Graz. Burgtor-Hofgasse

Blick durch das Burgtor in Richtung Hofgass

Differential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites.

ACE2 is a membrane protein that regulates the cardiovascular system. Additionally, ACE2 acts as a receptor for host cell infection by human coronaviruses, including SARS-CoV-2 that emerged as the cause of the on-going COVID-19 pandemic and has brought unprecedented burden to economy and health. ACE2 binds the spike protein of SARS-CoV-2 with high affinity and shows little variation in amino acid sequence meaning natural resistance is rare. The discovery of a novel short ACE2 isoform (deltaACE2) provides evidence for inter-individual differences in SARS-CoV-2 susceptibility and severity, and likelihood of developing subsequent 'Long COVID'. Critically, deltaACE2 loses SARS-CoV-2 spike protein binding sites in the extracellular domain, and is predicted to confer reduced susceptibility to viral infection. We aimed to assess the differential expression of full-length ACE2 versus deltaACE2 in a panel of human tissues (kidney, heart, lung, and liver) that are implicated in COVID-19, and confirm ACE2 protein in these tissues. Using dual antibody staining, we show that deltaACE2 localises, and is enriched, in lung airway epithelia and bile duct epithelia in the liver. Finally, we also confirm that a fluorescently tagged SARS-CoV-2 spike protein monomer shows low binding at lung and bile duct epithelia where dACE2 is enriched.This research was funded in whole, or in part by: Wellcome Trust (WT107715/Z/15/Z, A.P.D., and J.J.M.); Wellcome Trust Programme in Metabolic and Cardiovascular Disease (203814/Z/16/A, T.L.W., D.N.), Wellcome Trust Major Award (208363/Z/17/Z) for Imaging Core (G.S.); British Heart Foundation (FS/17/61/33473 A.P.D., R.G.C.M; TG/18/4/33770, A.P.D., J.J.M.; FS/18/46/33663, S.S.). Cambridge Biomedical Research Centre Biomedical Resources Grant (University of Cambridge, Cardiovascular Theme, RG64226). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

Identifying outcome-based indicators and developing a curriculum for a continuing medical education programme on rational prescribing using a modified Delphi process

<p>Abstract</p> <p/> <p>Background</p> <p>Continuing medical education (CME) is compulsory for physicians in Iran. Recent studies in Iran show that modifications of CME elements are necessary to improve the effectiveness of the educational programmes. Other studies point to an inappropriate, even irrational drug prescribing. Based on a needs assessment study regarding CME for general physicians in the East Azerbaijan province in Iran, rational prescribing practice was recognized as a high priority issue. Considering different educational methods, outcome-based education has been proposed as a suitable approach for CME. The purpose of the study was to obtain experts' consensus about appropriate educational outcomes of rational prescribing for general physicians in CME and developing curricular contents for this education.</p> <p>Methods</p> <p>The study consisted of two phases: The first phase was conducted using a two-round Delphi consensus process to identify the outcome-based educational indicators regarding rational prescribing for general physicians in primary care (GPs). In the second phase the agreed indicators were submitted to panels of experts for assessment and determination of content for a CME program in the field.</p> <p>Results</p> <p>Twenty one learning outcomes were identified through a modified Delphi process. The indicators were used by the panels of experts and six educational topics were determined for the CME programme and the curricular content of each was defined. The topics were 1) Principles of prescription writing, 2) Adverse drug reactions, 3) Drug interactions, 4) Injections, 5) Antibiotic therapy, and 6) Anti-inflammatory agents therapy. One of the topics was not directly related to any outcome, raising a question about the need for a discussion on constructive alignment.</p> <p>Conclusions</p> <p/> <p>Consensus on learning outcomes was achieved and an educational guideline was designed. Before suggesting widespread use in the country the educational package should be tested in the CME context.</p

A giant among dwarfs: a new species of galago (Primates: Galagidae) from Angola

Objectives: Based on vocalization recordings of an unknown galago species, our main objectives were to compare morphology and call structure with known closely-related taxa and describe a new species of galago. Materials and Methods: We conducted field surveys in three forest habitats along the escarpment region in western Angola (Kumbira Forest, Bimbe Area and Northern Scarp Forest), and examined galago specimens from museums worldwide. We digitized and analyzed calls using Avisoft SASLab Pro software. We also compared museum specimens from Angola with other Galago and Galagoides specimens, and conducted comparative analyses (ANOVA and between group principle component analysis) based on a set of twelve linear measurements of skulls and teeth. Results: We describe the new species to which we give the name Angolan dwarf galago, Galagoides kumbirensis sp. nov. The new species has a loud and characteristic crescendo call, used by other Galagoides spp. (sensu stricto) in West Africa to attract companions and repel rivals. However, this call shows species-typical differences from its closest relatives. Galagoides kumbirensis sp. nov. is also distinguished by differences in the skull morphology, pelage color and facial markings, as well as a larger body size, similar to that of Galago moholi, which is not known to be sympatric. Conclusion: This discovery points to the importance of Angolan forests as refuges for endemic biodiversity. These forests are under severe threat from over-exploitation, and there is an urgent need to establish conservation measures and designate protected areas

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Enhancing Abiotic Stress Tolerance in Cereals Through Breeding and Transgenic Interventions

The success of plant breeding in the 20th century led to new cultivars that, to date, have provided enough food for an increasing world population (Conway and Toenniessen 1999; Mifflin 2000). The results of the Green Revolution-led in the 1960s by Henry M. Beachell andNormanE. Dotlaug—resulted in a dramatic increase in rice and wheal grain yields (Milford and Runge 2007; Ortiz et al. 2007). However, abiotic stresses and climate change are becoming increasingly serious threats to crop production worldwide at a time when food staple supply will need to be significantly higher to meet the demand of the growing human population. Water scarcity (Rockstrom et al. 2007], salinity (Rengasamy 2006). and low soil fertility (Sanchez and Swaminathan 2005) rank among the moat important abiotic stresses worldwide. Similarly, increased climatic disturbances due to global warming are causing the major stresses that necessitate crop improvements to safeguard grain supply, particularly in the developing world (Kumar 2006). Hence, genetic enhancement of cereal crops with respect to abiotic stress tolerance will be essential far ensuring grain yields in water-limited, increasingly hotter agricultural zones, particularly If these conditions combine with poor and saline soils, conditions that prevail in parts of the developing world. Crop breeding for adaptation to abiotic stress-prone environments remains a challenging task, not least because of the complexity of the stress-adaptive mechanisms in plants and particularly cereal crops, which are the staple of most of the world's population (Reynolds et al. 2005}

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone