Complete genome sequence of a Pseudomonas putida clinical isolate, strain H8234

We report the complete genome sequence of Pseudomonas putida strain H8234, which was isolated from a hospital patient presenting with bacteremia. This strain has a single chromosome (6,870,827 bp) that contains 6,305 open reading frames. The strain is not a pathogen but exhibits multidrug resistance associated with 40 genomic islands

The Importance of Design in the Development of a Portable and Modular Iot-Based Detection Device for Clinical Applications

The integration of human factors engineering methods within the medical device design and development process has been highlighted by international standards organizations. Such methods are contributing to the development of safer medical devices, more suitable to users' needs. Errors during device operation might hamper effective patient diagnosis and treatment, or eventually lead to injury or death. Thus, the designing process of a medical device is indeed crucial to user experience and safety operation. This paper presents a human-centred design analysis of a novel IoT-based screening prototype (iLoF) based on Artificial Intelligence algorithms built-in in a patented-photonics system developed by a deep tech startup. The influence of the design process during the development of the prototype was addressed, based on a human-centred design methodology and considering the device's application environment. iLoF's prototype on-field applicability was evaluated considering a single case-study carried out at one of the main hospitals in Portugal through interviews to ten healthcare professionals with high experience in laboratorial testing. A benchmark assessment and a comparison matrix along with the market products are also presented to fully understand the technology state and to find new solutions that can influence iLoF's product development. © Published under licence by IOP Publishing Ltd

Effect of Zinc Supplementation on Growth of Low Birth Weight Infants Aged 1–6 Mo in Ardabil, Iran

Objective To assess the effect of zinc supplementation on growth of low birth weight (LBW) infants aged 1–6 mo. Methods LBW infants were enrolled at birth and randomly assigned to receive 5 mg elemental Zn per day (n=45) or placebo (n=45) until 6 mo of age. They were followed monthly for information on compliance; anthropometric measurements were performed monthly. Results After randomization, 5 infants from zinc group and 9 from placebo group were excluded. At 6 mo of age, significantly greater weight gains were observed in the zinc than in the placebo group (4995±741g in zinc group vs. 3896±865 g in placebo group, p = 0.036). Length gain during the study period improved in zinc group (16.9±8.2 cm vs. 15.1±4.1 cm, p = 0.039); after zinc supplementation head circumference were increased (8.7±1.4 cm vs.7.4± 1.5 cm p<0.001). In male infants, total weight gain and height and head circumference gain were higher in the zinc than in the placebo group. However, only head circumference change was statistically significant. A similar trend was observed among female infants, but these differences were not statistically significant. There was no significant relation between breast-feeding status and the main outcome variables. Conclusions Infants in the present study showed improve¬ments in growth rate, but more studies are required in this field to confirm this fact

Novel hydrogel obtained by chitosan and dextrin-VA co-polymerization

A novel hydrogel was obtained by reticulation of chitosan with dextrin enzymatically linked to vinyl acrylate (dextrin-VA), without cross-linking agents. The hydrogel had a solid-like behaviour with G′ (storage modulus) >> G″ (loss modulus). Glucose diffusion coefficients of 3.9 × 10−6 ± 1.3 × 10−6 cm2/s and 2.9 × 10−6 ± 0.5 × 10−6 cm2/s were obtained for different substitution degrees of the dextrin-VA (20% and 70% respectively). SEM observation revealed a porous structure, with pores ranging from 50 µm to 150 µm

Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain

[EN] Objective This study aims to assess the cost utility of Brivaracetam compared with the third-generation anti-epileptic drugs used as standard care. Methods A cost utility analysis of Brivaracetam was carried out with other third-generation comparators. The treatment pathway of a hypothetical cohort over a period of 2 years was simulated using the Markov model. Data for effectiveness and the QALYs of each health status for epilepsy, as well as for the disutilities of adverse events of treatments, were analyzed through a studies review. The cost of the anti-epileptics and the use of medical resources linked to the different health statuses were taken into consideration. A probabilistic sensitivity analysis was performed using a Monte Carlo simulation. Results Brivaracetam was shown to be the dominant alternative, with Incremental Cost Utility Ratio (ICUR) values from -11,318 for Lacosamide to -128,482 for Zonisamide. The probabilistic sensitivity analysis validates these results. The ICUR sensitivity is greater for increases in the price of Brivaracetam than for decreases, and for Eslicarbizapine over the other adjunctives considered in the analysis. Conclusions Treatment with Brivaracetam resulted in cost effective and incremental quality adjusted life years come at an acceptable cost.Barrachina Martínez, I.; Vivas-Consuelo, D.; Reyes-Santias, F. (2020). Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain. Expert review of pharmacoeconomics & outcomes research (Online). 1-10. https://doi.org/10.1080/14737167.2021.1838899S110WHO | Epilepsy: aISBN public health imperative. ISBN 978-92-4-151593-1. World Health Organization. 2019. Printed in Thailand.Ngugi, A. K., Kariuki, S. M., Bottomley, C., Kleinschmidt, I., Sander, J. W., & Newton, C. R. (2011). Incidence of epilepsy: A systematic review and meta-analysis. Neurology, 77(10), 1005-1012. doi:10.1212/wnl.0b013e31822cfc90Henning, O., Landmark, C. J., Henning, D., Nakken, K. O., & Lossius, M. I. (2019). Challenges in epilepsy—The perspective of Norwegian epilepsy patients. Acta Neurologica Scandinavica, 140(1), 40-47. doi:10.1111/ane.13098Brodie, M. J. (2005). Diagnosing and predicting refractory epilepsy. Acta Neurologica Scandinavica, 112(s181), 36-39. doi:10.1111/j.1600-0404.2005.00507.xGarcía-Ramos, R., Pastor, A. G., Masjuan, J., Sánchez, C., & Gil, A. (2011). FEEN: Informe sociosantario FEEN sobre la epilepsia en España. Neurología, 26(9), 548-555. doi:10.1016/j.nrl.2011.04.002Kwan, P., & Brodie, M. J. (2000). Early Identification of Refractory Epilepsy. New England Journal of Medicine, 342(5), 314-319. doi:10.1056/nejm200002033420503Brodie, M. J. (2008). Epilepsy: randomised trials and genetic tribulations. The Lancet Neurology, 7(1), 7-8. doi:10.1016/s1474-4422(07)70301-0French, J. A. (2006). Refractory Epilepsy: One Size Does Not Fit All. Epilepsy Currents, 6(6), 177-180. doi:10.1111/j.1535-7511.2006.00137.xLaxer, K. D., Trinka, E., Hirsch, L. J., Cendes, F., Langfitt, J., Delanty, N., … Benbadis, S. R. (2014). The consequences of refractory epilepsy and its treatment. Epilepsy & Behavior, 37, 59-70. doi:10.1016/j.yebeh.2014.05.031Giordano, C., Marchiò, M., Timofeeva, E., & Biagini, G. (2014). Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets. Frontiers in Neurology, 5. doi:10.3389/fneur.2014.00063European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). Briviact brivaracetam. Assessment Report EMA/CHMP/822086/2015 Nov.Markham, A. (2016). Brivaracetam: First Global Approval. Drugs, 76(4), 517-522. doi:10.1007/s40265-016-0555-6Willems, L. M., Bauer, S., Rosenow, F., & Strzelczyk, A. (2019). Recent advances in the pharmacotherapy of epilepsy: brivaracetam and perampanel as broad-spectrum antiseizure drugs for the treatment of epilepsies and status epilepticus. Expert Opinion on Pharmacotherapy, 20(14), 1755-1765. doi:10.1080/14656566.2019.1637420Craig, D., Rice, S., Paton, F., Fox, D., & Woolacott, N. (2013). Retigabine for the Adjunctive Treatment of Adults with Partial-Onset Seizures in Epilepsy with and without Secondary Generalization. PharmacoEconomics, 31(2), 101-110. doi:10.1007/s40273-012-0018-1Charokopou, M., Harvey, R., Srivastava, K., Brandt, C., & Borghs, S. (2019). Relative performance of brivaracetam as adjunctive treatment of focal seizures in adults: a network meta-analysis. Current Medical Research and Opinion, 35(8), 1345-1354. doi:10.1080/03007995.2019.1584501Chhatwal J. Changing cycle lengths in state-transition models: doing it the right way; [cited 2018 Jan 23]. Available from: https://www.ispor.org/News/Connections_methodology_state-transition-models.PDFMulhern, B., Rowen, D., Snape, D., Jacoby, A., Marson, T., Hughes, D., … Brazier, J. (2014). Valuations of epilepsy-specific health states: a comparison of patients with epilepsy and the general population. Epilepsy & Behavior, 36, 12-17. doi:10.1016/j.yebeh.2014.04.011Kristian, B., Wachtmeister, K., Stefan, F., & Forsgren, L. (2013). Retigabine as add-on treatment of refractory epilepsy - a cost-utility study in a Swedish setting. Acta Neurologica Scandinavica, 127(6), 419-426. doi:10.1111/ane.12077Vera-Llonch, M., Brandenburg, N. A., & Oster, G. (2008). Cost-effectiveness of Add-on Therapy with Pregabalin in Patients with Refractory Partial Epilepsy. Epilepsia, 49(3), 431-437. doi:10.1111/j.1528-1167.2007.01279.xSimoens, S. (2010). Pharmacoeconomics of anti-epileptic drugs as adjunctive therapy for refractory epilepsy. Expert Review of Pharmacoeconomics & Outcomes Research, 10(3), 309-315. doi:10.1586/erp.10.18Wijnen, B. F. M., van Mastrigt, G. A. P. G., Evers, S. M. A. A., Gershuni, O., Lambrechts, D. A. J. E., Majoie, M. H. J. M., … de Kinderen, R. J. A. (2017). A systematic review of economic evaluations of treatments for patients with epilepsy. Epilepsia, 58(5), 706-726. doi:10.1111/epi.13655Boeck, J. D., Verpoorten, K., Luyten, K., & Coninx, K. (2007). A Comparison between Decision Trees and Markov Models to Support Proactive Interfaces. 18th International Conference on Database and Expert Systems Applications (DEXA 2007). doi:10.1109/dexa.2007.94Zhang, Y., Wu, H., Denton, B. T., Wilson, J. R., & Lobo, J. M. (2017). Probabilistic sensitivity analysis on Markov models with uncertain transition probabilities: an application in evaluating treatment decisions for type 2 diabetes. Health Care Management Science, 22(1), 34-52. doi:10.1007/s10729-017-9420-8Swallow, E., Fang, A., Signorovitch, J., Plumb, J., & Borghs, S. (2017). Can Matching-Adjusted Indirect Comparison Methods Mitigate Placebo Response Differences Among Patient Populations in Adjunctive Trials of Brivaracetam and Levetiracetam? CNS Drugs, 31(10), 899-910. doi:10.1007/s40263-017-0462-8Malyshkina NV, Mannering FL. Markov switching multinomial logit model: an application to accident injury severities; 2008 [cited 2019 Sep 25]. Available from: http://arxiv.org/abs/0811.3644Hawkins, N., Epstein, D., Drummond, M., Wilby, J., Kainth, A., Chadwick, D., & Sculpher, M. (2005). Assessing the Cost-Effectiveness of New Pharmaceuticals in Epilepsy in Adults: The Results of a Probabilistic Decision Model. Medical Decision Making, 25(5), 493-510. doi:10.1177/0272989x05280559Agencia Española del Medicamento. Utilización de medicamentos antiepilépticos en España durante el periodo 2008–2016 [Internet]; 2017 [cited 2019 Sep 25]. Available from: https://www.aemps.gob.es/medicamentosUsoHumano/observatorio/docs/antiepilepticos-periodo-2008-2016.pdfMegiddo, I., Colson, A., Chisholm, D., Dua, T., Nandi, A., & Laxminarayan, R. (2016). Health and economic benefits of public financing of epilepsy treatment in India: An agent‐based simulation model. Epilepsia, 57(3), 464-474. doi:10.1111/epi.13294De Andrés-Nogales, F., Oyagüez, I., Álvarez-Sala, L. A., García-Bragado, F., Navarro, A., González, P., … Soto, J. (2017). Análisis coste-efectividad y coste-utilidad de apixaban frente a dabigatrán y rivaroxaban en el tratamiento y prevención secundaria del tromboembolismo venoso. PharmacoEconomics Spanish Research Articles, 14(1), 7-18. doi:10.1007/s40277-016-0064-8Fricke-Galindo, I., Jung-Cook, H., LLerena, A., & López-López, M. (2018). Farmacogenética de reacciones adversas a fármacos antiepilépticos. Neurología, 33(3), 165-176. doi:10.1016/j.nrl.2015.03.005Steinhoff, B. J., Bacher, M., Bucurenciu, I., Hillenbrand, B., Intravooth, T., Kornmeier, R., … Staack, A. M. (2017). Real-life experience with brivaracetam in 101 patients with difficult-to-treat epilepsy—A monocenter survey. 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Molecular Binding Mechanism of TtgR Repressor to Antibiotics and Antimicrobials

