Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations.

Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85α/p55α/p50α subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis. In 3 of these 4, plasma adiponectin was preserved, as in insulin receptor dysfunction. The fourth patient and her healthy mother had low plasma adiponectin associated with a potentially novel mutation, p.Asp231Ala, in adiponectin itself. Cells studied from one patient with the p.Tyr657X PIK3R1 mutation expressed abundant truncated PIK3R1 products and showed severely reduced insulin-stimulated association of mutant but not WT p85α with IRS1, but normal downstream signaling. In 3T3-L1 preadipocytes, mutant p85α overexpression attenuated insulin-induced AKT phosphorylation and adipocyte differentiation. Thus, PIK3R1 C-terminal mutations impair insulin signaling only in some cellular contexts and produce a subphenotype of insulin resistance resembling INSR dysfunction but unlike AKT2 dysfunction, implicating PI3K in the pathogenesis of key components of the metabolic syndrome.IHD was supported by the Raymond and Beverly Sackler Foundation via the University of Cambridge MB/PhD programme; RKS, IB, DBS, and SO were supported by the Wellcome Trust (grants WT098498, WT098051, WT107064, and WT095515, respectively and Strategic Award 100574/Z/12/Z), the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/5), and the United Kingdom National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The work was also supported by the Innovative Medicines Initiative Joint Undertaking under European Medical Information Framework (EMIF) grant agreement number 115372. UK10K was funded by the Wellcome Trust under award WT091310.This is the final version of the article. It first appeared from the American Society for Clinical Investigation via https://doi.org/10.1172/jci.insight.8876

Comparative research after reconstruction of the anterior cruciate ligament in Single bundle, Double bundle and TransFix AM technique

Abstrakt Das Ziel dieser Studie ist der Vergleich des Outcomes dreier unterschiedlicher Operationstechniken zur Versorgung von Patienten mit vorderer Kreuzbandruptur in Relation zur Kniestabilität und unterschiedlichen Scores. Genutzt wurden der Lysholm Score, der IKDC-Evaluationsbogen (subjektiver und objektiver Teil), der Marshall Score, der Tegner Score, Pivot shift und Lachman Test und eine Untersuchung mit dem Rolimetertestgerät. Vervollständigt durch die radiologische Ausmessung der tibialen und femoralen Bohrkanallage. Alle ermittelten Daten wurden statistisch aufgearbeitet. Die Hypothese war, dass die anatomische Doppelbündelrekonstruktion die der anatomischen Einzelbündel- versorgung überlegen ist. Es wurden dazu 78 Patienten, welche sich zwischen 2006 und 2010 einer vorderen Kreuzbandrekonstruktion unterzogen hatten, untersucht. 25 Patienten unterzogen sich einer Versorgung mittel der TransFix AM-Technik, 28 Patienten unterzogen sich der anatomischen SB-Technik und 25 Patienten der DB-Technik. Die genutzten Hamstringssehnen wurden femoral mit dem TransFix Pin oder einem Retrobutton fixiert, tibial erfolgte eine Fixation mit bioabsorbierbaren Interferenzschrauben. Die Zusammensetzung des Patientenalters liegt zwischen 13 und 71 Jahren, das Follow-up bewegt sich zwischen 67 und 113 Monaten. Die Auswertung der Untersuchungen konnte keine wesentlichen statistischen Unterschiede zwischen den drei Gruppen darlegen. Zur Zeit sind viele unter- schiedliche Techniken zur Rekonstruktion der vorderen Kreuzbandverletzung möglich, jedoch in der vorliegenden Studie ist keine Technik deutlich überlegen. Es empfielt sich ein individuelles Vorgehen unter Berücksichtigung aller patientenspezifischer Faktoren, um die optimale Wiederherstellung des VKB durchzuführen.Abstract The aim of this study is the comparison of clinical outcomes of three different techniques for reconstruction in patients with anterior cruciate ligament injury in relation to knee stability and different scores, using Lysholm score, International Knee Documentation Commitee (IKDC) forms (subjective and objective parts), Marshall Score, Tegener score, Pivot shift test, Lachman test, and rolimeter control and the assessment of the X-rays with the placement of tibial and femoral tunnels. All results underwent a statistical analysis. The hypothesis was anatomic double-bundle ACL reconstruction is better than anatomic single-bundle reconstruction. A total number of 78 patients were evaluated with ACL reconstruction between 2006 till 2010. 25 patients underwent TransFix AM ACL replacement, 28 patients underwent anatomic single-bundle technique and 25 patients underwent anatomic double-bundle reconstruction surgery. The hamstrings tendon were fixed on the femoral site with TransFix pin or retrobutton and on the tibial site with a bioabsorbable interference screw. The patients age vary from 13 till 71 years. The follow-up ranging between 67 and 113 months. The evaluation revealed no essential significant difference between these three groups. Today, many different techniques for reconstruction of the anterior cruciate ligament injury is available, whether none of the past reconstruction methods have shown to be superior to one another. All of them require individualized action between patient specific factors before the decision can be make of one of the possible ACL surgery

Supporting the well-being of new university teachers through teacher professional development

Over the last decades, changes within higher education have created increased pressure and uncertainty for academics, increasing their risk for cognitive, behavioral, physical, as well as psychological issues due to high job demands. Specifically, for new academics in teaching roles, their lack of knowledge and skills can contribute to a negative effect of these job demands on their well-being. This study therefore explored how teaching-related professional development programs can enhance new university teachers’ well-being, through semi-structured interviews with 10 university teachers participating in such a program at a mid-sized Dutch university. We pay special attention to the relationship between specific learning activities integrated in the program (such as learning communities, formal workshops, and reflecting) and various dimensions of the psychological model of well-being by Ryff and Keyes (such as self-acceptance, autonomy, environmental mastery, and positive relationships). Using co-occurrence analysis and content analysis, we found that different learning activities had distinct relationships with different well-being facets. For example, formal workshops were mainly related to environmental mastery, a purpose in life and personal growth, while reflecting seemed to be especially connected to teachers’ self-acceptance, and participating in a learning community was mainly related to positive relations with others and personal growth. Our findings have implications for research on teacher well-being as well as for the design of professional development programs for higher education teaching staff

Development of a Risk Stratification Model for Delayed Inpatient Recovery of Physical Activities in Patients Undergoing Total Hip Replacement

Study Design Prospective cohort design using data derived from usual care. Background It is important that patients are able to function independently as soon as possible after total hip replacement. However, the speed of regaining activities differs significantly. Objectives To develop a risk stratification model (RSM) to predict delayed inpatient recovery of physical activities in people who underwent total hip replacement surgery. Methods This study was performed in 2 routine orthopaedic settings: Diakonessenhuis Hospital (setting A) and Nij Smellinghe Hospital (setting B). Preoperative screening was performed for all consecutive patients. In-hospital recovery of activities was assessed with the Modified Iowa Level of Assistance Scale. Delayed inpatient recovery of activities was defined as greater than 5 days. The RSM, developed using logistic regression analysis and bootstrapping, was based on data from setting A (n = 154). External validation was performed on the data set from setting B (n = 271). Results Twenty-one percent of the patients in setting A had a delayed recovery of activities during their hospital stay. Multivariable logistic regression modeling yielded a preliminary RSM that included the following factors: male sex (odds ratio [OR] = 0.8; 95% confidence interval [CI]: 0.2, 2.6), 70 or more years of age (OR = 1.2; 95% CI: 0.4, 3.4), body mass index of 25 kg/m2 or greater (OR = 2.2; 95% CI: 0.7, 7.4), an American Society of Anesthesiologists score of 3 (OR = 1.2; 95% CI: 0.3, 4.4), a Charnley score of B or C (OR = 6.1; 95% CI: 2.2, 17.4), and a timed up-and-go score of 12.5 seconds or greater (OR = 3.1; 95% CI: 1.1, 9.0). The area under the receiver operating characteristic (ROC) curve was 0.82 (95% CI: 0.74, 0.90) and the Hosmer-Lemeshow test score was 3.57 (P>.05). External validation yielded an area under the ROC curve of 0.71 (95% CI: 0.61, 0.81). Conclusion We demonstrated that the risk for delayed recovery of activities during the hospital stay can be predicted by using preoperative data

Nutrition assessment in process-driven, personalized dietetic intervention - The potential importance of assessing behavioural components to improve behavioural change:results of the EU-funded IMPECD project

BACKGROUND & AIMS: Although up-to-date definitions for nutrition assessment integrate behavioural components, it is not clear what behavioural components are to be assessed. Since behavioural modification is linked to effective therapeutic dietetic interventions, assessing behaviour and factors influencing behaviour might be beneficial to improve personalized dietetic outcome. The aim of the following report is to emphasize the role of behavioural components and factors affecting behaviour at baseline nutrition assessment in personalized dietetic intervention. METHODS: The present work is part of the EU-funded project IMPECD ("Improvement of Education and Competences in Dietetics", www.impecd.eu). The project aims to improve the clarity and consistency of national dietetic process models to unify education and training of future dietitians. Experts from five European Universities of Applied Sciences (UAS) in Antwerp (BE), Fulda (DE), Groningen (NL), Neubrandenburg (DE) and St. Pölten (AT) developed a Massive Open Online Course (MOOC) consisting of several clinical cases. It warranted a detailed evaluation of all dietetic care process steps, starting with nutrition assessment. RESULTS: Results for motivation assessed during nutrition assessment are not consistently positively associated with outcome and the added value of assessing them at baseline is still unclear. However, depressive symptoms, emotional distress, and anxiety negatively affect eating and physical activity and therefore limit the efficacy of the dietetic intervention. Assessing behavioural components including nutrition literacy is an important precondition for influence on behavioural modification. CONCLUSION: Indisputably, baseline assessment of behavioural components and factors influencing behaviour are important to increase the therapeutic efficacy of personalized dietetic interventions

Process models in dietetic care:a comparison between models in Europe

Using a Dietetic Care Process (DCP) can lead to improved application of evidence-based guidelines and critical thinking in dietetics. One aim of the project Improvement of Education and Competences in Dietetics (IMPECD) is to develop a unified DCP for international educational purposes. Therefore, a comparison of European DCPs was needed.A concise literature search and semi-structured interviews with experts representing the full EFAD (European Federation of the Associations of Dietitians) member states were conducted from June to October 2017.16 out of 23 EFAD member states responded (70%) from which 13 indicated to use a DCP. Eight different DCPs were found, with four to six core steps and three graphical representations. In one country the use of a dietetic process is indicated by law. The DCPs have more similarities than differences as they follow the same principles. Differences in language or form may not limit the improvement in collaboration and international exchange in dietetic practice. These results provide a good basis for the development of a unified DCP for educational purposes