Drug-Resistant Bacterial Infections in HIV Patients

The human immunodeficiency virus (HIV) was first detected in 1982 among homosexual men, and subsequently, it was further detected in various regions of world. In 2016, WHO estimated that 36.7 million people were living with HIV, 1.9 million were newly infected HIV patients and approximately 1 million people died worldwide. HIV attacks CD4 T cells and causes immunodeficiency. Weakened immune system of HIV patients increases the opportunity to acquire various infections caused by fungi, bacteria, parasites and other viruses. Bacterial infections that cause huge threats to HIV patients are tuberculosis, syphilis, bacterial enteric diseases and bacterial pneumonia. Important bacterial etiologies are Streptococcus pneumoniae, Salmonella spp. Haemophilus influenzae, Staphylococcus aureus, Citrobacter freundii, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Pseudomonas aeruginosa and Mycobacterium tuberculosis. Frequent bacterial infections in HIV patients increase the usage and also highly expose bacteria to antibiotics. Most problematic multidrug-resistant bacteria are extended-spectrum β-lactamases producing P. aeruginosa, Acinetobacter baumannii, E. coli and K. pneumoniae; vancomycin-resistant enterococci; methicillin-resistant S. aureus and multidrug-resistant and extensively drug-resistant M. tuberculosis. These antibiotic-resistant bacteria complicate the treatment of infections in HIV patients with available antibiotics and sometimes cause death. It also causes higher medical costs, prolonged hospital stays, increased mortality and economic burden on families and societies

Effect of Noni ( Morinda citrifolia

This study examined the effect of methanolic extract of Morinda citrifolia Linn. (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC (1–40 mg/mL), scopoletin (1–200 μg/mL), and rutin hydrate (0.6–312.6 μg/mL) dose-dependently inhibited the contractility evoked by submaximal concentrations of both dopamine and noradrenaline, respectively. Haloperidol and prazosin, reference dopamine D2, and α1-adrenoceptors antagonists significantly reversed the dopamine- and noradrenaline-induced contractions, respectively, in a dose-dependent manner. Interestingly, MMC per se at higher doses (60–100 mg/mL) showed dose-dependent contractile response in rat vas deferens which was partially inhibited by high doses of haloperidol but not by prazosin. These results demonstrated the biphasic effects of MMC on dopaminergic system; that is, antidopaminergic effect at lower concentrations (60 mg/mL). However, similar contractile response at high doses of scopoletin (0.5–5 mg/mL) and rutin hydrate (0.5–5 mg/mL) per se was not observed. Therefore, it can be concluded that the bioactive principles of MMC, scopoletin, and rutin might be responsible for the antidopaminergic and antiadrenergic activities of MMC

TUMOR NECROSIS FACTOR-ALPHA LEVEL IN SERA OF SOUTH INDIAN PATIENTS WITH RHEUMATOID ARTHRITIS: CORRELATION WITH ANTICYCLIC CITRULLINATED PEPTIDE ANTIBODY LEVEL

Objective: The present study was aimed to find out the anticyclic citrullinated peptide (CCP) antibody level and expression level Th2 cytokine-liketumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) from South India.Methods: The patients attending the Arthritis and Rheumatism Care Centre, Vadapalani, Chennai and healthy individuals from the Presidency College, Chennai, were enrolled for this study. The study group included 74 patients with RA and 50 healthy individuals without history of RA. 3-5 ml of blood samples was aseptically collected using Vacutainer, and the separated serum samples were transported to the Department of Microbiology, Presidency College, Chennai, Tamil Nadu, in cold chain. Anti-CCP antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Serum concentrations of TNF-α were studied in patients with RA and in healthy controls, using an ELISA method.Results: The results of anti-CCP enzyme immunoassay revealed that out of 74 patients, all were anti-CCP positive, which included 65 females and 9 males. Higher levels of anti-CCP (456 IU/ml) were present in the age group between 41 and 50 followed by 21-30 years age group which shows 335.28 IU/ml of anti-CCP antibody level. The level of serum TNF-α was measured in the range of 4.6-1082.84 pg/ml for RA patients and6.630-459.74 pg/ml for the healthy control group.Conclusion: TNF-α levels were significantly increased in RA patients compared to healthy individuals. A negative correlation was found between anti- CCP antibody and TNF-α level in RA patients.Keywords: Rheumatoid arthritis, Tumor necrosis factor-alpha, Enzyme-linked immunosorbent assay, Anticyclic citrullinated peptide antibodie

