Fate of Tableted Freeze-Dried siRNA Lipoplexes in Gastrointestinal Environment

The incorporation of siRNA into nanocarriers is mandatory to facilitate its intracellular delivery, as siRNA itself cannot enter cells. However, the incorporation of these nanocarriers into oral, solid dosage forms and their fate in the gastrointestinal environment is yet to be explored. In the present work, the fate of, (i) naked siRNA, (ii) freshly prepared siRNA lipoplexes, and (iii) tableted siRNA lipoplexes, in simulated gastric and intestinal fluids was studied. The siRNA, either released from or protected within the lipoplexes, was quantified by gel electrophoresis and siRNA efficacy was assessed in cell transfection. The freshly prepared lipoplexes kept their siRNA load and transfection efficiency totally preserved during 1 h of incubation in simulated gastric fluid at 37 °C. However, in simulated intestinal fluid, despite no release of siRNA from lipoplexes after 6 h of incubation, gene silencing efficacy was dramatically decreased even after 1 h of exposure. The lipoplexes obtained from tablets efficiently protected siRNA in simulated gastric fluid, thus preserving the gene silencing efficacy, whereas their incubation in simulated intestinal fluid resulted in a marked siRNA release and decreased gene silencing efficacy. These results provided a detailed explanation for understanding the fate of siRNA in gastrointestinal conditions, when simply loaded in lipoplexes or formulated in the form of tablets

Prevalência de infecções sexualmente transmissíveis na população carcerária feminina de Anápolis - Goiás

RESUMO: O Brasil se encontra na quarta posição mundial em relação ao tamanho absoluto de mulheres encarceradas em que em sua a maioria são solteiras (62%), jovens com idade de 18 a 29 anos (50%) e negras (62%). Assim, os determinantes sociais desse grupo são, muitas vezes, responsáveis pelas iniquidades de saúde que essas pessoas vivem, representados pelo baixo fator socioeconômico, escolar além de oriundas de camadas sociais desfavorecidas. O objetivo do trabalho é identificar as condições de prevalência de Infecções Sexualmente Transmissíveis e de saúde de mulheres encarceradas em um sistema penitenciário de Anápolis, Goiás. Por meio dessa caracterização, almeja-se reconhecer suas demandas e histórico de saúde, buscando comportamentos de risco. Trata-se de um estudo descritivo transversal, que tem por intuito discutir a prevalência de hepatite B, sífilis e HIV no período de 2020 à 2021 em mulheres encarceradas. Para isso serão utilizadas a aplicação de testes rápidos para diagnóstico de IST e questionários adaptados de outros validados para mapear qualitativamente o perfil sociodemográfico dessas mulheres. Dessa forma é fundamental proporcionar uma atenção integral voltada à saúde dessa população, diminuindo o estigma, preconceitos e principalmente a perpetuação dessas IST presentes nesse meio.     &nbsp

Tomografia de corpo todo no trauma e seus desfechos na mortalidade: uma revisão sistemática: Whole body tomography in trauma and its outcomes in mortality: a systematic review

A tomografia computadorizada de corpo inteiro é altamente sensível e representa o padrão-ouro no cenário de diagnóstico da sala de trauma. WBCT fornece uma ferramenta de diagnóstico rápido, que reduz a mortalidade em pacientes gravemente feridos. A lesão traumática é a terceira principal causa de morte em geral. Para otimizar os resultados nesses pacientes, os hospitais empregam imagens de tomografia computadorizada de corpo inteiro (WBCT) devido ao alto rendimento diagnóstico e potencial para identificar lesões perdidas. No entanto, isso atrasa intervenções de tempo crítico. Atualmente, há uma ausência de qualquer evidência de alto nível para apoiar ou refutar qualquer visão. Uma busca sistemática da literatura foi realizada nas bases de dados MEDLINE, Embase, Web of Science, Cochrane Library e demais bases dedados eletrônicas. As publicações eram elegíveis se contivessem dados originais comparando TC de corpo total imediata em pacientes com trauma e associação com a mortalidade. A análise mostra que a TC está associada a melhores resultados, incluindo uma menor taxa de mortalidade geral, entretanto estudos randomizados e controlados merecem ser realizados para que se possa estabelecer de forma fidedigna essa relação

Generalidades sobre o quadro clínico da Rinossinusite: uma revisão narrativa de literatura: Generalities about the clinical picture of Rhinosinusitis: a narrative literature reviewv

A rinossinusite é um processo inflamatório da mucosa dos seios paranasais e da cavidade nasal. O sistema nasossinusal é responsável pelo balanço adequado entre a fabricação e o clearence de muco nas cavidades paranasais. A fisiologia deste é de vital importância para a proteção das vias aéreas superiores. No advém, determinados fatores podem acarretar um desbalanço nesse complexo, consequentemente um processo inflamatório. Qualquer fator que altere a drenagem, seja por obstrução, maior produção ou espessamento do muco, como processo infecciosos ou alérgicos, haverá uma impactação de secreções e a facilitação de colonização bacteriana, dando início ao processo infeccioso. A identificação da inflamação do nariz e seios paranasais é basicamente clínica. A suspeição desta ocorre através da manifestação de dois ou mais sintomatologias. As quais são o bloqueio ou obstrução nasal, a descarga nasal, pressão ou dor facial e redução ou perda do olfato. De modo geral, é essencial à prevenção básica das rinossinusites agudas é barrar a infecção viral. O suporte inclui medidas gerais de higiene, alimentação e hidratação, imunização para o combate de vírus respiratórios , administração de fármacos para turbinar o sistema imune se necessário

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.Peer reviewe

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe