HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox".

BackgroundProprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and improve outcomes in the general population. HIV-infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.Methods and resultsWe studied 567 participants from a clinic-based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL-C level was 100 mg/dL (IQR 77-124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV-coinfected patients versus controls (95% CI 9-34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3-20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8-33%, P=0.001). Interleukin-6 levels increased in a stepwise fashion from controls (lowest) to HIV-infected to HIV/HCV-coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).ConclusionsDespite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection

Superpixel-based Two-view Deterministic Fitting for Multiple-structure Data

This paper proposes a two-view deterministic geometric model fitting method, termed Superpixel-based Deterministic Fitting (SDF), for multiple-structure data. SDF starts from superpixel segmentation, which effectively captures prior information of feature appearances. The feature appearances are beneficial to reduce the computational complexity for deterministic fitting methods. SDF also includes two original elements, i.e., a deterministic sampling algorithm and a novel model selection algorithm. The two algorithms are tightly coupled to boost the performance of SDF in both speed and accuracy. Specifically, the proposed sampling algorithm leverages the grouping cues of superpixels to generate reliable and consistent hypotheses. The proposed model selection algorithm further makes use of desirable properties of the generated hypotheses, to improve the conventional fit-and-remove framework for more efficient and effective performance. The key characteristic of SDF is that it can efficiently and deterministically estimate the parameters of model instances in multi-structure data. Experimental results demonstrate that the proposed SDF shows superiority over several state-of-the-art fitting methods for real images with single-structure and multiple-structure data.Comment: Accepted by European Conference on Computer Vision (ECCV

Edge-Enhancement DenseNet for X-ray Fluoroscopy Image Denoising in Cardiac Electrophysiology Procedures

PURPOSE: Reducing X‐ray dose increases safety in cardiac electrophysiology procedures but also increases image noise and artifacts which may affect the discernibility of devices and anatomical cues. Previous denoising methods based on convolutional neural networks (CNNs) have shown improvements in the quality of low‐dose X‐ray fluoroscopy images but may compromise clinically important details required by cardiologists. METHODS: In order to obtain denoised X‐ray fluoroscopy images whilst preserving details, we propose a novel deep‐learning‐based denoising framework, namely edge‐enhancement densenet (EEDN), in which an attention‐awareness edge‐enhancement module is designed to increase edge sharpness. In this framework, a CNN‐based denoiser is first used to generate an initial denoising result. Contours representing edge information are then extracted using an attention block and a group of interacted ultra‐dense blocks for edge feature representation. Finally, the initial denoising result and enhanced edges are combined to generate the final X‐ray image. The proposed denoising framework was tested on a total of 3262 clinical images taken from 100 low‐dose X‐ray sequences acquired from 20 patients. The performance was assessed by pairwise voting from five cardiologists as well as quantitative indicators. Furthermore, we evaluated our technique's effect on catheter detection using 416 images containing coronary sinus catheters in order to examine its influence as a pre‐processing tool. RESULTS: The average signal‐to‐noise ratio of X‐ray images denoised with EEDN was 24.5, which was 2.2 times higher than that of the original images. The accuracy of catheter detection from EEDN denoised sequences showed no significant difference compared with their original counterparts. Moreover, EEDN received the highest average votes in our clinician assessment when compared to our existing technique and the original images. CONCLUSION: The proposed deep learning‐based framework shows promising capability for denoising interventional X‐ray fluoroscopy images. The results from the catheter detection show that the network does not affect the results of such an algorithm when used as a pre‐processing step. The extensive qualitative and quantitative evaluations suggest that the network may be of benefit to reduce radiation dose when applied in real time in the catheter laboratory

Poly-ε-Caprolactone/Fibrin-Alginate Scaffold: A New Pro-Angiogenic Composite Biomaterial for the Treatment of Bone Defects

We hypothesized that a composite of 3D porous melt-electrowritten poly-ɛ-caprolactone (PCL) coated throughout with a porous and slowly biodegradable fibrin/alginate (FA) matrix would accelerate bone repair due to its angiogenic potential. Scanning electron microscopy showed that the open pore structure of the FA matrix was maintained in the PCL/FA composites. Fourier transform infrared spectroscopy and differential scanning calorimetry showed complete coverage of the PCL fibres by FA, and the PCL/FA crystallinity was decreased compared with PCL. In vitro cell work with osteoprogenitor cells showed that they preferentially bound to the FA component and proliferated on all scaffolds over 28 days. A chorioallantoic membrane assay showed more blood vessel infiltration into FA and PCL/FA compared with PCL, and a significantly higher number of bifurcation points for PCL/FA compared with both FA and PCL. Implantation into a rat cranial defect model followed by microcomputed tomography, histology, and immunohistochemistry after 4- and 12-weeks post operation showed fast early bone formation at week 4, with significantly higher bone formation for FA and PCL/FA compared with PCL. However, this phenomenon was not extrapolated to week 12. Therefore, for long-term bone regeneration, tuning of FA degradation to ensure syncing with new bone formation is likely necessary

Evolution in intergenerational exchanges between elderly people and their grandchildren in Taiwan; data from a multiple round cross-sectional study from 1993 to 2007

<p>Abstract</p> <p>Background</p> <p>This study aimed to evaluate social evolution in Taiwan in recent decades using the changing pattern of care provided by grandparents for their grandchildren as an indicator.</p> <p>Methods</p> <p>Data from the second, fourth and sixth wave surveys of the <it>Study of Health and Living Status of the Middle-Aged and Elderly in Taiwan </it>were used for the analysis. This survey collected individual characteristics, including age, gender, education, ethnicity, dwelling place, living with partners, co-resident with children, employment status, self-reported health status and their provision of care for their grandchildren. Information about the attitudes toward National Health Insurance (NHI) was further collected in a questionnaire of 1999 following the implementation of NHI in 1995. By elders, we mean persons 60 or more years old. By grandchildren, we mean persons under 16 years of age. First, changes in individual characteristics were compared during these study periods (chi-square test). Then the logistic regression was performed to determine how significantly elders' grandchild-care behavior was associated with their individual characteristics.</p> <p>Results</p> <p>The percentage of elders providing grandchild care increased from 7.7% in 1993 to 13.6% in 1999, and then to 19.4% in 2007. By analysis, significant association was found between behavior in taking care of grandchildren and individuals of lower age, grandmothers, those living with partners or co-residing with children, those unemployed and those with better self-reported health status. And the effect of year was confirmed in the multivariable analysis.</p> <p>Conclusions</p> <p>This study pointed out the changing pattern of elders' behavior in taking care of their grandchildren as the main indicator and their related individual characteristics. We argue the need for improving social security policies in an ageing society. We suggest that the interaction between population policies and those of social welfare, including policies for health care and childcare, should be carefully evaluated.</p

CREACIÓN DE TRES NUEVAS VARIEDADES DE TRIGO EN EL PARAGUAY.

En este trabajo se presentan las características principales de las tres variedades comerciales de trigo que fueron liberadas por el Programa de Investigación de Trigo en el año 2000. Estas variedades sobresalen por su alta calidad comercial e industrial

Pre-screening the intrinsic angiogenic capacity of biomaterials in an optimised ex ovo chorioallantoic membrane model

Biomaterial development for clinical applications is currently on the rise. This necessitates adequate in vitro testing, where the structure and composition of biomaterials must be specifically tailored to withstand in situ repair and regeneration responses for a successful clinical outcome. The chorioallantoic membrane of chicken embryos has been previously used to study angiogenesis, a prerequisite for most tissue repair and regeneration. In this study, we report an optimised ex ovo method using a glass-cling film set-up that yields increased embryo survival rates and has an improved protocol for harvesting biomaterials. Furthermore, we used this method to examine the intrinsic angiogenic capacity of a variety of biomaterials categorised as natural, synthetic, natural/synthetic and natural/natural composites with varying porosities. We detected significant differences in biomaterials’ angiogenesis with natural polymers and polymers with a high overall porosity showing a greater vascularisation compared to synthetic polymers. Therefore, our proposed ex ovo chorioallantoic membrane method can be effectively used to pre-screen biomaterials intended for clinical application

Enhanced transport of plant-produced rabies single chain antibody-RVG peptide fusion protein across an in cellulo blood-brain barrier device

The biomedical applications of antibody engineering are developing rapidly and have been expanded to plant expression platforms. In this study, we have generated a novel antibody molecule in planta for targeted delivery across the blood–brain barrier (BBB). Rabies virus (RABV) is a neurotropic virus for which there is no effective treatment after entry into the central nervous system. This study investigated the use of a RABV glycoprotein peptide sequence to assist delivery of a rabies neutralizing single-chain antibody (ScFv) across an in cellulo model of human BBB. The 29 amino acid rabies virus peptide (RVG) recognizes the nicotinic acetylcholine receptor (nAchR) at neuromuscular junctions and the BBB. ScFv and ScFv-RVG fusion proteins were produced in Nicotiana benthamiana by transient expression. Both molecules were successfully expressed and purified, but the ScFv expression level was significantly higher than that of ScFv-RVG fusion. Both ScFv and ScFv-RVG fusion molecules had potent neutralization activity against RABVin cellulo. The ScFv-RVG fusion demonstrated increased binding to nAchR and entry into neuronal cells, compared to ScFv alone. Additionally, a human brain endothelial cell line BBB model was used to demonstrate that plant-produced ScFv-RVGP fusion could translocate across the cells. This study indicates that the plant-produced ScFv-RVGP fusion protein was able to cross the in celluloBBB and neutralize RABV

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Zinc status and its association with the health of adolescents: a review of studies in India

Background: Zinc is important in adolescence because of its role in growth and sexual maturation. Adolescents from developing countries such as India may be at high risk of zinc deficiency because of unwholesome food habits and poor bioavailability of zinc from plant-based diets. Objectives: (1) to study zinc status and its association with profile of other micronutrients, (2) to construct a simple tool in the form of Adolescent Micronutrient Quality Index (AMQI) to assess quality of diets of the girls and (3) to examine the effect of zinc supplement on health of adolescent girls. Methods: Girls (10&#x2013;16 years) from two secondary schools of Pune, Maharashtra state, in Western India were enrolled in a cross-sectional study (n = 630). Data were collected on dietary intake, cognitive performance, taste acuity, haemoglobin, erythrocyte zinc and plasma levels of zinc, vitamin C, &#x03B2;-carotene and retinol. AMQI was developed using age&#x2013;sex-specific Indian dietary guidelines and healthy foods and habits described in the recent US dietary guidelines. Zinc-rich recipes were developed considering habitual diets of the girls and vegetarian sources of zinc. An intervention trial (n = 180) was conducted to assess the effect of zinc-rich dietary supplements and ayurvedic zinc (Jasad) supplementation. Results: Prevalence of micronutrient deficiencies was high in these girls. Poor cognitive performance was seen in half of the girls, and salt taste perception was affected in 45%. AMQI was correlated with nutrient intakes and blood micronutrient levels (p &#60; 0.01), indicating the potential of AMQI to measure micronutrient quality of diets of adolescent girls. Results of the intervention trial indicated that supplementation of zinc-rich recipes vis-a-vis ayurvedic Jasad zinc has the potential to improve plasma zinc status, cognitive performance and taste acuity in adolescent girls. Conclusion: Review of the studies on Indian adolescent girls demonstrates the necessity of adopting zinc and micronutrient-rich diets for positive health building in adolescents