Experiências de semicidadania, descidadanização e a sujeição dos migrantes e refugiados ao projeto de subcidadania em Roraima

El artículo presenta algunos extractos de una investigación realizada con migrantes y refugiados venezolanos entre 2021 y 2022. Basado en la metodología cualitativa, el método etnográfico y la investigación teórica, el artículo presenta fragmentos de informes de investigación y la comunicación de un estudio en curso en la maestría de el Programa de Posgrado en Sociedad y Fronteras de la Universidad Federal de Roraima. Pretende ampliar el debate en torno a los programas de acogida de migrantes y refugiados y aportar elementos para repensar el modelo de inserción del migrante en la sociedad de acogida. Presenta categorías de análisis capaces de identificar experiencias de semiciudadanía, procesos de descendencia y sujeción de los migrantes y refugiados al proyecto de subciudadanía históricamente importante para las clases más pobres y vulnerables de la sociedad brasileña. Impulsa a la sociedad a identificar el protagonismo de las personas migrantes y refugiadas y constatar su lucha por ser reconocidas como sujetos de derechos.O artigo apresenta alguns recortes de pesquisas realizados com migrantes e refugiados venezuelanos entre 2021 e 2022. Pautado na metodologia qualitativa, no método etnográfico e na pesquisa teórica, o artigo apresenta fragmentos de relatórios de pesquisas e a comunicação de estudo em andamento no curso de mestrado do Programa de Pós-Graduação em Sociedade e Fronteiras da Universidade Federal de Roraima. Objetiva ampliar o debate em torno dos programas de acolhimento aos migrantes e refugiados e fornecer elementos para se repensar o modelo inserção dos migrantes na sociedade de acolhida.  Apresenta categorias de análises capazes de identificar vivências de semicidadania, processos de descidadanização e a sujeição dos migrantes e refugiados ao projeto de subcidadania imposto historicamente às classes mais pobres e vulneráveis da sociedade brasileira. Encoraja a sociedade a identificar o protagonismo dos migrantes e refugiados e confirmar sua luta para serem reconhecidos como sujeitos de direitos.  &nbsp

Influence of drug–drug interactions on effectiveness and safety of direct-acting antivirals against hepatitis C virus

[Abstract] Objectives Direct-acting antivirals are the recommended treatment for hepatitis C-infected patients. Drug–drug interactions with concomitant treatments can cause lack of effectiveness and/or safety. The objective of this study is to characterise drug–drug interactions of direct-acting antivirals and to analyse their influence both on the effectiveness of antiviral treatment and on the overall safety of pharmacological treatment in hepatitis C-infected patients. Methods Observational and prospective cohort study for 3 years in the pharmaceutical care outpatient consultation of a general hospital, undertaking detection, evaluation and management of drug–drug interactions by clinical pharmacists and physicians. The main outcome measures were sustained virologic response at week 12 for effectiveness and serious drug-related adverse events for safety. Multivariate statistical analysis applied to: (a) patient basal characteristics related to presence of drug–drug interactions; (b) previous antiviral treatments, viral genotype, cirrhosis, decompensations and presence of drug–drug interactions related to the effectiveness of direct-acting antivirals. Results Of a total of 1092 patients, the majority of them were men, around 60 years old and HCV-genotype 1 mono-infected, with a high basal viral load, naive to antiviral treatment, treated with ledipasvir/sofosbuvir and without cirrhosis. 24.5% had drug–drug interactions. Proton pump inhibitors were the concomitant drugs that caused the most drug–drug interactions. Age ≥65 years and direct-acting antivirals based on protease inhibitors were independently related to the presence of drug-drug interactions (p≤0.012). All (100%) of the therapeutic recommendations based on detected drug–drug interactions were implemented; 97.7% of patients with interactions versus 99.0% without them reached sustained virologic failure (p=0.109). The serious adverse events rates were 1.5% and 1.3% in patients with and without drug-drug interactions, respectively (p=0.841). Conclusions Drug–drug interactions are frequent among hepatitis C-infected patients receiving treatment with direct-acting antivirals. However, the collaboration between physicians and clinical pharmacists makes it possible to detect, evaluate, avoid or clinically manage these drug–drug interactions, in order to maintain whole treatment therapeutic safety and the effectiveness of direct-acting antivirals

Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status

Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis

Neuromodulatory effects of guanine-based purines in health and disease

The function of guanine-based purines (GBPs) is mostly attributed to the intracellular modulation of heteromeric and monomeric G proteins. However, extracellular effects of guanine derivatives have also been recognized. Thus, in the central nervous system (CNS), a guanine-based purinergic system that exerts neuromodulator effects, has been postulated. The thesis that GBPs are neuromodulators emerged from in vivo and in vitro studies, in which neurotrophic and neuroprotective effects of these kinds of molecules (i.e., guanosine) were demonstrated. GBPs induce several important biological effects in rodent models and have been shown to reduce seizures and pain, stabilize mood disorder behavior and protect against gliomas and diseases related with aging, such as ischemia or Parkinson and Alzheimer diseases. In vitro studies to evaluate the protective and trophic effects of guanosine, and of the nitrogenous base guanine, have been fundamental for understanding the mechanisms of action of GBPs, as well as the signaling pathways involved in their biological roles. Conversely, although selective binding sites for guanosine have been identified in the rat brain, GBP receptors have not been still described. In addition, GBP neuromodulation may depend on the capacity of GBPs to interact with well-known membrane proteins in glutamatergic and adenosinergic systems. Overall, in this review article, we present up-to-date GBP biology, focusing mainly on the mechanisms of action that may lead to the neuromodulator role of GBPs observed in neurological disorders

Renal profile of patients treated with elvitegravir/ cobicistat/emtricitabine/tenofovir alafenamide fumarate and dolutegravir/abacavir/lamivudine: 120-week results from a real-world cohort

[Abstract] Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) and dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) are currently available for HIV patients. Objectives: This study evaluated modifications in the renal safety profile in a large real-world cohort of patients who had received EVG/c/FTC/TAF or DTG/ABC/3TC. Methods: A retrospective observational study of HIV-infected patients who received EVG/c/FTC/TAF or DTG/ABC/3TC between March 2015 and June 2019 at a reference hospital in north-western Spain was conducted. Epidemiological, clinical, immunovirological data and information regarding antiretroviral therapy were recorded. The statistical differences between treatments were calculated. Results: A total of 457 patients were evaluated, 266 using EVG/c/FTC/TAF and 191 using DTG/ABC/3TC. Up to week 120, serum creatinine improved in both study groups among experienced patients (EVG/c/FTC/TAF 1.01±0.24 vs 0.91±0.19, p<0.001; DTG/ABC/3TC 1.08±0.24 vs 1.02±0.31, p<0.001), while in naïve patients serum creatinine remained stable compared with baseline. Statistically significant differences were found in serum creatinine when comparing both treatments at week 48 in experienced (0.94±0.21 vs 1.09±0.28, p<0.001) and naïve patients (0.89±0.16 vs 1.06±0.20, p=0.001), and among experienced patients at week 120 (0.91±0.19 vs 1.02±0.31, p=0.015) for the EVG/c/FTC/TAF and DTG/ABC/3TC groups, respectively. During the follow-up, 39 patients in EVG/c/FTC/TAF and 33 in DTG/ABC/3TC (p=0.449) discontinued treatment. The main reason for stopping treatment was adverse events, which were similar in both groups. Conclusions: During the follow-up, patients experienced changes that were not clinically relevant in both treatment groups. Differences in renal events were not found

Impact of introducing assisted electronic prescription on paediatric patient safety

[Resumen] Objetivo. El efecto de la implantación de la prescripción electrónica asistida en la seguridad de los pacientes pediátricos ha sido poco estudiado. El objetivo de este estudio es comparar los errores de medicación antes y después de su implantación en un hospital terciario. Material y métodos. Estudio cuasiexperimental comparativo de los errores de medicación detectados antes y después de la implantación de la prescripción electrónica. Se analizaron todas las líneas de tratamiento y se recogió el punto de la cadena donde ocurrió el error, el tipo de error y su causa. Se realizó un estudio Delphi sobre la importancia de cada error en el que participaron médicos, enfermeros y farmacéuticos. Resultados. Se incluyeron 166 pacientes (83 en cada etapa). Se detectó algún error en el 92% de los pacientes en la etapa preimplantacional (2,8 ± 2,1 errores/paciente) y en el 7,2% en la etapa postimplantacional (0,1 ± 0,4 errores/paciente). La prescripción electrónica asistida supuso una reducción absoluta del riesgo de error de un 40% (intervalo de confianza del 95% = 35,6-44,4%). Los lapsus/despistes fueron la principal causa de error en ambos grupos. En la etapa preimplantacional se consideraron graves el 9,5% de los errores, y en la etapa postimplantacional todos fueron leves o moderados. Conclusiones. La implantación de la prescripción electrónica con sistemas de ayuda a la prescripción, validación y administración de medicamentos reduce de forma significativa los errores de medicación y elimina los errores graves.[Abstract] Objective. There have been very few studies on the effect of assisted electronic prescription on paediatric patient safety. The objective of this study is to compare medication errors that occurred before and after its introduction in a tertiary hospital. Material and methods. A quasi-experimental comparative study of medication errors detected before and after assisted electronic prescription introduction. All treatment lines were analysed in order to detect the point in the chain where the medication error occurred, as well as its type and cause. A Delphi study was conducted on the importance of each medication error involving doctors, nurses, and pharmacists. Results. The study included 166 patients (83 at each stage). At least one medication error was detected in 92% in the pre-introduction phase patients (2.8 ± 2.1 errors/patient) and 7.2% of post-introduction phase patients (0.1 ± 0.4 errors/patient). The assisted electronic prescription led to an absolute risk reduction of 40% (95% confidence interval = 35.6-44.4%). The main cause of error was lapses and carelessness in both stages. Medication errors were considered serious in 9.5% of cases in the pre-introduction phase, while all of them were mild or moderate in the post-introduction phase. Conclusions. The assisted electronic prescription implementation with prescription, validation and medication administration assistance systems significantly reduces medication errors and eliminates serious errors

Setting performance indicators for coastal marine protected areas: An expert-based methodology

Marine Protected Areas (MPAs) require effective indicators to assess their performance, in compliance with the goals of relevant national and international commitments. Achieving and prioritizing shortlists of multidisciplinary indicators demands a significant effort from specialists to depict the multiple conservation and socioeconomic interests, and the large complexity of natural systems. The present paper describes a structured expert-based methodology (process and outputs) to co-define a list of multidisciplinary MPA performance indicators. This work was promoted by the management authority of coastal MPAs in mainland Portugal to gather a consensual and feasible list of indicators that would guide the design of a future national monitoring program. Hence, Portuguese coastal MPAs served as a case study to develop such a process between 2019 and 2020. In the end, participants (1) agreed on a shortlist of prioritized indicators (i.e., environmental, governance, and socioeconomic indicators) and (2) defined minimum monitoring frequencies for the indicators in this list, compatible with the potential replicability of the associated survey methods. The present approach recommends that management plans incorporate monitoring procedures and survey methods, with a validated list of indicators and associated monitoring periodicity, agreed among researchers, MPA managers and governance experts. The proposed methodology, and the lessons learned from it, can support future processes aiming to define and prioritize MPA performance indicatorsFundação para a Ciência e Tecnologia - FCT, European Maritime and Fisheries Fund (EMFF)info:eu-repo/semantics/publishedVersio

