Application of physiologically based pharmacokinetic (PBPK) modeling to study the impact of Roux-en-Y gastric bypass (RYGB) surgery on the bioavailability of oral antibiotics

Understanding the mechanisms that govern drug absorption and elimination is a critical component in pharmaceutical research and development, as the oral route remains the most common method of drug administration. The utilization of in silico physiologically based pharmacokinetic modeling and simulation (PBPK M&S) has enabled the extrapolation of modeling and simulation in special populations where concerns regarding alteration in overall drug exposure may arise, such as following gastrointestinal surgery. Roux-en-Y Gastric bypass (RYGB), or partial resection of the gastrointestinal tract, leads to multiple physiological alterations that affect drug absorption. The inability to generalize and predict changes in oral drug bioavailability (Foral) following gastric bypass surgery presents a considerable therapeutical challenge to clinicians. PBPK M&S is a widely used approach for predicting the bioavailability changes in different clinical scenarios. Infection post-surgery is the most common risk factor and should be monitored and treated with utmost care. There is limited literature assessing the bioavailability changes of oral antibiotics post-gastric bypass surgery. This thesis aimed to determine the impact of gastric bypass surgery on oral drug absorption and metabolism for antibiotics such as azithromycin, cefuroxime axetil, and metronidazole. This was accomplished by applying the PBPK M&S approach to identify and define essential intrinsic elements and parameters, model implementation, and validation within a general model development framework. The developed post gastric bypass surgery PBPK model provides a framework for investigating physiological mechanisms associated with changes in systemic drug exposure after oral administration, which may result from the interplay of disintegration, dissolution, absorption, and presystemic metabolism by the intestine and liver. The developed PBPK models of azithromycin, cefuroxime axetil, and metronidazole were used to evaluate the changes in antibiotic exposure in gastric bypass surgery patients after a solid and liquid formulation. The results from solid formulation bioavailability post gastric bypass surgery model simulations suggest that the current dosing regimen for azithromycin and cefuroxime axetil may not be sufficient for treating infections, and dose modifications might be necessary. At the same time, no significant changes were observed for metronidazole bioavailability post-surgery. The results from liquid formulations of these antibiotics suggest that the azithromycin suspension presents enhanced absorption and bioavailability than the tablet formulation. In contrast, the suspension of cefuroxime axetil followed the same trend as solid formulation. Overall, this thesis demonstrates the application of PBPK M&S in the extrapolation of oral drug exposure to special populations (e.g., RYGB). The PBPK approach shows oral bioavailability to provide clinicians with an evidence-based dose selection to prevent the risk of treatment failure due decreased drug exposure of oral antibiotics post gastric bypass surgery

Teaching Innovation to Graduate Students in Computer Information Systems (CIS)

The goal of this paper is to show how graduate students in a computer information systems (CIS) masters program can learn innovation and can complete innovative thesis or projects in information systems. Graduate MS students in the CIS program are taught how to use information systems, but not taught how to create and innovate new information systems. To be competitors in the global economy today, “Innovate or Evaporate” is the message for organizations in the United States (US). US employees must know how to innovate, but current CIS programs rarely teach innovation to their students. To foster innovation, this paper proposes an approach which systematically introduces innovation in a step wise fashion in three courses. The approach in the three courses include: (i) introducing innovative technologies in the CINS 5073 course, (ii) use of innovative technologies by organizations to remain competitive in the CINS 5013 course, and (iii) research innovative information systems in the CINS 5003 course. The approach presented in this paper fosters innovation throughout the program and the use of common systems – something that a student is very familiar with its construction and use, and converting them to intelligent systems using innovative thinking. The benefit of this approach is to create a new breed of workforce consisting of effective thinkers and innovators. It also teaches students that innovation is a never ending process and that innovation will enable them to survive long-term in the constantly changing field of information systems. The approach can be used in other CIS programs nationwide to enable them to teach innovation using cost-effective industry standard technologies and systems

Microbiological surveillance of operation theatres, intensive care units and labor room of a teaching hospital in Telangana, India

Background: Hospital-associated infections are the major cause of patient morbidity and mortality. Environmental monitoring by the microbiological testing of surfaces and equipments is useful to detect changing trends of types and counts of microbial flora. The aims of the study were to count CFU (colony forming unit) rate of indoor air, to identify bacterial colonization of surface and equipments isolated from Operation theatres, ICUs and Labor room of a teaching hospital in Telangana, India.Methods: Air sampling of 10 OT’s, 4 ICU’s and 1 LR were done by settle plate method. Swabs were taken from different sites and equipments and bacterial species were isolated and identified from them.Results: Gynaecology OT-2 and 3 showed less bacterial CFU rate of air (6 CFU/m3) followed by Opthamology OT (16 CFU/m3) and highest in Orthopaedics minor OT (72 CFU/m3) and Dental OT (42 CFU/m3 with 1 fungal CFU/m3). Pediatric ICU showed less bacterial CFU rate (28 CFU/m3) followed by Surgery ICU (40 CFU/m3) and highest in Medical ICU (100 CFU/m3 and 5 fungal CFU/m3). Labor room showed 65 CFU/m3. Bacterial species were isolated from 48 (43%) out of total 111 swab samples taken from all OTs and ICUs. The most common isolate was Bacillus species 36 (75%) followed by micrococcus (54%). Pathogenic organisms isolated were 12 Gram negative bacilli and 6 gram positive cocci, the common isolate was Klebsiella spp (7 of 12).Conclusions: The study shows that OTs were having bacterial CFU rate of air varying from 6-72 CFU/m3 and colonized by contaminants like Bacillus sp and pathogens like Klebsiella sp. ICUs were having bacterial CFU rate of air varying from 28-100 CFU/m3 and colonized with contaminant like Bacillus sp., as well as potential pathogens like Klebsiella, Pseudomonas etc. Fungal CFU were also seen both in OTs and ICUs. High level of microbial contamination indicates the needs for periodic surveillance aimed at early detection of bacterial contamination levels and prevention of hospital acquired infections

Comparative Analysis Association and Prediction of Various Phenotypic Traits of Oryza Sativa

Understanding the genotype-phenotype relationship and accurately predicting breeding values are crucial aspects of crop improvement programs. This paper investigates the genetic basis ,association of phenotypic trait height and yield and predicts the phenotypic traits of Oryza Sativa (rice) through a comprehensive approach encompassing genome-wide association studies (GWAS), phylogenetic analysis, machine learning algorithms, and the development of a graphical user interface (GUI) application. Genotypic and phenotypic data were collected from the RiceVarMap database. The genotypic information consisted of gene variation IDs, while the phenotype data included plant height. Data preprocessing involved the creation of a sequence. fasta file and multiple sequence alignment using the ClustalW tool. A phylogenetic tree was then constructed to analyse the subpopulations of Oryza Sativa. Clustering techniques were applied to further explore the genetic relationships among the samples. A GWAS file was generated to identify associations between genotype and phenotype. Subsequently, machine learning algorithms were employed for the classification and prediction of genomic estimated breeding values (GEBV) for height and yield traits. Random Forest emerged as the most accurate algorithm with 85% accuracy. To facilitate user interaction and data exploration, a GUI application was developed using Flask, allowing users to access the phylogenetic tree, height, and yield information, GWAS results, and make predictions.  We explored there is a strong positive association between phenotypic trait height and yield

BIOCHEMICAL ROLE OF XANTHINE OXIDOREDUCTASE AND ITS NATURAL INHIBITORS: AN OVERVIEW

Xanthine oxidoreductase (XOR) is a widely distributed housekeeping enzyme in mammals that catalyzes the last two steps in human purine catabolism to produce uric acid. The enzyme exists as a homodimer with independent electron transfer in each monomer. This has been studied extensively as a major constituent of the milk fat globule membrane (MFGM) which surrounds fat globules in cow's milk even though purine catabolism is the most accepted function of XOR. A huge number of literature highlights on the different catalytic forms of XOR and their importance in the generation of reactive oxygen species/reactive nitrogen species (ROS/RNS) and synthesis of uric acid which are involved in many physiological and pathological processes. However, a slight ambiguity resides in their biochemical functions. The aim of this article was to review the literature published on the structural, catalytical, physiological and pathological role of XOR and to resolve the ambiguity in biochemical processes and to firm up various natural inhibitors of XOR collectively. Uric acid, the product of purine catabolism shows antioxidant activity, and XOR-derived ROS and RNS play a role in innate immunity, milk secretion and also be involved in signaling and metabolism of xenobiotics. Furthermore, XOR is likely to be engaged in pathology because of excessive production of uric acid and ROS/RNS. This review also reports natural XOR inhibitors in plants which inhibit the enzyme to treat XOR associated pathology

A Comparative Study on Prediction of Endometriosis Causing Infertility Using Machine Learning Techniques: in Detail

The purpose of this study is to utilize Artificial Intelligence to analyse and predict endometriosis problem in women. All traditional methods are used before to develop or to predict the likelihood of endometriosis based on the symptoms presented. By identifying the symptoms of endometriosis, the machine learning algorithms can determine the type of endometriosis and the appropriate course of action for patients. This technology can be used to educate women globally on the signs and symptoms of endometriosis and help them take preventive measures to avoid this deadly disease. The results of this research demonstrate the potential of advanced technology to revolutionize healthcare by providing early detection and treatment options for endometriosis. In areas with limited access to medical care, this tool can aid in identifying ovarian cancer and reducing mortality rates. By detecting and diagnosing endometriosis at an early stage, this program can play a significant role in promoting women's health and wellbeing. The methodology proposed in this study produces classification results that are on par with cutting-edge deep learning techniques. In addition, the methodology provides visual explanations that offer valuable insights into the inner workings of each model and enhance the accuracy and reliability of the predictions

