Epithelial Alterations Research Articles

Multimodal Imaging in Choroidal Metastasis

Background: Choroidal metastasis represents the most common malignant intraocular tumours. Objectives: The objective of this study is to detect the structural and vascular features of choroidal metastasis by multimodal imaging. Methods: Sixteen eyes of 16 patients with choroidal metastasis were enrolled in this prospective study. The multimodal imaging was performed in all patients: fluorescein angiography, indocyanine green angiography, enhanced depth imaging optical coherence tomography (EDI-OCT), OCT angiography (OCTA), and ultrasonography. Results: The choroidal metastasis was located in the macula region in 9 eyes (57%) and in the extramacular region in 7 eyes (43%). EDI-OCT showed a mean thickness of 950 ± 246 µm, a smooth anterior tumour surface in 5 eyes (31%), and a lumpy bumpy appearance in 11 eyes (69%). The most frequent EDI-OCT features were represented by choriocapillaris thinning (100%), shaggy photoreceptors (82%), subretinal fluid with speckles (69%), subretinal lipofuscin pigment (6%), absence of drusen (100%), optical shadowing (94%), low-internal optical reflectivity (75%), and retinal pigment epithelium alterations (43%). OCTA revealed an absence of intratumoral vascular network in all cases. Conclusions: The multimodal imaging contributed to greater insights into the anatomical and vascular features of choroidal metastasis. It allows for the collection of useful information to establish an appropriate diagnosis and follow-up.

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.

Complex Odontoma: An Overview

The dental tissues comprising of dentin, enamel,sometimes pulp, and cementum are the hamartomas whichare known as odontoma. These have behavior not so aggressive. The common type of tumor of odontogenicorigin about (35-76)% is the odontoma. It is a tumor of benign type arising from epithelial and mesenchymaldifferentiated alteration, odontogenic cells. These odontomas are of two types–complex and compound,the both are differentiated from each other by the organization of the tissue of dental origin in a ratio of1:2. Although the etiology is not known till now but may be related to anomalies of hereditary origin,infection,also by trauma and by hyperactivity of odontoblast process. By the means of radiological viewthese odontomas can be recognized and these in very few case causes expansion of the cortical bone. Theseodontomas occur in the second decade in number and usually takes place in the mandibular second or thirdmolar tooth. This particular article summarizes the complex composite odontoma.

Updated definition and classification of dry eye disease: Renewed proposals using the nominal group and Delphi techniques.

The aim of our research was to obtain expert consensus for updated definition and classification of dry eye disease using formal methodology. The nominal group technique (NGT) involved a steering committee of four ophthalmologists began with collection of ideas followed by group discussion. The ideas were collated, refined, and voted upon. The main characteristics considered, each with different degrees of severity in types I, II, and III, were the ability or not of the ocular surface to re-equilibrate itself, frequency of symptoms, presence of inflammation, epithelial alterations, and possible alterations in the quality of vision. This was followed by three rounds of a "mini-Delphi" involving an expert panel of 13 ophthalmologists, with the last round including all 17 ophthalmologists. Consensus in the final round of voting (⩾75% of votes) was reached on the definition of dry eye disease and on criteria for its classification in three forms. Type I is a transient and reversible form with subclinical inflammation, possible epithelial alterations, and occasional alterations in vision. Type II is a recurrent form characterized by a reduced ability to re-equilibrate the ocular surface, frequent symptoms and alterations in vision with clinically-evident inflammation, and clear evidence of epithelial alterations. Type III is a chronic form with inability to re-equilibrate the ocular surface and accompanied by clinically-evident and chronic inflammation, persistent epithelial alterations, and frequent alterations in quality of vision. The vast majority of patients with dry eye disease can be easily classified into one of these three forms. Dry eye disease definition was updated accordingly.

Intrathymic Selection and Defects in the Thymic Epithelial Cell Development.

