Intercalated degree Interview Flashcards
1
Q
Cancer biology
A
- Delivered by lectures
- Starts will definition of neoplasia and describes the macro and micro appearance of a range of specific tumours and current ideas on the molecular and genetic basis of their pathogenesis
- Transformation from normal to malignant tissue also covered
- End with tumour diagnosis and treatment
2
Q
Experimental neuropathology
A
- Delivered through lectures
- Covers lab techniques designed to diagnose and model neuropathological diseases
- Covers techniques such as PCR, imaging and animal models
- Biology of neural cells will be covered such as demyelination, axonal transplant, cell death pathways and stem cell replacement
- Clinical aspects include trauma, alzheimer’s disease, parkinsons disease, motor neurone disease, picks disease and tauopathies
3
Q
Cardiovascular pathophysiology
A
- Taught and delivered by lectures
- Covers the normal development of the cardiovascular system in terms of the changing demands due to growth and ageing
- Elucidate the pathogensis of cardiovascular disease in terms of the response of cells in the vascular wall to changes in mechanical load such as increased blood pressure or reduced flow
- Module integrates the model of vascular pathology with epidemiological factors such as foetal malnutrition which affects vessel development in early life and which are linked to an increased incidence of vascular disease in middle age
- Diagnosis and treatment of these problems
4
Q
Stem cell and regenerative medicine
A
- Comprehensive overview and foundation in stem cell biology including applications in regenerative medicine
- Module will cover topics including developmental origin of stem cells, comparing/contrasting different types of stem cells, biological regulation of stem cells and tissue specific functions
- Module will cover fundamental principles of tissue engineering cellular reporgramming
5
Q
Molecular basis of peronsalised medicine
A
- Module will build on the basic information on the pathological processes and cancer biology to provide an in-depth analysis of the tools available to analyse hetrogenetiy in disease and how these can be used to stratify disease and then exploited to develop individualised treatment
- Examine strategies being developed to refine treatment programmes and investigate how such analysis can be used to predict risk and develop preventive strategies
6
Q
Advanced biocompatibility science
A
- Concepts related to and underpinning biocomparibility
- Cover topics including proteins and protein adsorption, biomaterial-cell, blood and tissue interactions, inflammation, wound healing, foregin body response, toxicity, hypersnesitvity and infection
- Pre-clinical testing of biomaterials will be considered with respect to chemical exchange and degradation, cell response (proliferation vs differentiation), evaluation of material compatibility, evaluation of device functionality (biomechanics, remodelling/adaption)
- clinical trials and regulatory approval will be discussed
7
Q
Oxford vaccine trial
A
- 4 randomised controlled trials in brazil, south Africa and the UK using participants aged 18 and over, they were randomly assigned a oxford coronavirus vaccine or the meningococcal group ACWY vaccine
- Received two doses
- Between April 23rd and November 4th 2020 23848 participants
- It was initially claimed that participants who received two standard doses the vaccine efficacy was 62.1% and in participants who received a low dose followed by a standard dose the efficacy was 90%
- 3 studies were single blind and one was double blind
- Had to contact the study site if they experience specific symptoms associated with COVID-19 – were swabbed if they thought they had it
8
Q
aortic calcification and TLRs
A
- Study highlighted how calficiation of the aortic valve is no longer considered a degenerative process related to aging but an actively regulated process in which many pathogenetic factors remain unknown – they base this on the epidemiological association of risk factors leading to high prevlacne and faster progression of CAVD, the histiopathologic identification in excised stenotic valves of chronic inflammation features, lipoprortien deposition, RAAS system composnents and molecular mediators of calcification and finally the elucidation of cell signalling pathways and genetic factors linked to valve disease pathogenesis
- Finding pathogen cargo in stenotic aortic valve cusps prompted researchers to investigate the role of TLR in CAVD
- Chlamydia pneumoniae and bacteria associated with chronic periodontal infection have been detected in stenotic valves at the level of the valvular fibrosa and inoculation of oral bacteria has been found to cause aortic valve calficiation in a rabbit model of recurrent low grade endocarditis
- TLR4 and TLR2 was found to be expressed in aortic valve tissue,
- TLR2 found to promote a pro calcific phenotype in VIC via Map Kinase pathway
- TLR4/2 in osteongensis since LPS promotes early aortic valve leaflet thickenss in mice
- TLR4/2 ligands differ according to cardiac valve site being their effects stronger in aortic VICs as compared to pulmonary mitral or tricuspid VICs
- DAMPs such as Biglycan, HMGB1 and Matrilin-2 are extracellular proteins exporessed in different tissue and accumulates in the calcific nodules of human aortic valves by increasing the osteogenic activity via TLR2/4 in VICs
- Need to see if TLRs could be relevant in the onset of clinically relevant calcification which needs to be replicated using in vivo models capitulating hyperphophatemic and or inflammatory calcification triggers
- Then look at the therapeutic potential of TLRs
9
Q
Polymeric valves
A
- Current heart valve solutions are expensive and labor intestive to manufacture – have short life spans and contain anaimal derived tissue or metallic elements that require immunosuppression or antithrombogenic drugs and tend not to fit perfectly into the patients aorta
- Heart valves customized to fit the anatomy of the patients and match the softness of the surrounding tissue and adapt to the pathology and growth of diseased host tissue represent the next frontier in treatment
- Digital fabrication of tissue like aortic heart valves using customizable geometry and leaflet architectures that resemble those of native valve issue using biocompatible silicones with tunable mechanical properties
- Offer the durability of mechanical valves but the haemodynamic function of tissue valves
- Computer simulations showed that the bioinspired leaflet architectures strongly affect the stress distribution throughout the valves and minimize stresses on the leaflet during a cardiac cycle – replicated the physiological pressure cycles
- Tries to replciat eth three layers of the valve – the ventricularis, the spongiosa and the fibrosa as one moves from the ventricle to the aorta
- Looked at where during the cardiac cycle the pressure is exposed on the native valve and tried to replicate that
- Made It patient custimozied by using – 3D imaging of the aorta anatomy by CT or MRI, the create of a virtual heart valve replacement system based on the reconstructed imaged aorta and the additive manufacture of the complete prosthesis suing spraying and extrusion based irect ink writing techniques
- Found that if they increased the thickenss by 35% this reduced the stress, also found that if they included bioinspired fibres which replicate our own collagen fibres this reduced stress by 26%
- Diastole puts the entire leaflet under stress whereas the systolic state high stresses develop mostly along the inter leaflet triangle
- Looked at the cardiac cycle and the parts of the valve that experience most stress
- Found that diastole experiences the most stress in on the whole of the valve whereas systole is only on the intertranagle parts of the vavle
- Picked silicone as their choice of material for the valve
- Put the valve in the cardiac cycle
- Foun that if they increased the thickenss by 35% this reduced the stress, also found that if they included bioinspired fibres which replicate our own collagen fibres this reduced stress by 26%
- Stems from the idea of trying to replicate the structure of our own valves, thereby having our own haemodynamic effects as well as reducing the stress which increases the length of time the valve lasts
- ## Need to be trialed in humans
10
Q
What was your critical appraisal on
A
- Study on long term behavioural changes in group housed rat models of brain and spinal cord injury using an automated home cage recording system
11
Q
What research project would you like to do
A
- While thinking about what research project I would like to do I read someo of the abstracts that you sent to me from the intercalated degree fare
- Impact of traumatic haemorrhagic injury on cardiomycocyte survival – liked the idea of monitoring biomarkers to investigate cardiacmyocycte
- Also liked the acoustic localisation of coronary artery stenosis – used a cylindrical agarose gel with an electromagnetic vibrator connected to a bead embedded within the gel and measure the surface movement by high speed video tracking of reflective partciles and then input this data into a 2D computational solver to derive the shear wave source, gathered reproducible results and found that maximal surface displacent due to the vibratiosn of the embedded bead occurred at positions near the free surface of the speickmen for all bead positiosn, next steps will involvement measurments and computational modelling of a more relastic chest models contained stenosed arter perfused with pulsatile flow
- So that got me thinking about the SSC2a I did around valve disease, and one of the research papers that I read was talking about how aortic valve disease could be more of a pathogenic process involving TLRs activating MAP kinase and triggering pro calfiic molecules cuaisng the calification, so If I were to do any research that I could