Honeywell experion system for teaching purposes

Honeywell Experion Process Knowledge System (PKS) is an advanced Distributed Control system with integrated advanced process automation platform. The platform integrates both DCS and SCADA topologies which makes the software more versatile. Experion is extensively used for several applications across the process industry. The platform was purchased by Murdoch University and served as a valuable asset to the University. It is a great teaching tool for students pursuing a career in engineering as it introduces an industrial prospective to the course. The main objective of the thesis project involves development of Honeyell Experion software to be integrated into the industrial computer systems facility for students to gain an understanding of the operation of the system. The entire scope of the thesis project mediated around the Honeywell Experion Process Knowledge System software. The ultimate goal of the project was integration of the Honeywell Experion teaching system into the Industrial Computer Systems facility. Before conquering the mammoth goal of the thesis, it is proprietary to understand the basic driving concepts of the Experion system. The previous works undertaken on the project included some basic setup of a test server, and basic simulation and configuration aspects. This thesis would be a continuation of the work undertaken during previous years. However to proceed to further stages of the thesis the first step would be to surpass the initial configuration of the project elements. Therefore initial weeks of the thesis project were spent on understanding the structure of the Experion software and configuring basic elements. Following these initial steps the primary focus of the project was brought towards understanding the operation of some of the Regulatory Control Blocks present in the Experion environment. The functionality of regulatory control blocks was explored by undertaking research on the PID control block. Many features offered by the PID control block were explored and understood. Following this step some systems were simulated in Microsoft Office Excel and controlled by the PID control block configured in the Experion system. The data exchange between both the mediums was done by Microsoft Office data Exchange add-in provided by Honeywell. These simulations were designed to demonstrate the use of options provided by the PID block. Similar research was performed on other regulatory control blocks present in the Experion environment such as PIDFF, PIER and PID-PL blocks. The functionalities researched and simulations created were documented. The report provides a brief overview of the tasks accomplished. Firstly describing the operation of Experion software and functionalities offered, it moves on to describing the primary attention area of the project

Synthesis and Structure of a Substituted Pyridazine

Pyridazines are heterocyclic compounds with an N-N bond in their ring structure. Heterocyclic aromatic compounds are of great interest as a result of their novel properties and commercial applications. Our current research is focused on the potential role of pyridazines in next generation electronic devices that utilize organics as the semiconducting material. The synthesis of 5, 6-fused ring pyridazines beginning from fulvenes (Scheme 1) is described herein. These fused heterocycles will serve as synthetic models and building blocks for potential organic or organometallic conducting polymers. Our goal was to modify the route of Snyder et al. previously reported for the direct synthesis of pyridazine 2. This required improved synthesis of fulvene 1 and higher yields of 5. Additionally, a thorough analysis of the x-ray data was obtained to better understand the 3D aspects of this compound (pyridazine 2).This route was quite general and features an efficient and convenient synthesis. Single crystal X-ray analysis confirms the molecular structure of pyridazine 2. Full synthesis and characterization of newly formed pyridazine 2 and Fulvene 1 are reported

PHARMACOLOGICAL EVALUATION OF ANTIANXIETY ACTIVITY OF DESMOSTACHYA BIPINNATA LEAVES IN ANIMAL MODELS

Objective: Anxiety is a widespread psychiatric disorder affecting around 5% of the population. Furthermore, it is difficult to predict patient's response to any given treatment. In the traditional systems of medicine, many plants have been used to treat anxiety and depression for thousands of years. Desmostachyabipinnata belongs to the family Poaceae, have pharmacological actions like dysentery and menorrhagia, and as a diuretic. The present study was designed to evaluate the antianxiety activity of the alcoholic and aqueous extracts of Desmostachyabipinnata leaves in rodents.Methods: Antianxiety activity was screened by different methods like elevated plus maze model and actophotometer.Results: The results infer that reduced aversion fear elicits anti-anxiety activity.Conclusion: It was concluded that alcoholic and aqueous extracts of Desmostachyabipinnata leaves are having anti-anxiety activity among which alcoholic extract of Desmostachyabipinnata leaves showing more significant activity over the aqueous extract.Â

Effect of medium, explants, cytokinins and node position on in vitro shoot multiplication of Caralluma lasiantha (Wight) N.E.Br., an endemic and medicinally important plant

An efficient shoot multiplication protocol was developed for Caralluma lasiantha, an endemic medicinal plant belonging to the family Asclepiadaceae. Mature explants were cultured on Murashige and Skoog (MS), (1962) medium, Gamborg's B5 (B5) and woody plant medium (WPM) supplemented with 6-benzyladenine (BA), 8.87 µM, for shoot induction. The nodal explants exhibited maximum shoot sprouting frequency when cultured on MS medium supplemented with BA (8.87 µM). Nodal explants cultured on MS medium supplemented with different concentrations of cytokinins with 3% sucrose exhibited 100% sprouting frequency. Maximum number of three to four shoots was induced from mature second nodal explants on MS medium containing BA (8.87 µM). The isolated microshoots were rooted on half strength MS medium supplemented with naphthalene acetic acid (NAA), 0.54 µM. The plantlets thus developed were hardened and successfully established in soil.Key words: 6-Benzyl adenine, nodal explant, naphthalene acetic acid, Caralluma lasiantha, micro  propagation