Binding selectivity analysis of new delhi metallo-beta-lactamase-1 inhibitors using molecular dynamics simulations: Exploring possibilities for decoding antimicrobial drug resistance.

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.

Breaking Bad: Spontaneous Rupture of Incisional Hernia.

Spontaneous bowel evisceration from a ruptured, long-standing abdominal wall hernia is a very rare complication with significant morbidity and mortality, usually occurring in incisional or recurrent groin hernias. In this case report, we elucidate an unexpected scenario of spontaneous incisional hernia rupture leading to bowel evisceration, detailing the clinical presentation, diagnostic workup, and surgical management. By highlighting this rare complication, we emphasise the significance of vigilance in monitoring hernia patients and the necessity of expedited surgical intervention to prevent complications, optimise outcomes, and minimise morbidity.

SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure.

SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission. Here, we investigated the interaction of SARS-CoV-2 with cells lining the blood-retinal barrier (BRB) and the role of the eye in its transmission and tropism. The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein presence in different ocular tissues but also induces a hyperinflammatory immune response in the retina. Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations. Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.

The multifaceted functions of long non-coding RNA HOTAIR in neuropathologies and its potential as a prognostic marker and therapeutic biotarget.

Long non-coding RNAs (lncRNAs) are progressively being perceived as prominent molecular agents controlling multiple aspects of neuronal (patho)physiology. Amongst these is the HOX transcript antisense intergenic RNA, often abbreviated as HOTAIR. HOTAIR epigenetically regulates its target genes via its interaction with two different chromatin-modifying agents; histone methyltransferase polycomb-repressive complex 2 and histone demethylase lysine-specific demethylase 1. Parenthetically, HOTAIR elicits trans-acting sponging function against multiple micro-RNA species. Oncological research studies have confirmed the pathogenic functions of HOTAIR in multiple cancer types, such as gliomas and proposed it as a pro-oncological lncRNA. In fact, its expression has been suggested to be a predictor of the severity/grade of gliomas, and as a prognostic biomarker. Moreover, a propound influence of HOTAIR in other aspects of brain heath and disease states is just beginning to be unravelled. The objective of this review is to recapitulate all the relevant data pertaining to the regulatory roles of HOTAIR in neuronal (patho)physiology. To this end, we discuss the pathogenic mechanisms of HOTAIR in multiple neuronal diseases, such as neurodegeneration, traumatic brain injury and neuropsychiatric disorders. Finally, we also summarize the results from the studies incriminating HOTAIR in the pathogeneses of gliomas and other brain cancers. Implications of HOTAIR serving as a suitable therapeutic target in neuropathologies are also discussed.

Effect of Microwave-Based Dry Blanching on Drying of Potato Slices: A Comparative Study.

Microwave (MW)-based dry blanching can inactivate oxidative enzymes like peroxidase (POD) and polyphenol oxidase (PPO) rapidly and retain a higher amount of water-soluble nutrients, like ascorbic acid. This study compared the MW-based dry blanching of potato slices of various thicknesses (5, 8, and 10 mm) with conventional methods (water and steam blanching). The time required for water and steam blanching was longer than that required for MW blanching. Potato slices of 10 mm thickness required a longer blanching duration compared with slices of a lesser thickness (5 and 8 mm). The MW-blanched samples (77.37-83.5%) retained a higher content of ascorbic acid, followed by steam-blanched (69.15-74.92%) and water-blanched (67.18-71.54%) samples. The Page, modified Page, Midilli-Kucuk, and Hii, Law, and Cloke models predicted the thin layer drying of potato slices (5 mm thickness) better with a higher coefficient of determination values (0.9607-0.9976) compared to Fick's and Exponential models (0.8942-0.9444).

Performance of risk models to predict mortality risk for patients with heart failure: evaluation in an integrated health system.

BACKGROUND: Referral of patients with heart failure (HF) who are at high mortality risk for specialist evaluation is recommended. Yet, most tools for identifying such patients are difficult to implement in electronic health record (EHR) systems. OBJECTIVE: To assess the performance and ease of implementation of Machine learning Assessment of RisK and EaRly mortality in Heart Failure (MARKER-HF), a machine-learning model that uses structured data that is readily available in the EHR, and compare it with two commonly used risk scores: the Seattle Heart Failure Model (SHFM) and Meta-Analysis Global Group in Chronic (MAGGIC) Heart Failure Risk Score. DESIGN: Retrospective, cohort study. PARTICIPANTS: Data from 6764 adults with HF were abstracted from EHRs at a large integrated health system from 1/1/10 to 12/31/19. MAIN MEASURES: One-year survival from time of first cardiology or primary care visit was estimated using MARKER-HF, SHFM, and MAGGIC. Discrimination was measured by the area under the receiver operating curve (AUC). Calibration was assessed graphically. KEY RESULTS: Compared to MARKER-HF, both SHFM and MAGGIC required a considerably larger amount of data engineering and imputation to generate risk score estimates. MARKER-HF, SHFM, and MAGGIC exhibited similar discriminations with AUCs of 0.70 (0.69-0.73), 0.71 (0.69-0.72), and 0.71 (95% CI 0.70-0.73), respectively. All three scores showed good calibration across the full risk spectrum. CONCLUSIONS: These findings suggest that MARKER-HF, which uses readily available clinical and lab measurements in the EHR and required less imputation and data engineering than SHFM and MAGGIC, is an easier tool to identify high-risk patients in ambulatory clinics who could benefit from referral to a HF specialist.

Gum Ghatti: A Comprehensive Review on Production, Processing, Remarkable Properties, and Diverse Applications.

Gum ghatti, popularly known as Indian gum and obtained from Anogeissus latifolia, is a complex high-molecular-weight, water-soluble, and swellable nonstarch polysaccharide comprised of magnesium and calcium salts of ghattic acids and multiple monosugars. Unlike other nontimber forest produce, gums ghatti is a low-volume but high-value product. It has several applications and is widely used as food, in pharmaceuticals, and for wastewater treatment and hydrogel formation, and it has attracted a great deal of attention in the fields of energy, environmental science, and nanotechnology. Industrial applications of gum ghatti are primarily due to its excellent emulsification, stabilization, thickening, heat tolerance, pH stability, carrier, and biodegradable properties. However, utilization of gum ghatti is poorly explored and implemented due to a lack of knowledge of its production, processing, and properties. Nevertheless, there has been interest among investigators in recent times for exploring its production, processing, molecular skeleton, and functional properties. This present review focuses on production scenarios, processing aspects, structural and functional properties, and potential applications in the food, pharmaceuticals, nonfood, and other indigenous and industrial usages.

Ineffective ventilation in a very low birth weight infant with H-type Tracheoesophageal Fistula with bilateral chemical pneumonitis. A lesson learned.

Tracheoesophageal fistula (TEF) with or without associated esophageal atresia (EA) in the neonate is challenging to diagnose and manage its complications like aspiration, respiratory distress, and other associated anomalies. To stabilize, ventilate and prepare for surgical correction, understanding the H-nature of disease and anticipation of problems and their management will improve survival. We present a newborn with tracheoesophageal fistula without atresia from resource-limited settings and lessons we learned from the case.

Multirole of the internet of medical things (IoMT) in biomedical systems for managing smart healthcare systems: An overview of current and future innovative trends.

Internet of Medical Things (IoMT) is an emerging subset of Internet of Things (IoT), often called as IoT in healthcare, refers to medical devices and applications with internet connectivity, is exponentially gaining researchers' attention due to its wide-ranging applicability in biomedical systems for Smart Healthcare systems. IoMT facilitates remote health biomedical system and plays a crucial role within the healthcare industry to enhance precision, reliability, consistency and productivity of electronic devices used for various healthcare purposes. It comprises a conceptualized architecture for providing information retrieval strategies to extract the data from patient records using sensors for biomedical analysis and diagnostics against manifold diseases to provide cost-effective medical solutions, quick hospital treatments, and personalized healthcare. This article provides a comprehensive overview of IoMT with special emphasis on its current and future trends used in biomedical systems, such as deep learning, machine learning, blockchains, artificial intelligence, radio frequency identification, and industry 5.0.

Roles of HOTAIR Long Non-coding RNA in Gliomas and Other CNS Disorders.

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA (lncRNA) which is increasingly being perceived as a tremendous molecular mediator of brain pathophysiology at multiple levels. Epigenetic regulation of target gene expression carried out by HOTAIR is thorough modulation of chromatin modifiers; histone methyltransferase polycomb repressive complex 2 (PRC2) and histone demethylase lysine-specific demethylase 1 (LSD1). Incidentally, HOTAIR was the first lncRNA shown to elicit sponging of specific microRNA (miRNA or miR) species in a trans-acting manner. It has been extensively studied in various cancers, including gliomas and is regarded as a prominent pro-tumorigenic and pro-oncogenic lncRNA. Indeed, the expression of HOTAIR may serve as glioma grade predictor and prognostic biomarker. The objective of this timely review is not only to outline the multifaceted pathogenic roles of HOTAIR in the development and pathophysiology of gliomas and brain cancers, but also to delineate the research findings implicating it as a critical regulator of overall brain pathophysiology. While the major focus is on neuro-oncology, wherein HOTAIR represents a particularly potent underlying pathogenic player and a suitable therapeutic target, mechanisms underlying the regulatory actions of HOTAIR in neurodegeneration, traumatic, hypoxic and ischemic brain injuries, and neuropsychiatric disorders are also presented.

Neuroprotective, Anti-Inflammatory and Antifibrillogenic Offerings by Emodin against Alzheimer's Dementia: A Systematic Review.

Background: Alzheimer's disease (AD) is among the major causes of dementia in the elderly and exerts tremendous clinical, psychological and socio-economic constraints. Currently, there are no effective disease-modifying/retarding anti-AD agents. Emodin is a bioactive phytochemical with potent multimodal anti-inflammatory, antioxidant, and antifibrillogenic properties. In particular, emodin may result in significant repression of the pathogenic mechanisms underlying AD. The purpose of this review is to accumulate and summarize all the primary research data evaluating the therapeutic actions of emodin in AD pathogenesis. Methodology: The search, selection, and retrieval of pertinent primary research articles were systematically performed using a methodically designed approach. A variety of keyword combinations were employed on online scholarly web-databases. Strict preset inclusion and exclusion criteria were used to select the retrieved studies. Data from the individual studies were summarized and compiled into different sections, based upon their findings. Results: Cellular and animal research indicates that emodin exerts robust multimodal neuroprotection in AD. While emodin effectively prevents tau and amyloid-beta (Aß) oligomerization, it also mitigates their neurotoxicity by attenuating neuroinflammatory, oxidative, and bioenergetic defects. Evidences for emodin-mediated enhancements in memory, learning, and cognition were also found in the literature. Conclusion: Emodin is a potential anti-AD dietary supplement; however, further studies are warrantied to thoroughly understand its target players and mechanisms. Moreover, human clinical data on emodin-mediated amelioration of AD phenotype is largely lacking, and must be addressed in the future. Lastly, the safety of exogenously supplemented emodin must be thoroughly evaluated.

Mind Matters: Exploring the Intersection of Psychological Factors and Cognitive Abilities of University Students by Using ANN Model.

Purpose: While previous studies have suggested close association of psychological variables of students withtheir higher-order cognitive abilities, such studies have largely been lacking for third world countries like India, with their unique socio-economic-cultural set of challenges. We aimed to investigate the relationship between psychological variables (depression, anxiety and stress) and cognitive functions among Indian students, and to predict cognitive performance as a function of these variables. Patients and Methods: Four hundred and thirteen university students were systematically selected using purposive sampling. Widely used and validated offline questionnaires were used to assess their psychological and cognitive statuses. Correlational analyses were conducted to examine the associations between these variables. An Artificial Neural Network (ANN) model was applied to predict cognitive levels based on the scores of psychological variables. Results: Correlational analyses revealed negative correlations between emotional distress and cognitive functioning. Principal Component Analysis (PCA) reduced the dimensionality of the input data, effectively capturing the variance with fewer features. The feature weight analysis indicated a balanced contribution of each mental health symptom, with particular emphasis on one of the symptoms. The ANN model demonstrated moderate predictive performance, explaining a portion of the variance in cognitive levels based on the psychological variables. Conclusion: The study confirms significant associations between emotional statuses of university students with their cognitive abilities. Specifically, we provide evidence for the first time that in Indian students, self-reported higher levels of stress, anxiety, and depression are linked to lower performance in cognitive tests. The application of PCA and feature weight analysis provided deeper insights into the structure of the predictive model. Notably, use of the ANN model provided insights into predicting these cognitive domains as a function of the emotional attributes. Our results emphasize the importance of addressing mental health concerns and implementing interventions for the enhancement of cognitive functions in university students.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial.

OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.

Utilities of Isolated Nerve Terminals in Ex Vivo Analyses of Protein Translation in (Patho)physiological Brain States: Focus on Alzheimer's Disease.

Synapses are the cellular substrates of higher-order brain functions, and their dysfunction is an early and primary pathogenic mechanism across several neurological disorders. In particular, Alzheimer's disease (AD) is categorized by prodromal structural and functional synaptic deficits, prior to the advent of classical behavioral and pathological features. Recent research has shown that the development, maintenance, and plasticity of synapses depend on localized protein translation. Synaptosomes and synaptoneurosomes are biochemically isolated synaptic terminal preparations which have long been used to examine a variety of synaptic processes ex vivo in both healthy and pathological conditions. These ex vivo preparations preserve the mRNA species and the protein translational machinery. Hence, they are excellent in organello tools for the study of alterations in mRNA levels and protein translation in neuropathologies. Evaluation of synapse-specific basal and activity-driven de novo protein translation activity can be conveniently performed in synaptosomal/synaptoneurosomal preparations from both rodent and human brain tissue samples. This review gives a quick overview of the methods for isolating synaptosomes and synaptoneurosomes before discussing the studies that have utilized these preparations to study localized synapse-specific protein translation in (patho)physiological situations, with an emphasis on AD. While the review is not an exhaustive accumulation of all the studies evaluating synaptic protein translation using the synaptosomal model, the aim is to assemble the most relevant studies that have done so. The hope is to provide a suitable research platform to aid neuroscientists to utilize the synaptosomal/synaptoneurosomal models to evaluate the molecular mechanisms of synaptic dysfunction within the specific confines of mRNA localization and protein translation research.

Comparative antimicrobial use in coronavirus disease 2019 (COVID-19) and non-COVID-19 inpatients from 2019 to 2020: A multicenter ecological study.

OBJECTIVE: We sought to determine whether increased antimicrobial use (AU) at the onset of the coronavirus disease 2019 (COVID-19) pandemic was driven by greater AU in COVID-19 patients only, or whether AU also increased in non-COVID-19 patients. DESIGN: In this retrospective observational ecological study from 2019 to 2020, we stratified inpatients by COVID-19 status and determined relative percentage differences in median monthly AU in COVID-19 patients versus non-COVID-19 patients during the COVID-19 period (March-December 2020) and the pre-COVID-19 period (March-December 2019). We also determined relative percentage differences in median monthly AU in non-COVID-19 patients during the COVID-19 period versus the pre-COVID-19 period. Statistical significance was assessed using Wilcoxon signed-rank tests. SETTING: The study was conducted in 3 acute-care hospitals in Chicago, Illinois. PATIENTS: Hospitalized patients. RESULTS: Facility-wide AU for broad-spectrum antibacterial agents predominantly used for hospital-onset infections was significantly greater in COVID-19 patients versus non-COVID-19 patients during the COVID-19 period (with relative increases of 73%, 66%, and 91% for hospitals A, B, and C, respectively), and during the pre-COVID-19 period (with relative increases of 52%, 64%, and 66% for hospitals A, B, and C, respectively). In contrast, facility-wide AU for all antibacterial agents was significantly lower in non-COVID-19 patients during the COVID-19 period versus the pre-COVID-19 period (with relative decreases of 8%, 7%, and 8% in hospitals A, B, and C, respectively). CONCLUSIONS: AU for broad-spectrum antimicrobials was greater in COVID-19 patients compared to non-COVID-19 patients at the onset of the pandemic. AU for all antibacterial agents in non-COVID-19 patients decreased in the COVID-19 period compared to the pre-COVID-19 period.

