Incidentally detected primary corneal squamous neoplasia in an elderly man presenting with cataract

2020 ◽  
Vol 13 (11) ◽  
pp. e235789
Author(s):  
Rinky Agarwal ◽  
Vatika Jain ◽  
Seema Sen ◽  
Prafulla Kumar Maharana
Keyword(s):  
Cataract Surgery ◽  
Clinical Symptoms ◽  
Anterior Segment ◽  
Impression Cytology ◽  
Visual Axis ◽  
Ocular Irritation ◽  
Cancerous Lesion ◽  
Visual Disturbances

Primary corneal neoplasia (PCN) is a rare cancerous lesion of cornea usually encountered in elderly. The clinical symptoms are generally non-specific, with ocular irritation, redness, cosmetic disfigurement and varying degrees of visual disturbances depending on visual axis involvement. Corneal neoplasia is usually associated with surrounding conjunctival lesions and incidentally detected PCN is rarely encountered in clinical practice. Presently, we report a case of isolated unilateral PCN diagnosed incidentally in an elderly man presenting with cataract. In vivo confocal microscopy aided in its diagnosis after impression cytology was repeatedly negative. Cataract surgery was deferred and the patient was administered three cycles of mitomycin C 0.04% 4 times/day. The tumour margins receded as evident on clinical examination and on anterior segment optical coherence tomography. We discuss the role of various corneal imaging modalities in diagnosis and management of PCN besides highlighting importance of comprehensive slit-lamp examination in patients planned for cataract surgery.

scholarly journals Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

2015 ◽  
Vol 89 (21) ◽  
pp. 10959-10969 ◽  
Author(s):  
Donata Hoffmann ◽  
Annika Franke ◽  
Maria Jenckel ◽  
Aistė Tamošiūnaitė ◽  
Julia Schluckebier ◽  
...  
Keyword(s):  
Respiratory Symptoms ◽  
Clinical Symptoms ◽  
Common Vole ◽  
Reservoir Host ◽  
High Dose ◽  
Cowpox Virus ◽  
Common Voles ◽  
Highly Virulent

ABSTRACTThe incidence of human cowpox virus (CPXV) infections has increased significantly in recent years. Serological surveys have suggested wild rodents as the main CPXV reservoir. We characterized a CPXV isolated during a large-scale screening from a feral common vole. A comparison of the full-length DNA sequence of this CPXV strain with a highly virulent pet rat CPXV isolate showed a sequence identity of 96%, including a large additional open reading frame (ORF) of about 6,000 nucleotides which is absent in the reference CPXV strain Brighton Red. Electron microscopy analysis demonstrated that the vole isolate, in contrast to the rat strain, forms A-type inclusion (ATI) bodies with incorporated virions, consistent with the presence of completeatiandp4cgenes. Experimental infections showed that the vole CPXV strain caused only mild clinical symptoms in its natural host, while all rats developed severe respiratory symptoms followed by a systemic rash. In contrast, common voles infected with a high dose of the rat CPXV showed severe signs of respiratory disease but no skin lesions, whereas infection with a low dose led to virus excretion with only mild clinical signs. We concluded that the common vole is susceptible to infection with different CPXV strains. The spectrum ranges from well-adapted viruses causing limited clinical symptoms to highly virulent strains causing severe respiratory symptoms. In addition, the low pathogenicity of the vole isolate in its eponymous host suggests a role of common voles as a major CPXV reservoir, and future research will focus on the correlation between viral genotype and phenotype/pathotype in accidental and reservoir species.IMPORTANCEWe report on the first detection and isolation of CPXV from a putative reservoir host, which enables comparative analyses to understand the infection cycle of these zoonotic orthopox viruses and the relevant genes involved.In vitrostudies, including whole-genome sequencing as well asin vivoexperiments using the Wistar rat model and the vole reservoir host allowed us to establish links between genomic sequences and thein vivoproperties (virulence) of the novel vole isolate in comparison to those of a recent zoonotic CPXV isolated from pet rats in 2009. Furthermore, the role of genes present only in a reservoir isolate can now be further analyzed. These studies therefore allow unique insights and conclusions about the role of the rodent reservoir in CPXV epidemiology and transmission and about the zoonotic threat that these viruses represent.

scholarly journals Locus Coeruleus Modulates Neuroinflammation in Parkinsonism and Dementia

2020 ◽  
Vol 21 (22) ◽  
pp. 8630
Author(s):  
Filippo Sean Giorgi ◽  
Francesca Biagioni ◽  
Alessandro Galgani ◽  
Nicola Pavese ◽  
Gloria Lazzeri ◽  
...  
Keyword(s):  
Experimental Data ◽  
Locus Coeruleus ◽  
Clinical Symptoms ◽  
Experimental Studies ◽  
Anatomy And Physiology ◽  
The Central Nervous System ◽  
Near Future

