Impact of Combined Clenbuterol and Metoprolol Therapy on Reverse Remodelling during Mechanical Unloading

Clenbuterol (Cl), a β2 agonist, is associated with enhanced myocardial recovery during left ventricular assist device (LVAD) support, and exerts beneficial remodelling effects during mechanical unloading (MU) in rodent heart failure (HF). However, the specific effects of combined Cl+β1 blockade during MU are unknown.We studied the chronic effects (4 weeks) of β2-adrenoceptor (AR) stimulation via Cl (2 mg/kg/day) alone, and in combination with β1-AR blockade using metoprolol ((Met), 250 mg/kg/day), on whole heart/cell structure, function and excitation-contraction (EC) coupling in failing (induced by left coronary artery (LCA) ligation), and unloaded (induced by heterotopic abdominal heart transplantation (HATx)) failing rat hearts. Combined Cl+Met therapy displayed favourable effects in HF: Met enhanced Cl's improvement in ejection fraction (EF) whilst preventing Cl-induced hypertrophy and tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MU-induced myocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+ transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Met mono-therapy, but these benefits, together with Cl's enhancement of sarcomeric contraction speed, and MU-induced recovery of Ca2+ spark frequency, disappeared during combined therapy.Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appears inferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined β2-AR simulation +β1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective as mono-therapy in enhancing myocardial recovery during LVAD support

Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation

Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca2+-induced Ca2+ release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart–lung trans-plantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca2+ release synchronicity was reduced at 8 weeks moderate unloading only. Ca2+ sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule mor-phology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37 % reduction in cell volume at 4 weeks compared to 56 % reduction after severe mechanical unloading) and did not cause depres-sion and delay of the Ca2+ transient, increased Ca2+ spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiologi-cal states of increased and reduced cell size, without pathological changes are possible

Using empirical science education in schools to improve climate change literacy

Providing children with a clear understanding of climate change drivers and their mitigation is crucial for their roles as future earth stewards. To achieve this, it will be necessary to reverse the declining interest in STEM (Science, Technology, Engineering and Mathematics) education in schools in the UK and other countries, as STEM skills will be critical when designing effective mitigation solutions for climate change. The ‘Heat-Cool Initiative’ was co-designed and successfully implemented in five primary/secondary UK schools, as a playful learning tool to unleash student interest in STEM subjects. 103 students from two cohorts (years 5–6 and 7–9) participated in five Heat-Cool activity sessions where they used infrared cameras to explore the issue of urban heat. Their learning was evaluated using a multi-functional quantitative assessment, including pre- and postsession quizzes. Climate change literacy increased by 9.4% in primary school children and by 4.5% in secondary school children. Analyses of >2000 infrared images taken by students, categorised into 13 common themes, revealed age-related differences in children’s cognitive development. At primary school age, images of the ‘self’ dominated; secondary school children engaged more with their physical environment. This novel approach demonstrated the importance of developing tailored technology-enhanced STEM education programmes for different age cohorts, leading to a high capacity for improving learning outcomes regarding climate change. Such programmes, embedded in school curricula nationally and internationally, could become a much-needed positive contribution to reaching the United Nation’s Sustainable Development Goals, especially Goals 4 (Quality Education) and 13 (Climate Action)

Feasibility and reproducibility of left ventricular rotation by speckle tracking echocardiography in elderly individuals and the impact of different software

Background Changes in ventricular rotation measured by two-dimensional speckle tracking echocardiography (2DSTE) are early indicators of cardiac disease. Data on the clinical feasibility of this important measure are scarce and there is no information on the comparability of different software versions. We assessed the feasibility, reproducibility and within patient temporal variability of 2DSTE in a large community based sample of older adults. We additionally compared 2DSTE results to those generated by 3DSTE. Methods and results 1408 participants underwent transthoracic echocardiography. Using Philips Qlab 8.1 peak LV rotation at either the base or the apex was analysable in 432 (31%) participants. Peak twist measurements were achieved in 274 (20%) participants. 66 participants were randomly selected for the reproducibility study. 20 additional participants had scans 4–6 weeks apart for temporal variability and 3D echocardiography to assess the agreement between 2DSTE and 3DSTE. Reproducibility was evaluated using the intraclass coefficient of correlation (ICC). Better reproducibility for rotation and twist were obtained when measured at the endocardium, and when using more recent software versions, Peak twist and rotation were significantly different using two versions of the same software. Agreement with 3DSTE was better using newer software. Conclusion Feasibility of 2DSTE is low in this cohort of elderly individuals severely limiting its utility in clinical settings. However if high quality images can be acquired assessment of ventricular rotation by 2DSTE is reproducible. Caution should be taken when comparing measurements of ventricular rotation by software from different vendors or different versions of software from the same vendor

