4-Meth­oxy-N-[6-methyl-2,3-dihydro-1,3-benzothia­zol-2-yl­idene]benzene­sulfonamide

The title compound, C15H14N2O3S2, is of inter­est with respect to its biological activity. The crystal structure is stabilized by inter­molecular N—H⋯N, C—H⋯O and C—H⋯π hydrogen-bonding inter­actions, as well as offset π–π inter­actions [distance between the centroids of the aryl and thiazole rings of adjacent molecules of 3.954 (2) Å]

NON-PETROLEUM-BASED BINDERS FOR PAVING APPLICATIONS: RHEOLOGICAL AND CHEMICAL INVESTIGATION ON AGEING EFFECTS

The massive exploitation of non-renewable natural resources which has taken place in the last decade has led to significant global environmental concerns. In such a context, the use of non-petroleum-based binders for the construction of bound layers of flexible pavements can represent an effective solution to limit crude oil depletion. The research work presented in this paper focused on the effects of ageing on the rheological and chemical characteristics of a non-bituminous binder, indicated in the study as a “biobinder”, and a traditional neat bitumen selected as a reference material. Binders were analyzed in four ageing conditions obtained by making use of the Rolling Thin Film Oven and of the Pressure Ageing Vessel. Rheological behaviour of binders was investigated by means of oscillatory tests carried out in a wide range of temperatures and frequencies with a dynamic shear rheometer. Chemical structure was explored via Thin Layer Chromatographic analyses and Fourier Transform Infrared Spectroscopy. The experimental work demonstrated that mechanisms of ageing which are involved in biobinders completely differ from those experienced by petroleum-based binders. Concerns were expressed with respect to the applicability to non-conventional binders of currently available ageing techniques and of chemical characterization methods

Surgical Management of Fistulating Perianal Crohn's Disease - A UK Survey.

AIM: Around one-third of patients with Crohn's disease are affected by Crohn's fistula-in-ano (pCD). It typically follows a chronic course and patients undergo long-term medical and surgical therapy. We set out to describe current surgical practice in the management of pCD in the UK. METHODS: A survey of surgical management of pCD was designed by an expert group of colorectal surgeons and gastroenterologists. This assessed acute, elective, multidisciplinary and definitive surgical management. A pilot of the questionnaire was undertaken at the Digestive Disease Federation 2015 meeting. The survey was refined and distributed nationally through the trainee collaborative networks. RESULTS: National rollout obtained responses from 133 surgeons of 179 approached (response rate 74.3%). At first operation, 32% surgeons would always consider drainage of sepsis and 31.1% would place a draining seton. At first elective operation, 66.6% would routinely insert of draining seton, and 84.4% would avoid cutting seton. The IBD multidisciplinary team was available to 87.6% respondents, although only 25.1% routinely discussed pCD patients. Anti-TNF-α therapy was routinely considered by 64.2%, although 44.2% left medical management to gastroenterology. Common definitive procedures were removal of seton only (70.7%), fistulotomy (57.1%), advancement flap (38.9%), fistula plug (36.4%) and ligation of intersphincteric track (LIFT) procedure (31.8%). Indications for diverting stoma or proctectomy were intractable sepsis, incontinence, and poor quality of life. DISCUSSION: This survey has demonstrated areas of common practice, but has also highlighted divergent practice including choices of definitive surgery and multimodal management. Practical guidelines are required to support colorectal surgeons in the UK. This article is protected by copyright. All rights reserved

Real-time crowd density mapping using a novel sensory fusion model of infrared and visual systems

Crowd dynamic management research has seen significant attention in recent years in research and industry in an attempt to improve safety level and management of large scale events and in large public places such as stadiums, theatres, railway stations, subways and other places where high flow of people at high densities is expected. Failure to detect the crowd behaviour at the right time could lead to unnecessary injuries and fatalities. Over the past decades there have been many incidents of crowd which caused major injuries and fatalities and lead to physical damages. Examples of crowd disasters occurred in past decades include the tragedy of Hillsborough football stadium at Sheffield where at least 93 football supporters have been killed and 400 injured in 1989 in Britain's worst-ever sporting disaster (BBC, 1989). Recently in Cambodia a pedestrians stampede during the Water Festival celebration resulted in 345 deaths and 400 injuries (BBC, 2010) and in 2011 at least 16 people were killed and 50 others were injured in a stampede in the northern Indian town of Haridwar (BBC, 2011). Such disasters could be avoided or losses reduced by using different technologies. Crowd simulation models have been found effective in the prediction of potential crowd hazards in critical situations and thus help in reducing fatalities. However, there is a need to combine the advancement in simulation with real time crowd characterisation such as the estimation of real time density in order to provide accurate prognosis in crowd behaviour and enhance crowd management and safety, particularly in mega event such as the Hajj. This paper addresses the use of novel sensory technology in order to estimate people’s dynamic density du ring one of the Hajj activities. The ultimate goal is that real time accurate estimation of density in different areas within the crowd could help to improve the decision making process and provide more accurate prediction of the crowd dynamics. This paper investigates the use of infrared and visual cameras supported by auxiliary sensors and artificial intelligence to evaluate the accuracy in estimating crowd density in an open space during Muslims Pilgrimage to Makkah (Mecca)

