Endocrine disrupting chemicals (EDCs) have been known to adversely affect the endocrine system leading to compromised functions of hormones. The presence of these compounds in everyday products such as canned food, water bottles, plastics, cosmetics, fertilizers, kid’s toys and many others goods is a greater concern for general population. The persistent and long-term use of EDCs has deleterious effects on human reproductive health by interfering with the synthesis and mechanism of action of sex hormones. Any change during the synthesis or action of the sex hormones may result in abnormal reproductive functions which includes developmental anomalies in the reproductive tract and decline in semen quality. The present paper provides an overview of the EDCs and their possible impact on male reproductive health with major focus on semen quality which leads to male infertility.

It is increasingly appreciated that 3D cultures are more predictive of in vivo therapeutic efficacy than 2D cultures. Using in vitro 3D type I collagen cultures of human colorectal cancer (CRC) cell line HCA-7 derivatives CC, SC, and CC-CR, we previously identified that activation of receptor tyrosine kinases (RTKs) MET and RON contributed to resistance to the EGF receptor (EGFR)-directed therapeutic antibody cetuximab. The de novo mode of cetuximab resistance in SC cells could be overcome by crizotinib, a multi-RTK inhibitor that also targets MET and RON. We now show that crizotinib also overcomes acquired cetuximab resistance in CC-CR cells. Phospho-RTK array analysis showed increased phosphorylation of several RTKs, including MET and RON, in SC and CC-CR cells compared to cetuximab-sensitive CC counterparts. Furthermore, other multi-RTK inhibitors cabozantinib and BMS-777607 helped overcome cetuximab resistance, as measured by 3D colony growth and activation state of key signaling molecules. Conversely, addition of RTK ligands HGF and NRG1 induced cetuximab resistance in CC cells, which could be blocked by addition of crizotinib. We further determined the mechanism of the cooperative effect of cetuximab and crizotinib by FACS analysis and observed increased cell cycle arrest in G1 phase in cetuximab-resistant CRC 3D cultures. Finally, we show that crizotinib overcomes cetuximab resistance in vivo in SC nude mice xenografts. Thus, our work shows that multi-RTK inhibition strategy is a potent, broadly applicable strategy to overcome resistance to EGFR-targeted therapeutics in CRC and highlights the relevance of 3D cultures in these studies. Statement of implication: Using in vitro 3D CRC cultures and in vivo CRC xenografts, we show that parallel inhibition of multiple RTKs with small molecule inhibitors overcomes de novo and acquired resistance to EGFR-directed therapies in CRC.

The purpose of this study was to investigate the prevalence and configuration of Middle Mesial Canals (MMC) and isthmi in mandibular molars in Pakistani population using Cone Beam Computed Tomography (CBCT). METHODOLOGY: Sixty CBCTs of patients were selected randomly from database of University College of Dentistry, Lahore. First and second permanent mandibular molars without evidence of previous endodontic treatment, full coverage restoration or root resorption were evaluated for the number of roots, canals and the presence and configuration of MMC and isthmi. The age and gender of patients were also recorded. SPSS was used for statistical analysis using chi-square test. Significance level was set at 5% (P < 0.05). RESULTS: Out of 189 mandibular molars, MMCs were found in 9 and isthmi in 62 teeth. No statistical association was found between the presence of MMC and age, gender, side or tooth type. Significantly more isthmi were found in second molars, females and younger patients, P < 0.05. CONCLUSION: MMC and isthmi in mesial roots of mandibular molars are not unusual findings in our population and CBCT can be a valuable tool for their detection.

Authors' Contribution WN gave the idea and provided the facilities and guidance and also helped in writing the manuscript. BB collected the samples and provided the data. NQ and JG performed the experiments and wrote the manuscript. ED analyzed the data. SW helped in writing the manuscript. CG helped in experimentation. HG helped in bioinformatics analysis. HJ helped in sample collection. BR helped in figure preparation. TH helped in data analysis. All authors reviewed the article.

Introduction: Overuse of antibiotics can lead to antimicrobial resistance and unnecessary costs. Although early studies reported improved outcomes following use of perioperative antibiotics for tonsillectomy, more recent studies have not been able to demonstrate a significant benefit on post tonsillectomy morbidity. Objective: To determine the need for postoperative antibiotics in children undergoing tonsillectomy under aseptic conditions at two tertiary care hospitals of Peshawar. Materials & Methods: Children aged 5-14 years admitted to the departments of Otorhinolaryngology-A unit of Hayatabad Medical Complex and Rehman Medical Institute, Peshawar from March 01, 2018 to September 30, 2018 for recurrent sore throat and recurrent quinsy were included in this quasi-experimental study based on prospective data collection and convenience sampling. Children with blood dyscrasias, upper and lower respiratory tract infections, and cardiopulmonary diseases were excluded. Routine preoperative investigations were done, and all were given postoperative analgesics. The patients were divided into two consecutive groups of 60 each; Group-A was given Co-amoxiclav 20mg/5mg/kg/day for 10 days and Group-B was not given any antibiotic. During their stay in the hospital and on follow up they were asked about pain via Visual Analogue Scale, and presence of fever and/or bleeding were documented. Results: Of 120 children, 50 (41.6%) were males and 70 (58.4%) were females, of ages 05-14 years; 01(1.6%) from Group-A and 01(1.6%) from Group-B presented with reactionary hemorrhage. However, 01(1.6%) from Group-A and 25(40%) from Group-B presented with secondary hemorrhage for which they were readmitted and put on injectable antibiotics. Similarly, 05(8.3%) from Group-A and 14(23.3%) from Group-B presented with pain for which pain killers were prescribed. Conclusion: Post tonsillectomy antibiotics may have a role in reducing the morbidities associated with the procedure in our setup. Keywords: Tonsillectomy; Postoperative Infections; Antibiotic Resistance; Hemorrhage.