Discrete microstructural cues for the attenuation of fibrosis following myocardial infarction

Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. We have developed a therapeutic materials strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructures to mechanically alter the microenvironment. Polymeric microstructures were fabricated using photolithographic techniques and studied in a three-dimensional culture model of the fibrotic environment and by direct injection into the infarct zone of adult rats. Here, we show dose-dependent down-regulation of expression of genes associated with the mechanical fibrotic response in the presence of microstructures. Injection of this microstructured material into the infarct zone decreased levels of collagen and TGF-β, increased elastin deposition and vascularization in the infarcted region, and improved functional outcomes after six weeks. Our results demonstrate the efficacy of these discrete anti-fibrotic microstructures and suggest a potential therapeutic materials approach for combatting pathologic fibrosis.     

Combining cell sheet technology and electrospun scaffolding for engineered tubular,aligned, and contractile blood vessels

Herein we combine cell sheet technology and electrospun scaffolding to rapidly generate circumferentially aligned tubular constructs of human aortic smooth muscles cells with contractile gene expression for use as tissue engineered blood vessel media. Smooth muscle cells cultured on micropatterned and N-isopropylacrylamide-grafted (pNIPAm) polydimethylsiloxane (PDMS), a small portion of which was covered by aligned electrospun scaffolding, resulted in a single sheet of unidirectionally aligned cells. Upon cooling to room temperature, the scaffold, its adherent cells, and the remaining cell sheet detached and were collected on a mandrel to generating tubular constructs with circumferentially aligned smooth muscle cells which possess contractile gene expression and a single layer of electrospun scaffold as an analogue to a small diameter blood vessel's internal elastic lamina (IEL). This method improves cell sheet handling, results in rapid circumferential alignment of smooth muscle cells which immediately express contractile genes, and introduction of an analogue to small diameter blood vessel IEL.     

Singapore Paediatric Resuscitation Guidelines 2021

We present the 2021 Singapore Paediatric Resuscitation Guidelines. The International Liaison Committee on Resuscitation’s Pediatric Taskforce Consensus Statements on Science and Treatment Recommendations, which was published in October 2020, and the updated resuscitation guidelines from the American Heart Association and European Resuscitation Council, were reviewed and discussed by the committee. These recommendations were derived after deliberation of peer-reviewed evidence updates on paediatric resuscitation and took into consideration the local setting and clinical practice.     

The hemodynamic and pain impact of peripheral nerve block versus spinal anesthesia in diabetic patients undergoing diabetic foot surgery

Clinical Autonomic Research - Comparison of hemodynamic profiles and pain scores in diabetic patients undergoing diabetic foot surgery receiving peripheral nerve block (PNB) or spinal anesthesia...     

The NoGo P300 'anteriorization' effect and response inhibition.

OBJECTIVE: The P300 event-related potential shows anterior P300 increases on NoGo tasks (target stimulus=withhold response) relative to Go tasks (target stimulus=commit response). This 'NoGo anteriorization' has been hypothesized to reflect response inhibition. However, silent-count tasks show similar P300 anteriorization. The P300 anteriorization on silent-count tasks relative to Go tasks cannot reflect inhibition-related processes, and questions the degree to which anteriorization observed on NoGo trials can be ascribed to response inhibition. Comparison of anteriorization between the silent-count and NoGo tasks is thus essential. P300 topography on NoGo and silent-count tasks has not been previously compared. METHODS: P300 on Go, NoGo, and silent-count auditory oddball tasks were compared. If the NoGo P300 anteriorization reflects response inhibitory processes, the NoGo P300 should be larger anteriorly than the Go P300 (overt responses) and the silent-count P300s (covert responses). If anteriorization primarily reflects negative voltage Go task motor activity that reduces the normal frontal P300 amplitude, then the Go task P300 should be smaller than both the NoGo and silent-count P300s, which should not differ from one another. RESULTS: The Go task elicited a bilaterally reduced frontal P300 and asymmetrical frontal P300 relative to both the NoGo and silent-count tasks. The NoGo task P300 and silent-count task P300 showed similar amplitude and topography. P300 and slow wave on the NoGo task were not asymmetrical. CONCLUSIONS: The increased frontal P300 in NoGo tasks cannot be attributed solely to a positive-going inhibitory process, but likely reflects negative voltage response execution processes on Go trials. However, the alternative explanation that memory-related processes increase the silent-count P300 anteriorly to the same degree as NoGo inhibitory processes cannot be ruled out.     

Clinical and economic outcomes of a multidisciplinary team approach in a lower extremity amputation prevention programme for diabetic foot ulcer care in an Asian population: A case‐control study

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case‐control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow‐up (33% vs 76%, P < .001), decrease in 1‐year minor amputation rate (14% vs 3%, P = .007), and decrease in 1‐year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.     

The major cockroach allergen Bla g 4 binds tyramine and octopamine

Bla g 4 is a male cockroach specific protein and is one of the major allergens produced by Blattella germanica (German cockroach). This protein belongs to the lipocalin family that comprises a set of proteins that characteristically bind small hydrophobic molecules and play a role in a number of processes such as: retinoid and pheromone transport, prostaglandin synthesis and mammalian immune response. Using NMR and isothermal titration calorimetry we demonstrated that Bla g 4 binds tyramine and octopamine in solution. In addition, crystal structure analysis of the complex revealed details of tyramine binding. As tyramine and octopamine play important roles in invertebrates, and are counterparts to vertebrate adrenergic transmitters, we speculate that these molecules are physiological ligands for Bla g 4. The nature of binding these ligands to Bla g 4 sheds light on the possible biological function of the protein. In addition, we performed a large-scale analysis of Bla g 4 and Per a 4 (an allergen from American cockroach) homologs to get insights into the function of these proteins. This analysis together with a structural comparison of Blag 4 and Per a 4 suggests that these proteins may play different roles and most likely bind different ligands.     

Fenfluramine suppresses snack intake among carbohydrate cravers but not among noncarbohydrate cravers

Two groups of obese individuals who consume excessive calories primarily as snack foods have been distinguished: carbohydrate cravers and noncarbohydrate cravers. Both groups consume about 800 calories from snacks (860 kcal vs 879 kcal) and about 2000 calories from meals (1906 kcal vs 2080 kcal) daily. The carbohydrate-cravers consume almost all of their snacks as carbohydrate-rich foods (7 ± 0.4 CHO snacks/day vs 0.9 ± 0.12 protein snacks/day) whereas the noncarbohydrate cravers consume approximately equal numbers of protein and carbohydrate snacks (4.5 ± 0.6 carbohydrate snacks/day vs 3.5 ± 0.5 protein snacks/day). D-fenfluramine significantly reduced the intakes of calories (range 24–44%) and carbohydrates (range 28–41%) from snacks among the carbohydrate cravers over a three month treatment period. The drug did not affect snack intake by the noncarbohydrate cravers until the third month of treatment when the consumption of both types of snacks decreased significantly. D-fenfluramine decreased mealtime carbohydrate intake among the carbohydrate cravers throughout the treatment period (range 16–23%); mealtime protein intake declined comparably (range 14–18%) during the first and third treatment months. The drug had no effect on mealtime carbohydrate nor protein intake by noncarbohydrate cravers.     

A longitudinal analysis of the experiences of nursing staff on an inpatient eating disorders unit

The present study assessed whether nurses working in an inpatient eating disorders unit experience any increased risk as a result of treating patients with anorexia nervosa, bulimia, and variants of these two disorders. There were 23 newly hired or just transferred primary care nurses (12 in an eating disorders program and 11 in other service areas) who were weighed monthly and completed the following instruments either monthly or semimonthly for 13 months: Beck Depression Inventory, Eating Attitudes Test, Impressions of Patient Population Survey, job Satisfaction Inventory, and Attitudes toward Patient Questionaire. Results indicated that nurses in the eating disorders program had less distorted eating attitudes, less positive impressions of their patients, and greater job satisfaction than their counterparts from other service areas. Nurses from both groups had progressively less positive impressions of their patients and lower job satisfaction over the course of the study. These findings suggest that when certain team-building experiences (e.g., inservice training, interdisciplinary team meetings) are incorporated into an eating disorders unit, nurses face no special risks in the areas of mood and eating disturbance.