Antipsychotic-like activity of Noni (Morinda citrifolia Linn.) in mice

Background: Noni fruit is widely consumed in tropical regions of Indonesia to the Hawaiian Islands. The noni plant has a long history of use as a medicinal plant to treat a wide variety of ailments including CNS disorders. The present investigation was designed to evaluate the antipsychotic effect of noni fruits (Morinda citrifolia Linn.) using mouse models of apomorphine-induced climbing behaviour and methamphetamine-induced stereotypy (licking, biting, gnawing and sniffing).Methods: In acute study, the methanolic extract of Morinda citrifolia (MMC) at different doses 1, 3, 5, 10 g/kg was administered orally one hour prior to apomorphine (5 mg/kg, i.p) and methamphetamine ( 5 mg/kg, i.p) injection respectively in Swiss albino mice. In chronic studies, (TAHITIAN NONI® Juice, TNJ) was made available freely in daily drinking water at 30, 50 and 100 v/v for 7 days; 30 and 50 v/v for 21 days respectively. On the test day, an equivalent average daily divided dose of TNJ was administered by oral gavage one hour prior to apomorphine treatment. Immediately after apomorphine/ methamphetamine administration, the animals were placed in the cylindrical metal cages and observed for climbing behaviour/ stereotypy and climbing time.Results: The acute treatment of MMC (1, 3, 5, 10 g/kg, p.o) significantly decreased the apomorphine-induced cage climbing behaviour and climbing time in mice in a dose dependent manner. The MMC also significantly inhibited methamphetamine-induced stereotypy behaviour and climbing time in mice dose-dependently. The 7 and 21 days treatment of TNJ in drinking water at 50 and 100v/v significantly alleviated the apomorphine-induced climbing behaviour and climbing time in mice.Conclusions: The present study results demonstrated the antidopaminergic effect of Morinda citrifolia Linn. in mice, suggesting that noni has antipsychotic-like activity which can be utilized in the treatment of psychiatric disorders. However further studies are warranted to identify the active principles responsible for the antipsychotic activity of noni. © 2012 Pandy et al.; licensee BioMed Central Ltd

Operator Theoretic Model Predictive Control of Moving Boundary Dynamical Systems: Application to Hydraulic Fracturing

Many chemical processes are characterized by nonlinear models with moving boundaries that describe their dynamics. Such a nonlinear trajectory can explore many regions of the state space and the spatial domains of interest as well as the dominant spatial patterns of the system change with time. Therefore, traditional model approximation methods may fail to accurately capture the dynamics. This underlines the need to develop strategies for obtaining computationally efficient yet highly accurate models that aid in the prediction and control of these systems. In such systems, care should be taken to capture the local behavior of every portion of the solution trajectory in the state space. To achieve this, the first step of this research work computes (temporally) local reduced order models by first performing time-domain partitioning using a novel clustering strategy based on Mixed Integer Nonlinear Programming. The reduced bases are then derived within each cluster using two model reduction methods, Proper Orthogonal Decomposition (POD) and Dynamic Mode Decomposition (DMD). The proposed framework is tested on a nonlinear hydraulic fracturing process, and a Model Predictive Controller (MPC) is formulated using the (temporally) local reduced order models to design an optimum pumping schedule that ensures uniform proppant concentration for maximum oil and gas extraction. The idea of model reduction is then extended to the parameter space in order to estimate unknown rock properties that directly affect the hydraulic fracturing process. Owing to the complex dynamics exhibited, this results in the formulation of a large- scale inverse problem that is ill-posed. To deal with this unidentifiability issue, the number of unknown model parameters are reduced while preserving the spatial features in the geological properties via POD. The statistical information is then updated using the available process measurements via a Monte Carlo data assimilation technique, the Ensemble Kalman Filter. Although the local model reduction framework is superior in performance, a single model that is accurate within a larger domain in the state space would be beneficial in some cases. Therefore, the next part explores an alternative approach that uses Koopman operator theory to develop linear predictors to approximate nonlinear systems. Before employing it to process systems, we address several key challenges associated with it. In particular, we solve a sparse regression problem over a large set of candidate functional forms to effectively identify the required nonlinear transformation (observable functions). The developed models are shown to reveal important physical phenomena such as proppant transport and fracture propagation inside a fracture. It also highlights how a priori knowledge can be incorporated easily into the algorithm and results in accurate models that are used for controller synthesis. Finally, Koopman theory is integrated with Lyapunov-based MPC (LMPC) for stabilizing nonlinear systems. LMPC possesses all the advantages of a standard MPC with added explicit Lyapunov constraints and is particularly suited as it explicitly characterizes a set of initial conditions starting from where the closed–loop stability can be guaranteed. By leveraging the linear structure of the Koopman models, control Lyapunov functions (CLFs) within LMPC are embedded in the nonlinear transformation to yield a standard convex (quadratic) optimization problem. This method is then improved by formulating the controller in Koopman eigenfunction coordinates, which leads to a bilinear model for control affine systems. Provided there exists a continuously differentiable inverse mapping between the original state space and (lifted) function space, the designed controller is capable of translating the feedback stabilizability of the Koopman bilinear system to the original nonlinear system. Due to the bilinear structure of the Koopman model, seeking a CLF is no longer a bottleneck for LMPC. Benchmark numerical examples demonstrate the utility of the proposed feedback control design

