Detection of macular atrophy in age-related macular degeneration aided by artificial intelligence

INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment worldwide. The endpoint of AMD, both in its dry or wet form, is macular atrophy (MA) which is characterized by the permanent loss of the RPE and overlying photoreceptors either in dry AMD or in wet AMD. A recognized unmet need in AMD is the early detection of MA development. AREAS COVERED: Artificial Intelligence (AI) has demonstrated great impact in detection of retinal diseases, especially with its robust ability to analyze big data afforded by ophthalmic imaging modalities, such as color fundus photography (CFP), fundus autofluorescence (FAF), near-infrared reflectance (NIR), and optical coherence tomography (OCT). Among these, OCT has been shown to have great promise in identifying early MA using the new criteria in 2018. EXPERT OPINION: There are few studies in which AI-OCT methods have been used to identify MA; however, results are very promising when compared to other imaging modalities. In this paper, we review the development and advances of ophthalmic imaging modalities and their combination with AI technology to detect MA in AMD. In addition, we emphasize the application of AI-OCT as an objective, cost-effective tool for the early detection and monitoring of the progression of MA in AMD

Thunderstorms, lightning, sprites and magnetospheric whistler-mode radio waves

Thunderstorms and the lightning that they produce are inherently interesting phenomena that have intrigued scientists and mankind in general for many years. The study of thunderstorms has rapidly advanced during the past century and many efforts have been made towards understanding lightning, thunderstorms and their consequences. Recent observations of optical phenomena above an active lightning discharge along with the availability of modern technology both for data collection and data analysis have renewed interest in the field of thunderstorms and their consequences in the biosphere. In this paper, we review the electrification processes of a thunderstorm, lightning processes and their association with global electric circuit and climate. The upward lightning discharge can cause sprites, elves, jets, etc. which are together called transient luminous events. Their morphological features and effects in the mesosphere are reviewed. The wide spectrum of electromagnetic waves generated during lightning discharges couple the lower atmosphere with the ionosphere/ magnetosphere. Hence various features of these waves from ULF to VHF are reviewed with reference to recent results and their consequences are also briefly discussed. © Springer Science+Business Media B.V. 2009

Mechanism of faster NO scavenging by older stored red blood cells

The blood storage lesion involves morphological and biochemical changes of red blood cells (RBCs) that occur during storage. These include conversion of the biconcave disc morphology to a spherical one, decreased mean corpuscular hemoglobin concentration, varied mean corpuscular volume, reduced integrity of the erythrocyte membrane with formation of microparticles, and increased cell-free hemoglobin. We studied the extent that older stored red blood cells scavenge nitric oxide (NO) faster than fresher stored red blood cells. Using electron paramagnetic resonance spectroscopy and stopped-flow absorption spectroscopy to measure the rate of NO uptake and reaction with hemoglobin in red cells, we found that older stored red blood cells scavenge NO about 1.8 times faster than fresher ones. Based on these experimental data, we simulated NO scavenging by fresher or older stored red blood cells with a biconcave or spherical geometry, respectively, in order to explore the mechanism of NO scavenging related to changes that occur during blood storage. We found that red blood cells with a spherical geometry scavenges NO about 2 times slower than ones with a biconcave geometry, and a smaller RBC hemoglobin concentration or volume increases NO scavenging by red blood cells. Our simulations demonstrate that even the most extreme possible changes in mean corpuscular hemoglobin concentration and mean corpuscular volume that favor increased NO scavenging are insufficient to account for what is observed experimentally. Therefore, RBC membrane permeability must increase during storage and we find that the permeability is likely to increase between 5 and 70 fold. Simulations using a two-dimensional blood vessel show that even a 5-fold increase in membrane permeability to NO can reduce NO bioavailability at the smooth muscle. Background: Transfusion of older stored blood may be harmful. Results: Older stored red blood cells scavenge nitric oxide more than fresher cells. Conclusion: As stored red blood cells age, structural and biochemical changes occur that lead to faster scavenging. Significance: Increased nitric oxide scavenging by red blood cells as a function of storage age contributes to deleterious effects upon transfusion. © 2014 The Authors

Development of NMR and thermal shift assays for the evaluation of Mycobacterium tuberculosis isocitrate lyase inhibitors.