Intimate interactions between thymic epithelial cells (TECs) and thymocytes (T) have been repeatedly reported as essential for performing intrathymic T-cell education. Nevertheless, it has been described that animals exhibiting defects in these interactions were capable of a proper positive and negative T-cell selection. In the current review, we first examined distinct types of TECs and their possible role in the immune surveillance. However, EphB-deficient thymi that exhibit profound thymic epithelial (TE) alterations do not exhibit important immunological defects. Eph and their ligands, the ephrins, are implicated in cell attachment/detachment and govern, therefore, TEC–T interactions. On this basis, we hypothesized that a few normal TE areas could be enough for a proper phenotypical and functional maturation of T lymphocytes. Then, we evaluated in vivo how many TECs would be necessary for supporting a normal T-cell differentiation, concluding that a significantly low number of TEC are still capable of supporting normal T lymphocyte maturation, whereas with fewer numbers, T-cell maturation is not possible.

RARE PRESENTATION OF MEDIASTINAL ABSCESS SUPERINFECTION IN AN INFLUENZA B PATIENT

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Influenza is generally a self-limited infection, however complicated with bacterial superinfection, it has been associated with increased morbidity and mortality[1]. We present the first case report in the literature of an immunocompetent Influenza B patient complicated with methicillin-sensitive Staphylococcus aureus (MSSA) mediastinal abscess and necrotizing pneumonia. CASE PRESENTATION: A 33-year-old male patient with past medical history of asthma presented to ED with myalgias, productive cough with rusty sputum and intermittent low-grade fever for 2 weeks. Initial vitals showed temperature of 100.6 F, heart rate of 106 bpm, respiratory rate of 24 with normal blood pressure and oxygen saturation. Physical examination was unremarkable. Initial workup revealed leukocytosis with WBC of 18 k/ul. CXR showed asymmetric enlargement of the right hilum with suspicion of central mass and to further analyze CT Chest with IV contrast was done showing consolidation in the right lower lobe (RLL) with mass-like consolidation in right hilum with mediastinal extension. (Figure 1) Patient was treated empirically with Piperacillin/Tazobactam, Vancomycin and Azithromycin. Nasopharyngeal swab for Influenza B PCR came back positive and blood cultures grew MSSA after which antibiotics were de-escalated to Oxacillin. His hospital course was complicated by clinical deterioration and repeat CT Chest revealed RLL Necrotizing Pneumonia and anterior mediastinal abscess. (Figure 2) He had emergent median sternotomy with radical thymectomy and debridement of mediastinal tissues. No histological evidence of malignancy was present, and cultures grew MSSA. He improved clinically and was discharged on IV oxacillin course for 6 weeks. His follow up CT chest showed complete resolution of mediastinal and resolving RLL infiltrate. DISCUSSION: Pneumonia is considered the most common complication of influenza. It could be primary viral pneumonia or secondary to bacterial superinfection due to epithelium disruption and alteration in host immunity response. Mediastinal abscess has not been reported before in the literature as post influenza complication. Our case is first in literature for such life-threatening complication and the key to success is early imaging detection, keeping high level of suspicion when the patient is not responding appropriately to the initial therapy and aggressive surgical and medical management. CONCLUSIONS: Clinical deterioration or inappropriate response to antibiotic therapy in post influenza bacterial pneumonia should raise the suspicion for uncommon complications such as mediastinal abscess and should be investigated with advanced imaging, CT chest with IV contrast or MRI. Reference #1: Martin, C.M., et al., Asian influenza A in Boston, 1957-1958. I. Observations in thirty-two influenza-associated fatal cases. AMA Arch Intern Med, 1959. 103(4): p. 515-31. DISCLOSURES: No relevant relationships by Saira Afzal, source=Web Response No relevant relationships by Mahmoud Alwakeel, source=Web Response No relevant relationships by kuttetoor Gopalakrishna, source=Web Response No relevant relationships by Talha Saleem, source=Web Response

Morphometric and topograpical analysis of retinal abnormalities in central serous chorioretinopathy

