Chondroitin Sulfate Promotes Interstitial Cell Activation and Calcification in an In Vitro Model of the Aortic Valve.

PURPOSE: Calcific aortic valve disease (CAVD), has been characterized as a cascade of cellular changes leading to leaflet thickening and valvular calcification. In diseased aortic valves, glycosaminoglycans (GAGs) normally found in the valve spongiosa migrate to the collagen I-rich fibrosa layer near calcified nodules. Current treatments for CAVD are limited to valve replacement or drugs tailored to other cardiovascular diseases. METHODS: Porcine aortic valve interstitial cells and porcine aortic valve endothelial cells were seeded into collagen I hydrogels of varying initial stiffness or initial stiffness-matched collagen I hydrogels containing the glycosaminoglycans chondroitin sulfate (CS), hyaluronic acid (HA), or dermatan sulfate (DS). Assays were performed after 2 weeks in culture to determine cell gene expression, protein expression, protein secretion, and calcification. Multiple regression analyses were performed to determine the importance of initial hydrogel stiffness, GAGs, and the presence of endothelial cells on calcification, both with and without osteogenic medium. RESULTS: High initial stiffness hydrogels and osteogenic medium promoted calcification, while for DS or HA the presence of endothelial cells prevented calcification. CS was found to increase the expression of pro-calcific genes, increase activated myofibroblast protein expression, induce the secretion of collagen I by activated interstitial cells, and increase calcified nodule formation. CONCLUSION: This study demonstrates a more complete model of aortic valve disease, including endothelial cells, interstitial cells, and a stiff and disease-like ECM. In vitro models of both healthy and diseased valves can be useful for understanding the mechanisms of CAVD pathogenesis and provide a model for testing novel therapeutics.

Improper Use of Topical Corticosteroids in Tinea Infections in a Tertiary Care Hospital.

BACKGROUND: Steroid-modified tinea, also known as tinea incognito, is an infection by the dermatophytes, where the clinical morphology is modified due to corticosteroids, either systemic or topical. Rampant use of topical corticosteroids has led to increasing recurrence in tinea infections. METHODS: All consenting cases of tinea presenting to outpatient department of dermatology department of Civil Service Hospital from March to August 2020 for a total of 6 months were included in this study. Tinea infection involving only the palms, soles, nails or scalp were excluded. RESULTS: A total of 200 patients were included in this study. Among these, 175 patients (87.5%) were using topical corticosteroids. A significant association was noted between dermatophyte infection of more than one month and topical corticosteroids use (p<0.05). This study revealed that males were using super-potent topical corticosteroids more as compared to females (p<0.05). Moreover, no association was noted between the level of education attained and the use of topical corticosteroids (p=0.91). Only 25 (12%) patients were either using correct or no topical medications during the time of consultation with the dermatologist. Among the patients using topical corticosteroids, 155 (88.6%) patients were using them on recommendation of the local pharmacist and only 2 (1.2%) patients were prescribed by a physician. CONCLUSIONS: In short, use of topical steroids was rampant among patients with tinea whilst 77.5% patients procured steroid topicals over-the-counter. Hence, a tougher law and strict regulatory guidelines deemed necessary to curb the unauthorized and rampant sale of these medicines.

Laparoscopic Management of Dermoid Cyst of Ovary is a Safe Procedure.

BACKGROUND: Dermoid cyst, a common benign neoplasm of ovary in women, needs treatment because of the risk of torsion, rupture, and malignant change. Laparoscopic surgery nowadays is the preferred treatment modality, but the only issue is its safety in case of rupture and spillage of its contents with the risk of chemical peritonitis and malignant dissemination. Aim of the study was to find out the safety of laparoscopic surgery for dermoid cyst of ovary. METHODS: It was a retrospective study done from January 2017 to December 2019. All the women with diagnosis of dermoid cyst of ovary managed laparoscopically either salpingoophorectomy or cystectomy were taken into study. Analysis of size of the cyst operated, the time taken, spillage rate, duration of hospital stay, and post-operative complications especially chemical peritonitis was done. RESULTS: There were 61 women who had undergone laparoscopic surgery. Laparoscopic cystectomy was done in 68.9% (n=42), laparoscopic salpingoophorectomy in 29.5% (n=18). Mean age of the patient was 31.74±8.38 years. Mean size was 6.21±1.99 cm. Rupture and spillage were observed in 21.3% (n=13) that were > 5cm in diameter (X2= 3.62, p=0.05). Larger the size of the cyst, more the surgical time was noted (X2=6.26, p=0.04). Significant difference in mean operating time in case of cyst rupture and spillage (p=0.004) was observed. Mean hospital stay was 53.5±1.3 hours. No case of chemical peritonitis was observed with spillage. All cases had histopathology of mature cystic teratoma. CONCLUSIONS: Laparoscopic surgery is safe for dermoid cyst of ovary even with rupture and spillage of its contents.

Extracellular Matrix Rigidity Modulates Human Cervical Smooth Muscle Contractility-New Insights into Premature Cervical Failure and Spontaneous Preterm Birth.