JNK signalling in cancer: In need of new, smarter therapeutic targets

Copyright © 2013 The British Pharmacological Society. This is the accepted version of the following article: Bubici, C. and Papa, S. (2014), JNK signalling in cancer: in need of new, smarter therapeutic targets. British Journal of Pharmacology, 171: 24–37, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/bph.12432/abstract.The JNKs are master protein kinases that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival and death. It is increasingly apparent that persistent activation of JNKs is involved in cancer development and progression. Therefore, JNKs represent attractive targets for therapeutic intervention with small molecule kinase inhibitors. However, evidence supportive of a tumour suppressor role for the JNK proteins has also been documented. Recent studies showed that the two major JNK proteins, JNK1 and JNK2, have distinct or even opposing functions in different types of cancer. As such, close consideration of which JNK proteins are beneficial targets and, more importantly, what effect small molecule inhibitors of JNKs have on physiological processes, are essential. A number of ATP-competitive and ATP-non-competitive JNK inhibitors have been developed, but have several limitations such as a lack of specificity and cellular toxicity. In this review, we summarize the accumulating evidence supporting a role for the JNK proteins in the pathogenesis of different solid and haematological malignancies, and discuss many challenges and scientific opportunities in the targeting of JNKs in cancer.Kay Kendall Leukemia Fund, Italian Association for Cancer Research and Foundation for Liver Research

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Evidence of genome-wide G4 DNA-mediated gene expression in human cancer cells

Guanine-rich DNA of a particular sequence adopts four-stranded structural forms known as G-quadruplex or G4 DNA. Though in vitro formation of G4 DNA is known for several years, in vivo presence of G4 DNA was only recently noted in eukaryote telomeres. Recent bioinformatics analyses showing prevalence of G4 DNA within promoters of human and related species seems to implicate G4 DNA in a genome-wide cis-regulatory role. Herein we demonstrate that G4 DNA may present regulatory sites on a genome-wide scale by showing widespread effect on gene expression in response to the established intracellular G4 DNA-binding ligands. This is particularly relevant to genes that harbor conserved potential G4 DNA (PG4 DNA) forming sequence across human, mouse and rat promoters of orthologous genes. Genes with conserved PG4 DNA in promoters show co-regulated expression in 79 human and 61 mouse normal tissues (z-score > 3.5; P < 0.0001). Conservation of G4 DNA across related species also emphasizes the biological importance of G4 DNA and its role in transcriptional regulation of genes; shedding light on a relatively novel mechanism of regulation of gene expression in eukaryotes

Systemic zinc redistribution and dyshomeostasis in cancer cachexia

Cachexia affects up to two thirds of all cancer patients and is a significant cause of morbidity and mortality. It is a complex metabolic syndrome associated with the underlying illness and characterized by loss of skeletal muscle tissue with or without loss of fat mass. Cachexia’s other prominent clinical symptoms include anorexia, systemic inflammation, pediatric growth failure, and hypogonadism. The relationship between the symptoms of cancer cachexia and the underlying illness is unclear, and there is an urgent need for a better understanding of the pathophysiology of this syndrome. Normal Zn metabolism is often disrupted in cancer patients, but the possible effects of systemic Zn dyshomeostasis in cachexia have not been investigated. We propose that the acute phase response can mediate Zn redistribution and accumulation in skeletal muscle tissue and contribute to the activation of the ubiquitin–proteasome pathway that regulates protein catabolism. This chronic redistribution deprives Zn from other tissues and organs and compromises critical physiological functions in the body. The cardinal symptoms of Zn deficiency are anorexia, systemic inflammation, growth failure in children, and hypogonadism. These symptoms also prominently characterize cancer cachexia suggesting that the role of systemic Zn dyshomeostasis in cachexia should be investigated