Objective: Quantitative morphometric and topographic analysis of specific changes of the retina in patients with the acute central serous chorioretinopathy (CSC) based on annotated tomograms.Methods: 39 patients with the acute CSC (44 eyes – 45 scans) were examined. A complex ophthalmological examination was carried out including 3D optical coherence tomography of maculae. The data was uploaded into CVAT. Three classes of pathological changes were differentiated: 1) retinal neuroepi‑ thelium detachment; 2) retinal pigment epithelium alteration; 3) percolation zones. The analysis of topographical localization of changes and their morphological relations were assessed with a programming language Python.Results: A moderate trend towards vertical asymmetry of the neuroepithelial detachment zone with an excess of cumulative distribution in the lower part of the macula was revealed. Retinal pigment epithelium alteration sites and percolation zones demonstrated a relative peak of representation in the upper nasal part of the macula. In 69.9% and 80% of cases, respectively, abnormalities of retinal pigment epithelium and percolation zones were localized within the limits of neuroepithelial detachment. Direct correlation between the area of neuroepithelial detachment and the area of percolation zones; the area of percolation zones and the area of retinal pigment epithelium alteration; the area of neuroepithelial detachment and the area of retinal pigment epithelium alteration.Conclusions: Percolation zones and abnormalities of retinal pigment epithelium demonstrate similar trends in topo‑ graphical localization and quantitative characteristics and are related to the area of neuroepithelial detachment in CSC. Thus, the number of retinal pigment epithelium abnormalities can serve as an indicator of disease severity.

Evaluation of Corneal Aberration Alterations After Accelerated Transepithelial Corneal Crosslinking

Objective: This study aimed to report the corneal aberration alterations after accelerated transepithelial corneal crosslinking (A-TE CXL) and to investigate the relationship between corrected distance visual acuity (CDVA) and corneal aberrations.
 Methods: Fifty-six eyes of 45 progressive keratoconus (KCN) patients who underwent A-TE CXL were retrospectively evaluated. Total ocular aberrations (TOA), high-order aberrations (HOA), low order aberrations (LOA), and spectacle-CDVA values were recorded preoperatively, 6, and 12 months after the procedure. The alterations of the parameters were compared and correlation analysis was performed between corneal aberrations and CDVA.
 Results: The mean age of the patients was 22.23±3.14 years. The preoperative, postoperative 6 and 12 months median CDVAs were 0.50 (0.20-0.90), 0.60 (0.20-1.0) and 0.60 (0.10-0.90), respectively. The preoperative root means square (RMS)-TOA, RMS-HOA, and RMS-LOA values were 2.4±0.88μm, 1.50±0.59μm, and 1.78±0.88μm, respectively. The CDVA values increased significantly at postoperative-6 month examinations. After the A-TE CXL procedure, the aberrations were detected as 2.58±0.94μm, 1.62±0.57μm, 1.90±0.99μm and 2.38±0.81μm, 1.46±0.57μm, 1.77±0.85μm at 6th and 12th months, respectively. The TOA and HOA values significantly decreased 6 and 12 months after A-TE CXL. The LOA alterations were not statistically significant. The correlation analysis between corneal aberrations and CDVA revealed no significance at any time point.
 Conclusion: Although the TOA and HOA values significantly decreased and CDVA significantly increased in the early postoperative period, a relationship between the CDVA and corneal aberration alterations was not detected. Even the corneal aberration improvement had contributed to the increase in CDVA, evaluation of epithelial structural alterations can be suggested to better understand the clinical outcomes.

Multimodal imaging of chorioretinal folds induced by orbital vascular malformation in two cases.

