Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans

Background: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP-1) lowers glycaemia by stimulation of insulin, inhibition of glucagon, and delay of gastric emptying.Aims: To assess the effects of endogenous GLP-1 on endocrine pancreatic secretion and antro-pyloro-duodenal motility by utilising the GLP-1 receptor antagonist exendin(9-39)amide (ex(9-39)NH2).Methods: Nine healthy volunteers underwent four experiments each. In two experiments with and without intravenous infusion of ex(9-39)NH2 300 pmol/kg/min, a fasting period was followed by intraduodenal glucose perfusion at 1 and 2.5 kcal/min, with the higher dose stimulating GLP-1 release. Antro-pyloro-duodenal motility was measured by perfusion manometry. To calculate the incretin effect (that is, the proportion of plasma insulin stimulated by intestinal hormones) the glycaemia observed during the luminal glucose experiments was mimicked using intravenous glucose in two further experiments.Results: Ex(9-39)NH2 significantly increased glycaemia during fasting and duodenal glucose. It diminished plasma insulin during duodenal glucose and significantly reduced the incretin effect by approximately 50%. Ex(9-39)NH2 raised plasma glucagon during fasting and abolished the decrease in glucagon at the high duodenal glucose load. Ex(9-39)NH2 markedly stimulated antroduodenal contractility. At low duodenal glucose it reduced the stimulation of tonic and phasic pyloric motility. At the high duodenal glucose load it abolished pyloric stimulation.Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic \textgreeka cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogastrone in humans

Developing LGBT+ Inclusive Supporter Groups in the Big Bash League

Sport is an integral part of both Australian culture and identity. However, the lesbian, gay, bisexual and transgender communities (LGBT+) face extra barriers and challenges to engagement and participation in sport. This study, formed through a partnership between Western Sydney University and Cricket Victoria, aimed to better understand how LGBT+ supporter/ coterie groups could be initiated and supported in the Big Bash League. Twenty-Four key stakeholders and informants drawn from Australian Football League (AFL) LGBT+ supporter groups, AFL administrators, cricket administrators, and LGBT+ cricket fans were interviewed to collect comprehensive data on the requirements for successful LGBT+ supporter group formation in cricket and the Big Bash League. Our results reveal a strong desire to include more LGBT+ communities in cricket, with the Big Bash League identified as an ideal opportunity due to its family-oriented nature. However, it was felt by participants that there was a lack of understanding and education of LGBT+-related issues within the cricket community. The experiences of those involved in AFL support groups have been overwhelmingly positive and provide a compelling case for the introduction of LGBT+ supporter groups in cricket, from both a social inclusion and financial management perspective. We conclude that the introduction of LGBT+ supporter groups in cricket has the potential to impact positively the lives of LGBT+ communities, providing a platform for them to engage with sport in a meaningful and positive way. Three key messages were identified for those wishing to set up LGBT+ supporter groups: 1. Groups should be developed from the bottom up, being driven by LGBT+ fans and members rather than purely from the organisation. A partnership approach between Cricket Victoria/Big Bash League clubs and local LGBT+ communities also provides an avenue to facilitate training and education on LGBT+-related issues for staff and players. 2. Institutional support is crucial for such an initiative to succeed; 3. Clear policies are needed to support supporter groups and to address any negative responses. This policy should also address behaviour by players and staff to ensure that the institutional commitment to inclusion is not undermined

Topical and Systemic Cannabidiol Improves Trinitrobenzene Sulfonic Acid Colitis in Mice

Background/Aims: Compounds of Cannabis sativa are known to exert anti-inflammatory properties, some of them without inducing psychotropic side effects. Cannabidiol (CBD) is such a side effect-free phytocannabinoid that improves chemically induced colitis in rodents when given intraperitoneally. Here, we tested the possibility whether rectal and oral application of CBD would also ameliorate colonic inflammation, as these routes of application may represent a more appropriate way for delivering drugs in human colitis. Methods: Colitis was induced in CD1 mice by trinitrobenzene sulfonic acid. Individual groups were either treated with CBD intraperitoneally (10 mg/kg), orally (20 mg/kg) or intrarectally (20 mg/kg). Colitis was evaluated by macroscopic scoring, histopathology and the myeloperoxidase (MPO) assay. Results: Intraperitoneal treatment of mice with CBD led to improvement of colonic inflammation. Intrarectal treatment with CBD also led to a significant improvement of disease parameters and to a decrease in MPO activity while oral treatment, using the same dose as per rectum, had no ameliorating effect on colitis. Conclusion: The data of this study indicate that in addition to intraperitoneal application, intrarectal delivery of cannabinoids may represent a useful therapeutic administration route for the treatment of colonic inflammation. Copyright (C) 2012 S. Karger AG, Base

Conflicting theories on addiction aetiology and the strengths and limitations of substance use disorder disease modelling

A lack of cross-disciplinary unanimity prevails within addiction research. Theories conceptualizing addiction through the three-stage brain disease model contest other theories that substance use disorder is of behavioural or genetic origin. The reverberations of this lack of consensus are noticeable throughout addiction research and within the foundations of disease modelling. The availability of methods to investigate substance use disorder are inconsistent and sometimes unrepresentative. This review discusses theories of addiction aetiology, available models for addiction research and the strengths and limitations of current practical experimental methods of study

