Nitric oxide treatments as adjuncts to reperfusion in acute myocardial infarction: a systematic review of experimental and clinical studies

Unmodified reperfusion therapy for acute myocardial infarction (AMI) is associated with irreversible myocardial injury beyond that sustained during ischemia. Studies in experimental models of ischemia/reperfusion and in humans undergoing reperfusion therapy for AMI have examined potential beneficial effects of nitric oxide (NO) supplemented at the time of reperfusion. Using a rigorous systematic search approach, we have identified and critically evaluated all the relevant experimental and clinical literature to assess whether exogenous NO given at reperfusion can limit infarct size. An inclusive search strategy was undertaken to identify all in vivo experimental animal and clinical human studies published in the period 1990–2014 where NO gas, nitrite, nitrate or NO donors were given to ameliorate reperfusion injury. Articles were screened at title and subsequently at abstract level, followed by objective full text analysis using a critical appraisal tool. In twenty-one animal studies, all NO treatments except nitroglycerin afforded protection against measures of reperfusion injury, including infarct size, creatinine kinase release, neutrophil accumulation and cardiac dysfunction. In three human AMI RCT’s, there was no consistent evidence of infarct limitation associated with NO treatment as an adjunct to reperfusion. Despite experimental evidence that most NO treatments can reduce infarct size when given as adjuncts to reperfusion, the value of these interventions in clinical AMI is unproven. Our study raises issues for the design of further clinical studies and emphasises the need for improved design of animal studies to reflect more accurately the comorbidities and other confounding factors seen in clinical AMI

Dissecting the Mid-Infrared Heart of M83 with JWST

We present a first look at the MRS observations of the nucleus of the spiral galaxy M83, taken with MIRI onboard JWST. The observations show a rich set of emission features from the ionized and warm molecular gas, as well as traces of the dust properties in this highly star forming environment. To begin dissecting the complex processes taking place in this part of the galaxy, we divide the nucleus observations into four different regions. We find that the strength of the emission features appears to strongly vary in all four regions, with the south-east region displaying the weakest features tracing both the dust continuum and ISM properties. Comparison between the cold molecular gas traced by the $^{12}$CO (1-0) transition with ALMA and the H$_2$ 0-0 S(1) transition showed a similar spatial distribution throughout the nucleus. This is in contrast to the distribution of the much warmer H$_2$ emission from the S(7) transition found to be concentrated mainly around the optical nucleus. We modeled the H$_2$ excitation using the rotational emission lines and estimate a total molecular gas mass accounting for the warm H$_2$ component of M($>$50 K)$_{\rm H_{2}}$ = 59.33 ($\pm 4.75$) $\times$ 10$^{6}$ M$_{\odot}$. We compared this value to the total molecular gas mass inferred by probing the cold H$_2$ gas through the $^{12}$CO (1-0) emission, M(CO)$_{\rm H_{2}}$ = 14.99 $\times$ 10$^{6}$ M$_{\odot}$. Our findings indicate that $\sim$75\% of the total molecular gas mass in the core of M83 is contained in the warm H$_2$ component. We also identify [OIV]25.89 $\mu$m and [FeII]25.99 $\mu$m emission (indicative of shocks) in all four nuclear regions with the strongest emission originating from the north-west section. We propose that the diffuse [FeII]25.99 $\mu$m emission is an indication of the combined effects of both the collective supernova explosions and the starbursts themselves.Comment: 13 pages, 3 Tables, 8 Figures, to be submitted to Ap

Perceived barriers and facilitators of exercise and healthy dietary choices : a study of employees and managers within a large transport organisation

Objective. The objective of the research was to examine employees’ perceived barriers and facilitators of physical activity and healthy dietary choices, and managers’ perceptions of how to facilitate physical activity and healthy dietary choices among their team members. Design. A cross-sectional and qualitative design was used. Setting. Participants were employees from a large public sector organisation (N= 121), who were asked about the barriers to and facilitators of maintaining regular exercise and healthy dietary choices. Managers were additionally asked about methods for facilitating physical activity and healthy dietary choices among their team members. Methods. The research used both quantitative and qualitative methodology, with categorical and open ended survey questions. Results. Thematic analysis revealed similar themes for both physical activity and healthy dietary choices, with participants citing working patterns, commuting times, family commitments, job characteristics, and lack of motivation as barriers to exercise and healthy dietary choices. Both employees and managers identified similar facilitators of exercise and healthy dietary choices, such as improved information, facilities, and working routines. Conclusion. The results provide an insight into the perceived barriers and facilitators to adopting a healthy lifestyle among a sample of employees with differing shift patterns and job roles. The results are discussed in relation to suggested methods for promoting physical activity and healthy dietary choices at work

Roundtable: Transcultural fan studies in practice: a conversation

At the end of 2018, a group of fan scholars led by Lori Morimoto journeyed to Japan for a fan studies field trip. The purpose was multifaceted: to speak at a symposium on transcultural popular culture; to bring together fans and fandom studies from both sides of the Pacific; and to augment their classrooms with practical experience. Eight participants share their experiences and reflect on what it means to be a transcultural fan scholar at the dawning of the 2020s

Enzymatic Late‐Stage Modifications: Better Late Than Never

From Wiley via Jisc Publications RouterHistory: received 2020-11-08, rev-recd 2021-01-15, pub-electronic 2021-03-08, pub-print 2021-07-26Article version: VoRPublication status: PublishedFunder: EPSRC; Grant(s): EP/S005226/1Funder: BBSRC; Grant(s): EP/S005226/1Funder: AstraZeneca plc; Id: http://dx.doi.org/10.13039/100004325; Grant(s): EP/S005226/1Funder: European Research Council; Id: http://dx.doi.org/10.13039/100010663; Grant(s): 742987-BIO-H-BORROW-ERC-2016-ADG, 788231-ProgrES-ERC-2017-ADGAbstract: Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means of bioinformatics and enzyme engineering opens up an immense variety of selective reactions. Biocatalysis especially provides excellent opportunities for late‐stage modification often superior to conventional de novo synthesis. Enzymes have proven to be useful for direct introduction of functional groups into complex scaffolds, as well as for rapid diversification of compound libraries. Particularly important and highly topical are enzyme‐catalysed oxyfunctionalisations, halogenations, methylations, reductions, and amide bond formations due to the high prevalence of these motifs in pharmaceuticals. This Review gives an overview of the strengths and limitations of enzymatic late‐stage modifications using native and engineered enzymes in synthesis while focusing on important examples in drug development

Enzymkatalysierte späte Modifizierungen: Besser spät als nie

From Wiley via Jisc Publications RouterHistory: received 2020-11-08, rev-recd 2021-01-15, pub-electronic 2021-03-08, pub-print 2021-07-26Article version: VoRPublication status: PublishedFunder: EPSRC; Grant(s): EP/S005226/1Funder: BBSRC; Grant(s): EP/S005226/1Funder: AstraZeneca plc; Id: http://dx.doi.org/10.13039/100004325; Grant(s): EP/S005226/1Funder: European Research Council; Id: http://dx.doi.org/10.13039/100010663; Grant(s): 742987-BIO-H-BORROW-ERC-2016-ADG, 788231-ProgrES-ERC-2017-AD

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Predicting range shifts of African apes under global change scenarios

Aim: Modelling African great ape distribution has until now focused on current or past conditions, while future scenarios remain scarcely explored. Using an ensemble forecasting approach, we predicted changes in taxon-specific distribution under future scenarios of climate, land use and human populations for (1) areas outside protected areas (PAs) only (assuming complete management effectiveness of PAs), (2) the entire study region and (3) interspecies range overlap. Location: Tropical Africa. Methods: We compiled occurrence data (n = 5,203) on African apes from the IUCN A.P.E.S. database and extracted relevant climate-, habitat- and human-related predictors representing current and future (2050) conditions to predict taxon-specific range change under a best- and a worst-case scenario, using ensemble forecasting. Results: The predictive performance of the models varied across taxa. Synergistic interactions between predictors are shaping African ape distribution, particularly human-related variables. On average across taxa, a range decline of 50% is expected outside PAs under the best scenario if no dispersal occurs (61% in worst scenario). Otherwise, an 85% range reduction is predicted to occur across study regions (94% worst). However, range gains are predicted outside PAs if dispersal occurs (52% best, 21% worst), with a slight increase in gains expected across study regions (66% best, 24% worst). Moreover, more than half of range losses and gains are predicted to occur outside PAs where interspecific ranges overlap. Main Conclusions: Massive range decline is expected by 2050, but range gain is uncertain as African apes will not be able to occupy these new areas immediately due to their limited dispersal capacity, migration lag and ecological constraints. Given that most future range changes are predicted outside PAs, Africa\u27s current PA network is likely to be insufficient for preserving suitable habitats and maintaining connected ape populations. Thus, conservation planners urgently need to integrate land use planning and climate change mitigation measures at all decision-making levels both in range countries and abroad