To investigate the alterations in the retinal pigment epithelium (RPE) in the crest and trough portions of chorioretinal folds (CRFs) induced by an orbital vascular tumor. Review of multimodal imaging in two eyes of two patients with globe compression and CRFs from an orbital vascular tumor. Fundus photography demonstrated obliquely extending CRFs with alternating hyperpigmented and hypopigmented linear alterations in both eyes. Fundus autofluorescence (AF) imaging showed obliquely oriented hypoAF lines, incompletely alternating with hyperAF lines. In Case 1, the hyperAF lines had interspersed hypoAF segments and Case 2 had peripapillary mottling of AF. Fluorescein angiography (FA) showed alternating hyper and hypofluorescent lines in the late phase in Case 1. Optical coherence tomography (OCT) documented relative thinning of RPE at the folded crests in Case 1 and preservation of RPE in Case 2. Swept-source OCT angiography (SS-OCTA) demonstrated oblique hyporeflective lines in the outer retina and choriocapillaris layers in Case 2. These findings suggest that the crest of a CRF represents thinned or rarified RPE with hypoAF, transmission hyperfluorescence (FA), partially attenuated RPE layer (OCT), and isoreflectivity (SS-OCTA) while the trough represents compressed RPE with irregular hyperAF, transmission hypofluorescence (FA), thickened RPE layer (OCT), and hyporeflectivity (SS-OCTA). The anatomic and functional status of the RPE in CRFs based on multimodal imaging reveals normal to attenuated RPE with hypofunctionality at the fold crest and compacted, thickened RPE at the trough with segmental functional impairment on AF imaging. Anatomic information regarding CRFs is evident on OCT, FA, and SS-OCTA while the functional status is depicted on AF.

Altered paracellular permeability in intestinal cell monolayer challenged with lipopolysaccharide: Modulatory effects of pterostilbene metabolites

Epithelial barrier alteration is a central event in the pathogenesis of inflammatory bowel diseases. Lipopolysaccharide, correlated to the pathogenesis of such pathologies, has been demonstrated to cause altered membrane permeability, through the disruption and/or relocation of tight junction proteins, following redox-sensitive mitogen-activated protein kinases (MAPKs) modulation. Pterostilbene and its metabolite pinostilbene are natural stilbenoids which may reach relevant concentrations at intestinal level, together with their glucuronide and sulfate metabolites. The aim of our study was to evaluate the ability of these compounds to inhibit lipopolysaccharide-induced toxic effects on intestinal cell monolayer integrity and to explore the mechanism of action. Caco-2 cells, differentiated as enterocytes, were treated with lipopolysaccharide following pretreatment with the phenolic compounds at 1 μM physiological concentration. Caco-2 monolayer's permeability was monitored with time, measuring the transepithelial electrical resistance. Tight junction proteins were assessed by western blotting and immunofluorescence in lipopolysaccharide-treated cells, in relation to MAPK p38 and ERK1/2 activation. Pretreatment with all the phenolic compounds significantly slowed lipopolysaccharide-induced transepithelial electrical resistance decrease, preserved tight junction proteins levels and reduced MAPKs phosphorylation. The reported findings indicate that pterostilbene and its metabolites may counteract lipopolysaccharide-induced alteration of epithelial permeability, one of the initial events in the intestinal inflammatory process.

Abstract 3377: NSCLC subtype-associated molecular and cellular alterations in the normal-appearing bronchial epithelium

Abstract Rationale: We have previously identified lung cancer-associated gene expression alterations in normal bronchial airway epithelial cells of ever smokers with and without lung cancer. It is unclear, however, whether or not gene expression in the bronchial airway also reflects non-small cell lung cancer (NSCLC) subtypes. In this study, we sought to identify airway gene expression differences between patients with squamous (LUSC) and adenocarcinoma (LUAD) NSCLC and determine if these reflect changes in cell type composition or cell type-specific expression. Methods: Bronchial brushings from ever smokers with NSCLC from the AEGIS I (153 LUSC; 148 LUAD; 154 benign) & II (82 LUSC; 102 LUAD; 74benign) trials were profiled by whole-genome microarrays. The NSCLC-associated gene expression alterations were identified using a linear model adjusting for smoking status in AEGIS I and confirmed in AEGIS II via GSEA. Enriched biological pathways were identified using EnrichR. In parallel, bronchial airway brushings collected from ever smokers undergoing bronchoscopy for suspect lung cancer (17 subjects) were profiled via scRNA-seq using the CEL-Seq2 protocol (3264 cells). Seurat was used to correct for batch effects and identify distinct cell populations. Genes differentially expressed between cell populations using a negative binomial model were clustered into gene sets using WGCNA. Per patient metagene scores were computed across the datasets for each gene set, and differences in these scores between NSCLC subtypes were evaluated using a linear model adjusting for smoking status. Results: 451 differentially expressed genes were found between LUSC v LUAD patients (FDR < 0.05). Genes involved in ciliary function were enriched among genes up-regulated in LUAD whereas keratinization and cancer-associated pathway genes were enriched among LUSC up-regulated genes (FDR < 0.05). In the scRNA-seq data, 15 populations of cells were identified that expressed known epithelial or immune cell type markers. Using WGCNA to cluster genes that distinguish the cell populations (5148 genes, FDR < 0.05) identified 12 gene sets (GS). In AEGIS I, LUSC patients had higher expression of a mitochondrial GS expressed highly in basal cells, a secretory-cell GS, and lower expression of a ionocyte-specific GS than LUAD patients (p = 0.041, 0.0043 and 2.06e-06 respectively). Both LUAD and LUSC patients have lower expression levels of the immune GSs than the benign patients (p = 0.00034 and 0.0008). Concordant results were found in the AEGIS II samples with the same methods. Conclusion: We leveraged bulk and single cell gene expression data and identified molecular differences in the airway field of injury among ever smokers with LUSC versus LUAD that are highly expressed specific cell populations. Our results suggest that there are different responses to injury in the normal-appearing airway that are associated with NSCLC subtype. Citation Format: Xingyi Shi, Jiarui Zhang, Steven Callori, Joshua Campbell, Denise Fine, Yaron Gesthalter, Gang Liu, Xiaohui Xiao, Avrum Spira, Marc Lenburg, Jennifer Beane. NSCLC subtype-associated molecular and cellular alterations in the normal-appearing bronchial epithelium [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3377.

A Comparative Study of the Effect of Melatonin Versus Vitamin C on Aged Labial Tissues in Albino Rats

Background: Structural changes occur with aging, associated with fibrosis and inflammation in body tissues. Aging of oral mucosa causes alterations in oral epithelium and sub-epithelial tissues, due to reduction in certain growth factors, endogenous anti-oxidant enzymes, or both. Aim: to assess anti-aging potential of melatonin & vitamin C on albino rats’ lips.Materials and Methods: 28 male albino rats were used, divided into: Group I: 7 rats aged 6 months (18 years in humans), Group II: 21 rats aged 24 months (72 years in humans), were equally subdivided into 3 subgroups 7 rats each as follows: Subgroup IIA: positive control for other subgroups; Subgroup IIB: received melatonin via gastric gavage (10mg/kg/day) for six consecutive weeks; Subgroup IIC: received vitamin C via gastric gavage (2mg/ml/day) for six consecutive weeks. At the end of the experiment, rats were sacrificed by a high dose of anesthesia. The lips were excised. Specimens were processed for histological examination, stained by H&E, Masson’s Trichrome& Anti-VEGF, examined by light microscope.Results: Subgroup IIA showed statistically significant increase in number of vacuolated epithelial cells, statistically significant reduction in VEGF positive cells, apparent decrease in epithelial thickness, statistically significant reduction in immature collagen fibers’ percentage within connective tissue (CT). Subgroups IIB & IIC, showed significant reduction in number of vacuolated epithelial cells and significant increase in VEGF positive cells and area percentage of immature collagen fibers in CT. However, subgroup IIB’s epithelial structure showed better image and subgroup IIC’s CT structure presented better image.Conclusion: Aging showed structural changes in skin & mucous membrane sides of rat lips, observed within both epithelium and CT. Melatonin & vit. C exhibited efficiency in counteracting these effects. Melatonin presented superior effect on keratinocytes, vit. C showed superiority in repairing senile CT components.

