Characterization of Tetrazolium Salts and Formazans using Computational Chemistry for Radiochromic Dosimetry

Computational chemistry is a powerful tool to model different materials and predict their physical and chemical properties. The goal of this thesis was to apply different computational chemistry tools to model the properties of two classes of closely related organic compounds: formazans and tetrazolium salts for ionizing radiation dosimetry in water-based gels, whereby the absorbed dose is registered by optical detection of formazan formation from tetrazolium salts. The structural parameters of phenyl and benzothiazolyl-substituted tetrazolium salts and formazans were computed using the APFD density functional theory (DFT) model and 6-311+G(2d,p) basis set. Conformational searching of stereoisomers (TSCA and TATA structures) and tautomeric forms of formazans were analyzed in gaseous state, methanol, and chloroform solutions. It was found that formazans exist as a mixture of conformers. Two compounds, 2-(2-benzothiazolyl)-3-(4-nitrophenyl)-5-phenyltetrazolium and 1‑(2-benzothiazolyl)-5-(4-nitrophenyl)-3-phenylformazan were used as model molecules for frontier molecular orbital analysis (FMOA), charge distribution, IR and NMR (1H and 13C) spectra. The FMOA allowed for quantitative comparison of the reactivity of the tested molecules, while the spectrum modelling showed good agreement with experimental data. The UV-Visible spectra of tetrazolium salts and formazans was examined using seven select molecules and two models. Finally, the wavelengths of maximum absorbance for twelve formazans important for radiation dosimetry were calculated using multiple DFT models and compared with experimental data, obtained from in-gel dosimetry. In conclusion, DFT modelling showed excellent results and proved to be useful as a tool for predicting the properties of formazans and tetrazolium salts

A safe and energy efficient robotic system for industrial automatic tests on domestic appliances: Problem statement and proof of concept

In this paper, the design and the development of a robotic platform conceived to perform accelerated life tests on a newly manufactured domestic appliances is presented. The proposed system aims at improving the safety of human operators that share the workspace with the robotic platform which is a common scenario of test laboratories. A deep learning algorithm is used for the human detection and pose estimation, while the integration between a conventional motion planning algorithm with a fast 3D collision checker has been implemented as a global planner plugin for the ROS navigation stack. With the twofold objective of improving safety and saving energy in the battery-powered mobile manipulator used in this project, the problem of minimizing the overall kinetic energy is addressed through a properly designed task priority controller, in which the manipulator inertia matrix is used to weight the joint speeds while satisfying multiple robotic tasks according to a hierarchy designed to interact with the appliances while preserving the safety of the human operators. Simulations are carried out to evaluate the overall control architecture and preliminary results indicate the effectiveness of the developed system in the test laboratory floors

Traumatic brain injury: Association between the Glasgow Coma Scale score and intensive care unit mortality

Background. Traumatic brain injury (TBI) prevalence in Botswana is high and this, coupled with a small population, may reduce productivity. There is no previous study in Botswana on the association between mortality from TBI and the Glasgow Coma Scale (GCS) score although global literature supports its existence. Objectives. Our primary aim was to determine the association between the initial GCS score and the time to mortality of adults admitted with TBI at the Princess Marina Hospital, Gaborone, Botswana, between 2014 and 2019. Secondary aims were to assess the risk factors associated with time to mortality and to estimate the mortality rate from TBI. Methods. This was a retrospective cohort design, medical record census conducted from 1 January 2014 to 31 December 2019. Results. In total, 137 participants fulfilled the inclusion criteria, and the majority, 114 (83.2%), were male with a mean age of 34.5 years. The initial GCS score and time to mortality were associated (adjusted hazard ratio (aHR) 0.69; 95% confidence interval (CI) 0.508 - 0.947). Other factors associated with time to mortality included constricted pupil (aHR 0.12; 95% CI 0.044 - 0.344), temperature (aHR 0.82; 95% CI 0.727 - 0.929), and subdural haematoma (aHR 3.41; 95% CI 1.819 - 6.517). Most cases of TBI (74 (54%)) were due to road traffic accidents. The number of deaths was 48 (35% (95% CI 27.1% - 43.6%)), entirely due to severe TBI. Conclusion. The study confirmed significant association between GCS and mortality. Males were mainly involved in TBI. These findings lack external validity because of the small sample size, and therefore a larger multicentre study is required for validation

Polio Outbreak Response in Ethiopia

Background: Ethiopia had been polio-free for almost four years until December 2004. However, between December 2004 and February 2006, 24 children were paralysed as a result of infection with wild poliovirus imported from the neighbouring country of Sudan. In response, the country has attempted to document the impact of various response measures on the containment of wild poliovirus transmission. Objectives: This study aims at systematic and epidemiological assessment of the extent of the outbreak, its determinants, and the lessons learned as well as the implications for future control strategies to interrupt wild poliovirus transmission. Design: A cross-sectional study design with qualitative and quantitative data collection approaches was used to conduct the epidemiologic assessment. Subjects: All confirmed wild poliovirus cases, and reported acute flaccid paralysis cases in close proximity to the confirmed polio cases were the study subjects. Child caretakers and health service providers were interviewed as part of the investigation. Results: Between December 2004 and February 2006, eight children from Tigray Regional State, nine children from Amhara Regional State and seven children from Oromia Regional State were paralysed as a result of infection with wild poliovirus type 1. Genetic sequencing demonstrated two separate importations to Ethiopia. Risk factors that may have facilitated spread of the outbreak within the country included gaps in vaccination coverage and interruption of the cold chain system, gaps in acute flaccid paralysis surveillance performance, high population mobility, poor environmental sanitation, crowded living conditions and unsafe drinking water. In response to the outbreak, Ethiopia conducted detailed outbreak investigations within two days of confirmation of the index cases. Large-scale, house-to-house vaccination campaigns were also implemented. As a result, the three regions interrupted the wild poliovirus transmission within the regions within one year of confirmation of the index case. Conclusion: Outbreak response activities were successful in interrupting the imported wild poliovirus transmission in Tigray, Amhara and Oromia Regional States of Ethiopia within a oneyear period of time. In Ethiopia, programme strategies should be intensified to contain further spread and prevent future importation of wild poliovirus. Large-scale immunisation campaigns should reach every child, including those isolated by geography, poverty and security. East African Medical Journla Vol. 85 (5) 2008: pp. 222-23

Wnt5a Increases Cardiac Gene Expressions of Cultured Human Circulating Progenitor Cells via a PKC Delta Activation

Background: Wnt signaling controls the balance between stem cell proliferation and differentiation and body patterning throughout development. Previous data demonstrated that non-canonical Wnts (Wnt5a, Wnt11) increased cardiac gene expression of circulating endothelial progenitor cells (EPC) and bone marrow-derived stem cells cultured in vitro. Since previous studies suggested a contribution of the protein kinase C (PKC) family to the Wnt5a-induced signalling, we investigated which PKC isoforms are activated by non-canonical Wnt5a in human EPC. Methodology/Principal Findings: Immunoblot experiments demonstrated that Wnt5a selectively activated the novel PKC isoform, PKC delta, as evidenced by phosphorylation and translocation. In contrast, the classical Ca2+-dependent PKC isoforms, PKC alpha and beta2, and one of the other novel PKC isoforms, PKC epsilon, were not activated by Wnt5a. The PKC delta inhibitor rottlerin significantly blocked co-culture-induced cardiac differentiation in vitro, whereas inhibitors directed against the classical Ca2+-dependent PKC isoforms or a PKC epsilon-inhibitory peptide did not block cardiac differentiation. In accordance, EPC derived from PKC delta heterozygous mice exhibited a significant reduction of Wnt5a-induced cardiac gene expression compared to wild type mice derived EPC. Conclusions/Significance: These data indicate that Wnt5a enhances cardiac gene expressions of EPC via an activation of PKC delta

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Stem Cell Therapy: Pieces of the Puzzle

Acute ischemic injury and chronic cardiomyopathies can cause irreversible loss of cardiac tissue leading to heart failure. Cellular therapy offers a new paradigm for treatment of heart disease. Stem cell therapies in animal models show that transplantation of various cell preparations improves ventricular function after injury. The first clinical trials in patients produced some encouraging results, despite limited evidence for the long-term survival of transplanted cells. Ongoing research at the bench and the bedside aims to compare sources of donor cells, test methods of cell delivery, improve myocardial homing, bolster cell survival, and promote cardiomyocyte differentiation. This article reviews progress toward these goals