Locus Coeruleus (LC) is the main noradrenergic nucleus of the central nervous system, and its neurons widely innervate the whole brain. LC is severely degenerated both in Alzheimer’s disease (AD) and in Parkinson’s disease (PD), years before the onset of clinical symptoms, through mechanisms that differ among the two disorders. Several experimental studies have shown that noradrenaline modulates neuroinflammation, mainly by acting on microglia/astrocytes function. In the present review, after a brief introduction on the anatomy and physiology of LC, we provide an overview of experimental data supporting a pathogenetic role of LC degeneration in AD and PD. Then, we describe in detail experimental data, obtained in vitro and in vivo in animal models, which support a potential role of neuroinflammation in such a link, and the specific molecules (i.e., released cytokines, glial receptors, including pattern recognition receptors and others) whose expression is altered by LC degeneration and might play a key role in AD/PD pathogenesis. New imaging and biochemical tools have recently been developed in humans to estimate in vivo the integrity of LC, the degree of neuroinflammation, and pathology AD/PD biomarkers; it is auspicable that these will allow in the near future to test the existence of a link between LC-neuroinflammation and neurodegeneration directly in patients.

scholarly journals Knockout of myoc Provides Evidence for the Role of Myocilin in Zebrafish Sex Determination Associated with Wnt Signalling Downregulation

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 98
Author(s):  
Raquel Atienzar-Aroca ◽  
José-Daniel Aroca-Aguilar ◽  
Susana Alexandre-Moreno ◽  
Jesús-José Ferre-Fernández ◽  
Juan-Manuel Bonet-Fernández ◽  
...  
Keyword(s):  
Sex Determination ◽  
Anterior Segment ◽  
Premature Termination Codon ◽  
Wnt Signalling ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Ocular Tissues ◽  
Key Factor

Myocilin is a secreted glycoprotein with a poorly understood biological function and it is mainly known as the first glaucoma gene. To explore the normal role of this protein in vivo we developed a myoc knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries a homozygous variant (c.236_239delinsAAAGGGGAAGGGGA) that is predicted to result in a loss-of-function of the protein because of a premature termination codon p.(V75EfsX60) that resulted in a significant reduction of myoc mRNA levels. Immunohistochemistry showed the presence of myocilin in wild-type embryonic (96 h post-fertilization) anterior segment eye structures and caudal muscles. The protein was also detected in different adult ocular and non-ocular tissues. No gross macroscopic or microscopic alterations were identified in the KO zebrafish, but, remarkably, we observed absence of females among the adult KO animals and apoptosis in the immature juvenile gonad (28 dpf) of these animals, which is characteristic of male development. Transcriptomic analysis showed that adult KO males overexpressed key genes involved in male sex determination and presented differentially expressed Wnt signalling genes. These results show that myocilin is required for ovary differentiation in zebrafish and provides in vivo support for the role of myocilin as a Wnt signalling pathway modulator. In summary, this myoc KO zebrafish line can be useful to investigate the elusive function of this protein, and it provides evidence for the unexpected function of myocilin as a key factor in zebrafish sex determination.

scholarly journals JNK signaling provides a novel therapeutic target for Rett syndrome

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Clara Alice Musi ◽  
Anna Maria Castaldo ◽  
Anna Elisa Valsecchi ◽  
Sara Cimini ◽  
Noemi Morello ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Clinical Symptoms ◽  
Neurodevelopmental Disorder ◽  
Loss Of Function ◽  
Jnk Signaling ◽  
Functional Changes ◽  
Jnk Activation ◽  
Stress Pathway

Abstract Background Rett syndrome (RTT) is a monogenic X-linked neurodevelopmental disorder characterized by loss-of-function mutations in the MECP2 gene, which lead to structural and functional changes in synapse communication, and impairments of neural activity at the basis of cognitive deficits that progress from an early age. While the restoration of MECP2 in animal models has been shown to rescue some RTT symptoms, gene therapy intervention presents potential side effects, and with gene- and RNA-editing approaches still far from clinical application, strategies focusing on signaling pathways downstream of MeCP2 may provide alternatives for the development of more effective therapies in vivo. Here, we investigate the role of the c-Jun N-terminal kinase (JNK) stress pathway in the pathogenesis of RTT using different animal and cell models and evaluate JNK inhibition as a potential therapeutic approach. Results We discovered that the c-Jun N-terminal kinase (JNK) stress pathway is activated in Mecp2-knockout, Mecp2-heterozygous mice, and in human MECP2-mutated iPSC neurons. The specific JNK inhibitor, D-JNKI1, promotes recovery of body weight and locomotor impairments in two mouse models of RTT and rescues their dendritic spine alterations. Mecp2-knockout presents intermittent crises of apnea/hypopnea, one of the most invalidating RTT pathological symptoms, and D-JNKI1 powerfully reduces this breathing dysfunction. Importantly, we discovered that also neurons derived from hiPSC-MECP2 mut show JNK activation, high-phosphorylated c-Jun levels, and cell death, which is not observed in the isogenic control wt allele hiPSCs. Treatment with D-JNKI1 inhibits neuronal death induced by MECP2 mutation in hiPSCs mut neurons. Conclusions As a summary, we found altered JNK signaling in models of RTT and suggest that D-JNKI1 treatment prevents clinical symptoms, with coherent results at the cellular, molecular, and functional levels. This is the first proof of concept that JNK plays a key role in RTT and its specific inhibition offers a new and potential therapeutic tool to tackle RTT.

scholarly journals Lactoferrin as Antiviral Treatment in COVID-19 Management: Preliminary Evidence

2021 ◽  
Vol 18 (20) ◽  
pp. 10985
Author(s):  
Elena Campione ◽  
Caterina Lanna ◽  
Terenzio Cosio ◽  
Luigi Rosa ◽  
Maria Pia Conte ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Antiviral Treatment ◽  
Standard Of Care ◽  
Antiviral Effect ◽  
Preliminary Evidence ◽  
Home Based ◽  
Negative Conversion

Lactoferrin (Lf), a multifunctional cationic glycoprotein synthesized by exocrine glands and neutrophils, possesses an in vitro antiviral activity against SARS-CoV-2. Thus, we conducted an in vivo preliminary study to investigate the antiviral effect of oral and intranasal liposomal bovine Lf (bLf) in asymptomatic and mild-to-moderate COVID-19 patients. From April 2020 to June 2020, a total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided into three groups. Thirty-two patients (14 hospitalized and 18 in home-based isolation) received only oral and intranasal liposomal bLf; 32 hospitalized patients were treated only with standard of care (SOC) treatment; and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, untreated, healthy subjects were added for ancillary analysis. Liposomal bLf-treated COVID-19 patients obtained an earlier and significant (p < 0.0001) SARS-CoV-2 RNA negative conversion compared to the SOC-treated and untreated COVID-19 patients (14.25 vs. 27.13 vs. 32.61 days, respectively). Liposomal bLf-treated COVID-19 patients showed fast clinical symptoms recovery compared to the SOC-treated COVID-19 patients. In bLf-treated patients, a significant decrease in serum ferritin, IL-6, and D-dimers levels was observed. No adverse events were reported. These observations led us to speculate a potential role of bLf in the management of mild-to-moderate and asymptomatic COVID-19 patients.

scholarly journals Venting incision of cornea and intracameral air repairs Descemet membrane detachment three months after phacoemulsification surgery

2020 ◽  
Author(s):  
Mae-Lynn Catherine Bastion ◽  
Yiing Cheong Wong ◽  
Aida Zairani Zahidin
Keyword(s):  
Cataract Surgery ◽  
Anterior Segment ◽  
Late Presentation ◽  
Air Injection ◽  
Case Review ◽  
Visual Axis ◽  
Retrospective Case ◽  
Descemet Membrane ◽  
Initial Surgery ◽  
Descemet Membrane Detachment

Introduction: Cataract surgery is one of the most commonly performed operations in the world. Descemet membrane detachment (DMD) is a potentially blinding complication of this operation. Aim: To describe the successful treatment of DMD three months after initial surgery. Case study: Retrospective case review. Results and discussion: A 69-year-old bilateral pseudophakic man presented with persistent blurring of vision in his left eye despite having undergone left eye cataract surgery for phacomorphic glaucoma 10 weeks previously. Examination and anterior segment optical coherence tomography (AS-OCT) showed left descemet detachment involving the visual axis. Despite the long duration, he underwent left cornea venting incision combined with intracameral air injection which successfully improved the cornea clarity and reattached the descemet on AS-OCT. When this was combined with treatment for cystoid macula oedema, he was able to attain best corrected visual acuity of 6/6-2, N5 3 months after the cornea venting procedure. Conclusions: Treatment with cornea venting incision combined with air injection is an effective method of reattaching the descemet membrane in late presentation of DMD.

scholarly journals Knockout of myoc reveals the role of myocilin in zebrafish sex determination associated with Wnt signalling downregulation

2020 ◽  
Author(s):  
Raquel Atienzar-Aroca ◽  
José-Daniel Aroca-Aguilar ◽  
Susana Alexandre-Moreno ◽  
Jesús-José Ferre-Fernández ◽  
Juan-Manuel Bonet-Fernández ◽  
...  
Keyword(s):  
Sex Determination ◽  
Anterior Segment ◽  
Premature Termination Codon ◽  
Wnt Signalling ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Ocular Tissues ◽  
Key Factor

Myocilin is a secreted glycoprotein with a poorly understood biological function and it is mainly known for its association with glaucoma. To explore the normal role of this protein in vivo we developed a myoc knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries a homozygous variant (c.236_239delinsAAAGGGGAAGGGGA) that is predicted to result in a loss-of-function of the protein because of a premature termination codon p.(V75EfsX60) that resulted in a significant reduction of myoc mRNA levels. Immunohistochemistry showed the presence of myocilin in wild-type embryonic (96 hours post-fertilization) anterior segment eye structures and caudal muscles. The protein was also detected in different adult ocular and non-ocular tissues. No gross macroscopic or microscopic alterations were identified in the KO zebrafish, but remarkably, we observed absence of females among the adult KO animals and apoptosis in the immature juvenile gonad (28 dpf) of these animals, which is characteristic of male development. Transcriptomic analysis showed that adult KO males overexpressed key genes involved in male sex determination and presented differentially expressed Wnt signalling genes. These results show that myocilin is required for ovary differentiation in zebrafish and provide in vivo support for the role of myocilin as a Wnt signalling pathway modulator. In summary, this myoc KO zebrafish line can be useful to investigate the elusive function of this protein, and it provides evidence for the unexpected function of myocilin as a key factor in zebrafish sex determination.

scholarly journals Carnosine alleviates diabetic nephropathy by targeting GNMT, a key enzyme mediating renal inflammation and fibrosis

2020 ◽  
Vol 134 (23) ◽  
pp. 3175-3193
Author(s):  
Xue-qi Liu ◽  
Ling Jiang ◽  
Lei Lei ◽  
Zhen-yong Nie ◽  
Wei Zhu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Clinical Symptoms ◽  
Protective Role ◽  
Renal Tubules ◽  
Protective Effects ◽  
Functional Protein ◽  
Key Enzyme

Abstract Diabetic nephropathy (DN) is a common microvascular complication of diabetes and the main cause of end-stage nephropathy (ESRD). Inflammation and fibrosis play key roles in the development and progression of diabetic nephropathy. By using in vivo and in vitro DN models, our laboratory has identified the protective role of carnosine (CAR) on renal tubules. Our results showed that carnosine restored the onset and clinical symptoms as well as renal tubular injury in DN. Furthermore, carnosine decreased kidney inflammation and fibrosis in DN mice. These results were consistent with high glucose (HG)-treated mice tubular epithelial cells (MTECs). Using web-prediction algorithms, cellular thermal shift assay (CETSA) and molecular docking, we identified glycine N-methyltransferase (GNMT) as a carnosine target. Importantly, we found that GNMT, a multiple functional protein that regulates the cellular pool of methyl groups by controlling the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), was down-regulated significantly in the serum of Type 1 DM patients and renal tissues of DN mice. Moreover, using cultured TECs, we confirmed that the increased GNMT expression by transient transfection mimicked the protective role of carnosine in reducing inflammation and fibrosis. Conversely, the inhibition of GNMT expression abolished the protective effects of carnosine. In conclusion, carnosine might serve as a promising therapeutic agent for DN and GNMT might be a potential therapeutic target for DN.

scholarly journals Objective Imaging Diagnostics for Dry Eye Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Sang Beom Han ◽  
Yu-Chi Liu ◽  
Karim Mohamed-Noriega ◽  
Louis Tong ◽  
Jodhbir S. Mehta
Keyword(s):  
Dry Eye ◽  
Clinical Symptoms ◽  
Imaging Techniques ◽  
Anterior Segment ◽  
Tear Film ◽  
Optical Quality ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Break Up

Traditional diagnostic tests for dry eye disease (DED), such as fluorescein tear film break-up time and the Schirmer test, are often associated with poor reproducibility and reliability, which make the diagnosis, follow-up, and management of the disease challenging. Advances in ocular imaging technology enables objective and reproducible measurement of changes in the ocular surface, tear film, and optical quality associated with DED. In this review, the authors will discuss the application of various imaging techniques, such as, noninvasive tear break-up time, anterior segment optical coherence tomography, in vivo confocal microscopy, meibography, interferometry, aberrometry, thermometry, and tear film imager in DED. Many studies have shown these devices to correlate with clinical symptoms and signs of DED, suggesting the potential of these imaging modalities as alternative tests for diagnosis and monitoring of the condition.

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