Histological Patterns of Epithelial Alterations in Keratoconus.

Purpose The purpose of this study was to confirm the presence of specific patterns of epithelial response in corneal buttons from keratoconus patients. Methods This was a retrospective and descriptive study. 90 penetrating keratoplasty specimens obtained from patients diagnosed with keratoconus were evaluated using bright-field microscopy. Morphologically identifiable characteristics including epithelial cell density and epithelial thickness were analyzed on hematoxylin and eosin- (H&E-) and periodic acid of Schiff- (PAS-) stained slides. Results Three distinctive patterns of epithelial alteration of the central cornea were established. Pattern 3, in which the central epithelium was as thick as peripheral epithelium, was the commonest (44.4%), followed by the pattern 2, defined as central epithelium thinner than periphery epithelium (38.9%), and the uncommonest pattern was number 1, with central epithelium thicker than the periphery (16.7%). Conclusions Three distinctive histologic patterns that could potentially have a diagnostic and prognostic value in keratoconus patients were found.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) induce epigenetic alterations and promote human breast cell carcinogenesis in vitro

Gene–environment interactions are involved in the development of breast cancer, the tumor type that accounts for the majority of the cancer-related deaths among women. Here, we demonstrate that exposure to PFOS (10 µM) and PFOA (100 µM)—two contaminants ubiquitously found in human blood—for 72 h induced breast epithelial cell (MCF-10A cell line) proliferation and alteration of regulatory cell-cycle proteins (cyclin D1, CDK6, p21, p53, p27, ERK 1/2 and p38) that persisted after a multitude of cell divisions. The contaminants also promoted cell migration and invasion by reducing the levels of E-cadherin, occludin and β-integrin in the unexposed daughter cells. The compounds further induced an increase in global DNA methylation and differentially altered histone modifications, epigenetic mechanisms implicated in tumorigenesis. This mechanistic evidence for PFOS- and PFOA-induced malignant transformation of human breast cells supports a role of these abundant contaminants in the development and progression of breast cancer. Increased knowledge of contaminant-induced effects and their contribution to breast tumorigenesis is important for a better understanding of gene–environment interactions in the etiology of breast cancer.

Evaluation of larvicidal activity of Piper longum leaf against the dengue vector, Aedes aegypti, malarial vector, Anopheles stephensi and filariasis vector, Culex quinquefasciatus

Vector-borne diseases impose enormous menace worldwide including India. The principal strategies for combating diseases are vector control including the use of ovicide and larvicide against mosquitoes. The present study assessed the role of larvicidal and ovicidal properties of dried leaf extract of Piper longum and also determined their toxicity against three important 3rd instar mosquito larvae, viz., Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus. The plant extracts with different concentrations caused a significant mortality as assayed by WHO (2005) procedure. The aqueous extract of P. longum (PLWE) showed the highest larval mortality on 24 h post treatment. PLWE showed ovicidal activity with the mean percent hatchability of egg(s) raft of three vectors on 48 h post treatment. The initial phytochemical screening of PLWE showed terpenoids, alkaloids etc. and gas chromatography–mass spectroscopy (GC–MS) analysis showed chemical constituents such as Eugenol, n-Hexadecanoic acid, Phytol, Oleic Acid, 4-Chromanol, 2,4-Di‑tert‑butylphenol, Tetradecanoic acid etc. Further, the study of histopathology showed alterations in the midgut epithelium with PLWE treatment causing larval death. Thus, our data suggest that the PLWE is the promising larvicidal activity to control the disease vectors and to our knowledge, larvicidal properties of PLWE are the first report so far. Further in-depth study is needed to establish mechanism of action of larvicidal activity of plant extract at molecular level.