The enzymes isocitrate lyase (ICL) isoforms 1 and 2 are essential for Mycobacterium tuberculosis survival within macrophages during latent tuberculosis (TB). As such, ICLs are attractive therapeutic targets for the treatment of tuberculosis. However, there are few biophysical assays that are available for accurate kinetic and inhibition studies of ICL in vitro. Herein we report the development of a combined NMR spectroscopy and thermal shift assay to study ICL inhibitors for both screening and inhibition constant (IC50) measurement. Operating this new assay in tandem with virtual high-throughput screening has led to the discovery of several new ICL1 inhibitors

Development and validation of a novel high performance liquid chromatography-coupled with Corona charged aerosol detector method for quantification of glucosamine in dietary supplements

Introduction: Glucosamine dietary supplements are commonly used for the management of osteoarthritis (OA). However, clinical trials have reported varying outcomes with regard to joint function and disease progression. One of the possible reasons for variability in observed effects of glucosamine could be that, unlike prescription drugs, the quality of manufactured dietary supplements is not closely monitored in many countries. Therefore, there is the possibility that the actual amount of glucosamine present in a dietary supplement is different from that claimed on the label. The quality control of glucosamine supplements is further complicated by the unavailability of a simple and effective analytical method for the analysis of glucosamine. Therefore, the aim of this study was to develop a simple analytical method that could be easily adapted by the pharmaceutical industry for routine analysis of glucosamine.Aims: To develop a novel high-performance liquid chromatography (HPLC) method for the quantification of glucosamine, and determine the amount of glucosamine present in a sample of dietary supplements commercially available in Australia and India.Methods: Chromatographic separation of glucosamine was achieved using a zwitter-ionic hydrophilic interaction liquid chromatography column with a mobile phase consisting of 60% acetonitrile and 40% of 85 mM ammonium acetate, at a flow rate of 0.3 mL/min and column temperature 40°C. The developed method was validated for intra- and inter-day linearity, accuracy, precision, and reproducibility. The newly-developed method was subsequently used to analyse 12 glucosamine supplements.Results: The developed method was selective for glucosamine, which had a retention time of 5.9 min. The standard curve was linear with a correlation coefficient (r2) exceeding 0.99, over the range of 10–200 μg/mL for glucosamine. The relative standard deviations for intra- and inter-day accuracy, precision and reproducibility were all less than 4%. The amount of glucosamine determined in six Australian and six Indian glucosamine supplements ranged between 98.7–101.7% and 85.9–101.8% of the labelled values, respectively.Discussion: Unlike previous HPLC methods, this newly-developed HPLC technique does not require pre-derivatisation and can separate glucosamine from both hydrochloride and sulphate salts, and from other amino sugars, such as chondroitin sulphate present in dietary supplements. This simple and effective technique can be employed by analytical laboratories for the quality control of glucosamine dietary supplements.Conclusion: The current study has developed a new analytical technique using HPLC-Corona CAD, which can analyse underivatised glucosamine hydrochloride and sulphate within 6 minutes. Using the novel assay, we confirmed that unlike the tested Australian dietary supplements, only half of the tested Indian products had a glucosamine content within ±10% of what was claimed on the label

Role of oxidative stress in the pathology and management of human tuberculosis

Copyright © 2018 Madhur D. Shastri et al. Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR-TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first-/second-line antitubercle antibiotics are administered in an inactive form and subsequently transformed into their active form by components of the OS responses of both host (nitric oxide, S-oxidation) and pathogen (catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in the host, including the increased bacterial NADH/NAD+ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin, superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug-susceptible and drug-resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host's OS response

Development and initial psychometric properties of the Warwick–Edinburgh Mental Wellbeing Scale-Intellectual Disability version

Background: The Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS; Tennant et al., 2007) is yet to be validated in the intellectual disability (ID) population. The aim of this study was to report the development process and assess the psychometric properties of a newly adapted version of the WEMWBS and the Short WEMWBS for individuals with mild to moderate IDs (WEMWBS-ID/SWEMWBS-ID). / Method: The WEMWBS item wordings and response options were revised by clinicians and researchers expert in the field of ID, and a visual aid was added to the scale. The adapted version was reviewed by 10 individuals with IDs. The measure was administered by researchers online using screenshare, to individuals aged 16+ years with mild to moderate IDs. Data from three UK samples were collated to evaluate the WEMWBS-ID (n = 96). A subsample (n = 22) completed the measure again 1 to 2 weeks later to assess test–retest reliability, and 95 participants additionally completed an adapted version of the adapted Rosenberg Self-Esteem Scale to examine convergent validity. Additional data from a Canadian sample (n = 27) were used to evaluate the SWEMWBS-ID (n = 123). / Results: The WEMWBS-ID demonstrated good internal consistency (ω = 0.77–0.87), excellent test–retest reliability [intraclass correlation coefficient (ICC) =.88] and good convergent validity with the self-esteem scale (r =.48–.60) across samples. A confirmatory factor analysis for a single factor model demonstrated an adequate fit. The SWEMWBS-ID showed poor to good internal consistency (ω = 0.36–0.74), moderate test–retest reliability (ICC =.67) and good convergent validity (r =.48–.60) across samples, and a confirmatory factor analysis indicated good model fit for a single factor structure. / Conclusions: The WEMWBS-ID and short version demonstrated promising psychometric properties, when administered virtually by a researcher. Further exploration of the scales with larger, representative samples is warranted

Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators.

Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted