Irreversible Effects of Ivermectin on Adult Parasites in Onchocerciasis Patients in the Onchocerciasis Control Programme in West Africa

Ivermectin is an effective drug for the treatment of human onchocerciasis, a disease caused by the parasitic filarial nematode Onchocerca volvulus. When humans are treated, the microfilariae normally found in the skin are rapidly and very nearly completely eliminated. Nonetheless, after a delay, microfilariae gradually reappear in the skin. This study is concerned with the causes of this delay. Hypotheses are tested by comparing the results of model calculations with skin microfilaria counts collected from 114 patients during a trial of five annual treatments in the focus area of Asubende, Ghana. The results obtained strongly suggest that annual treatment with ivermectin causes an irreversible decline in microfilariae production of ∼30%/treatment. This result has important implications for public health strategies designed to eliminate onchocerciasis as a significant health hazar

A new method for fine-scale assessments of the average urban Heat island over large areas and the effectiveness of nature-based solutions

People living in cities experience extra heat stress due to the so-called Urban Heat Island (UHI) effect. To gain an insight into the spatial variability of the UHI for the Netherlands, a detailed map (10 m horizontal resolution) has been calculated that shows the summer-averaged daily maximal UHI situation. The map is based on a relationship between the UHI, mean wind speed at 10 m height and the number of people living within a distance of 10 km, derived from simulations of over 100 European cities with the extensively validated urban climate model UrbClim. The cooling effect of green and blue infrastructure is also taken into account in the map, based on these simulation results. The presented map will help local authorities in defining target areas for climate adaptation measures and estimate the impact of nature-based solutions

A computational pipeline for quantification of mouse myocardial stiffness parameters

The mouse is an important model for theoretical–experimental cardiac research, and biophysically based whole organ models of the mouse heart are now within reach. However, the passive material properties of mouse myocardium have not been much studied. We present an experimental setup and associated computational pipeline to quantify these stiffness properties. A mouse heart was excised and the left ventricle experimentally inflated from 0 to 1.44 kPa in eleven steps, and the resulting deformation was estimated by echocardiography and speckle tracking. An in silico counterpart to this experiment was built using finite element methods and data on ventricular tissue microstructure from diffusion tensor MRI. This model assumed a hyperelastic, transversely isotropic material law to describe the force–deformation relationship, and was simulated for many parameter scenarios, covering the relevant range of parameter space. To identify well-fitting parameter scenarios, we compared experimental and simulated outcomes across the whole range of pressures, based partly on gross phenotypes (volume, elastic energy, and short- and long-axis diameter), and partly on node positions in the geometrical mesh. This identified a narrow region of experimentally compatible values of the material parameters. Estimation turned out to be more precise when based on changes in gross phenotypes, compared to the prevailing practice of using displacements of the material points. We conclude that the presented experimental setup and computational pipeline is a viable method that deserves wider application.acceptedVersio

Left bundle branch block increases left ventricular diastolic pressure during tachycardia due to incomplete relaxation

We investigated whether tachycardia in left bundle branch block (LBBB) decreases left ventricular (LV) diastolic distensibility and increases diastolic pressures due to incomplete relaxation, and if cardiac resynchronization therapy (CRT) modifies this response. Thirteen canines were studied at baseline heart rate (120 beats/min) and atrial paced tachycardia (180 beats/min) before and after induction of LBBB and during CRT. LV and left atrial pressures (LAP) were measured by micromanometers and dimensions by sonomicrometry. The time constant τ of exponential pressure decay and degree of incomplete relaxation at mitral valve opening (MVO) and end diastole (ED) based on extrapolation of the exponential decay were assessed. Changes in LV diastolic distensibility were investigated using the LV transmural pressure-volume (PV) relation. LBBB caused prolongation of τ ( P < 0.03) and increased the degree of incomplete relaxation during tachycardia at MVO ( P < 0.001) and ED ( P = 0.08) compared with normal electrical activation. This was associated with decreased diastolic distensibility seen as upward shift of the PV relation at MVO by 18.4 ± 7.0 versus 12.0 ± 5.0 mmHg, at ED by 9.8 ± 2.3 versus 4.7 ± 2.3 mmHg, and increased mean LAP to 11.4 ± 2.7 versus 8.5 ± 2.6 mmHg, all P < 0.006. CRT shifted the LV diastolic PV relation downwards during tachycardia, reducing LAP and LV diastolic pressures ( P < 0.03). Tachycardia in LBBB reduced LV diastolic distensibility and increased LV diastolic pressures due to incomplete relaxation, whereas CRT normalized these effects. Clinical studies are needed to determine whether a similar mechanism contributes to dyspnea and exercise intolerance in LBBB and if effects of CRT are heart rate dependent. NEW & NOTEWORTHY Compared with normal electrical conduction, tachycardia in left bundle branch block resulted in incomplete relaxation during filling, particularly of the late activated left ventricular lateral wall. This further resulted in reduced left ventricular diastolic distensibility and elevated diastolic pressures and thus amplified the benefits of cardiac resynchronization therapy in this setting