A Clinicopathological Approach to Odontogenic Cysts: the Role of Cytokeratin 17 and bcl2 Immunohistochemistry in Identifying Odontogenic Keratocysts

Odontogenic keratocysts (OKCs) are developmental cysts of the jaws that require proper diagnosis due to their potential for local aggressive growth and recurrences. OKCs have a typical parakeratotic epithelium demonstrating transepithelial cytokeratin 17 (CK17) and basal bcl2 staining on immunohistochemistry (IHC), which distinguishes them from other common jaw cysts. Secondary to inflammation, the epithelial lining may be altered and loses the typical IHC phenotype. The aim of the present study was to analyse a series of consecutive jaw cysts for their expression of CK17 and bcl2 and assess how these IHC stains may help in their diagnosis. All cysts were retrospectively assessed for available clinical, radiological and pathological findings and diagnoses were revised whenever needed. 85 cysts from 72 patients were collected from two departments. The series had 21 OKCs, the remaining non-OKCs included radicular/residual, dentigerous, paradental, lateral periodontal, botryoid odontogenic cysts. OKCs with typical epithelium showed the typical IHC phenotype, which was generally lost in inflammation-associated altered epithelium. Contrarily to earlier descriptions, a wide variety of CK17 positivity was seen in the majority of non-OKCs, including focal transepithelial staining. Basal bcl2 staining was also seen in 16 non-OKCs. These stainings were never as strong in intensity as seen in OKCs. One case was histopathologically identified as OKC due to focally maintained IHC profile. CK17 and bcl2 IHC may help in the diagnosis of OKCs, but must be interpreted with caution and is not a yes or no tool in the diagnostic puzzle.

P73 C-terminus is dispensable for multiciliogenesis

ABSTRACT The p53 family transcriptional factor p73 plays a pivotal role in development. Ablation of p73 results in severe neurodevelopmental defects, chronic infections, inflammation and infertility. In addition to this, Trp73−\\- mice display severe alteration in the ciliated epithelial lining and the full-length N-terminal isoform TAp73 has been implicated in the control of multiciliogenesis transcriptional program. With our recently generated Trp73Δ13/Δ13 mouse model, we interrogate the physiological role of p73 C-terminal isoforms in vivo. Trp73Δ13/Δ13 mice lack exon 13 in Trp73 gene, producing an ectopic switch from the C-terminal isoforms p73α to p73β. Trp73Δ13/Δ13 mice show a pattern of expression of TAp73 comparable to the wild-type littermates, indicating that the α to β switch does not significantly alter the expression of the gene in this cell type. Moreover, Trp73Δ13/Δ13 do not display any significant alteration in the airway ciliated epithelium, suggesting that in this context p73β can fully substitute the function of the longer isoform p73α. Similarly, Trp73Δ13/Δ13 ciliated epithelium of the brain ependyma also does appear defective. In this district however expression of TAp73 is not detectable, indicating that expression of the gene might be compensated by alternative mechanisms. Overall our work indicates that C-terminus p73 is dispensable for the multiciliogenesis program and suggests a possible tissue-specific effect of p73 alternative splicing.

Physiological and behavioral interactions of a predator with its prey under indirect exposure to the insect growth regulator lufenuron

Growth regulating insecticides, such as lufenuron, are recommended for pest management due to their action on the ecdysis process and low toxicity to non-target species. However, these insecticides affect some non-target insects, such as Podisus nigrispinus Dallas, and can interfere with the control of lepidopteran pests by this predator. This study evaluated the impacts of indirect ingestion of lufenuron on the nutritional and histological characteristics of P. nigrispinus, as well as this predator's consumption rate, prey preference, and the weight and nutritional aspects of the prey, Alabama argillacea Hübner. Fourth and fifth instar P. nigrispinus nymphs preying upon A. argillacea larvae fed on cotton leaves that were either untreated or treated with lufenuron were evaluated. For the prey analysis, third instar A. argillacea larvae that had fed on cotton leaves treated or untreated with lufenuron were used. Exposure of P. nigrispinus to lufenuron resulted in a reduction in lipid, sugar, and glycogen contents in fourth instar nymphs; a greater number of treated than untreated prey was chosen by fourth instar nymphs, in a no-choice test; increased lipid content in fifth instar nymphs; histological alterations, such as cellular disorganization and desquamation, lysis of the epithelium; and decreased survival were observed in both evaluation instars. Prey preference was not affected. Lufenuron-treated A. argillacea larvae exhibited a reduction in glycogen content, while prey weight was not affected. These results provide an important resource for pest management decisions, since lufenuron induced biochemical and histological alterations in the midgut epithelium of P. nigrispinus, affecting its survival and possibly compromising its potential as a biological control agent.

Minoxidil induced central serous Chorioretinopathy treated with oral Eplerenone \u2013 a case report

BackgroundMinoxidil solution has routinely been used for decades for the treatment of androgenic alopecia. Central serous chorioretinopathy (CSCR) is a rare side-effect noted following prolonged topical minoxidil therapy for androgenic alopecia. In this report, we describe a case of a 41-year-old young man who developed CSCR following prolonged therapy with topical Minoxidil solution and was treated with oral eplerenone.Case presentationA 41-year-old male presented to the retina clinic with complaints of seeing a black spot, blurred vision and metamorphopsia involving the right eye for the past 4 months. He was on treatment for androgenic alopecia with topical 5% Minoxidil application on scalp two times a day. He noticed the symptoms 8 months after starting the treatment and had stopped the medication since the past 2 months. On examination, best-corrected visual acuity was 20/20 in both eyes. Fundoscopic examination of the right eye with +78D lens on slit lamp revealed the presence of subretinal fluid and few focal spots of retinal pigment epithelial alterations. Optical coherence tomography scan evaluation showed the presence of subretinal fluid (SRF) and pachychoroid supporting the diagnosis of CSCR. Indocyanine green angiography revealed dilated hyperpermeable choroidal vasculature on the nasal side of the fovea in the early and later phases of the angiogram. The patient was diagnosed with CSCR as a possible consequence of the topical minoxidil solution. Patient was asked to avoid future use of Minoxidil and was started on oral eplerenone therapy 50 mg/day for 4 consecutive weeks. One month later, there was complete resolution of his symptoms and SRF. At the final follow-up visit, 2 months after starting the therapy, there was no recurrence of SRF.ConclusionCSCR is a rare side-effect noted following prolonged topical minoxidil therapy for androgenic alopecia. While we found oral eplerenone to be safe and effective, further studies would be required before it can be routinely used in the population.

Epithelial Alteration Associated With Recovery From Laryngeal Squamous Metaplasia in Rats: Kinetics of Recovery From a Test Item-Related Change.

Squamous metaplasia is a nonspecific adaptive response to chronic irritation in the larynx and is often diagnosed as a test item-related change in rat inhalation studies. Investigating scientists are frequently asked to assess the adversity of laryngeal squamous metaplasia and to interpret its relevance to human risk. One factor in predicting relevance to human risk is the kinetics (degree and speed) of recovery following the cessation of exposure to the test item. Most reports describing recovery from squamous metaplasia in the rat larynx discuss the more severe end of the spectrum of metaplastic change (moderate to severe) and include relatively long (6 weeks or more) recovery periods. We conducted 2 studies to evaluate the toxicity and recovery from any potential effects of 4-(Chloro-2-methylphenoxy) butyric (MCPB) acid, a herbicide, when administered by inhalation to young male Sprague Dawley rats for 3 to 4 weeks. The studies resulted in minimal to moderate laryngeal squamous metaplasia for which we describe the kinetics of recovery over 1 to 4 weeks. We found that the microscopic change epithelial alteration, which is normally considered to be a precursor in the development of squamous metaplasia, can occur as a transitional stage between squamous and normal epithelium during recovery.