Project description:Sex and gender-related factors are strongly associated with patients' illness trajectories, underscoring their essential role in epidemiological research and healthcare. Ignoring sex and gender in research and health inevitably results in inequities between women and men in terms of detection of disease, preventative measures, and effectiveness of treatment. Historical influences, including ideas of female inferiority and conservative notions of women's health only comprising reproductive health, reinforced the perceived irrelevance of sex and gender to health. Currently, these ideas are largely abandoned and epidemiology is becoming increasingly sensitive to sex. Gender-sensitivity, however, is lagging behind. This is potentially due to lacking knowledge and awareness about the relevance of both sex and gender to health and challenges in operationalizing gender in epidemiological research. Here, we thoroughly discuss the relevance of sex and gender to health, and pay special attention to the time, place, and culture-dependent embodiment of gender. We also discuss the operationalization of gender via composite gender scores in epidemiological studies. We argue to move beyond solely using these. Rather we should consider sex and gender in the initial stages of designing a study, to facilitate relevant, reproducible, and person-centric research.
Project description:The present work aims to combine the unique properties of cellulose nanofibers (CNF) with polyvinyl alcohol (PVA) to obtain high-performance nanocomposites. CNF were obtained by means of TEMPO-mediated ((2,2,6,6-Tetramethylpiperidin-1-yl)oxyl) oxidation, incorporated into the PVA matrix by means of compounding in a single-screw co-rotating internal mixer and then processed by means of injection molding. It was found that CNF were able to improve the tensile strength of PVA in 85% when 4.50 wt % of CNF were added. In addition, the incorporation of a 2.25 wt % of CNF enhanced the tensile strength to the same level that when 40 wt % of microsized fibers (stone groundwood pulp, SGW) were incorporated, which indicated that CNF possessed significantly higher intrinsic mechanical properties than microsized fibers. SGW was selected as reference for microsized fibers due to their extended use in wood plastic composites. Finally, a micromechanical analysis was performed, obtaining coupling factors near to 0.2, indicating good interphase between CNF and PVA. Overall, it was found that the use of CNF is clearly advantageous to the use of common cellulosic fibers if superior mechanical properties are desired, but there are still some limitations that are related to processing that restrict the reinforcement content at low contents.
Project description:A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue. To overcome this problem, researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems. In this review, we summarize the epidemiology, basic pathophysiology, current clinical treatment, the establishment of models, and the evaluation indicators that are commonly used for traumatic brain injury. We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles. Nanocarriers can overcome a variety of key biological barriers, improve drug bioavailability, increase intracellular penetration and retention time, achieve drug enrichment, control drug release, and achieve brain-targeting drug delivery. However, the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.
Project description:Mouse models provide a valuable tool for exploring pathogenic mechanisms underlying inherited human disease. Here, we describe seven mouse models identified through the Translational Vision Research Models (TVRM) program, each carrying a new allele of a gene previously linked to retinal developmental and/or degenerative disease. The mutations include four alleles of three genes linked to human nonsyndromic ocular diseases (Aipl1tvrm119, Aipl1tvrm127, Rpgrip1tvrm111, RhoTvrm334) and three alleles of genes associated with human syndromic diseases that exhibit ocular phentoypes (Alms1tvrm102, Clcn2nmf289, Fkrptvrm53). Phenotypic characterization of each model is provided in the context of existing literature, in some cases refining our current understanding of specific disease attributes. These murine models, on fixed genetic backgrounds, are available for distribution upon request and may be useful for understanding the function of the gene in the retina, the pathological mechanisms induced by its disruption, and for testing experimental approaches to treat the corresponding human ocular diseases.
Project description:Sequence capture enrichment (SCE) strategies and massively parallel next generation sequencing (NGS) are expected to increase the rate of gene discovery for genetically heterogeneous hereditary diseases, but at present, there are very few examples of successful application of these technologic advances in translational research and clinical testing. Our study assessed whether array based target enrichment followed by re-sequencing on the Roche Genome Sequencer FLX (GS FLX) system could be used for novel mutation identification in more than 1000 exons representing 100 candidate genes for ocular birth defects, and as a control, whether these methods could detect two known mutations in the PAX2 gene. We assayed two samples with heterozygous sequence changes in PAX2 that were previously identified by conventional Sanger sequencing. These changes were a c.527G>C (S176T) substitution and a single basepair deletion c.77delG. The nucleotide substitution c.527G>C was easily identified by NGS. A deletion of one base in a long polyG stretch (c.77delG) was not registered initially by the GS Reference Mapper, but was detected in repeated analysis using two different software packages. Different approaches were evaluated for distinguishing false positives (sequencing errors) and benign polymorphisms from potentially pathogenic sequence changes that require further follow-up. Although improvements will be necessary in accuracy, speed, ease of data analysis and cost, our study confirms that NGS can be used in research and diagnostic settings to screen for mutations in hundreds of loci in genetically heterogeneous human diseases.
Project description:: Clinician-scientists bridge the gap between basic research and patient care. At the 2012 Annual Meeting, a symposium highlighting the application of cutting-edge optometric research within the anterior segment was held to present and discuss some of the recent basic scientific advances that will both shape and guide the development of future clinical care practices. This article summarizes this work, bringing together four experts, all clinician-scientists in the field of cornea and ocular surface. Collectively, this work provides new insights to clinicians and researchers alike, as well as brings forth a greater appreciation of the impact of ongoing optometric bench research in advancing clinical care.