A disturbing phenomenon in contemporary medicine is the prevalence of multidrug-resistant pathogenic bacteria. Efflux pumps contribute strongly to this antimicrobial drug resistance, which leads to the subsequent failure of clinical treatments. The TtgR protein of Pseudomonas putida is a HTH-type transcriptional repressor that controls expression of the TtgABC efflux pump, which is the main contributor to resistance against several antimicrobials and toxic compounds in this microbe. One of the main strategies to modulate the bacterial resistance is the rational modification of the ligand binding target site. We report the design and characterization of four mutants-TtgRS77A, TtgRE78A, TtgRN110A and TtgRH114A - at the active ligand binding site. The biophysical characterization of the mutants, in the presence and in the absence of different antimicrobials, revealed that TtgRN110A is the variant with highest thermal stability, under any of the experimental conditions tested. EMSA experiments also showed a different dissociation pattern from the operator for TtgRN110A, in the presence of several antimicrobials, making it a key residue in the TtgR protein repression mechanism of the TtgABC efflux pump. We found that TtgRE78A stability is the most affected upon effector binding. We also probe that one mutation at the C-terminal half of helix-α4, TtgRS77A, provokes a severe protein structure distortion, demonstrating the important role of this residue in the overall protein structure and on the ligand binding site. The data provide new information and deepen the understanding of the TtgR-effector binding mechanism and consequently the TtgABC efflux pump regulation mechanism in Pseudomonas putida.This work was supported by Spanish Ministry of Economy and Competitiveness, National programme for Recruitment and Incorporation of Human Resources, Subprogramme: Ramon y Cajal RYC-2009-04570 and grant P11-CVI-7391 from Junta de Andalucía and EFDR (European Regional Development Fund)

A Stokes polarimetric light microscopy view of liquid crystal droplets

The optical characteristics of materials, such as their magnetooptical effects, birefringence, optical activities, linear and circular dichroism, are probed via the polarisation states of light transmitted through or reflected from the specimens. As such, the measurements of the polarisation states play an important role in many research disciplines. Experimentally, Stokes parameters provide a full description of the polarisation states of light. We report the implementation of a dual- photoelastic modulator based polarimeter in a light microscope, enabling the determination of Stokes parameters at each pixel. As a case study, polarimetric images of liquid crystal droplets of different internal structures are obtained, showing their distinct polarisation characteristics. We demonstrate that the prototype Stokes polarimetric microscope allows the quantitative determination of the polarisation characteristics of light at the object plane and enables the access of the information of full polarisation states as compared to a conventional cross polariser microscope. This work shows that Stokes polarimetric microscopy may find potential applications in a wide range of research fields

Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways

Background: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host. Methodology/Principal Findings: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior. Conclusions: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context

Machine learning and feature selection methods for egfr mutation status prediction in lung cancer

The evolution of personalized medicine has changed the therapeutic strategy from classical chemotherapy and radiotherapy to a genetic modification targeted therapy, and although biopsy is the traditional method to genetically characterize lung cancer tumor, it is an invasive and painful procedure for the patient. Nodule image features extracted from computed tomography (CT) scans have been used to create machine learning models that predict gene mutation status in a noninvasive, fast, and easy-to-use manner. However, recent studies have shown that radiomic features extracted from an extended region of interest (ROI) beyond the tumor, might be more relevant to predict the mutation status in lung cancer, and consequently may be used to significantly decrease the mortality rate of patients battling this condition. In this work, we investigated the relation between image phenotypes and the mutation status of Epidermal Growth Factor Receptor (EGFR), the most frequently mutated gene in lung cancer with several approved targeted-therapies, using radiomic features extracted from the lung containing the nodule. A variety of linear, nonlinear, and ensemble predictive classification models, along with several feature selection methods, were used to classify the binary outcome of wild-type or mutant EGFR mutation status. The results show that a comprehensive approach using a ROI that included the lung with nodule can capture relevant information and successfully predict the EGFR mutation status with increased performance compared to local nodule analyses. Linear Support Vector Machine, Elastic Net, and Logistic Regression, combined with the Principal Component Analysis feature selection method implemented with 70% of variance in the feature set, were the best-performing classifiers, reaching Area Under the Curve (AUC) values ranging from 0.725 to 0.737. This approach that exploits a holistic analysis indicates that information from more extensive regions of the lung containing the nodule allows a more complete lung cancer characterization and should be considered in future radiogenomic studies.This work is financed by the ERDF—European Regional Development Fund through the Operational Programme for Competitiveness and Internationalisation—COMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT—Fundação para a Ciência e a Tecnologia within project POCI-01-0145-FEDER-030263