We assessed the association of spatiotemporal hot spots of critically ill small for gestational age (ciSGA) newborns and industrial air emissions. Using neonatal admission data from the Canadian Neonatal Network between 2006 and 2010 (n = 32,836 infants), we aggregated maternal residential postal codes from nineteen census metropolitan areas (CMA) into space-time cubes and applied emerging hot spot analyses. Using National Pollutant Release Inventory data (n = 161 chemicals) and Environment Canada weather station data (n = 19 sites), we estimated monthly wind-dispersion of air emissions and calculated hot spots. We associated the patterns using logistic regression, with covariates for low socioeconomic status, NO2 pollution, and number of infants. A total of 5465 infants were identified as ciSGA and the larger CMAs had more and larger hot spots (i.e. accumulation of events in space and time). Seventy-eight industrial chemical hot spots were associated with ciSGA hot spots. The highest number of positive associations were for 28 different pollutants, which differed by CMA. Twenty-one were known or suspected developmental toxicants, such as particulate matter, carbon monoxide, heavy metals, and volatile organic compounds. Associations with hot spots of industrial chemical emissions were geographically specific and may help explain the space-time trends of ciSGA. OBJECTIVE Mitochondria exist in a constantly remodelling network, and excessive fragmentation can be pathophysiological. Mitochondrial dysfunction can accompany enteric inflammation, but any contribution of altered mitochondrial dynamics (i.e. fission/fusion) to gut inflammation is unknown. We hypothesised that perturbed mitochondrial dynamics would contribute to colitis. DESIGN qPCR for markers of mitochondrial fission and fusion was applied to tissue from dextran sodium-sulphate (DSS)-treated mice. An inhibitor of mitochondrial fission, P110 (prevents dynamin related protein (Drp)-1 binding to mitochondrial fission 1 protein (Fis1)), was tested in the DSS and di-nitrobenzene sulphonic acid (DNBS) models of murine colitis and the impact of DSS ± P110 on intestinal epithelial and macrophage mitochondria assessed in vitro. RESULTS Analysis of colonic tissue from mice with DSS-colitis revealed increased mRNA for molecules associated with mitochondrial fission (i.e. Drp1, Fis1) and fusion (optic atrophy factor 1), and increased phospho-Drp1 compared to control. Systemic delivery of P110, in prophylactic or treatment regimens, reduced the severity of DSS- or DNBS-colitis, and the subsequent hyperalgesia in DNBS-mice. Application of DSS to epithelial cells or macrophages caused mitochondrial fragmentation. DSS-evoked perturbation of epithelial cell energetics and mitochondrial fragmentation, but not cell death, were ameliorated by in vitro co-treatment with P110. CONCLUSION We speculate that the anti-colitic effect of systemic delivery of the anti-fission drug, P110, works, at least partially, by maintaining enterocyte and macrophage mitochondrial networks. Perturbed mitochondrial dynamics can be a feature of intestinal inflammation, the suppression of which is a potential novel therapeutic direction in inflammatory bowel disease. INTRODUCTION We recently proposed a scale for assessment of patient-relevant functional limitations following an episode of venous thromboembolism (VTE). Further development of this post-VTE functional status (PVFS) scale is still needed. METHODS Guided by the input of VTE experts and patients, we refined the PVFS scale and its accompanying manual, and attempted to acquire broad consensus on its use. RESULTS A Delphi analysis was performed involving 53 international VTE experts with diverse scientific and clinical backgrounds. In this process, the number of scale grades of the originally proposed PVFS scale was reduced and descriptions of the grades were improved. After these changes, a consensus was reached on the number/definitions of the grades, and method/timing of the scale assessment. The relevance and potential impact of the scale was confirmed in three focus groups totaling 18 VTE patients, who suggested additional changes to the manual, but not to the scale itself. Using the improved manual, the Îș-statistics between PVFS scale self-reporting and its assessment via the structured interview was 0.75 (95%CI 0.58-1.0), and 1.0 (95%CI 0.83-1.0) between independent raters of the recorded interview of 16 focus groups members. CONCLUSION We improved the PVFS scale and demonstrated broad consensus on its relevance, optimal grades, and methods of assessing among international VTE experts and patients. The interobserver agreement of scale grade assignment was shown to be good-to-excellent. The PVFS scale may become an important outcome measure of functional impairment for quality of patient care and in future VTE trials. Investigator-initiated studies are invaluable, especially in fields that are not particularly of interest for the pharmaceutical industry because they are either less profitable or concern special patient groups such as pregnant women. However, designing, conducting, and completing an investigator-initiated randomised controlled trial is challenging. Selleckchem ATG-017 Patients and physicians' preferences, ethics requirements, (international) legislation and funding are all areas where such challenges are encountered. The Anticoagulants for LIving FEtuses (ALIFE)2 study (NTR3361) is an example of an investigator initiated international multicenter trial that progresses slowly, at least initially, as many challenges had to be overcome. Here, we discuss the challenges we faced during the course of the ALIFE2 study up till now and we explain how some of these challenges can be tackled or even avoided. PURPOSE Inappropriate knowledge and attitude toward pain management of professionals has been pointed to be major obstacles to effective pain management in long-term care setting. The purpose of this study was to develop the Knowledge and Attitudes Survey on Pain Management for Korean long-term care (LTC) professionals (KASP-K). METHODS To develop the KASP-K, the Knowledge and Attitudes Survey Regarding Pain (NKAS) developed by Ferrell and McCaffery in 2014 was amended after a review of broad literature and the latest pain management standards. A rigorous validation process of the KASP-K was performed by testing the content validity, item difficulty and discrimination index, construct validity, test-retest reliability, and internal consistency. RESULTS The KASP-K consisted of 22 items and showed a content validity index of >0.7. The average difficulty of the KASP-K was 0.56 and the discrimination index was >0.2. The construct validity of the KASP-K was verified because of the differences in the sum scores depending on pain education (t = 2.Selleckchem ATG-017
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