Emerging Developments on Pathogenicity, Molecular Virulence, Epidemiology and Clinical Symptoms of Current Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently reported virus that is associated with severe, life threatening and rapidly spreading primarily respiratory illness called the Middle East respiratory syndrome. MERS-CoV possesses a unique positive-sense single-stranded RNA and can undergo rapid mutation in the viral genome. This results in antigenic switching and genetic variation, finally leading to the emergence of novel and new MERS-CoV subtypes which are uncontrollable by vaccines. Researchers are also finding difficulties to sort out therapeutic intervention strategies for MERS-CoV. This virus can spread from human to human, but transmission from dromedary camels to humans plays a crucial epidemiological significance. Dromedary camel acts as “gene mixing vessels” for MERS-CoV and these virus particles undergo rapid change in them. Viral receptors called dipeptidyl peptidase-4 are important receptors for attachment and spread of MERS-CoV in humans. The current method of laboratory confirmation is through real-time polymerase chain reaction on bronchoalveolar lavage, sputum and tracheal aspirates. Unfortunately, till today there are no definite anti-viral drugs available for MERS-CoV

Invasive Bacterial Pathogens and their Antibiotic Susceptibility Patterns in Jimma University Specialized Hospital, Jimma, Southwest Ethiopia

BACKGROUND: Presence of microorganisms in the circulating blood whether continuously or intermittently is a threat to every organ in the body. Approximately 200,000 cases of bacteraemia occur annually with mortality rates ranging from 20-50%. Early diagnosis and appropriate treatment of these infections can make the difference between life and death. The aim of the present study was to determine the bacterial flora of the blood stream infections and their antibiotic susceptibility pattern. METHODS: A cross sectional study was conducted on 260 adult febrile patients in Jimma University Specialized Hospital from 27 October 2009 to 26 March 2010. The positive blood cultures were examined and the organisms were identified as per standard procedures. Antimicrobial testing was performed for all isolates by disk diffusion techniques, according to Clinical Laboratory Standards Institute guide lines. The data was analyzed using SPSS for windows version 16 and Microsoft Office Excel. RESULTS: From the total of two hundred sixty blood specimens only 23(8.8%) were positive to seven different types of bacteria. The isolated bacteria were: Coagulase negative staphylococci 6(26.1%), S. aureus 5 (21.7%), S. pyogens 3 (13.0%), E. coli 4(17.4%), K. pneumoniae 3(13.0%), Salmonella spp. 1(4.3%), and Citrobacter spp. 1(4.3%). The isolates showed high rates of resistance to most antibiotics tested. The range of resistance for gram positive bacteria were 0% to 85.7%, and for gram negative from 0% to 100%. None of the isolates were resistance to ciprofloxacin and ceftriaxone. CONCLUSION: Our study result showed the presence of invasive bacterial pathogens with high rate of resistance to most commonly used antibiotics used to treat bacterial infections. Therefore, timely investigation of bacterial flora of the blood stream infections and monitoring of their antibiotic resistance pattern plays an important role in reduction of the incidence of blood stream infections. KEYWORDS: invasive bacteria, antimicrobial resistance, Jimma, Ethiopi

Molecular identification of diarrheal Aeromonas using immuno magnetic polymerase chain reaction (IM-PCR) technique: a comparative study with conventional culture method

Background: Aeromonas are ubiquitous bacteria causing many clinical conditions including acute diarrhea. Diarrheagenic Aeromonas harbors aerolysin gene secreting virulent enterotoxin, aerolysin.Objectives: To develop a molecular and immunological based method for detection of Aeromonas.Methods: Diarrheal Aeromonas strains were identified from stool samples using culture, enterotoxicity testing using mice model. During immune magnetic polymerase chain reaction IM-PCR protocol, aerolysin specific antibodies were bound with immuno magnetic binding. Sensitivity and specificity tests for IM-PCR were conducted.Results: There was high detection of Aeromonas using IM-PCR (12.4 %) technique when compared to low isolation with culture (5.1%). Our study confirmed that some strains of enterotoxic Aeromonas strains were uncultivable. Enterotoxicity tests on culture isolates revealed many strains were negative. IM-PCR detected high, (62/500) rate of identification of Aeromonas with aerolysin toxin gene. Aeromonas species identified after IM-PCR were A. hydrophila (40.3% ), A. veronii (17.7 %), A. caviae (14.5%), A. trota (11.2 %), A. jandei (9.6 %) and A. schuberti (6.4%). All A. trota strains were undetected by cultivation.Conclusion: High sensitivity and specificity of IM-PCR are due to preparation of aerolysin antibodies and immuno magnetic binding, prior to PCR. Since diseases due to Aeromonas are increasingly reported, IM-PCR is recommended for detection from clinical specimens.Keywords: Aeromonas, IM-PCR, acute diarrhea, aerolysin, enterotoxicity

