Spit bubbles, speech bubbles, and COVID-19: creating comics in the age of post-infection India.

Positioning this essay at intersection of comics studies, visual literacy studies, and information literacy studies, we investigate an interdisciplinary liaison between crisis in the age of COVID-19 and its awareness campaign through Indian comics. With a focus on awareness programme, Indian artists designed comics to demonstrate their vital position in social engagement through this visual medium. Following impending threats and growing concerns, people of all ages glued themselves to social media, newspapers, and television to keep them updated on the impact of COVID-19. Indian comics e.g. Nagraj Strikes: The Attack of Coronaman (2020), Priya's Mask (2020), Kids, Vaayu, and Corona: Who Wins the Fight? (2020), and 'Be aware of Droplets & Bubbles!!' (2020) aimed to help children comprehend the precautionary steps to be taken to save themselves from getting infected with Coronavirus. While the first three comics showcase spit-bubbles primarily as the source of COVID-19, infusing the content with a tinge of superhero fantasy, 'Be aware of Droplets & Bubbles!!' (2020) unveils the microbiological evolution and mutation of the pathogen in comics format. The objective of the article is to show how Indian comics on COVID-19 can be an advantageous communicative medium to nurture knowledge and edutainment in post-infection India.

Current state of the global operational aerosol multi-model ensemble: An update from the International Cooperative for Aerosol Prediction (ICAP).

Since the first International Cooperative for Aerosol Prediction (ICAP) multi-model ensemble (MME) study, the number of ICAP global operational aerosol models has increased from five to nine. An update of the current ICAP status is provided, along with an evaluation of the performance of ICAP-MME over 2012-2017, with a focus on June 2016-May 2017. Evaluated with ground-based Aerosol Robotic Network (AERONET) aerosol optical depth (AOD) and data assimilation quality MODerate-resolution Imaging Spectroradiometer (MODIS) retrieval products, the ICAP-MME AOD consensus remains the overall top-scoring and most consistent performer among all models in terms of root-mean-square error (RMSE), bias and correlation for total, fine- and coarse-mode AODs as well as dust AOD; this is similar to the first ICAP-MME study. Further, over the years, the performance of ICAP-MME is relatively stable and reliable compared to more variability in the individual models. The extent to which the AOD forecast error of ICAP-MME can be predicted is also examined. Leading predictors are found to be the consensus mean and spread. Regression models of absolute forecast errors were built for AOD forecasts of different lengths for potential applications. ICAP-MME performance in terms of modal AOD RMSEs of the 21 regionally representative sites over 2012-2017 suggests a general tendency for model improvements in fine-mode AOD, especially over Asia. No significant improvement in coarse-mode AOD is found overall for this time period.

A cross-sectional study on the prevalence of anxiety among school students in Teliamura municipality area of Tripura.

BACKGROUND: Anxiety in adolescence has been a serious problem nowadays. It is seen that anxiety among students cause many harms to their mental and physical health affecting their career. OBJECTIVE: The objective of this study is to know about the burden of anxiety among school students and to find out the association of different grades of anxiety with sociodemographic characteristics and any other factors. MATERIALS AND METHODS: In a cross-sectional study, 400 school students of Class IX-XII, from four schools of Teliamura Municipality area of Tripura were included during May 2016-June 2016. Required sample from each school was selected by proportion probability sampling. Then, students were selected using systematic random sampling technique until the sample size from each school was reached. Beck anxiety inventory was used to assess the different grades of anxiety among students. RESULTS: Most of the students were suffering from mild anxiety (49.4%) followed by moderate anxiety (43.3%) and severe anxiety (7.3%). The mean anxiety score of the school students was 16.90 ± 9.02. Female students (10.9%) had more severe anxiety compared to male students (3.8%) and this difference of different grades of anxiety with gender was statistically significant. The association of different grades of anxiety with a history of stressful events in the past 6 months was found to be statistically significant. CONCLUSION: Anxiety was present in each age group and females were suffering more with severe anxiety. Future research on academic anxiety should be done to combat against this problem of anxiety among school students.

LncEGFL7OS regulates human angiogenesis by interacting with MAX at the EGFL7/miR-126 locus.

In an effort to identify human endothelial cell (EC)-enriched lncRNAs,~500 lncRNAs were shown to be highly restricted in primary human ECs. Among them, lncEGFL7OS, located in the opposite strand of the EGFL7/miR-126 gene, is regulated by ETS factors through a bidirectional promoter in ECs. It is enriched in highly vascularized human tissues, and upregulated in the hearts of dilated cardiomyopathy patients. LncEGFL7OS silencing impairs angiogenesis as shown by EC/fibroblast co-culture, in vitro/in vivo and ex vivo human choroid sprouting angiogenesis assays, while lncEGFL7OS overexpression has the opposite function. Mechanistically, lncEGFL7OS is required for MAPK and AKT pathway activation by regulating EGFL7/miR-126 expression. MAX protein was identified as a lncEGFL7OS-interacting protein that functions to regulate histone acetylation in the EGFL7/miR-126 promoter/enhancer. CRISPR-mediated targeting of EGLF7/miR-126/lncEGFL7OS locus inhibits angiogenesis, inciting therapeutic potential of targeting this locus. Our study establishes lncEGFL7OS as a human/primate-specific EC-restricted lncRNA critical for human angiogenesis.

Expression, regulation and function of miR-126 in the mouse choroid vasculature.

MicroRNA miR-126 has been shown to be required for proper angiogenesis in several models. However, its expression, regulation and function in the mouse choroid remain unclear. Our previous data has shown that miR-126 expression is enriched in the endothelial cells (ECs) of the mouse choroid. Here we report that a 5.5 kb Egfl7/miR-126 promoter drives the expression of miR-126 in the choroid ECs during choroidal vascular development. The expression of miR-126 in the ECs is regulated by flow stress likely through Krüppel-like transcriptional factors. miR-126-/- mice show mildly delayed choroidal vascular development, but adult knockout mice develop periphery choroidal vascular lesions. This study suggests that miR-126 is largely dispensable for mouse choroidal development but required for maintaining choroidal vasculature integrity.

LRP-1 Pathway Targeted Inhibition of Vascular Abnormalities in the Retina of Diabetic Mice.

PURPOSE: The cell surface LDL (low-density lipoprotein) receptor-related protein-1 (LRP-1) is important for lipid transport and several cell signaling processes. Human apolipoprotein E (apoE) is a ligand of LRP-1. We previously reported that a short peptide (apoEdp) mimicking the LRP-1 binding region of apoE prevents hyperglycemia-induced retinal endothelial cell dysfunction in vitro. The in-vivo outcome of apoE-based peptidomimetic inhibition of LRP-1 in the treatment of diabetic retinopathy is unknown. METHODS: Six months after streptozotocin induction of diabetes, male C57Bl/6 mice were intravitreally inoculated with apoEdp in a controlled release formulation. On the 15th day post-apoEdp treatment, mouse retinas were harvested to examine (1) blood-retinal-barrier (BRB) permeability by Evans blue dye, inflammatory leukostasis by concanavalin staining of leukocytes and LRP-1 pathway-related protein expression by Western blot analysis and gelatin zymography. RESULTS: Intravitreal apoEdp treatment of diabetic mice significantly reduced Evans blue extravasation and the number of adherent leukocytes in the diabetic mouse retinas. ApoEdp treatment inhibited the expression of extracellular matrix (ECM) degrading proteases heparanase and MMP-2, and restores the BRB tight junction proteins occludin and ZO-1. ApoEdp treatment also inhibited Wnt/ß-catenin-related expression of pro-inflammatory molecules ICAM-1, HIF-1α, and VEGF through negative regulation by LRP-1. CONCLUSION: Intravitreal apoEdp treatment of diabetic mice resulted a significant decrease in retinal vascular abnormalities through downregulation of LRP-1-related ECM protein degradation and Wnt/ß-catenin-related pro-angiogenic molecules.

Sedative and Anxiolytic-Like Actions of Ethanol Extract of Leaves of Glinus oppositifolius (Linn.) Aug. DC.

Glinus oppositifolius is a small herb, widely used in the traditional medicine of Bangladesh in treatment of a variety of diseases and disorders such as insomnia, pain, inflammation, jaundice, and fever. The present study evaluated the sedative and anxiolytic potentials of the ethanol extract of leaves of G. oppositifolius (EEGO) in different behavioral models in mice. The sedative activity of EEGO was investigated using hole cross, open field, rotarod, and thiopental sodium- (TS-) induced sleeping time determination tests, where the elevated plus maze (EPM) and light-dark box (LDB) exploration tests were employed to justify the anxiolytic potentials in mice at the doses of 50, 100, and 200 mg/kg. The results demonstrated that EEGO significantly inhibited the exploratory behavior of the animals both in hole cross and in open field tests in a dose-dependent manner. It also decreased motor coordination and modified TS-mediated hypnosis in mice. In addition, EEGO showed anxiolytic potential by increasing the number and time of entries in the open arm of EPM, which is further strengthened by increase in total time spent in the light part of LDB. Therefore, this study suggests the sedative and anxiolytic properties of the leaves of G. oppositifolius and supports the traditional use of this plant in treatment of different psychiatric disorders including insomnia.

A novel rare sugar inhibitor of murine herpes simplex keratitis.

PURPOSE: To determine the therapeutic efficacy of a novel rare sugar, l-psicose, for the treatment of HSV-1 induced herpetic stromal keratitis (HSK) in a mouse eye model. METHODS: One rare sugar l-psicose was assayed for HSV-1 inhibition of in vitro virus adsorption. The IC50 and IC90 values of l-psicose were determined using plaque reduction assay (PRA) in CV-1 cell. Female Balb/c mice were corneally infected with HSV-1, strain KOS-GFP; A topical eye drop treatment of l-psicose was started 24 h after infection and continued four times daily for ten consecutive days. The severity of HSK was monitored by slit lamp examination in a masked fashion and Infectious HSV-1 shedding was determined by PRA. RESULTS: l-psicose was found to have anti-viral activity in vitro at an IC50 dose of 99.5 mM and an IC90 dose of 160 mM. Topical eye drop treatment with 200 mM l-psicose in PBS solution significantly reduced the severity of HSK compared to the mock treatment group. The in vivo mouse ocular model results of l-psicose therapy correlated with accelerated clearance of virus from eye swabs. CONCLUSION: The results suggest that topical treatment with rare sugar l-psicose has efficacy against HSK through inhibition of HSV-1.

Protective effects of bestatin in the retina of streptozotocin-induced diabetic mice.

CD13/APN (aminopeptidase N) was first identified as a selective angiogenic marker expressed in tumor vasculature and is considered a target for anti-cancer therapy. CD13 was also reported to express in non-diabetic, hypoxia-induced retinal neovascularization. Whether diabetes induces upregulation of CD13 expression in the retina is unknown. We hypothesize that at an early stage of non-proliferative diabetic retinopathy (NPDR) characterized by disruption of blood-retinal barrier (BRB) permeability is related to upregulated expression of CD13 because of its known role in extracellular matrix (ECM) degradation. The purpose of this study is to evaluate the role of CD13/APN and the therapeutic efficacy of a CD13/APN inhibitor in a mouse model of streptozotocin-induced NPDR. Hyperglycemic C57Bl/6 mice 26 weeks after streptozotocin (STZ) injection were intravitreally injected with a sustained release formulation of CD13/APN inhibitor bestatin. At 15th day of post-bestatin treatment, mouse retinas were evaluated for vascular permeability by Evans blue dye extravasation assay, fluorescent angiography of retinal vascular permeability and leukostasis. Retinal protein extracts were analyzed by Western blot to determine the effects of bestatin treatment on the expression of CD13/APN related inflammatory mediators of ECM degradation and angiogenesis. Intravitreal bestatin treatment significantly inhibited retinal vascular permeability and leukostasis. This treatment also significantly inhibited retinal expression of CD13, ECM degrading proteases (heparanase and MMP9 and angiogenic molecules (HIF-1α and VEGF). Intravitreal CD13 inhibition may relate to furthering our knowledge on the protective effect of bestatin against diabetic retinal vasculature abnormalities through inhibition of retinal permeability, leukostasis, inflammatory molecules of ECM degradation and angiogenesis.

Evaluation of antinociceptive activity of methanolic extract of leaves of Stephania japonica Linn.

ETHNAPHARMACOLOGICAL RELEVANCE: Stephania japonica is a common plant, widely distributed in all over Bangladesh. Traditionally, this plant is considered as one of the important ingredients in treatment of a variety of ailments including inflammation, pain, rheumatism, cancer, bone fracture, fever etc. However, the scientific reports regarding the antinociceptive effect of this plant are very limited. This study evaluated the antinociceptive effect of methanolic extract of S. japonica (MESJ) leaves. MATERIALS AND METHODS: The antinociceptive effect of MESJ was investigated using both heat- and chemical-induced nociceptive models such as hot plate, tail immersion, acetic acid-induced writhing, formalin and glutamate tests at the doses of 50, 100 and 200mg/kg. Morphine (5mg/kg) and diclofenac sodium (10mg/kg) were used as reference drugs in thermal and chemical models, respectively. Moreover, naloxone (2mg/kg) was used in the thermal models to justify the possible role of the opioid receptors. RESULTS: MESJ produced a significant and dose-dependent increase in the hot plate and tail immersion latencies which were reversed by the treatment with naloxone, suggests the possible involvement of opioid receptors in this activity. Moreover, MESJ inhibited acetic acid-induced writhing, formalin and glutamate-induced lickings in a dose-dependent manner. In parallel, the reference drugs also produced desired antinociceptive effects in this study. CONCLUSION: These results strongly support the antinociceptive activity of the leaves of Stephania japonica and rationalize the traditional use of the leaves in treatment of different painful conditions.

The implementation of NEMS GFS Aerosol Component (NGAC) Version 1.0 for global dust forecasting at NOAA/NCEP.

The NOAA National Centers for Environmental Prediction (NCEP) implemented NEMS GFS Aerosol Component (NGAC) for global dust forecasting in collaboration with NASA Goddard Space Flight Center (GSFC). NGAC Version 1.0 has been providing 5 day dust forecasts at 1°×1° resolution on a global scale, once per day at 00:00 Coordinated Universal Time (UTC), since September 2012. This is the first global system capable of interactive atmosphere aerosol forecasting at NCEP. The implementation of NGAC V1.0 reflects an effective and efficient transitioning of NASA research advances to NCEP operations, paving the way for NCEP to provide global aerosol products serving a wide range of stakeholders as well as to allow the effects of aerosols on weather forecasts and climate prediction to be considered.

Perspectives on CMIP5 model performance in the Nile River headwaters regions.

Ranking the performance of global climate models (GCMs) is a notoriously difficult exercise. Multi-model comparison studies nearly always show that each model has strengths and weaknesses relative to others, and for many purposes the multi-model ensemble mean delivers better estimates than any individual model. Nevertheless, in regions like East Africa, where there is little consensus between models on the magnitude or sign of 21st century precipitation change, the multi-model ensemble mean approach to climate projection provides little value for adaptation planning. Here, we consider several possible frameworks for model evaluation and ranking, and assess the differences in performance of a subset of models participating in the 5th Coupled Model Intercomparison Project (CMIP5) according to each framework. Our test case is precipitation in the Nile River headwaters regions. We find that there is little consistency in the relative performance of models across frameworks based on amount and seasonality of precipitation, interannual precipitation variability, precipitation teleconnections, and continental scale climate patterns. These analyses offer some guidance on which GCMs are most likely to provide meaningful results for specific applications, but they caution that any effort to select 'best performing' GCMs for the Nile River basin must carefully consider the purposes for which GCMs are being selected.

The antimicrobial agent C31G is effective for therapy for HSV-1 ocular keratitis in the rabbit eye model.

The amphoteric C31G solution contains equimolar alkyl dimethlyglycine and alkyl dimethyl amine oxide buffered with citric acid. C31G acts as a broad spectrum antiviral and an antibacterial. No previous in vivo studies have been done to test C31G in an animal model of HSV-1 ocular keratitis. We assessed the anti-herpetic activity of C31G in the rabbit eye model using three treatment groups: (1) 1% trifluorothymidine (TFT); (2) 0.25% C31G plus 0.5% hydroxypropyl methylcellulose (HPMC); and (3) vehicle, 0.5% HPMC. Scarified rabbit corneas were inoculated with the HSV-1 strain McKrae. On post inoculation (PI) day 3, rabbits were placed in three balanced groups based on slit-lamp examination (SLE) scores. Treatment began on PI day 3, five times a day for five consecutive days. In addition to the daily, masked SLE scoring, the eyes were assessed daily for stromal opacity, scleral inflammation, neovascularization, eyelid inflammation, inflammatory discharge, and epiphora. C31G and TFT were very effective in reducing the lesions and pathogenesis associated with HSV-1 ocular keratitis. The vehicle control scores were significantly higher and did not effectively treat HSV-1 keratitis. C31G has the potential to be used to treat herpetic keratitis as well as other herpetic topical lesions in humans.

HSV-1 latent rabbits shed viral DNA into their saliva.

BACKGROUND: Rabbits latent with HSV-1 strain McKrae spontaneously shed infectious virus and viral DNA into their tears and develop recurrent herpetic-specific corneal lesions. The rabbit eye model has been used for many years to assess acute ocular infections and pathogenesis, antiviral efficacy, as well as latency, reactivation, and recurrent eye diseases. This study used real-time PCR to quantify HSV-1 DNA in the saliva and tears of rabbits latent with HSV-1 McKrae. METHODS: New Zealand white rabbits used were latent with HSV-1 strain McKrae and had no ocular or oral pathology. Scarified corneas were topically inoculated with HSV-1. Eye swabs and saliva were taken from post inoculation (PI) days 28 through 49 (22 consecutive days). Saliva samples were taken four times each day from each rabbit and the DNA extracted was pooled for each rabbit for each day; one swab was taken daily from each eye and DNA extracted. Real-time PCR was done on the purified DNA samples for quantification of HSV-1 DNA copy numbers. Data are presented as copy numbers for each individual sample, plus all the copy numbers designated as positive, for comparison between left eye (OS), right eye (OD), and saliva. RESULTS: The saliva and tears were taken from 9 rabbits and from 18 eyes and all tested positive at least once. Saliva was positive for HSV-1 DNA at 43.4% (86/198) and tears were positive at 28.0% (111/396). The saliva positives had 48 episodes and the tears had 75 episodes. The mean copy numbers ± the SEM for HSV-1 DNA in saliva were 3773 ± 2019 and 2294 ± 869 for tears (no statistical difference). CONCLUSION: Rabbits latent with strain McKrae shed HSV-1 DNA into their saliva and tears. HSV-1 DNA shedding into the saliva was similar to humans. This is the first evidence that documents HSV-1 DNA in the saliva of latent rabbits.

Rabbit and mouse models of HSV-1 latency, reactivation, and recurrent eye diseases.

The exact mechanisms of HSV-1 establishment, maintenance, latency, reactivation, and also the courses of recurrent ocular infections remain a mystery. Comprehensive understanding of the HSV-1 disease process could lead to prevention of HSV-1 acute infection, reactivation, and more effective treatments of recurrent ocular disease. Animal models have been used for over sixty years to investigate our concepts and hypotheses of HSV-1 diseases. In this paper we present descriptions and examples of rabbit and mouse eye models of HSV-1 latency, reactivation, and recurrent diseases. We summarize studies in animal models of spontaneous and induced HSV-1 reactivation and recurrent disease. Numerous stimuli that induce reactivation in mice and rabbits are described, as well as factors that inhibit viral reactivation from latency. The key features, advantages, and disadvantages of the mouse and rabbit models in relation to the study of ocular HSV-1 are discussed. This paper is pertinent but not intended to be all inclusive. We will give examples of key papers that have reported novel discoveries related to the review topics.

Long-term use of doxycycline can improve chronic asthma and possibly remodeling: the result of a pilot observation.

UNLABELLED: Progressive loss of lung function and reversibility characterize chronic asthma. The conventional therapy is targeted to control the disease without targeting the loss of lung function or reversibility. In a prospective real-world observation of long-term use of add-on doxycycline as a matrix-metalloproteinase inhibitor, we documented significant improvement in lung function with possible reversal of remodeling. BACKGROUND: Chronic asthma shows progressive decline in lung function with reduction or even loss of reversibility secondary to remodeling. A set of endopeptidase enzymes known as matrix metalloproteinases are intimately related to the pathogenesis of asthma and remodeling. The inhibition of matrix metalloproteinases is recognized as a prospective way of treating asthma and its corresponding structural remodeling. METHODS: In a randomized, prospective, real-world study, we have observed the change in lung function (spirometry) with an add-on of long-term doxycycline to standard asthma therapy as per the Global Initiative for Asthma guidelines in a small asthmatic population. The change in terms of forced expiratory volume (FEV(1)), forced vital capacity (FVC), percent of FEV(1) (FEV(1)%), and forced expiratory flow (FEF(25-75)) were noted following variable duration of doxycycline therapy. RESULTS: There has been a global improvement in all the parameters in all the six patients suggesting improvement in obstruction, and reduction in air trapping following a treatment of add-on doxycycline for a mean duration of 162.83 ± 83.07 days. Of the changes seen, the post bronchodilator FEV(1), the FVC, and the FEF(25-75) showed significant improvements with the P-value set at 0.004, 0.054, and 0.031, respectively. There was also evidence of the reversal of remodeling from the improvement in the FEV(1)/FVC ratio. Moreover there was a greater than expected improvement of pre-bronchodilator FEV(1) after treatment that far surpassed the initial post-bronchodialator FEV(1) value. Even after such a change, there were presences of some reversibility suggesting room for further improvement. CONCLUSION: The results suggest significant improvements in the obstructive parameters used to evaluate asthma, with possible reversal of remodeling evident in chronic asthmatics when treated with doxycycline in addition to standard therapies. This observation needs further scientific validation.

High-glucose-induced endothelial cell injury is inhibited by a Peptide derived from human apolipoprotein E.

Although the importance of human apolipoprotein E (apoE) in vascular diseases has clearly been established, most of the research on apoE has focused on its role in cholesterol metabolism. In view of the observation that apoE and its functional domains impact extracellular matrix (ECM) remodeling, we hypothesized that apoE could also confer protection against ECM degradation by mechanisms independent of its role in cholesterol and lipoprotein transport. The ECM degrading enzyme, heparanase, is secreted by cells as pro-heparanase that is internalized through low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1) to become enzymatically active. Both apoE and pro-heparanase bind the LRP-1. We further hypothesized that an apoE mimetic peptide (apoEdp) would inhibit the production of active heparanase by blocking LRP-1-mediated uptake of pro-heparanase and thereby decrease degradation of the ECM. To test this hypothesis, we induced the expression of heparanase by incubating human retinal endothelial cells (hRECs) with high glucose (30 mM) for 72 hours. We found that elevated expression of heparanase by high glucose was associated with increased shedding of heparan sulfate (ΔHS) and the tight junction protein occludin. Treatment of hRECs with 100 µM apoEdp in the presence of high glucose significantly reduced the expression of heparanase, shedding of ΔHS, and loss of occludin as detected by Western blot analysis. Either eye drop treatment of 1% apoEdp topically 4 times a day for 14 consecutive days or intraperitoneal injection (40 mg/kg) of apoEdp daily for 14 consecutive days in an in vivo mouse model of streptozotocin-induced diabetes inhibited the loss of tight junction proteins occludin and zona occludin- 1 (ZO-1). These findings imply a functional relationship between apoE and endothelial cell matrix because the deregulation of these molecules can be inhibited by a short peptide derived from the receptor-binding region of apoE. Thus, strategies targeting ECM-degrading enzymes could be therapeutically beneficial for treating diabetic retinopathy.

Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases.