a predicted probability ≥22% the sensitivity of the model was 82%, with a negative predictive value of 85%. In the validation cohort the sensitivity of the model was 96%. Using this model, unnecessary broad-spectrum therapy would be recommended in 30% of cases whereas undertreatment would occur in only 6% of cases. CONCLUSIONS: For patients hospitalized with CAI and none of the following risk factors: atherosclerosis with functional impairment; previous invasive procedures; antimicrobial therapy; or MDRO colonization, CAI guidelines can safely be applied. Whereas, for those with some of these risk factors, particularly if more than one, alternative antimicrobial regimens should be considered.

Use of unlicensed and off-label drugs in neonates in a Brazilian university hospital

ABSTRACT This study was designed to investigate the use of off-label and unlicensed drugs in a Neonatal Care Unit (NCU) and to compare the frequency of use of off-label drugs according to the drug regulatory agencies in Brazil (Agência Nacional de Vigilância Sanitária-ANVISA) and the United States Food and Drug Administration (FDA). A prospective observational study was carried out in the NCU. Prescriptions were classified as off-label and unlicensed using both ANVISA and FDA criteria. A total of 157 newborns and 1187 prescriptions were analyzed. The most prescribed drug was fentanyl (9.3%), followed by multivitamin (8.4%) and gentamicin (7.9%). According to ANVISA criteria, there were 665 (56.0%) off-label prescriptions and 86 (7.2%) unlicensed prescriptions and 95.5% of newborns received at least one drug off-label. By contrast, according to FDA criteria, there were 592 (49.9%) off-label prescriptions and 84 (7.1%) unlicensed prescriptions, and 72.0% of newborns received at least one drug off-label. The off-label use of drugs registered by ANVISA differed significantly from that of drugs registered by the FDA. There was a high frequency of off-label and unlicensed drug use in the investigated NCU, and there was an inverse relationship between off-label and unlicensed usage and the gestational age of the newborns.

Classificação do nível da mobilidade fucional dos pacientes com paralisia cerebral da Reabilitação Pediátrica da Irmandade da Santa Casa de Misericórdia de São Paulo através do Sistema de Classificação da Função Motora Grossa (GMFCS) / Rating the level of functional mobility of patients with cerebral palsy in Pediatric Rehabilitation of the Irmandade da Santa Casa de Misericórdia de São Paulo through the Classification System of gross motor function (GMFCS)

A Paralisia Cerebral é uma desordem de movimento e postura devido a uma lesão do encéfalo em desenvolvimento. O Sistema de Classificação Motora grossa é baseado no movimento auto-iniciado, com ênfase no sentar e andar, contendo cinco níveis diferenciados pela limitação funcional e necessidade de assistência externa. O objetivo deste estudo foi avaliar o nível de mobilidade fucional das crianças com paralisia cerebral do Ambulatório de Reabilitação da Irmandade da Santa Casa da Misericórdia de São Paulo através da escala GMFCS. O resultado do estudo foi que a maioria das crianças avaliadas apresentou nível 1, observando resultados semelhantes na literatura.