A hybrid adaptive control strategy for a smart prosthetic hand

This paper presents a hybrid of a soft computing technique of adaptive neuro-fuzzy inference system (ANFIS) and a hard computing technique of adaptive control for a two- dimensional movement of a prosthetic hand with a thumb and index finger. In articular, ANFIS is used for inverse kinematics, and the adaptive control is used for linearized dynamics to minimize tracking error. The simulations of this hybrid controller, when compared with the proportional-integral-derivative (PID) controller showed enhanced performance. Work is in progress to extend this methodology to a five-fingered, three-dimensional prosthetic hand.Peer ReviewedPostprint (published version

Kinematic synthesis for smart hand prosthetics

The dream of a bionic replacement appendage is becoming reality through the use of mechatronic prostheses that utilize the body’s myoelectric signals. This paper presents a process to accurately capture the motion of the human hand joints; the obtained information is to be used in conjunction with myoelectric signal identification for motion control. In this work, the human hand is modeled as a set of links connected by joints, which are approximated to standard revolute joints. Using the methods of robotics, the motion of each finger is described as a serial robot, and expressed as Clifford algebra exponentials. This representation allows us to use the model to perform kinematic synthesis, that is, to adapt the model to the dimensions of real hands and to obtain the angles at each joint, using visual data from real motion captured with several cameras. The goal is to obtain an adaptable motion tracking system that can follow as many different motions as possible with sufficient accuracy, in order to relate the individual motions to myoelectric signals in future work.Postprint (author’s final draft

Implementation of a Hybrid Controller for Ventilation Control Using Soft Computing

Many industrial facilities utilize pressure control gradients to prevent migration of hazardous species from containment areas to occupied zones, often using Proportional-Integral-Derivative (PID) control systems. When operators rebalance the facility, variation from the desired gradients can occur and the operating conditions can change enough that the PID parameters are no longer adequate to maintain a stable system. As the goal of the ventilation control system is to optimize the pressure gradients and associated flows for the facility, Linear Quadratic Tracking (LQT) is a method that provides a time-based approach to guiding facility interactions. However, LQT methods are susceptible to modeling and measurement errors, and therefore the additional use of Soft Computing methods are proposed for implementation to account for these errors and nonlinearities

Generation of Oxygen Free Radicals by Proflavine: Implication in Protein Degradation

Proflavine, an acridine dye, is a known DNA intercalating agent. In the present study, we show that proflavine alone on photoillumination can generate reactive oxygen species (ROS). These proflavine-derived ROS cause damage to proteins, and this effect is enhanced when the divalent metal ion Cu (II) is included in the reaction. Bathocuproine, a specific Cu (I) sequestering agent, when present in the reaction mixture containing Cu (II), was found to inhibit the protein degradation, showing that Cu (I) is an essential intermediate in the reaction. The effect of several scavengers of ROS such as superoxide dismutase, sodium azide, potassium iodide, and thiourea were examined on the protein damaging reaction. Potassium iodide was found to be the most effective in inhibiting protein damage followed by sodium azide and thiourea. Our results indicate the involvement of superoxide, singlet oxygen, triplet oxygen, and hydroxyl radicals in proflavine-induced damage to proteins

A hybrid optimal control strategy for a smart prosthetic hand

ABSTRACT This paper presents a hybrid of a soft computing or control technique of adaptive neuro-fuzzy inference system (AN-FIS) and a hard computing or control technique of the hybrid finite-time linear quadratic optimal control for a two-fingered (thumb and index) prosthetic hand. In particular, the ANFIS is used for inverse kinematics, and the optimal control is used to minimize tracking error utilizing feedback linearized dynamics. The simulations of this hybrid controller, when compared with the proportional-integral-derivative (PID) controller showed enhanced performance. Work is underway to extend this methodology to a five-fingered, three-dimensional prosthetic hand

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer