A Solid Phase Assay For Topoisomerase I Interfacial Poisons And Catalytic Inhibitors

We report a mechanism based screening technique to rapidly identify eukaryotic topoisomerase I targeting agents. The method is based on genetic tagging of topoisomerase I to immobilize the enzyme on a solid surface in a microtiter well format. DNA is added to the wells and retained DNA is detected by Picogreen fluorescence. Compounds that result in an increase in Picogreen staining represent potential topoisomerase interfacial poisons while those that reduce fluorescence report catalytic inhibitors; therefore, the solid phase assay represents a „bimodal‟ readout that reveals mechanisms of action. The method has been demonstrated to work with known interfacial poisons and catalytic inhibitors. In addition to specific topoisomerase targeting drugs, the method also weakly detects other relevant anticancer agents, such as potent DNA alkylating and intercalating compounds; therefore, topoisomerase I HTS represents an excellent tool for searching and identifying novel genotoxic agents. This method is rapid, robust, economical and scalable for large library screens

RESPIRATORY SYNCYTIAL VIRUS INFECTION INDUCES NECROPTOTIC LYTIC CELL DEATH VIA ACTIVATION OF ENDOPLASMIC RETICULUM STRESS PATHWAYS

Human respiratory syncytial virus (RSV) is a major cause of viral bronchiolitis and pneumonia worldwide. Pneumonia and bronchiolitis during RSV infection are caused by hyper-inflammation in the airway. One of the key factors involved in exaggerated lung inflammation during RSV infection is necroptotic lytic cell death of RSV infected immune cells like macrophages. Intracellular components released in the extracellular milieu due to lytic cell death acts as Damage associated molecular patterns (DAMPs) to exaggerate inflammation. During infection, RSV glycoproteins compete with host proteins to activate ER stress pathway as part of the Unfolded protein response (UPR). ER stress pathway is activated via three ER stress sensors, namely PERK, IRE1 and ATF6. Although RSV infection induce both necroptotic lytic cell death in macrophages, whether RSV utilizes ER stress pathways to induce lytic cell death is unknown. Our study revealed that RSV induces lytic cell death in macrophages by using ATF6 mediated ER stress pathway. RSV infection led to significant induction in ATF6 protein expression. Furthermore, RSV infection resulted in ATF6 activation in macrophages as evident from the detection of the transcriptionally active cleaved ATF6p50 form of ATF6 in RSV infected macrophages. Thus, our studies have demonstrated a positive role of ATF6 dependent ER stress pathway during RSV-mediated necroptotic lytic cell death of macrophages via ATF6 protein induction and activation in RSV infected macrophages

Exploring Disparities in Oregon's Medicaid Patient health Care Experience: 2007 and 2011

Examining committee: Jessica Greene, faculty advisorCreating equitable access to health services is a key aim for U.S. health policy. In Oregon, House Bill 3650, which established Coordinated Care Organizations (CCO), seeks to eliminate racial and ethnic disparities in the Oregon Health Plan (OHP). Documented racial and ethnic disparities exist among OHP recipients in areas of health care utilization and patient experience. American Indian and Black children had lower rates of preventive services than Whites, American Indians had higher rates of potentially avoidable hospitalizations, and Latinos reported lower ratings of courteouse office staff and quick care than Whites. These findings are concerning because any issues exacerbated by upcoming changes to Medicaid may disproportionately affect these vulnerable populations

Awareness of eye donation among medical students of tertiary care hospital, Bangalore

Introduction: Blindness is a worldwide problem. Corneal blindness accounts for 0.9%of blindness in India. Approximately 0.12 million people are corneal blind. Restoration of their vision is possible only through transplantation. Though 45000 eyes are collected every year, it does not meet half the requirement. Well informed medical students could be expected to enhance eye donation rates. Objectives: To assess the awareness regarding eye donation among pre final and final year medical students of a tertiary care hospital in Bangalore. Methodology: A Cross sectional descriptive study was conducted among 160 pre final and final year medical students of a tertiary care hospital in Bangalore during September to November 2013.The study tool was pre tested semi structured self administered questionnaire Results:99.3% of students are aware of eye donation out of which only 9% pledged for donation. Objection by the family members (30.6%)is the main reason for not pledging. Knowledge of the fact that eyes should be removed within 6hours of death was found in 86.8%.A remarkable number of students (93%) were aware of shortage of donors in India. The main source of information is television among 41% of students. Conclusion: The results of the study indicate that although awareness regarding eye donation is high, there is lack of motivation related to eye donation

QOS ENHANCEMENTS THROUGH ADAPTING AIFSN PARAMETER

Enhanced Distributed Channel Access is a priority mechanism which supports access category (AC) wise QoS by differentiating initial contention window (CW) size and arbitration inter-frame space (AIFS) time. EDCA has fixed range of CW and AIFS that has been chosen initially. In contemporary EDCA model AIFS parameter for each AC remains static, irrespective of number of stations in a network. We propose a scheme where we vary AIFS time of each access category, depending on current congestion on network. The proposed model incorporates a mechanism where AIFS wait is smaller if there are fewer stations contending and moves to more AIFS wait time in case of many stations willing to transmit. Simulations are also conducted to validate our suggested enhancements for AIFSN parameter

Perception and Knowledge of Antibiotic Resistance: A Cross Sectional Study among Students in a Medical College, India

Background & Aims:  The threat of antibiotic resistance is rapidly progressing and intensifying. It is an important global issue and health-care problem that needs urgent attention. This study will help provide a better understanding of what the students know and believe about the issue of antibiotic resistance. This study was designed to assess the knowledge, attitude and perception level among students concerning antibiotic resistance as well as their self-reported practices related to antibiotic usage.  Materials and Methods: A cross sectional descriptive study was conducted among 230 study participants (Interns and post graduates).A semi structured questionnaire was administered to the participants. Results: All the participants are aware of antibiotic resistance.192 (83.4%) of the participants agreed that indiscriminate and injudicious use of antibiotics leads to ineffective treatment in future. The perception and attitude of the study participants showed that 144 (62.6%) of participants agreed that skipping one or two doses contributes to the development of antibiotic resistance. Majority of the study participants opined that they need more training in the antibiotic selec­tion and on antibiotic resistance. Conclusion: The findings of the study concluded that there is a need for proper planning and devising an effective and tailored educational intervention, which can unlock the initial step to curb the alarming increase in resistance

A Solid Phase Assay For Topoisomerase I Interfacial Poisons And Catalytic Inhibitors

To prevent subscriber churn, network service providers of VoD, SDV and IPTV have a pressing need to pro-actively detect, isolate and fix outages within an access network. Network induced degradations prove to be detrimental for streaming applications. This typically leads to a poor quality of experience (QoE) for subscribers. By monitoring key functional points of the access network for traces of degradation, service providers can devise mechanisms to mitigate the problem. In this work we propose a hierarchy of exporters, collectors and ANCON (ANalysis and CONtrol) nodes that can semi-autonomously monitor, detect and isolate impairments within an access network. Exporters on the data plane gather and disseminate statistics for individual subnets, which are streamed onto collector nodes on an orthogonal plane. Collector nodes aggregate traffic from various exporters, and stream them onto the root of the tree (ANCON). With an even placement of exporters, root cause analysis can now take the granularity of loss rates or delay rates in individual segments or subnets of an access network. As an extension to our architecture, we show that the overlay can support instrumentations of quality evaluation for streaming video. As an example, we use a simple MOS plugin that is in part an extension of the ITU-T Erlang model to predict the quality of a video stream much before it reaches the end user. We show that our overlay can support a wide variety of quality evaluation metrics. Through extensive simulations and an implementation, we discuss issues of engineering such an overlay, isolating impairments in access networks, instrumenting MOS plugins and predicting video quality of multimedia streams in transit. © 2011 Elsevier B.V. All rights reserved

Determining environmental and socioeconomic risk factors for dengue infection among the resident population of Kandy District, Sri Lanka

Taylor-Robinson, AW ORCiD: 0000-0001-7342-8348Dengue is a frequently debilitating and potentially life-threatening flaviviral infection of humans that is transmitted via Aedes spp. mosquitoes. The global incidence of dengue has escalated dramatically during and since the second half of the twentieth century to the point where today there are estimated to be some 400 million infections per annum, of which a quarter produce clinical symptoms. Currently, over 22,000 fatalities are attributed directly to severe disease complications, while many more suspected cases go unconfirmed. The increasing worldwide incidence of dengue correlates with the expanding distribution of vector mosquitoes in tropical and subtropical regions, together with other contributing factors such as rising urbanization and accelerated changes in climate. Like elsewhere in South Asia the disease has become endemic to Sri Lanka. All four authenticated dengue virus serotypes (DENV 1-4) co-circulate in the island nation, thereby posing a major public health risk. The country regularly experiences seasonal outbreaks of infection, usually following the monsoon rains that trigger an explosion of local mosquito populations. Kandy, the main city of the Central Highlands, is a hot spot for dengue incidence and was a regional focus of the 2016-17 epidemic. This significant outbreak highlighted the susceptibility of resident communities to dengue haemorrhagic fever and dengue shock syndrome, for which timely and accurate clinical diagnosis is required to enable implementation of an appropriate treatment regimen. Therapeutic intervention is a later step of an integrated approach to control and prevention of dengue. Here, we discuss environmental and socioeconomic risk factors for dengue pertaining to Kandy District, identify local knowledge gaps and propose ways in which these earlier steps should be explored. A deeper understanding of the variables affecting dengue prevalence and distribution will facilitate better disease management, vector surveillance and infection control in this increasingly endemic area

Effect of Coronavirus Disease 2019 lockdown on eating habits and lifestyle behavior

Background and Aim: The outbreak of coronavirus disease 2019 (COVID-19) affected the lives of all sections of society, as people were asked to self-quarantine in their homes to prevent the spread of the virus. The confinement and lockdown caused many lifestyle changes for Indian citizens, especially with diet and physical activity. The aim of the study was to assess the effect of COVID-19 lockdown on the dietary pattern and lifestyle behaviors in India. Materials and Methods: An online survey was conducted from July 2021 to September 2021 using a validated semi-structured questionnaire. The “snowball sampling” procedure was used to recruit the participants. The questions focused on changes experienced by the participants in their lifestyle before and during the lockdown. Results: Among the 624 study participants, the mean age was 25.81 ± 9.7 years. Nearly 71.8% (448) reported that their diet and consumption patterns changed during the lockdown. The mean body mass index before the lockdown was 24.11 ± 4.43, and after the lockdown was 23.46 ± 4.51. The change in sleep duration was reported by 494 (79.1%). Conclusion: These unprecedented circumstances provide an opportunity to better understand the negative impact of strict lockdown measures on lifestyles, and at the same time, help identify and initiate positive behavioral changes, which if consolidated, may improve chronic disease outcomes in the long run