Search results for: Reva G. McDowell

Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das

Abstract:

Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.

Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death

Procedia PDF Downloads 72

Authors: Katherine van Kampen, Reva Qiu, Patricia Farrugia

Abstract:

Orthopedic surgery has fallen behind when it comes to gender diversity despite medical school classes reaching gender parity. Studies have shown that orthopedic surgery would require 117 years to reach gender parity with the trainee population, the longest time than any other specialty, including neurosurgery, urology, and otolaryngology. The barriers that face women in orthopedic surgery have been well researched, with contributing factors being on-going stereotypes of the field, lack of women mentors, and gender roles outside of the hospital. Furthermore, women in orthopedic surgery face barriers to achieve promotion, publications, and leadership roles leading to a “leaky pipeline,” resulting in less and less women in key academic roles in the field. It is a complex topic with barriers and challenges faced in medical school, residency, and throughout employment. Our scoping review seeks to understand these challenges across a temporal timeline and to further characterize such barriers and the driving factors behind them. To this date, authors did not find a scoping review that seeks to look broadly at factors impacting the decreased amount of women entering orthopedics and the factors that cause women to hit a “glass ceiling”, the idea that women will not achieve the same success as men despite the same qualifications, upon entering the field. This scoping review is the first of its kind to attempt to summarize the large body of research focusing on women in orthopedic surgery from the preconceptions in medical school impacting their desire to pursue orthopedics all the way to employment, including challenges to academic success and financial success. Literature databases will be searched with the following key terms: women, gender inequity, workforce, orthopedics, and citations will be hand searched and collected. Articles included will discuss gender inequality within orthopedics with non-english, patient related articles excluded. Full-text review will seek to characterize the specific barriers faced by women across medical school, residency, and employment. Themes that are expected to be highlighted are workforce data, women in orthopedic leadership, medical student perspectives on the specialty, and gender bias and discrimination in the field.

Keywords: orthopedics, gender equity, workforce, women in surgery

Procedia PDF Downloads 59

Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

Abstract:

Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

Procedia PDF Downloads 231