Project description:PURPOSE: To develop a microarray for the rabbit that can be used for ocular gene expression research. METHODS: Messenger RNA was isolated from anterior segment tissues (cornea, conjunctiva, and iris) and posterior segment tissues (lens, retina, and sclera) of rabbit eyes and used to create two independent cDNA libraries through the NEIBank project. Clones from each of these libraries were sequenced from both the 5' and 3' ends. These sequences and those from the National Center for Biotechnology Information (NCBI) taxonomy database for rabbit were combined and electronically assembled into a set of unique nonoverlapping continuous sequences (contigs). For each contig, a homology search was performed using BLASTX and BLASTN against both the NCBI NR and NT databases to provide gene annotation. Unique contigs were sent to Agilent Technologies, where 60 base oligonucleotide probes were designed and synthesized, in situ, on two different arrays in an 8 array x 1900 element format. Glaucoma filtration surgery was performed on one eye of six rabbits. After 14 days, tissue was harvested from the conjunctiva and Tenon's capsule of both the surgically treated and untreated control eyes. Total RNA from each sample was labeled with cyanine dyes and hybridized to our custom microarrays. RESULTS: Of the 3,154 total probes present on the two arrays, 2,522 had a signal value above the background. The expression of 315 genes was significantly altered by glaucoma filtration surgery. Genes whose expression was altered included proteins associated with inflammatory response, defense response, and proteins involved in synthesis of the extracellular matrix. CONCLUSIONS: The results of this rabbit microarray study are consistent with those from other wound healing studies, indicating that this array can provide valid information on broad patterns of gene expression. This is the first microarray available for rabbit studies and is a valuable tool that can be used to study molecular events in the eye.
Project description:How to enhance the bioavailability and prolong the residence time of drugs in the eye present the major barriers to traditional eye delivery. Nanotechnology has been widely used in ocular drug delivery systems because of its advantages of minimizing adverse reactions, decreasing the frequency of administration, prolonging the release time, and improving the bioavailability of the drug in the eye. As natural product-based nanostructured systems, bioinspired nanostructured systems have presented as less toxic, easy to prepare, and cost-effective and have potential application value in the field of nanotechnology. A systematic classification of bioinspired nanostructured systems based on their inspiration source and formulation and their brief applications in disease are presented here. A review of recent research progress of the bioinspired nanostructured systems for the treatment of the anterior and posterior segment of ocular disorders is then presented in detail. Finally, current challenges and future directions with regard to manufacturing bioinspired nanomaterials are provided.
Project description:Limbal stem cells (LSCs) are adult stem cells located at the limbus ensuring the continuous renewal of the corneal epithelium, critical to maintain an optimal visual function. Damages to the LSCs or their niche microenvironment lead to limbal stem cell deficiency (LSCD), a potentially blinding disease. Transplantation of LSCs as a treatment for severe to total LSCD has gained popularity since 1980s, owing to the clinical success of the first direct limbal autograft transplantation. Recent advances in the understanding of the LSCs' molecular identity and regulation have enabled preclinical and clinical advancements of promising LSCs therapies. However, lack of standardization of the diagnostic methods, staging of the disease severity, manufacturing process, and clinical outcome measures have hindered the advancement of the therapy. To move these therapies to the clinic, optimization and standardization of the diagnostic strategy, cell product manufacturing, and assessment of clinical efficacy with potency assays are key points to the development of customized therapies. Recent findings suggest that residual LSCs exist in eyes presenting with clinical signs of total LSCD, which opens new therapeutic strategies for eyes with partial LSCD. Prospective, randomized, multicentric controlled clinical trials are necessary to determine the efficacy of different LSCs therapies for different stages of LSCD using a set of standardized outcome measures.
Project description:Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality despite current treatment strategies which focus on smoking cessation, pulmonary rehabilitation, and symptomatic relief. A focus of COPD care is to encourage self-management, particularly during COVID-19, where much face-to-face care has been reduced or ceased. Digital health solutions may offer affordable and scalable solutions to support COPD patient education and self-management, such solutions could improve clinical outcomes and expand service reach for limited additional cost. However, optimal ways to deliver digital medicine are still in development, and there are a number of important considerations for clinicians, commissioners, and patients to ensure successful implementation of digitally augmented care. In this narrative review, we discuss advantages, pitfalls, and future prospects of digital healthcare, which offer a variety of tools including self-management plans, education videos, inhaler training videos, feedback to patients and healthcare professionals (HCPs), exacerbation monitoring, and pulmonary rehabilitation. We discuss the key issues with sustaining patient and HCP engagement and limiting attrition of use, interoperability with devices, integration into healthcare systems, and ensuring inclusivity and accessibility. We explore the essential areas of research beyond determining safety and efficacy to understand the acceptability of digital healthcare solutions to patients, clinicians, and healthcare systems, and hence ways to improve this and sustain engagement. Finally, we explore the regulatory challenges to ensure quality and engagement and effective integration into current healthcare systems and care pathways, while maintaining patients' autonomy and privacy. Understanding and addressing these issues and successful incorporation of an acceptable, simple, scalable, affordable, and future-proof digital solution into healthcare systems could help remodel global chronic disease management and fractured healthcare systems to provide best patient care and optimisation of healthcare resources to meet the global burden and unmet clinical need of COPD.