Oral cancer patient\u27s profile and time to treatment initiation in the public health system in Rio de Janeiro, Brazil

BACKGROUND: This paper aims to describe the profile of oral cancer (OC) patients, their risk classification and identify the time between screening and treatment initiation in Rio de Janeiro Municipality. METHOD: Data were obtained from the healthcare Regulation System (SISREG) regarding the period January 2013 to September 2015. Descriptive, bivariate and multivariate analysis were performed identifying the factors associates with a diagnosis of OC as well as the time to treatment initiation (TTI) differences between groups. RESULTS: From 3,862 individuals with a potential OC lesion, 6.9 % had OC diagnosis. OC patients were 62.3 y.o. (mean), 64.7 % male, 36.1 % were white and 62.5 % of the records received a red/yellow estimated risk classification. Being older, male, white and receiving a high-risk classification was associated with having an OC diagnosis. OC TTI was in average 59.1 days and median of 50 days significantly higher than non-OC individuals (p = 0.007). TTI was higher for individuals older than 60 years old, male, and white individuals and for risk classification red and yellow, nevertheless while in average none of these differences were statistically significant, the median of individuals classified as low risk was significantly (p = 0.044) lower than those with high risk. CONCLUSIONS: Time to treatment initiation (TTI) was higher for OC patients related to non OC. Despite OC confirmed was associated with risk at screening classified as urgent or emergent, a high percentage of OC patients had their risk classified for elective care when specialized care was requested

Natural history and survival in stage 1 Val30Met transthyretin familial amyloid polyneuropathy

OBJECTIVE: To assess the natural history and treatment effect on survival among patients with transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) stage 1 Val30Met. METHODS: Multi-institutional, hospital-based study of patients with TTR-FAP Val30Met prospectively followed up until December 2016, grouped into untreated (n = 1,771), liver transplant (LTx)-treated (n = 957), or tafamidis-treated (n = 432) cohorts. Standardized mortality ratios, Kaplan-Meier, and Cox methods were used to estimate excess mortality, survival, and adjusted hazard ratios (HRs) for all-cause mortality. RESULTS: Disease-modifying treatments decreased TTR-FAP excess mortality from 10 to 4 (standardized mortality ratio 3.92, 95% confidence interval [CI] 2.64-5.59). Median overall survival of untreated and LTx-treated cohorts was 11.61 (95% CI 11.14-11.87) and 24.73 years (95% CI 22.90-27.09), respectively, and was not reached in the tafamidis-treated cohort (maximum follow-up, 10 years). Both disease-modifying treatments improved survival. Among early-onset patients (younger than 50 years of age), tafamidis reduced the mortality risk compared with untreated patients by 91% (HR 0.09, 95% CI 0.03-0.25, p < 0.001) and with LTx-treated patients by 63% (HR 0.37, 95% CI 0.14-1.00, p = 0.050). Previous tafamidis treatment did not affect mortality risk after LTx (HR 0.83, 95% CI 0.25-2.78, p = 0.763). Among late-onset patients (50 years and older), tafamidis reduced mortality risk by 82% compared with untreated patients (HR 0.18, 95% CI 0.06-0.49, p = 0.001). CONCLUSION: LTx and tafamidis convey substantial survival benefits, but TTR-FAP mortality remains higher than in the general population. These results strongly reinforce the importance of timely diagnosis and earlier treatment, boosting the pursuit for an increased life expectancy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with stage 1 Val30Met TTR-FAP, LTx and tafamidis increase survival

O desfecho clinico do paciente obeso submetido a cirurgia / The clinical outcome of the obese patient undergoing

A obesidade se trata de uma doença multifatorial e de caráter crônico, necessitando ser precocemente diagnosticada e tratada. O tratamento do excesso de peso corporal têm a finalidade de evitar exacerbações da doença e as comorbidades com ela associadas. O seguinte artigo objetivou por meio da literatura científica abordar e descrever o quadro clínico do paciente obeso e as opções cirúrgicas e seu prognóstico. O estudo em questão é uma revisão de literatura do tipo narrativa, fundamentada nas plataformas online do SciELo, Pubmed, Google Acadêmico, Brazilian Jornal of Health Review e LILACS. Desta pesquisa foram analisados 50 artigos, nos idiomas português, inglês e espanhol. Foram selecionados 20 estudos por estarem atuais, baseados em evidências e com linguagem clara e direta, descartando-se os demais sem relevância para a temática proposta. Na literatura existem muitas informações. Algumas perspectivas mais restritas classificam as causas da obesidade apenas entre o desequilíbrio entre a ingesta calórica e o gasto metabólico. Ademais, estudos mais atuais abordam a questão em sua perspectiva mais realista, ou seja, sua base multifatorial a qual incluem fatores genéticos, neurológicos, metabólicos e endócrinos, associados a um estilo de vida sedentário e a uma alimentação hipercalórica. O diagnóstico clínico se baseia em métodos simples e de fácil aplicabilidade, e a terapêutica se fundamenta em reeducação alimentar e a inclusão de atividades físicas. No advém, alguns pacientes são resistentes a esses meios e urgem ser submetidos a opção cirúrgica. Atualmente, a cirurgia bariátrica é a opção e esta conta com diversas técnicas promissoras e eficazes no combate ao excesso de peso e suas implicações adjacentes. E está possui benefícios e complicações que consoante o perfil clínico do paciente e o acompanhamento multidisciplinar pode resultar em bom prognóstico

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

Phase 2 open-label extention (OLE) study of patisiran, an investigational siRNA agent for familial amyloidotic polyneuropathy (FAP)

Background: Familial amyloidotic polyneuropathy (FAP) is a progressive and fatal, autosomal dominant disease caused by deposition of mutant and wild-type transthyretin (TTR). Patisiran is an investigational, systemically administered lipid nanoparticle (LNP) formulation of a small interfering RNA (siRNA) targeting wild-type and mutant TTR. This formulation delivers the siRNA predominantly to the liver, thereby inhibiting synthesis of TTR at the primary site of production. A recently completed multi-center, multi-dose Phase 2 trial of patisiran in FAP patients (N=29) showed &gt;80% sustained mean knockdown of serum TTR when administered at a dose of 0.3 mg/kg every 3 weeks with a generally favorable safety profile (Suhr O, ISA 2014). Methods: A Phase 2 open-label extension (OLE) study of patisiran in patients with FAP who participated in the aforementioned trial, was initiated in October 2013. The primary objective of the study is to evaluate the safety and tolerability of 0.3 mg/kg patisiran administered intravenously once every 3 weeks for up to 2 years. Secondary objectives include assessment of patisiran's effect on serum TTR levels, as well as evaluation every 6 months of its impact on clinical measures, including the mNIS+7 composite neurologic impairment score and quality of life (QOL). Results: Twenty-seven patients were enrolled; median age 64 years (range: 29-77 years). Chronic dosing with patisiran has been generally well tolerated. Three patients experienced serious adverse events unrelated to study drug. Flushing and infusion-related reactions were observed in 22.2% and 18.5% of the patients, respectively; these were mild in severity, and did not result in any discontinuations. Sustained mean serum TTR lowering of approximately 80% was achieved, with further mean nadir of up to 88% between doses for approximately 16 months. Stabilization of quality of life (QOL) measures was observed. Among the 20 evaluable patients at the time of data cutoff, neuropathy impairment scores were stable through 12 months with a mean change in mNIS+7 and NIS of -2.5 and 0.4 points, respectively; this compares favorably to the 10-18 point increase in neurologic impairment scores estimated at 12 months from prior FAP studies in a patient population with similar baseline NIS. Conclusion: Data from this Phase 2 OLE study demonstrate that 12-months of patisiran administration was well-tolerated, resulted in sustained mean serum TTR lowering, and has the potential to halt neuropathy progression. As of March 2015, dosing continues for all patients; 18-month results will be presented

Geotechnology applied to land use and sealing in urban areas

Through the geotechnology's use, the aim of this study was to characterize the urban occupation interference and occurrence of floods in the upstream area of watershed from the stream Wenzel (Rio Claro-SP/Brazil). Urbanized watersheds are composed of a variety of features and the development of cartographic material allowed the analysis of the evolution of land used for 1958 and 2006 scenarios. The thematic maps were generated using software Spring 4.3.3, wherein it got the separation of matters from vegetation cover and other intra urban features. Procedures of digital processes and classification of surface cover allowed quantifying the occupied area by each coverage type: woody vegetation, grass, grass with bare soil, bare soil, building, asphaltic sheets and exposed soil. Quantification of the different covers' occupied areas allowed relating the parameter Curve Number (Soil Conservation Service) as efficient methodology for runoff values estimative. The results indicate vegetation cover's reduction, intensive surface's sealing and suppression of water bodies. These factors imply changes of hydrological dynamics of the source, increasing flow and transfer of larger volumes of water and flood peaks to downstream sectors. The use of geotechnology allowed analyzing the evolution of urbanization and it permits also to infer about trends for future or inadequate occupancy to hydrological and environmental point of view. © 2013 IEEE

A theoretical investigation on the aminolysis of pyromellitic and 1,4,5,8-naphthalenetetracarboxylic dianhydrides

Aniline aminolysis reaction of pyromellitic (PMDA) and 1,4,5,8-naphthalenetetracarboxylic (NTDA) dianhydrides is investigated by means of density functional theory (BP86-D3(BJ)/def2-TZVP). The concerted mechanism is shown to be more favorable for both substrates, in comparison to the stepwise one, with the aminolysis of PMDA presenting lower activation energy than the reaction of NTDA. This result is shown to be related to the lower ring tension in NTDA. Solvation also shows significant influence on the kinetics and thermodynamics of these reactions, as determined by two different methods, implicit with the universal solvation model SMD, and explicit with alchemical FEP molecular dynamics simulations. The comparison between SMD and FEP enables us to explore possible inaccuracies on the SMD model, and examine the suitability of the FEP approach as a physics-based method for the calculation of the solvent contribution in different reactions11471319CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA E INOVAÇÃO DO ESTADO DE SANTA CATARINA - FAPESC140485/2017-1; 311963/2017-02010/18268-1não te