The benign nature and rare occurrence of cardiac myxoma as a possible consequence of the limited cardiac proliferative/ regenerative potential: a systematic review.

BACKGROUND: Cardiac Myxoma is a primary tumor of heart. Its origins, rarity of the occurrence of primary cardiac tumors and how it may be related to limited cardiac regenerative potential, are not yet entirely known. This study investigates the key cardiac genes/ transcription factors (TFs) and signaling pathways to understand these important questions. METHODS: Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving cardiac myxoma, cardiac genes/TFs/signaling pathways and their roles in cardiogenesis, proliferation, differentiation, key interactions and tumorigenesis, with focus on cardiomyocytes. RESULTS: The cardiac genetic landscape is governed by a very tight control between proliferation and differentiation-related genes/TFs/pathways. Cardiac myxoma originates possibly as a consequence of dysregulations in the gene expression of differentiation regulators including Tbx5, GATA4, HAND1/2, MYOCD, HOPX, BMPs. Such dysregulations switch the expression of cardiomyocytes into progenitor-like state in cardiac myxoma development by dysregulating Isl1, Baf60 complex, Wnt, FGF, Notch, Mef2c and others. The Nkx2-5 and MSX2 contribute predominantly to both proliferation and differentiation of Cardiac Progenitor Cells (CPCs), may possibly serve roles based on the microenvironment and the direction of cell circuitry in cardiac tumorigenesis. The Nkx2-5 in cardiac myxoma may serve to limit progression of tumorigenesis as it has massive control over the proliferation of CPCs. The cardiac cell type-specific genetic programming plays governing role in controlling the tumorigenesis and regenerative potential. CONCLUSION: The cardiomyocytes have very limited proliferative and regenerative potential. They survive for long periods of time and tightly maintain the gene expression of differentiation genes such as Tbx5, GATA4 that interact with tumor suppressors (TS) and exert TS like effect. The total effect such gene expression exerts is responsible for the rare occurrence and benign nature of primary cardiac tumors. This prevents the progression of tumorigenesis. But this also limits the regenerative and proliferative potential of cardiomyocytes. Cardiac Myxoma develops as a consequence of dysregulations in these key genes which revert the cells towards progenitor-like state, hallmark of CM. The CM development in carney complex also signifies the role of TS in cardiac cells.

Knowledge and Attitude of General Pakistani Population Towards Antibiotic Resistance.

Introduction The emergence and continuous spread of drug resistant bacteria has become one of the leading health concerns globally. Persistent failure to develop and/or discover new antibiotics along with irrational use of existing antibiotics is associated with rise in antibiotic resistance. There is poor understanding of antibiotics usage and their preciousness among the masses which result in careless utilization and hence, the emerging antibiotic resistance. The aim of this study is to evaluate the knowledge and attitude of Pakistanis towards antimicrobial resistance (AMR). Methods This observational cross-sectional survey was designed in the form of an online pro forma circulated in January 2019. It was a self-structured pro forma which included age, gender, and 10 questions - five to assess the knowledge and five to assess the attitude towards AMR. Each question was to be responded with a "Yes" or a "No." For knowledge assessing questions "do not know" was also an option. Data was entered and analysed using SPSS version 22 (IBM Corp., Armonk, NY). Results Of 1,132 participants, 837 (73.9%) thought that it was alright to stop antibiotics course whenever they felt better, 505 (44.6%) thought that frequent and unnecessary use of antibiotics actually decrease their effectiveness, and 208 (18.4%) participants thought it was correct to take antibiotics for cold and influenza. There were 157 (13.9%) participants who had not followed the duration of treatment as given in their doctor's prescription, 49 (4.4%) who had changed their antibiotic dose without doctor consultation, 467 (41.3%) who had reused leftover antibiotics from their previous prescription, 700 (61.8%) who had suggested it to their doctors to prescribe them antibiotics and 378 (33.4%) participants who had purchased antibiotics without any prescription in the last one year. Conclusion Pakistani individuals are not as knowledgeable about antibiotic resistance as severe the issue is in this region. Their attitude towards utilization of antibiotics is not very promising. It becomes essential to initiate antibiotic stewardship programs and educate the masses regarding efficacious and safe use of antibiotics in this region.