Oxidation mechanisms occurring in wines

The present review aims to show the state of the art on the oxidation mechanisms occurring in wines, as well as the methods to monitor, classify and diagnose wine oxidation. Wine oxidation can be divided in enzymatic oxidation and non-enzymatic oxidation. Enzymatic oxidation almost entirely occurs in grape must and is largely correlated with the content of hydroxycinnamates, such as caffeoyltartaric acid and para-coumaroyltartaric acid, and flavan-3-ols. Non-enzymatic oxidation, also called chemical oxidation of wine, prevails in fermented wine and begin by the oxidation of polyphenols containing a catechol or a galloyl group. These phenolic. reactions, both enzymatic and non-enzymatic, result in by-products named quinones. However, in non-enzymatic oxidation, oxygen does not react directly with phenolic compounds. The limitation on the reactivity of triplet oxygen is overcome by the stepwise addition of a single electron, which can be provided by reduced transition metal ions, essentially iron(II) and copper(I). The sequential electron transfer leads to the formation of hydroperoxide radical (HOO center dot), hydrogen peroxide (H2O2), and hydroxyl radical (HO center dot). The later radical will oxidize almost any organic molecule found in wine and will react with the first species it encounters, depending on their concentration. Sulfur dioxide (SO2) and ascorbic acid, when added to wine, are able to reduce the quinones. Alternative options have been assessed for the prevention of oxidation during wine storage; nevertheless, these are not fully understood or commonly accepted. During aging, aldehydes are important intermediates in the chemical transformations occurring in wines, leading to color and flavor changes. In the same way, a range of off-flavors can be formed from wine oxidation. At low concentrations these flavors may add to the complexity of a wine, but as these increase they begin to detract from wine quality. In addition to the major chemical browning involving wine phenols, the main oxidation reactions occurring during grape juice heating or storage are caramelization and Maillard reaction, which are temperature dependent. Different methods have been proposed in the literature, addressing the complexity and multi-scale related with the oxidation process, to attempt the quantification of antioxidant activity in wines. These methods can be broadly divided in: i) methods based on chemical reactions and ii) methods based on the chemical-physical properties of antioxidants

Hypertensive measures In schoolchildren: risk of central obesity and protective effect of moderate-to-vigorous physical activity

Fundamento: Aumento da prevalência de hipertensão arterial (HA) em crianças e adolescentes e sua associação com diversas comorbidades. Objetivo: Verificar a associação de HA, obesidade central e obesidade geral, e nível de atividade física em escolares.Métodos: Participaram do estudo 336 crianças e adolescentes, de 11 a 17 anos de idade. Aferiram-se estatura, peso corporal, circunferência da cintura (CC) e pressão arterial (PA). Foi calculado o índice de massa corporal escore z (IMC-z). O nível de atividade física foi avaliado pela versão curta do International Physical Activity Questionnaire (IPAQ), conforme a prática em atividades físicas moderadas-vigorosas (AF-mv). Consideraram-se hipertensos os escolares que apresentaram pressão arterial sistólica (PAS) e/ou diastólica (PAD) superiores ao percentil 95, de acordo com sexo, faixa etária e estatura, ou ≥120×80mmHg. Utilizaram-se os testes estatísticos de t-Student, Qui-quadrado, Mann-Whitney e modelo de regressão logistica binária, considerando-se o nível de significância de p<0,05. Resultados: Foram observados que 40,5% dos escolares apresentaram HA, 35,11% excesso de peso (12,5% obesos), 13,39% CC elevada e 40,2% foram considerados insuficientemente ativos em AF-mv. As chances de HA foram relacionadas à CC elevada (OR=6,11; IC95%:2,59 a 14,42) e ao excesso de peso (OR=2,91; IC95%:1,76 a 4,79). Além disso, os adolescentes que praticavam AF-mv apresentaram menor risco de PAD elevada (OR=0,33; IC95%:0,15 a 0,72). Conclusão: Concluiu-se que a obesidade central, a obesidade geral e o sexo masculino foram os melhores preditores de HA em crianças e adolescentes. A prática de AF-mv demonstrou efeito protetor na PAD elevada em escolares.O presente estudo foi financiado pela Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Centro de Investigação em Estudos da Criança (CIEC), pelo Projeto Estratégico UID/CED/00317/2013, por meio dos Fundos Nacionais da Fundação para a Ciência e a Tecnologia (FCT), cofinanciado pelo Fundo Europeu de Desenvolvimento Regional (FEDER) por meio do COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) com a referência POCI-01-0145-FEDER-007562

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission