A facile method for the stain-free visualization of hierarchical structures with electron microscopy

Diblock copolymers form hierarchical morphologies with numerous applications in drug delivery and as nanoreactors. Yet, the visualization of these structures by electron microscopy can be extremely difficult, requiring complex staining techniques with associated health risks and the potential to alter structural morphology. Reported here is the synthesis of diblock copolymers by RAFT containing 3,5-bis(trifluoromethyl)phenyl functionality allowing for facile visualization of their resulting hierarchical structures by TEM with no further sample preparation.P.E.W. thanks the AWE and E.A. thanks Schlumberger for financial support, and J.d.B is grateful for a Marie Curie Intraeuropean Fellowship (project # 273807). This work was also supported by an ERC Starting Investigator Grant (ASPiRe) and a Next Generation Fellowship provided by the Walters-Kundert Foundation.This is the accepted manuscript. The final published version is available from Wiley at http://onlinelibrary.wiley.com/doi/10.1002/pola.27517/abstract

Electrocardiographic Left Ventricular Hypertrophy Among Gambian Diabetes Mellitus Patients

Background: The global prevalence of diabetes and its complications is increasing worldwide. Its role in coronary heart disease has been linked with the presence of left ventricular hypertrophy (LVH). The present study aims to determine the prevalence of electrocardiographic left ventricular hypertrophy (ECG-LVH) in adult diabetic subjects, its epidemiological and clinical correlates.Methods: A descriptive cross-sectional study involving 534 patients was conducted at the Edward Francis Small Teaching Hospital (formerly Royal Victoria Teaching Hospital), The Gambia. Four hundred and forty patients were included using a standard questionnaire. Anthropometry, laboratory investigations and electrocardiogram were carried out. We used the Lewis, Cornell, and Sokolow-Lyon Voltage criteria to define ECG-LVH. MinitabTM statistical software version 13.20 was used for analysis.Results: 146 (35.2%) patients had ECG-LVH using all 3 criteria and this prevalence was higher among women being 116 (79.5%). A generally high prevalence of overweight (155/37.4%) and obesity (119/28.6%) was observed among study participants, and both clinic-day systolic and diastolic blood pressure (BP) were significantly higher in those with ECG-LVH. Poor diabetes control was observed in both groups.Conclusion: There was a high prevalence of ECGLVH and it is especially so with combining multiple criteria, hence the need for screening. Clinic-day hypertension was associated with ECG-LVH hence the need for diagnosing and aggressive treatment of hypertension in patients with diabetes mellitus.Keywords: Diabetes mellitus, ECG-LVH, The Gambia, voltage criteri

The significance of macrophage phenotype in cancer and biomaterials

Macrophages have long been known to exhibit heterogeneous and plastic phenotypes. They show functional diversity with roles in homeostasis, tissue repair, immunity and disease. There exists a spectrum of macrophage phenotypes with varied effector functions, molecular determinants, cytokine and chemokine profiles, as well as receptor expression. In tumor microenvironments, the subset of macrophages known as tumor-associated macrophages generates byproducts that enhance tumor growth and angiogenesis, making them attractive targets for anti-cancer therapeutics. With respect to wound healing and the foreign body response, there is a necessity for balance between pro-inflammatory, wound healing, and regulatory macrophages in order to achieve successful implantation of a scaffold for tissue engineering. In this review, we discuss the multitude of ways macrophages are known to be important in cancer therapies and implanted biomaterials

Clustering of childhood mortality in the Kintampo Health and Demographic Surveillance System in Ghana

Background: Childhood mortality in Ghana has generally declined in the last four decades. However, estimates tend to conceal substantial variability among regions and districts. The lack of population-based data in Ghana, as in other less developed countries, has hindered the development of effective programmes targeted specifically at clusters where mortality levels are significantly higher. Objective: This paper seeks to test for the existence of statistically significant clusters of childhood mortality within the Kintampo Health and Demographic Surveillance System (KHDSS) between 2005 and 2007. Design: In this study, mortality rates were generated using mortality data extracted from the health and demographic surveillance database of the KHDSS and exported into STATA. The spatial and spatio-temporal scan statistic by Kulldorff was used to identify significant clusters of childhood mortality within the KHDSS. Results: A significant cluster of villages with high under-five mortality in the south-eastern part of the KHDSS in 2006 was identified. This is a remote location where poverty levels are relatively higher, health facilities are more sparse and these are compounded by poor transport services in case of emergencies. Conclusion: This study highlights the potential of the surveillance platform to demonstrate the spatial dimensions of childhood mortality clustering. It is apparent, though, that further studies need to be carried out in order to explore the underlying risk factors for potential mortality clusters that could emerge later

Involvement of patients or their representatives in quality management functions in EU hospitals:implementation and impact on patient-centred care strategies

OBJECTIVE: The objective of this study was to describe the involvement of patients or their representatives in quality management (QM) functions and to assess associations between levels of involvement and the implementation of patient-centred care strategies. DESIGN: A cross-sectional, multilevel STUDY DESIGN: that surveyed quality managers and department heads and data from an organizational audit. SETTING: Randomly selected hospitals (n = 74) from seven European countries (The Czech Republic, France, Germany, Poland, Portugal, Spain and Turkey). PARTICIPANTS: Hospital quality managers (n = 74) and heads of clinical departments (n = 262) in charge of four patient pathways (acute myocardial infarction, stroke, hip fracture and deliveries) participated in the data collection between May 2011 and February 2012. MAIN OUTCOME MEASURES: Four items reflecting essential patient-centred care strategies based on an on-site hospital visit: (1) formal survey seeking views of patients and carers, (2) written policies on patients' rights, (3) patient information literature including guidelines and (4) fact sheets for post-discharge care. The main predictors were patient involvement in QM at the (i) hospital level and (ii) pathway level. RESULTS: Current levels of involving patients and their representatives in QM functions in European hospitals are low at hospital level (mean score 1.6 on a scale of 0 to 5, SD 0.7), but even lower at departmental level (mean 0.6, SD 0.7). We did not detect associations between levels of involving patients and their representatives in QM functions and the implementation of patient-centred care strategies; however, the smallest hospitals were more likely to have implemented patient-centred care strategies. CONCLUSIONS: There is insufficient evidence that involving patients and their representatives in QM leads to establishing or implementing strategies and procedures that facilitate patient-centred care; however, lack of evidence should not be interpreted as evidence of no effect

Hypertension alters the function and expression profile of the peptide cotransporters PEPT1 and PEPT2 in the rodent renal proximal tubule

Hypertension is a major risk factor for kidney and cardiovascular disease. The treatment of hypertensive individuals by selected ACE inhibitors and certain di-and tripeptides halts the progression of renal deterioration and extends life-span. Renal reabsorption of these low molecular weight substrates are mediated by the PEPT1 and PEPT2 cotransporters. This study aims to investigate whether hypertension and ageing affects renal PEPT cotransporters at gene, protein expression and distribution as well as function in the superficial cortex and the outer medulla of the kidney. Membrane vesicles from the brush border (BBMV) and outer medulla (OMMV) were isolated from the kidneys of young Wistar Kyoto (Y-WKY), young spontaneously hypertensive (Y-SHR), and middle aged SHR (M-SHR) rats. Transport activity was measured using the substrate, β-Ala-Lys (AMCA). Gene expression levels of PEPT genes were assessed with qRT-PCR while renal localisation of PEPT cotransporters was examined by immunohistochemistry with Western Blot validation. The Km and Vmax of renal PEPT1 were decreased significantly in SHR compared to WKY BBMV, whilst the Vmax of PEPT2 showed differences between SHR and WKY. By contrast to the reported cortical distribution of PEPT1, PEPT1-staining was detected in the outer medulla, whilst PEPT2 was expressed primarily in the cortex of all SHR; PEPT1 was significantly upregulated in the cortex of Y-SHR. These outcomes are indicative of a redistribution of PEPT1 and PEPT2 in the kidney proximal tubule under hypertensive conditions that has potential repercussions for nutrient handling and the therapeutic use of ACE inhibitors in hypertensive individuals

A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype

Pathogenic variants in retinol dehydrogenase 5 (RDH5) attenuate supply of 11-cis-retinal to photoreceptors leading to a range of clinical phenotypes including night blindness due to markedly slowed rod dark adaptation and in some patients, macular atrophy. Current animal models (such as Rdh5-/- mice) fail to recapitulate the functional or degenerative phenotype. Addressing this need for a relevant animal model we present a new domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val). As with patients, affected cats have a marked delay in recovery of dark adaptation. Additionally, the cats develop a degeneration of the area centralis (equivalent to the human macula). This recapitulates the development of macular atrophy that is reported in a subset of patients with RDH5 mutations and is shown in this paper in 7 patients with biallelic RDH5 mutations. There is notable variability in the age at onset of the area centralis changes in the cat, with most developing changes as juveniles but some not showing changes over the first few years of age. There is similar variability in development of macular atrophy in patients and while age is a risk factor, it is hypothesized that genetic modifying loci influence disease severity, and we suspect the same is true in the cat model. This novel cat model provides opportunities to improve molecular understanding of macular atrophy and test therapeutic interventions for RDH5-associated retinopathies

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

Fast character modeling with sketch-based PDE surfaces

© 2020, The Author(s). Virtual characters are 3D geometric models of characters. They have a lot of applications in multimedia. In this paper, we propose a new physics-based deformation method and efficient character modelling framework for creation of detailed 3D virtual character models. Our proposed physics-based deformation method uses PDE surfaces. Here PDE is the abbreviation of Partial Differential Equation, and PDE surfaces are defined as sculpting force-driven shape representations of interpolation surfaces. Interpolation surfaces are obtained by interpolating key cross-section profile curves and the sculpting force-driven shape representation uses an analytical solution to a vector-valued partial differential equation involving sculpting forces to quickly obtain deformed shapes. Our proposed character modelling framework consists of global modeling and local modeling. The global modeling is also called model building, which is a process of creating a whole character model quickly with sketch-guided and template-based modeling techniques. The local modeling produces local details efficiently to improve the realism of the created character model with four shape manipulation techniques. The sketch-guided global modeling generates a character model from three different levels of sketched profile curves called primary, secondary and key cross-section curves in three orthographic views. The template-based global modeling obtains a new character model by deforming a template model to match the three different levels of profile curves. Four shape manipulation techniques for local modeling are investigated and integrated into the new modelling framework. They include: partial differential equation-based shape manipulation, generalized elliptic curve-driven shape manipulation, sketch assisted shape manipulation, and template-based shape manipulation. These new local modeling techniques have both global and local shape control functions and are efficient in local shape manipulation. The final character models are represented with a collection of surfaces, which are modeled with two types of geometric entities: generalized elliptic curves (GECs) and partial differential equation-based surfaces. Our experiments indicate that the proposed modeling approach can build detailed and realistic character models easily and quickly