Ivermectin and albendazole coadministration: opportunities for strongyloidiasis control

7 páginas.In 2020, WHO recognised the importance of strongyloidiasis alongside soil-transmitted helminths (STH) in their 2021–30 roadmap, which aspires to target Strongyloides stercoralis with preventive chemotherapy by use of ivermectin. Combination treatment with both albendazole, the primary drug used to treat STH, and ivermectin, would improve the efficiency of mass drug administration targeting both STH and S stercoralis. In this Personal View, we discuss the challenges and opportunities towards the development of an efficient control programme for strongyloidiasis, particularly if it is to run concurrently with STH control. We argue the need to define the prevalence threshold to implement preventive chemotherapy for S stercoralis, the target populations and optimal dosing schedules, and discuss the added benefits of a fixed-dose coformulation of ivermectin and albendazole. Implementation of an efficient control programme will require improvements to current diagnostics, and validation of new diagnostics, to target and monitor S stercoralis infections, and consideration of the challenges of multispecies diagnostics for S stercoralis and STH control. Finally, the evolution of ivermectin resistance represents a credible risk to control S stercoralis; we argue that genome-wide approaches, together with improved genome resources, are needed to characterise and prevent the emergence of resistance. Overcoming these challenges will help to reduce strongyloidiasis burden and enhance the feasibility of controlling it worldwide.Our group, the Stopping Transmission of intestinal Parasites (STOP) consortium, is funded by the EDCTP2 programme supported by the European Union (RIA2017NCT-1845-STOP). The Barcelona Institute for Global Health (ISGlobal) acknowledges support from the Spanish Ministry of Science and Innovation and State Research Agency through the Centro de Excelencia Severo Ochoa 2019–2023 Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. SRD is supported by a UK Research and Innovation Future Leaders Fellowship [MR/T020733/1] and the Wellcome Trust through core funding to the Wellcome Sanger Institute [108413/A/15/D]. MC-P is supported by the Junta de Castilla y León and Fondo Social Europeo. The funders of the study had no role in the manuscript preparation or the decision to publish. The views, opinions, assumptions, or any other information set out in this Personal View are solely those of the authors and should not be attributed to the funders or any person connected with the funders.Peer reviewe

Generation of an anatomically based geometric coronary model

A discrete anatomically accurate finite element model of the largest six generations of the coronary arterial network is developed. Using a previously developed anatomically accurate model of ventricular geometry the boundaries of the coronary mesh are defined from measured epicardial coronaries. Network topology is then generated stochastically from published anatomical data. Spatial information is added to this topological data using an avoidance algorithm accounting for global network geometry and optimal local branch angle properties. The generated vessel lengths, radii and connectivity are consistent with the published studies and a relativity even spatial distribution of vessels within the ventricular mesh is achieved. The local finite element coordinates of the coronary nodes within the ventricular mesh are calculated such that the coronary geometry can be recalculated within a deformed ventricular mesh

Anatomically realistic torso model for studying the relative decay of gastric electrical and magnetic fields

10.1109/IEMBS.2006.260201Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings3158-3161CEMB

Altered T wave dynamics in a contracting cardiac model

INTRODUCTION: The implications of mechanical deformation on calculated body surface potentials are investigated using a coupled biophysically based model. METHODS AND RESULTS: A cellular model of cardiac excitation-contraction is embedded in an anatomically accurate two-dimensional transverse cross-section of the cardiac ventricles and human torso. Waves of activation and contraction are induced by the application of physiologically realistic boundary conditions and solving the bidomain and finite deformation equations. Body surface potentials are calculated from these activation profiles by solving Laplace's equation in the passive surrounding tissues. The effect of cardiac deformation on electrical activity, induced by contraction, is demonstrated in both single-cell and tissue models. Action potential duration is reduced by 7 msec when the single cell model is subjected to a 10% contraction ramp applied over 400 msec. In the coupled electromechanical tissue model, the T wave of the ECG is shown to occur 18 msec earlier compared to an uncoupled excitation model. To assess the relative effects of myocardial deformation on the ECG, the activation sequence and tissue deformation are separated. The coupled and uncoupled activation sequences are mapped onto the undeforming and deforming meshes, respectively. ECGs are calculated for both mappings. CONCLUSION: Adding mechanical contraction to a mathematical model of the heart has been shown to shift the T wave on the ECG to the left. Although deformation of the myocardium resulting from contraction reduces the T wave amplitude, cell stretch producing altered cell membrane kinetics is the major component of this temporal shift

Cardiac electromechanics and the forward/inverse problems of electrocardiology

Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings7 VOLS7198-7200CEMB

Modelling slow wave activity in the small intestine

10.1016/j.jtbi.2006.03.004Journal of Theoretical Biology2422356-362JTBI

Geometric modelling of the human torso using cubic Hermite elements

We discuss the advantages and problems associated with fitting geometric data of the human torso obtained from magnetic resonance imaging, with high order (bicubic Hermite) surface elements. These elements preserve derivative (C 1 ) continuity across element boundaries and permit smooth anatomically accurate surfaces to be obtained with relatively few elements. These elements are fitted to the data with a new non-linear fitting procedure that minimises the error in the fit whilst maintaining C 1 continuity with non-linear constraints. Non-linear Sobelov smoothing is also incorporated into this fitting scheme. The structures fitted along with their corresponding Root Mean Squared (RMS) error, number of elements used and number of degrees-of-freedom (dof) per variable are: epicardium (0.91 mm, 40 elements, 142 dof), left lung (1.66 mm, 80 elements, 309 dof), right lung (1.69 mm, 80 elements, 309 dof), skeletal muscle surface (1.67 mm, 264 elements, 1010 dof), fat layer (1.79 mm, 264 e..

Anatomically realistic multiscale models of normal and abnormal gastrointestinal electrical activity

World Journal of Gastroenterology1391378-1383WJGA