Electrospun polymer nanocomposite scaffolds containing metal oxide nanoparticles for diabetic wound healing
Authors: Khattab Ahmed , Streletz Leopold , Thavanesan Kamy , Jupp Becky , Ali Ibtisam , Hakim Eluzai , Naghotra Utpal , Black Toby , Jenkinson Damian , Abdulmawjood Ahmed , Mitchell Rebecca , Heath Stephanie , Gad Hoda , Malik Rayaz 
Published: June 2019

Background: Most of the evidence -so far- in support of the link between Transient Ischemic Attack (TIA) and the development of future stroke are -in fact- based on epidemiological rather than scientific evidence. Meanwhile, Current prediction models for long-term prognosis in TIA and stroke patients have limited validity as discrimination between patients at high risk and patients at low risk is relatively poor. Although the ABCD2 prediction model seems to be most adequate because of its applicability in clinical practice, the American Heart Association pointed out that validated prediction models for long term cardiovascular risk in patients with ischemic stroke or TIA were not available. Furthermore, it has been suggested that all these stroke-based prediction models were derived from trial populations with certain inclusion and exclusion criteria. It could therefore be argued that the best fitted model for everyday practice will probably need to be derived from a consecutive stroke/TIA population without exclusion criteria. Improvements (such as stronger predictors of outcome) are therefore needed. Aims: This study investigates the prevalence of microalbuminuria in patients who have suffered a TIA for the first time. The aim is to identify a subgroup of TIA patients who are at higher risk of developing future cerebrovascular events. Methods: This is an observational cohort study with two arms (in Qatar and UK). The Qatari arm involved 56 patients with acute TIAs or small stroke (TIAs with tissue evidence of infarction), attending a local hospital in Qatar; whereas, the UK arm involved 74 first time TIA patients, attending a TIA Clinic at a local hospital in the UK. Microalbuminuria was first measured by calculating the Albumin/Creatinine Ratio (ACR). Urine samples (with and without microalbuminuria) were then examined using SDS-PAGE electrophoresis. Protein bands were identified by their rate of migration in comparison with standard molecular weight (MW) markers. Results: The Qatari arm of the study recruited 56 patients (mean age 55.50 years); 35 Males: 21 Females), attending a Stroke/TIA Clinic in Qatar. 19 (33.92%) TIA patients showed evidence of microalbuminuria (30-300 mg/24 hr) and 37 (66.08%) showed normal albuminuria ( < 30 mg/24 hr). The UK arm of the study recruited 74 first TIA patients (mean age 74.75 years; age range 52-91); 38 Males: 36 Females). 25 (33.78%) TIA patients showed evidence of microalbuminuria and 49 (66.22%) showed normal albuminuria. Out of the 25 TIA patients with microalbuminuria, 92% of them have a blood pressure of more than 140 mmHg. SDS-PAGE electrophoresis of urine samples obtained from patients recruited (for both arms of the study) revealed a similar pattern of 3 major protein bands. Band (A) is heavily stained, representing albumin (MW = 70 kDa) in patients with micro-albuminuria, and less intensity in patients with normal-albuminuria. Band (B) was shown in all urine samples of patients with microalbuminuria, but not in patients with normal-albuminuria. Its position on the gel is roughly equidistant between bands A and C. Band (C), denoting a slower migration band, representing Tamm-Horsfall protein. Tamm-Horsfall protein is suspected since not only is it the most abundant protein in urine after albumin, but also its position is in concordance with the relative molecular weight of Tamm-Horsfall protein (between 85 and 110 kDa). The intensity of this band is generally not as great as band A. Other bands (MW < 50 kDa and < 40 kDa) were also seen; they may represent degradation products of albumin due to storage. Discussion: Microalbuminuria has been proven to be a predictor of cardiovascular disease and mortality in both diabetic and non-diabetic patients, and it is a reflection of an overall vascular damage. This study aims to identify a subgroup of TIA patients who are at higher risk of developing future cerebrovascular events. Our data confirmed that microalbuminuria is very common in TIA patients as one third of participants (in both arms of the study) presented with microalbuminuria, most of whom have a history of high blood pressure. However, it is important to highlight here that participants in the Qatari cohort are much younger and their microalbuminuria is more severe than the UK cohort. This might be due to the severity of their condition, the presence of co-morbidity, ethnicity and genetic susceptibility. With such a high prevalence of microalbuminuria (in first time TIA patients), such a prognostic marker cannot be ignored in TIA Clinics. There is now a case for microalbuminuria to be considered for possible adding it to the current ABCD2 predictive model, taking into account the fact that microalbuminuria can now be easily measured using a urine dip stick testing. The clinical applications of our findings may include an aggressive approach to antihypertensive management. Conclusion: Microalbuminuria following TIA is likely to be an added marker of risk and could indicate a more aggressive approach to hypertension management or the choice of ACE inhibitors angiotensin 2 receptor blockers over other antihypertensive drugs. The novelty of this project stems from the fact that it investigates two predictive makers; one biochemical (microalbuminuria, presented in this study) and one physiological (auto-regulation of cerebral blood flow, still being analyzed). No previous research has combined the two predictive markers together in a cohort group of first time TIA patients. These two predictive parameters will provide us with more evidence to predict further stroke and whether current intervention is sufficient enough to prevent future stroke. If this is proven to be correct, both predictors will add more validity to the current conventional risk models predictors. If there is such a link between these two measures then changes to the regulation of blood flow in the brain can be predicted by a simple urine test. This will help predict how well patients will recover after TIA. Furthermore, if microalbuminuria is associated with impaired cerebral auto-regulation (following TIA) then one might take more caution with anti-hypertensive treatment early after TIA. By identifying impairment in auto-regulation this study may provide an important reason for caution which may otherwise be overlooked. «This study was made possible by grant NPRP 6-565-3-141 from Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the author[s].»