MOLECULAR DOCKING OF COMPONENTS FROM THE EXTRACTS OF ENDOPHYTIC BACTERIA OF CISSUS QUADRANGULARIS AGAINST AURORA B KINASE

Compounds that inhibit the activity of Aurora kinase enzyme are potential drug candidates for a variety of cancers including osteosarcoma. Endophytes of medicinal plants have potential to produce several anticancer compounds having pharmaceutical applications. Cissus quadrangularis Linn. is a versatile medicinal plant with various therapeutic properties including bone fracture healing. Endophytes of this plant may be a promising source of anticancer compounds. The compounds present in the extracellular extract of endophytic bacteria predicted by GCMS and the compound VX-680 (Tozasertib) were subjected to docking against Aurora B kinase using AutoDock 4.2. Molecular docking studies has revealed that, among the compounds docked, five of them and a known Aurora B Kinase inhibitor VX-680, hydrogen bonded with the amino acid ALA173 in the active site of the enzyme.VX-680; Dl-leucine, n-dl-leucyl-; Acetophenone 4'-methoxy; Benzaldehyde, 4-methoxy; 3-Nonanol, 1,2;6,7-Diepoxy-3,7-Dimethyl-Acetate; Cyclopropane,1,2-dibutyl and 2-Myristynoyl-Glycinamide; bind to Aurora B Kinase (2VRX) with a binding energy of, -8.53, -4.68, -4.65, -4.34, - 4.0, -3.93 and -3.75 kcal mol-1 respectively. Thus, virtual studies on the endophytic compounds, reveal that these compounds may possess the potential to hinder the activity of Aurora B kinase and thus can contribute as lead compounds in developing therapeutic agents for cancer.</jats:p

Exploring knowledge sharing in the Requirement Engineering phase of globally distributed Information Systems development : Perceived challenges and suggestions for improvement

The Master thesis explores the knowledge sharing that takes place during the requirement engineering phase of globally distributed information systems development. In recent years, due to globalization, information systems development activities have become increasingly distributed across different geographical locations. Requirement engineering is an important and knowledge intensive phase in the development of information systems. Requirement engineering is the process of identifying, analyzing, documenting, validating and managing the requirements of a system. Effective and efficient knowledge sharing during the requirement engineering is vital for the successful development of information systems. However, the global distribution of the stakeholders has affected knowledge sharing during requirement engineering in various ways making it more challenging.   Drawing on the theories of knowledge sharing within the field of information systems, this interpretive research study aims at exploring stakeholders’ perceptions about the challenges met during the knowledge sharing in requirement engineering phase of globally distributed information systems development projects. More specifically, this Master thesis explores the perceived challenges and generates a list of suggestions to overcome the challenges by conducting qualitative semi-structured interviews among the key stakeholders, both customers and business analysts.   The findings indicate that the knowledge sharing is influenced by challenges such as cultural differences, language barriers, communication issues, coordination issues arising from multiple stakeholders, time difference and difficulty in sharing tacit knowledge in the globally distributed settings. Participants’ suggestions for overcoming these challenges include cultural trainings, kick off meetings, language trainings, use of translator, face-to-face communication and interaction, video conferencing, scheduling important meetings in the common suitable timings, identification of the main stakeholders, having a mediator and making close observations with face-to-face interactions.     Keywords:  Information Systems, Information Systems Development, Requirement Engineering, Knowledge Sharing, Global Distribution, Outsourcing