Cochrane Centralised Search Service showed high sensitivity identifying randomized controlled trials: A retrospective analysis

BACKGROUND: The Cochrane Central Register of Controlled Trials (CENTRAL) is compiled from a number of sources, including PubMed and Embase. Since 2017, we have increased the number of sources feeding into CENTRAL and improved the efficiency of our processes through the use of APIs, machine learning and crowdsourcing. OBJECTIVES: Our objectives were twofold: (1) Assess the effectiveness of Cochrane's centralised search and screening processes to correctly identify references to published reports which are eligible for inclusion in Cochrane systematic reviews of randomised controlled trials (RCTs). (2) Identify opportunities to improve the performance of Cochrane's centralised search and screening processes to identify references to eligible trials. METHODS: We identified all references to RCTs (either published journal articles or trial registration records) with a publication or registration date between 1st January 2017 and 31st December 2018 that had been included in a Cochrane intervention review. We then viewed an audit trail for each included reference to determine if it had been identified by our centralised search process and subsequently added to CENTRAL. RESULTS: We identified 650 references to included studies with a publication year of 2017 or 2018. Of those, 634 (97.5%) had been captured by Cochrane's Centralised Search Service (CSS). Sixteen references had been missed by the CSS: six had PubMed-not-MEDLINE status, four were missed by the centralised Embase search, three had been misclassified by Cochrane Crowd, one was from a journal not indexed in MEDLINE or Embase, one had only been added to Embase in 2019, and one reference had been rejected by the automated RCT machine learning classifier. Of the sixteen missed references, eight were the main or only publication to the trial in the review in which it had been included. CONCLUSIONS: This analysis has shown that Cochrane's centralised search and screening processes are highly sensitive. It has also helped us to understand better why some references to eligible RCTs have been missed. The CSS is playing a critical role in helping to populate CENTRAL and is moving us towards making CENTRAL a comprehensive repository of RCTs

Young AGN outburst running over older X-ray cavities

Although the energetic feedback from active galactic nuclei (AGN) is believed to have a profound effect on the evolution of galaxies and clusters of galaxies, details of the AGN heating remain elusive. Here, we study NGC 193 - a nearby lenticular galaxy - based on X-ray (Chandra) and radio (VLA and GMRT) observations. These data reveal the complex AGN outburst history of the galaxy: we detect a pair of inner X-ray cavities, an outer X-ray cavity, a shock front, and radio lobes extending beyond the inner cavities. We suggest that the inner cavities were produced ~78 Myr ago by a weaker AGN outburst, while the outer cavity, the radio lobes, and the shock front are due to a younger (13-26 Myr) and (4-8) times more powerful outburst. Combining this with the observed morphology of NGC 193, we conclude that NGC 193 likely represents the first example of a second, more powerful, AGN outburst overrunning an older, weaker outburst. These results help to understand how the outburst energy is dissipated uniformly in the core of galaxies, and therefore may play a crucial role in resolving how AGN outbursts suppress the formation of large cooling flows at cluster centers.Comment: 6 pages, 3 figures, 1 table, accepted for publication in ApJ

Implementation research for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva infection prevention and control (IPC)-think tank (part 1)

Background Around 5–15% of all hospital patients worldwide suffer from healthcare-associated infections (HAIs), and years of excessive antimicrobial use in human and animal medicine have created emerging antimicrobial resistance (AMR). A considerable amount of evidence-based measures have been published to address these challenges, but the largest challenge seems to be their implementation. Methods In June 2017, a total of 42 experts convened at the Geneva IPC-Think Tank to discuss four domains in implementation science: 1) teaching implementation skills; 2) fostering implementation of IPC and antimicrobial stewardship (AMS) by policy making; 3) national/international actions to foster implementation skills; and 4) translational research bridging social sciences and clinical research in infection prevention and control (IPC) and AMR. Results Although neglected in the past, implementation skills have become a priority in IPC and AMS. They should now be part of any curriculum in health care, and IPC career paths should be created. Guidelines and policies should be aligned with each other and evidence-based, each document providing a section on implementing elements of IPC and AMS in patient care. International organisations should be advocates for IPC and AMS, framing them as patient safety issues and emphasizing the importance of implementation skills. Healthcare authorities at the national level should adopt a similar approach and provide legal frameworks, guidelines, and resources to allow better implementation of patient safety measures in IPC and AMS. Rather than repeating effectiveness studies in every setting, we should invest in methods to improve the implementation of evidence-based measures in different healthcare contexts. For this, we need to encourage and financially support collaborations between social sciences and clinical IPC research. Conclusions Experts of the 2017 Geneva Think Tank on IPC and AMS, CDC, and WHO agreed that sustained efforts on implementation of IPC and AMS strategies are required at international, country, and hospital management levels, to provide an adequate multimodal framework that addresses (not exclusively) leadership, resources, education and training for implementing IPC and AMS. Future strategies can build on this agreement to make strategies on IPC and AMS more effective