Attraction of human monocytes by the neuropeptide secretoneurin

AbstractSecretoneurin is a newly discovered 33-amino-acid peptide derived from secretogranin II (chromogranin C) that is found in sensory afferent C-fibers. We show here that secretoneurin triggers the selective migration of human monocytes in vitro and in vivo. Combinations of secretoneurin with the sensory neuropeptides, substance P or somatostatin, synergistically stimulate such migration. The attraction of monocytes represents the first established function of secretoneurin as a sensory neuropeptide

Reliability and Initial Validation of the Ulcerative Colitis Endoscopic Index of Severity

Background & AimsWe studied the reliability of the previously described Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and validated it with an independent cohort of investigators.MethodsWe created a new library of 57 videos of flexible sigmoidoscopy and stratified them based on disease severity. Twenty-five investigators were each randomly assigned to assess 28 videos (which included 4 duplicates to assess intraobserver reliability). Investigators were blinded to clinical details except for 2 of 4 duplicated videos (to assess the impact of knowledge of symptoms on assessment). Three descriptors (“vascular pattern”, “bleeding”, and “erosions and ulcers”) comprising the UCEIS were scored with a visual analogue scale (VAS) to assess overall severity. Intrainvestigator and interinvestigator agreement was characterized by κ statistical analysis; reliability ratios were used to compare VAS and UCEIS scores.ResultsThere was a high level of correlation between UCEIS scores and overall assessment of severity (correlation coefficient, 0.93). Internal consistency (Cronbach α analysis) was 0.86. Intrainvestigator and interinvestigator reliability ratios for UCEIS scores were 0.96 and 0.88, respectively. Intrainvestigator agreement in determination of the UCEIS score was good (κ = 0.72), with individual descriptors ranging from a κ of 0.47 (for bleeding) to 0.87 (for vascular pattern). Interinvestigator agreement in determination of UCEIS scores was moderate (κ = 0.50), with descriptors ranging from a κ of 0.48 (for bleeding) to 0.54 (for vascular pattern). Intrainvestigator variability in determining UCEIS scores did not change appreciably when a video was presented with clinical details.ConclusionsThe UCEIS and its components show satisfactory intrainvestigator and interinvestigator reliability. Among investigators, the UCEIS accounted for a median of 86% of the variability in evaluation of overall severity on the VAS when assessing the endoscopic severity of UC and was unaffected by knowledge of clinical details

Developing an instrument to assess the endoscopic severity of ulcerative colitis : The Ulcerative Colitis Endoscopic Index of Severity (UCEIS)

Full list of Investigators is given at the end of the article.Background: Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC). Objective: To evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated. Design: A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors. Results: There was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/ complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR2, Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity). Conclusion: The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.publishersversionPeer reviewe

Wear and degradation on retrieved zirconia femoral heads

Zirconia femoral heads retrieved from patients after different implantation periods (up to 13 years) were analysed using vertical scanning interferometry, atomic force microscopy and Raman microspectroscopy. A range of topographical and compositional changes on the surface of the retrievals are reported in this work. The study revealed that changes in roughness are the result of a combination of factors, i.e. scratching, surface upheaval due to transformation to the monoclinic phase and grain pull-out. Clusters of transformed monoclinic grains were observed on heads implanted for more than 3 years. The phase composition of these clusters was confirmed by Raman microspectroscopy. Increased abrasive wear and a higher monoclinic phase content concentrated on the pole of the femoral heads, confirming that the tetragonal to monoclinic phase transformation was not only induced by the tetragonal phase metastability and environmental conditions but mechanical and tribological factors, also affected the transformation kinetics. Additionally, the head implanted for 13 years showed evidence of a self-polishing mechanism leading to a considerable smoothening of the surface. These observations provide an insight into the interrelated mechanisms underlying the wear and transformation process on zirconia ceramics during implantation

Development of central nervous system metastases as a first site of metastatic disease in breast cancer patients treated in the neoadjuvant trials GeparQuinto and GeparSixto

Background: The incidence of central nervous system (CNS) metastases in breast cancer patients is rising and has become a major clinical challenge. Only few data are published concerning risk factors for the development of CNS metastases as a first site of metastatic disease in breast cancer patients. Moreover, the incidence of CNS metastases after modern neoadjuvant treatment is not clear. Methods: We analyzed clinical factors associated with the occurrence of CNS metastases as the first site of metastatic disease in breast cancer patients after neoadjuvant treatment in the trials GeparQuinto and GeparSixto (n = 3160) where patients received targeted treatment in addition to taxane and anthracycline-based chemotherapy. Results: After a median follow-up of 61 months, 108 (3%) of a total of 3160 patients developed CNS metastases as the first site of recurrence and 411 (13%) patients had metastatic disease outside the CNS. Thirty-six patients (1%) developed both CNS metastases and other distant metastases as the first site of metastatic disease. Regarding subtypes of the primary tumor, 1% of luminal A-like (11/954), 2% of luminal B-like (7/381), 4% of HER2-positive (34/809), and 6% of triple-negative patients (56/1008) developed CNS metastases as the first site of metastatic disease. In multivariate analysis, risk factors for the development of CNS metastases were larger tumor size (cT3–4; HR 1.63, 95% CI 1.08–2.46, p = 0.021), node-positive disease (HR 2.57, 95% CI 1.64–4.04, p < 0.001), no pCR after neoadjuvant chemotherapy (HR 2.29, 95% CI 1.32–3.97, p = 0.003), and HER2-positive (HR 3.80, 95% CI 1.89–7.64, p < 0.001) or triple-negative subtype (HR 6.38, 95% CI 3.28–12.44, p < 0.001). Conclusions: Especially patients with HER2-positive and triple-negative tumors are at risk of developing CNS metastases despite effective systemic treatment. A better understanding of the underlying mechanisms is required in order to develop potential preventive strategies

Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape

In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, the impact of fasting regimens on the regulation of AT immune infiltration is still elusive. Here we show that intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, this increase in LAM abundance is strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation during IF, increases the catabolic state of adipocytes, and enhances systemic metabolic flexibility and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to efficacy of a fasting-mimicking diet and that the expression of p53 and TREM2 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signalling in adipocytes dictates LAM accumulation in AT under IF and modulates fasting effectiveness in mice and humans

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

A framework for distributed intelligence for energy efficient operation of smart homes

Zsfassung in dt. SpracheThe world-wide energy demand and with it the greenhouse gas emissions are rising constantly. One of the main energy consumers are buildings, both in the commercial and residential area. Regardless if viewed from an international, European or Austrian vantage point, the consumption figures call for immediate actions also in the building sector to reach emission goals such as the European Union's 20-20-20 targets. The requirements concerning energy efficiency in households are considerably different to those in commercial environments, hence a differentiated strategy must be developed for both of them. The huge number of households, the ever increasing count of energy consuming devices in the homes and the complex relations between energy efforts and the expected environmental effects make them a promising candidate for significant improvements.In this context smart homes become increasingly popular as they offer improvements, such as increased comfort for their inhabitants at promised energy reductions. Nevertheless, in many cases smart homes cannot fully realize their promises, their systems are still complex to use, seldom tailored to pervasive energy savings and often not characterized by real smartness.Thus, a novel system concept for smart homes is developed from scratch in this dissertation. The residential area has special characteristics and introduces specific requirements for any control approaches. Most obvious, comfort plays a main role for humans, and mostly energy efficiency comes only second after it. Hence, focus in the system design is given to the realization of energy savings while fully preserving comfort parameters of the users. For this purpose a comprehensive system concept for energy efficiency and comfort in residential homes is developed. It is realized as a multiagent system that implements the main smart home characteristics such as adaptivity, reactivity and proactivity in a dedicated and extensible software framework. It is capable of controlling its environment by exploiting automation technology, adapts to its users, alleviates the users of routine tasks and supports the overall energy efficient operation of the smart home.The design starts with an extensive requirements analysis, follows an established design methodology and results in a detailed specification of a multiagent based smart home control system. Finally, this system concept is prototypically implemented, tested and evaluated by means of simulation.20

Wireless communication in home and building automation

Zsfassung in dt. Sprache11

Hur personer med schizofreni upplever sin livsvärld : En litteraturstudie av patografier

Bakgrund: Schizofreni är en psykossjukdom som kännetecknas av tankestörningar, hallucinationer och vanföreställningar. Personer med schizofreni kan uppleva att ingen förstår den inre upplevelsen av sjukdomens symtom samt ha en känsla av att leva i två världar: den vanliga världen och sjukdomens värld Syfte: Syftet var att belysa hur personer med schizofreni upplever sin livsvärld. Metod: En kvalitativ litteraturstudie baserad på två patografier. Patografier är självbiografier skrivna om livet med en sjukdom. Analysen utgjordes av en manifest innehållsanalys. Resultat: Resultatet utgår från tre kategorier; fånge i sin egen kropp, upplevelsen av ett kluvet sinne och ljus i mörkret. Det visade att personer med schizofreni upplevde rädsla och ångest i samband med sina hallucinationer och paranoida tankar samt en känsla av att aldrig vara ensam. De upplevde även att tillvaron med sjukdomen kunde kännas hopplös, främst beroende på att det var svårt att se en framtid med sjukdomen. Det fanns även tvivel mellan att vilja leva och dö samt om en frisk framtid var möjlig eller ej. Dock upplevde de även att viljan att leva var starkast och att de var redo att starta ett nytt kapitel i sitt liv. Slutsats: Sjuksköterskor kan uppleva personer med schizofreni som komplexa och svåra att förstå i större utsträckning än vad vårdare som är mer orienterade inom psykiatrin gör. Personer med schizofreni kan uppleva sig som osynliga i vården på grund av att sjuksköterskorna inte visar förståelse för deras verklighet och har förutfattade meningar om dem. Det beror främst på okunskap om sjukdomen. Således kan det vara av vikt att utföra vidare studier om hur personer med schizofreni blir och vill bli bemötta i vården för att sjuksköterskor skall få ett större kunskapsomfång av deras upplevelser i vårdsammanhang