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Qin Xiang Ng,1,2 Alex Yu Sen Soh,1 Wayren Loke,2 Donovan Yutong Lim,3 Wee-Song Yeo1 1National University Hospital, National University Health System, Singapore; 2MOH Holdings Pte Ltd, Singapore; 3Institute of Mental Health, Singapore Abstract: Irritable bowel syndrome (IBS) is a complex, functional gastrointestinal ­disorder characterized by chronic abdominal pain or discomfort and altered bowel habits. Despite the global prevalence and disease burden of IBS, its underlying pathophysiology remains unclear. Inflammation may play a pathogenic role in IBS. Studies have highlighted the persistence of mucosal inflammation at the microscopic and molecular level in IBS, with increased recruitment of enteroendocrine cells. Substantial overlaps between IBS and inflammatory bowel disease have also been reported. This review thus aimed to discuss the body of evidence pertaining to the presence of mucosal inflammation in IBS, its putative role in the disease process of IBS, and its clinical relevance. Increased mast cell density and activity in the gut may correlate with symptoms of visceral hypersensitivity. As evidenced by patients who develop postinfectious IBS, infective gastroenteritis could cause systemic inflammation and altered microbiome diversity, which in turn perpetuates a cycle of chronic, low-grade, subclinical inflammation. Apart from mucosal inflammation, neuroinflammation is probably involved in the pathophysiology of IBS via the “gut–brain” axis, resulting in altered neuroendocrine pathways and glucocorticoid receptor genes. This gives rise to an overall proinflammatory phenotype and dysregulated hypothalamic–pituitary–adrenal axis and serotonergic (5-HT) functioning, which could, at least in part, account for the symptoms of IBS. Although a definite and reproducible pattern of immune response has yet to be recognized, further research into anti-inflammatories may be of clinical value. Keywords: irritable bowel syndrome, postinfectious, inflammation, microbiome

Qin Xiang Ng,1,2 Michelle Lee Zhi Qing De Deyn,3 Nandini Venkatanarayanan,4 Collin Yih Xian Ho,2 Wee-Song Yeo,5 1Department of Medicine, National University Hospital, National University Health System, Singapore; 2MOH Holdings Pte Ltd, Singapore; 3Department of Medicine, James Cook University Hospital, Middlesbrough, UK; 4Department of Medicine, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham, UK; 5Department of Paediatrics, National University Hospital, National University Health System, Singapore Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are dermatologic emergencies with high morbidity and mortality risk. Cyclosporine, an immunomodulatory agent, is sometimes used off-label, and its role continues to be debated. This meta-analysis aimed to provide an update of current evidence and to clarify the role of cyclosporine in SJS/TEN treatment better.Methods: Using the keywords [cyclosporine OR cyclosporine OR ciclosporin OR CsA] AND [Steven-Johnson OR SJS OR toxic epidermal OR epidermal necrolysis OR TEN OR hypersensitivity OR dermatologic OR burns], a preliminary search on the PubMed, Ovid, Web of Science, and Google Scholar Database yielded 615 papers published in English between January 1, 1960 and July 1, 2017. The inclusion criteria for this review were: 1) published retrospective or prospective study (excluding single case reports); 2) patients with clinical diagnosis of SJS or TEN; 3) trial of cyclosporine treatment; and 4) available survival/mortality data.Results: A total of 12 studies, with a total of 358 SJS/TEN patients were reviewed. Two studies were excluded from the meta-analysis as they did not report SCORe of toxic epidermal necrosis/predicted mortality data; one was excluded because of possible data irregularities. Meta-analysis of nine studies revealed a significant reduction in mortality risk with cyclosporine therapy (standardized mortality ratio 0.320; 95% CI: 0.119–0.522; P=0.002). Cyclosporine was also generally well tolerated with little adverse effects or increased infection, albeit the patients tended to be critically ill. Publication bias was observed in the funnel plot and Egger test (P=0.0467).Conclusion: Currently available evidence are predominantly open trials and retrospective studies with a significant risk of bias, perhaps owing to the rarity and life-threatening nature of the condition. Given its immunomodulatory actions, cyclosporine could be a potential treatment option for SJS/TEN in addition to best supportive measures. Further confirmation with robust randomized, controlled trials or larger case series is necessary and should be encouraged. Keywords: SJS, TEN, epidermal necrolysis, cyclosporine, CsA, meta-analysis

The use of feedback created by electric guitars and amplifiers is problematic in musical settings. For example, it is difficult for a performer to accurately obtain specific pitch and loudness qualities. This is due to the complex relationship between these quantities and other variables such as the string being fretted and the positions and orientations of the guitar and amplifier. This research investigates corpus-based methods for controlling the level and pitch of the feedback produced by a guitar and amplifier. A guitar-amplifier feedback system was built in which the feedback is manipulated using (i) a simple automatic gain control system, and (ii) a band-pass filter placed in the signal path. A corpus of sounds was created by recording the sound produced for various combinations of the parameters controlling these two components. Each sound in the corpus was analysed so that the control parameter values required to obtain particular sound qualities can be recalled in the manner of concatenative sound synthesis. As a demonstration, a recorded musical target phrase is recreated on the feedback system.