Potential biomarkers and therapeutic targets for obsessive compulsive disorder: Evidences from clinical studies.

Obsessive compulsive disorder (OCD) is a prevalent behavioral disorder with a complex etiology. However, the underlying pathogenic molecular pathways and the associated risk factors are largely obscure. This has hindered both the identification of relevant prognostic biomarkers and the development of effective treatment strategies. Because of the diverse range of clinical manifestations, not all patients benefit from therapies currently practiced in the clinical setting. Nevertheless, several lines of evidence indicate that neurotrophic, neurotransmitter, and oxidative signaling are involved in the pathophysiology of OCD. Based upon evidences from clinical (and pre-clinical studies), the present review paper sets out to decipher the utilities of three parameters (i.e. brain-derived neurotrophic factor; BDNF, noradrenalin-synthesizing enzyme dopamine beta-hydroxylase; DBH; and oxidative damage marker malondialdehyde; MDA) as diagnostic peripheral biomarkers as well as bio-targets for therapeutic strategies. While the data indicates promising results, there is necessitation for future studies to further confirm and establish these. Further, based again on the available clinical data, we investigated the possibilities of exploiting the etiological links between disruptions in the sleep-wake cycle and insulin signaling, and OCD for the identification of potential anti-OCD ameliorative agents with the ability to elicit multimodal effects, including attenuation of the alterations in BDNF, noradrenergic and redox pathways. In this respect, agomelatine and metformin may represent particularly interesting candidates; however, further clinical studies are warranted to establish these as singular or complementary medications in OCD subjects.

Etiology and incidence of postpartum depression among birthing women in the scenario of pandemics, geopolitical conflicts and natural disasters: a systematic review.

Postpartum depression (PPD) is classified under postpartum psychiatric disorders and initiates soon after birthing, eliciting neuropsychological and behavioral deficits in mothers and offspring. Globally, PPD is estimated to be associated with 130-190 per 1000 birthing. The severity and incidences of PPD have aggravated in the recent years due to the several unfavorable environmental and geopolitical circumstances. The purpose of this systematic review hence is to explore the contributions of recent circumstances on the pathogenesis and incidence of PPD. The search, selection and retrieval of the articles published during the last three years were systematically performed. The results from the primary studies indicate that unfavorable contemporary socio-geopolitical and environmental circumstances (e.g. Covid-19 pandemic, political conflicts/wars, and natural calamities; such as floods and earthquakes) detrimentally affect PPD etiology. A combination of socio-economic and psychological factors, including perceived lack of support and anxiousness about the future may contribute to drastic aggravation of PPD incidences. Finally, we outline some of the potential treatment regimens (e.g. inter-personal psycho- and art-based therapies) that may prove to be effective in amelioration of PPD-linked symptoms in birthing women, either alone or in complementation with traditional pharmacological interventions. We propose these psychological and art-based intervention strategies may beneficially counteract the negative influences of the unfortunate recent events across multiple cultures, societies and geographical regions.

Recent Advances in the Extraction of Pectin from Various Sources and Industrial Applications.

Pectin is a structural polysaccharide present in plants that primarily consists of galacturonic acid units. This Review discusses the chemistry of pectin, including its composition and molecular weight. Pectin is conventionally extracted from agricultural waste (fruit and vegetable peels) using an acidic or basic aqueous medium at high temperatures. These processes are time- and energy-consuming and also result in severe environmental problems due to the production of acidic effluents and equipment corrosion. As pectin usage is increasing in food industries for developing different products and it is also used as an excipient in pharmaceutical products, better extraction procedures are required to maximize the yield and purity. The Review encompasses various alternate green approaches for the extraction of pectin, including traditional acid extraction and various emerging technologies such as deep eutectic solvent-based extraction, enzyme-assisted extraction, subcritical fluid extraction, ultrasound-assisted extraction, and microwave-based extraction, and evaluates the yield and physicochemical characteristics of the extracted pectin. This work aims to provide a platform for attracting more thorough research focused on the engineering of novel and more efficient green methods for the extraction of pectin and its utilization for various biotechnological purposes.

Viral infections and pathogenesis of glaucoma: a comprehensive review.

Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.