A Double-Blind Placebo-Controlled Crossover Study of the Effect of Beetroot Juice Containing Dietary Nitrate on Aortic and Brachial Blood Pressure Over 24 h

Dietary inorganic nitrate in beetroot can act as a source of nitric oxide and has been reported to lower brachial blood pressure (BP). This study examined the effect of inorganic nitrate in beetroot juice on aortic (central) BP acutely and over the subsequent 24-h period. A double blind, randomized, placebo-controlled crossover trial was performed in fifteen healthy, normotensive men and women (age 22–40 years). Participants were randomized to receive beetroot juice containing nitrate (6.5–7.3 mmol) or placebo beetroot juice from which nitrate had been removed (<0.06 mmol nitrate). Effects on aortic systolic BP were measured at 30 min (primary endpoint), 60 min and over a subsequent 24 h period using an ambulatory BP monitor. Carotid-femoral pulse wave velocity (cfPWV) was also measured at 30 min. Following a washout period, the procedure was repeated within 7 days with crossover to the opposite arm of the trial. Compared with placebo, ingestion of beetroot juice containing nitrate lowered aortic systolic BP at 30 min by 5.2 (1.9–8.5) mmHg [mean (95% confidence interval); p < 0.01]. A smaller effect on aortic systolic BP was observed at 60 min. There were minimal effects on brachial BP or cfPWV. Effects on aortic systolic BP were not sustained over the subsequent 24 h and there were no effects on other hemodynamic parameters during ambulatory monitoring. A single dose of beetroot juice containing nitrate lowers aortic BP more effectively than brachial BP in the short term, but the effects are comparatively short-lived and do not persist over the course of the same day

ROOM TEMPERATURE CURING OF BIO-BASED RESINS AND PREPARATION OF THEIR COMPOSITES

In today’s world the significance of bio-based materials are increasing rapidly because ofthe environmental concern. Material scientists are nowadays engaged in development ofsuch materials which have natural origin and degrade in its environment. Several workshave already been reported in area of thermoplastic biocomposites. However biocompositesbased on thermosets is comparatively new area of research. In this work biobasedcomposites have been developed from two different bio-based thermoset resins.The main objective of the work was room temperature curing of poly lactic acid basedresin (POLLIT™) and AESO, acrylated epoxidized soy-bean oil (TRIBEST®). These tworesin systems were impregnated with different natural fibre mats. Cure behavior wascharacterized by means of DSC (Differential Scanning Calorimeter) and results showsthat the resins have been cured at room temperature. The mechanical properties ofprepared composites were assessed by the means of flexural testing and charpy impacttesting. The viability of using these composites in structural applications are also beendiscussed.Uppsatsnivå:

The Development and Deployment of Mobile Apps and Server Platform for Real-World Screening of Pulmonary and Cardiovascular Disease in Low-Resource Areas

In order to address limited access to health care in low-resource parts of the world, our group at MIT, over the past 7 years, has developed a variety of health screening tools that rely on a smartphone with access to a remote server. This mobile health platform, known as "PyMed," consists of a Django server, Postgres data base, and a variety of Bayesian network machine learning and data processing algorithms implemented in Python. While several different server platforms have been demonstrated by our group over the past few years, a great deal of additional development was required to deploy these technologies in a real-world scenario. In addition to the mobile application software and machine learning algorithms, actual deployment of these technologies required the development of transaction sequences and work flows that enable a health worker, or doctor, in the field to collect data from a patient, process the result in real-time on the server, and then receive a complete and usable result on the mobile phone. In this thesis, I discuss the detailed workflow and underlying technology required to perform diagnostic health measurements in a real-world setting. I present the various software modules and server API work that needed to be developed. In addition, I describe how the health results were designed and ultimately presented in a simple and usable format that both the patient and health worker could use and understand. In this work, I describe two disease categories: cardiovascular disease and pulmonary disease. In total, our group has developed two separate servers, 11 mobile apps, and multiple algorithms for signal processing and diagnostic prediction for these two disease categories. The work in this thesis was completed in preparation for several field studies in Bangladesh: (1) a study with coronavirus patients in the NIDCH Hospital in Dhaka, Bangladesh; and (2) an efficacy study with private community health workers in two low-resource areas of Chittagong District and Jamalpur, Bangladesh.M.Eng