Notes

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BACKGROUND/AIMS Direct-acting antivirals (DAAs) provide an unprecedented opportunity for a "find-and-treat strategy." We aimed to report real-world clinical, patient reported and health economic outcomes of community-based hepatitis C virus (HCV) screening/treatment in people who use drugs (PWUDs). METHODS Project ITTREAT (2013-2021), established at a drug and alcohol treatment centre, offered a comprehensive service. Generic (SF-12v2 and EQ-5D-5L) and liver-specific (SFLDQoL) health-related quality of life (HRQoL) were assessed before and after HCV treatment. Costs/case detected and cured were calculated. Primary outcome measure was sustained virological response (SVR) (intention to treat). Apitolisib in vivo RESULTS Till March 2018, 573 individuals recruited, 462 (81%) males, mean age 40.5 ± 10.0 years. Of the 125 treated, 115 (92%) had past/current history of injecting drug use, 88 (70%) were receiving opioid agonist treatment and 50 (40%) were homeless. Twenty-six per cent received interferon-based and 74% DAA-only regimens. SVR (ITT) was 87% (90% with DAAs). Service uptake/HCV treatment completion rates were >95%, HCV reinfection being 2.63/100 person years (95% CI 0.67-10.33). HRQoL improved significantly at end of treatment (EOT) in those with SVR SFLDQoL (symptoms, memory, distress, loneliness, hopelessness, sleep and stigma) (P less then / = .011); SF-12 v2 physical and mental health domains (P less then .001); and EQ-5D-5L composite profile score (P = .009) and visual analogue scale, P less then .001. Cost (British pounds 2018) per case detected was £171; mean cost per cure (excluding medication) was £702 ± 188. CONCLUSIONS Excellent real-world SVRs in PWUDs with significant improvement in HRQoL can be achieved at modest costs. Project ITTREAT endorses community-based integrated services to help achieve HCV elimination. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Despite the increasing volume of evidence demonstrating the efficacy of solar water disinfection (SODIS) as a household water treatment technology, there still appear to be significant barriers to uptake in developing countries. The potential of SODIS is often treated with scepticism in terms of effective treatment, volume, and safety, and is dismissed in preference for more accepted technologies such as ceramic filters and dose chlorination. As part of WATERSPOUTT (EU H2020 688928), our study used a transdisciplinary methodology to co-create an innovative SODIS system in rural Malawi. The formative work focussed on the design of (1) an appropriate and acceptable system, and (2) a context specific intervention delivery programme using a behaviour centred design. Initial research identified specific water needs and challenges, which were discussed along with a co-creation process with potential end-users, through a series of shared dialogue workshops. Specifications from end-users outlined a desire for higher volume systems (20 litres), which were 'familiar' and could be manufactured locally. Development of the 'SODIS bucket' was then undertaken by design experts and local manufacturers, with input from end users, and subject to controlled testing to ensure efficacy and safety. Concurrent data was collated using questionnaires (n=777 households), water point mapping (n=121), water quality testing (n=46) and behaviour change modelling (n=100 households). These identified specific contextual issues (hydrogeology, water access, gender roles, social capital, and socio-economic status), and behavioural determinants (normative, ability and self-regulation factors) which informed the development and delivery mechanism for the implementation toolkit. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.We propose a label-free method for measuring intracellular temperature using a Raman image of a cell in the O-H stretching band. Raman spectra of cultured cells and the medium were first measured at various temperatures using a Raman microscope and the intensity ratio of the two regions of the O-H stretching band was calculated. The intensity ratio varies linearly with temperature in both the medium and cells, and the resulting calibration lines allow simultaneous visualization of both intracellular and extracellular temperatures in a label-free manner. We applied this method to the measurement of temperature changes after the introduction of FCCP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone) in living cells. We observed a temperature rise in the cytoplasm and succeeded in obtaining an image of the change in intracellular temperature after the FCCP treatment. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Differently 5-substituted 8-methoxypsoralens can be synthesized by an efficient synthetic route with various cross-coupling methodologies, such as Suzuki, Sonogashira and Heck reaction. Compared to previously synthesized psoralens, thereby promising daylight absorbing compounds as potentially active agents against certain skin diseases can be readily accessed. Extensive investigations of all synthesized psoralen derivatives reveal fluorescence in the solid state as well as several distinctly emissive derivatives in solution. Donor-substituted psoralens exhibit remarkable photophysical properties, such as high fluorescence quantum yields and pronounced emission solvatochromicity and acidochromicity, which were scrutinized by Lippert-Mataga and Stern-Volmer plots. The results indicate that the compounds exceed the limit of visible light, a significant factor for potential applications as an active agent. In addition, (TD)DFT calculations were performed to elucidate the underlying electronic structure and to assign experimentally obtained data. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Many skin diseases are defined by the presence of neutrophils, which are among the first cells to respond to infection and inflammation. Currently, neutrophil identification in the skin is costly and slow. The objectives of the present work are to investigate the feasibility of detecting the presence of neutrophils in live skin microsamples using chemiluminescence and develop a device and procedures that will enable preclinical and clinical investigations. Our approach consists of collecting skin microsamples and exposing them to reagents that activate neutrophils and amplify the light emission produced by chemiluminescence. Experiments using live pig skin with and without inflammation show that it is feasible to detect the presence of neutrophils in the skin. The proposed method is minimally invasive, simple, fast, and does not require user specialization. The developed system is compact in size with a small footprint, which makes it portable and suitable for point-of-care diagnostics. © 2020 WILEY-VCH Verlag GmbH & Co.
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