Characterization techniques for studying the properties of nanocarriers for systemic delivery

Nanocarriers have attracted a huge interest in the last decade as efficient drug delivery systems and diagnostic tools. They enable effective, targeted, controlled delivery of therapeutic molecules while lowering the side effects caused during the treatment. The physicochemical properties of nanoparticles determine their in vivo pharmacokinetics, biodistribution and tolerability. The most analyzed among these physicochemical properties are shape, size, surface charge and porosity and several techniques have been used to characterize these specific properties. These different techniques assess the particles under varying conditions, such as physical state, solvents etc. and as such probe, in addition to the particles themselves, artifacts due to sample preparation or environment during measurement. Here, we discuss the different methods to precisely evaluate these properties, including their advantages or disadvantages. In several cases, there are physical properties that can be evaluated by more than one technique. Different strengths and limitations of each technique complicate the choice of the most suitable method, while often a combinatorial characterization approach is needed

Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics

We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to the common ‘spaghetti-like’ structures but to dense matted deposits. Type 2 diabetes is a known inflammatory disease. In the present work, we found that the axial ratio of the erythrocytes of poorly controlled (as suggested by increased HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin morphologies were again highly aberrant. As judged by scanning electron microscopy and in the atomic force microscope, these could be reversed, to some degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox (DFX). As well as their demonstrated diagnostic significance, these morphological indicators may have prognostic value.Biotechnology and Biological Sciences Research Council (grant BB/L025752/1) as well as the National Research Foundation (NRF) of South Africa.http://www.cardiab.com/hb201

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Prevalência de portadores de DTM em pacientes avaliados no setor de otorrinolaringologia Prevalence of patients harboring temporomandibular disorders in an otorhinolaryngology departament

A interação entre disfunção temporomandibular e otalgia é, mesmo nos dias atuais, motivo para especulações e hipóteses. Vários pesquisadores sugerem causas, conseqüências e supostos tratamentos. OBJETIVO: Verificar a prevalência de pacientes portadores de DTM em um serviço de otorrinolaringologia. TIPO DE ESTUDO: Este é um estudo epidemiológico do tipo descritivo com amostra transversal. MATERIAL E MÉTODO: Foram avaliados 221 pacientes do Serviço de Otorrinolaringologia do Hospital da Cidade, em Passo Fundo, Rio Grande do Sul, durante um período de dois meses. Para captação e interpretação dos dados, bem como verificação da disfunção temporomandibular, foi utilizado um questionário auto-aplicado previamente validado. RESULTADO: Após coleta e interpretação dos dados de 221 pacientes, os resultados obtidos foram: 48 pacientes (21.72%) considerados como necessitando de tratamento para DTM (índice de DTM moderada e severa), dos quais 35 pertenciam ao gênero feminino (72.9%) e 13 ao masculino (21.1%). Apenas 15 indivíduos do total (7.24%) estavam totalmente livres de sintomas de DTM. Quanto aos demais, apresentaram: dor de cabeça (33,5%), dor no pescoço e ombro (28,5%), dor na região do ouvido (29%) e ruídos articulares (25%). CONCLUSÃO: A prevalência de DTM foi de 21.72% sendo significantemente maior no gênero feminino (p: 0.0001); e as prevalências, em relação aos índices, foram: DTM ausente 37.56%; DTM leve 40.72%; DTM moderada 19%, e DTM severa 2.72%.<br>The interaction between Temporomandibular disorders (TMD) and otalgia is, even nowadays, a reason for speculation and hypotheses raising. Several researchers suggest causes, consequences and alleged treatments. STUDY DESIGN: This is an epidemiological, sectional cohort study of prevalence. AIM: The study demonstrates the prevalence of patients harboring TMDs in an otorhinolaryngology department. MATERIAL AND METHODOS: During a two-month period, 221 patients from the Otorhinolaryngology Department of the Hospital da Cidade de Passo Fundo, State of Rio Grande do Sul, Brazil were analyzed. A previously validated questionnaire was applied for data collection. RESULTS: In the present study, the need for dental assessment was observed in 48 patients ( 21.72%). In this group there were 35 female (72.9%) and 13 males (27.1%). Only 15 patients (7.24%) were entirely free of TMD symptoms. The remaining patients reported the following TMD symptoms: headaches: 34.39%, neck and shoulder pain: 28.50%, pain on the ear region: 30.32% and joint noises in 23.98%. CONCLUSION: The prevalence of Temporomandibular disorders was 21.72%, being significantly higher among female subjects (p:0.0001). The prevalence regarding the indexes, was: TMD absent: 37.56%; mild TMD: 40.72%; moderate TMD 19% and severe TMD: 2.72%

Partial correlation network analyses to detect altered gene interactions in human disease: Using preeclampsia as a model

Differences in gene expression between cases and controls have been identified for a number of human diseases. However, the underlying mechanisms of transcriptional regulation remain largely unknown. Beyond comparisons of absolute or relative expression levels, disease states may be associated with alterations in the observed correlational patterns among sets of genes. Here we use partial correlation networks aiming to compare the transcriptional co-regulation for 222 genes that are differentially expressed in decidual tissues between preeclampsia (PE) cases and non-PE controls. Partial correlation coefficients (PCCs) have been calculated in cases (N = 37) and controls (N = 58) separately. For all PCCs, we tested if they were significant non-zero in the cases and controls separately. In addition, to examine if a given PCC is different between the cases and controls, we tested if the difference between two PCCs were significant non-zero. In the group with PE cases, only five PCCs were significant (FDR p value = 0.05), of which none were significantly different from the PCCs in the controls. However, in the controls we identified a total of 56 statistically significant PCCs (FDR p value = 0.05), of which 31 were also significantly different (FDR p value = 0.05) from the PCCs in the PE cases. The identified partial correlation networks included genes that are potentially relevant for developing PE, including both known susceptibility genes (EGFL7, HES1) and novel candidate genes (CFH, NADSYN1, DBP, FIGLA). Our results might suggest that disturbed interactions, or higher order relationships between these genes play an important role in developing the disease

Worldwide trends in blood pressure from 1975 to 2015 : a pooled analysis of 1479 population-based measurement studies with 19.1 million participants

Background Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7-128.3) in men and 122.3 mm Hg (121.0-123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9-79.5) for men and 76.7 mm Hg (75.9-77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4-27.1) in men and 20.1% (17.8-22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe. Funding Wellcome Trust. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license.Peer reviewe