Spontaneous preterm birth (sPTB), a major cause of infant morbidity and mortality, must involve premature cervical softening/dilation for a preterm vaginal delivery to occur. Yet, the mechanism behind premature cervical softening/dilation in humans remains unclear. We previously reported the non-pregnant human cervix contains considerably more cervical smooth muscle cells (CSMC) than historically appreciated and the CSMC organization resembles a sphincter. We hypothesize that premature cervical dilation leading to sPTB may be due to (1) an inherent CSMC contractility defect resulting in sphincter failure and/or (2) altered cervical extracellular matrix (ECM) rigidity which influences CSMC contractility. To test these hypotheses, we utilized immunohistochemistry to confirm this CSMC phenotype persists in the human pregnant cervix and then assessed in vitro arrays of contractility (F:G actin ratios, PDMS pillar arrays) using primary CSMC from pregnant women with and without premature cervical failure (PCF). We show that CSMC from pregnant women with PCF do not have an inherent CSMC contractility defect but that CSMC exhibit decreased contractility when exposed to soft ECM. Given this finding, we used UPLC-ESI-MS/MS to evaluate collagen cross-link profiles in the cervical tissue from non-pregnant women with and without PCF and found that women with PCF have decreased collagen cross-link maturity ratios, which correlates to softer cervical tissue. These findings suggest having soft cervical ECM may lead to decreased CSMC contractile tone and a predisposition to sphincter laxity that contributes to sPTB. Further studies are needed to explore the interaction between cervical ECM properties and CSMC cellular behavior when investigating the pathophysiology of sPTB.

Chronic Urticaria and Its Impact on the Quality of Life of Nepalese Patients.

Chronic urticaria (CU) is a skin condition characterized by sudden and recurrent episodes of wheals, angioedema, or both and commonly associated with itching for a duration of more than six weeks. The available data indicate that urticaria markedly affects both objective functioning and subjective well-being of patients. A review of patients' records with chronic urticaria attending Civil Service Hospital from January 2018 to December 2019 was done. A detailed demographic data of all patients with chronic urticaria was also retrieved. Dermatology Life Quality Index questionnaire (DLQI) Nepalese version was used for the assessment of the impact of disease on life quality. Mann-Whitney U-test was applied to compare means, and principle component analysis for factor analysis was used. A total of 149 patients were included, with a male-to-female ratio of 1 : 1.9. The mean age of the study population was 32.86 ± 12.837 years. The mean DLQI score was 8.30 ± 6.73 with men having a significantly greater score than women (p < 0.02). DLQI scores negatively correlated with age (p < 0.01). There was a high internal consistency among items (Cronbach's alpha 0.89), and all items had satisfactory correlation with each other as well. Principle component extraction revealed that there were two underlying factors in the DLQI questionnaire on measuring quality of life in chronic urticaria. Males had a greater impairment in quality of life than females due to chronic urticaria. Most severe impairment was seen in symptoms/feelings subdomain. It also revealed that there were two different underlying factors in DLQI questionnaire.

Functional Outcomes of Capitellum Fractures Treated by Open Reduction and Internal Fixation with Herbert Screw: A Descriptive Cross-sectional Study.

INTRODUCTION: Based on the complex intra-articular nature of capitellum fractures, it has been sometimes difficult to formulate a universally accepted method of surgical treatment. The purpose of this study is to present the functional outcomes of capitellum fractures after fixation with Herbert screw including the safety and tips of the surgical approach. METHODS: This descriptive cross-sectional study was done from December 2014 to November 2019. Ethical approval was taken. The study included 22 capitellum fractures treated by open reduction and internal fixation with Herbert screws either lateral or anterolateral approach. Functional outcomes were assessed with Mayo elbow performance index scores at the latest follow-up visit. Convenient sampling was done. Data entry was done using the Statistical Package for the Social Sciences (version16.0). RESULTS: Out of 22 surgeries, the average time to unite the fracture was 11.13±1.20 weeks (range 9 to 15). The mean range of movement for flexion and extension was 138.41±8.22 degree while the mean supination and pronation range was 161.59±6.79 degree. The average time of follow-up in this series was 37.45±9.43 weeks (range 22 to 58 weeks). Similarly, the mean Mayo elbow performance index score at the latest follow-up was 90.22±8.65 (range 70 to 100). CONCLUSIONS: Careful assessment and radiological evaluation, anatomical reduction, and stable fixation with Herbert screws maintaining the minimal damage to the articular cartilage can maximize the functional outcomes and minimize the incidence of complications.

Endothelial to mesenchymal transformation is induced by altered extracellular matrix in aortic valve endothelial cells.

Alterations in shear stress, mechanical deformation, extracellular matrix (ECM) composition and exposure to inflammatory conditions are known to cause endothelial to mesenchymal transformation (EndMT). This change in endothelial phenotype has only recently been linked to adult pathologies such as cancer progression, organ fibrosis, and calcific aortic valve disease; and its function in adult physiology, especially in response to tissue mechanics, has not been rigorously investigated. EndMT is a response to mechanical and biochemical signals that results in the remodeling of underlying tissues. In diseased aortic valves, glycosaminoglycans (GAGs) are present in the collagen-rich valve fibrosa, and are deposited near calcified nodules. In this study, in vitro models of early and late-stage valve disease were developed by incorporating the GAGs chondroitin sulfate (CS), hyaluronic acid, and dermatan sulfate into 3D collagen hydrogels with or without exposure to TGF-ß1 to simulate EndMT in response to microenvironmental changes. High levels of CS induced the highest rate of EndMT and led to the most collagen I and GAG production by mesenchymally transformed cells, which indicates a cell phenotype most likely to promote fibrotic disease. Mesenchymal transformation due to altered ECM was found to depend on cell-ECM bond strength and extracellular signal-regulated protein kinases 1/2 signaling. Determining the environmental conditions that induce and promote EndMT, and the subsequent behavior of mesenchymally transformed cells, will advance understanding on the role of endothelial cells in tissue regeneration or disease progression. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2729-2741, 2017.