Location and Conformation of the LK alpha 14 Peptide in Water/Ethanol Mixtures

It is widely recognized that solvation is one of the major factors determining structure and functionality of proteins and long peptides, however it is a formidable challenge to address it both experimentally and computationally. For this reason, simple peptides are used to study fundamental aspects of solvation. It is well established that alcohols can change the peptide conformation and tuning of the alcohol content in solution can dramatically affect folding and, as a consequence, the function of the peptide. In this work, we focus on the leucine and lysine based LK alpha 14 peptide designed to adopt an alpha-helical conformation at an apolar-polar interface. We investigate LK alpha 14 peptide's bulk and interfacial behavior in water/ethanol mixtures combining a suite of experimental techniques (namely, circular dichroism and nuclear magnetic resonance spectroscopy for the bulk solution, surface pressure measurements and vibrational sum frequency generation spectroscopy for the air-solution interface) with molecular dynamics simulations. We observe that ethanol highly affects both the peptide location and conformation. At low ethanol content LK alpha 14 lacks a clear secondary structure in bulk and shows a clear preference to reside at the air-solution interface. When the ethanol content in solution increases, the peptide's interfacial affinity is markedly reduced and the peptide approaches a stable alpha-helical conformation in bulk facilitated by the amphiphilic nature of the ethanol molecules

System Dynamics Modelling and System Analysis Applied in Complex Research Projects - the Case of VALUMICS

VALUMICS is a Horizon 2020 project funded by the European Commission (2017-2021). The project structure is highly integrated and transdisciplinary, building on the expertise of over 30 specialists in various fields of research including knowledge integration through systems analysis and system dynamics modelling, food science, supply chain management, life cycle assessment, logistics, economics and social science. The aim of the project is to analyze the dynamics of food supply- and value chain systems using a structural analysis including system analysis and perform system simulations using system dynamics. The VALUMICS research approach and the project design are explained and it is justified why system analysis is needed to obtain an understanding of the complex connections and interactions of the distinct parts of food systems. Patterns will be recognized and thus causes and effects of complex relations within the selected food supply system and networks will be identified. This understanding of the functioning of the system can in turn be used to identify policy interventions

Applying System Analysis and System Dynamics Modelling In Complex Research Projects - The Case Of VALUMICS

VALUMICS is a Horizon 2020 project funded by the European Commission (2017-2021). The project structure is highly integrated and transdisciplinary, building on the expertise of over 30 specialists in various fields of research including knowledge integration through systems analysis and system dynamics modelling, food science, supply chain management, life cycle assessment, logistics, economics and social science. The aim of the project is to analyze the dynamics of food supply systems using a structural analysis including system analysis and perform system simulations using system dynamics. The VALUMICS research approach and the project design are explained and it is justified why system analysis is needed to obtain an understanding of the complex connections and interactions of the distinct parts of food systems. Patterns will be recognized and thus causes and effects of complex relations within the selected food supply system and networks will be identified. This understanding of the functioning of the system can in turn be used to identify policy interventions

Geðrof í kjölfar ADHD-lyfjameðferðar : Sjúkratilfelli

Publisher Copyright: © 2023 Laeknafelag Islands. All rights reserved.In view of the ongoing rise of ADHD prescriptions among adults in Iceland, it is important that doctors are aware that psychosis is a rare but at times a serious adverse reaction to such treatment. In 2022 5% of adults were prescribed medication to treat ADHD in Iceland. In this case report we present a case of methylphenidate-induced psychosis in a young man with no previous history of psychotic episodes who required admission to the psychiatric intensive care unit.Peer reviewe

Serum levels of the IL-6 family of cytokines predict prognosis in renal cell carcinoma (RCC)

Purpose An improved understanding of RCC immunology should shed further light on RCC tumor biology. Our objective was to study to what extent serum levels of the IL-6 family of cytokines at diagnosis were relevant to survival. Methods A total of 118 consecutively patients with RCC, in which the tumor was surgically removed at Haukeland University Hospital during the period from 2007 to 2010, were included. The patients were followed-up for 10 years. The morning before surgery blood was sampled and serum frozen, with levels of IL-6, IL-27, IL-31, OSM, CNTF, IL-6Rα and gp130 determined. Results Among patients with the highest quartile of IL-6 (> 8 pg/ml) (n = 29), six of nine who had metastasis at diagnosis had such high IL-6 values. Among presumed radically treated patients, a high IL-6 and IL-27 strongly predicted recurrence. In particular, the predictions among patients with large (diameter > 7 cm) tumors were excellent regarding both IL-6 and IL-27 values. High gp130 serum levels predicted an overall survival (OS) among RCC patients with large tumors. Patients with a high IL-6 exhibited a strong expression of IL-6 in endothelial- and vascular smooth muscle cells. Moreover, the level of intra-tumoral CD3-positive cells predicted survival. Conclusions IL-6 and IL-27 seem to play a role in RCC biology. IL-6 enables the pinpointing of metastatic condition at diagnosis, as well as together with IL-27, the predicting of survival and recurrence. Endothelial cells and vascular smooth muscle cells are both suggested as important sources of IL-6.publishedVersio

Current Status of Intravesical Therapies for Bladder Pain Syndrome (BPS): A Narrative Review of Emerging Evidence

Bladder pain syndrome (BPS) is a complex condition, which can have debilitating sequelae for patients. Many elements of BPS remain poorly understood including pathophysiology, diagnosis and treatment. Navigating patient care can therefore be challenging for the clinician. Management mandates a multidisciplinary and symptom-based approach. Intravesical treatments such as instillation therapies remain a cornerstone of most treatment algorithms and there are a range of agents that can be selected. This review offers an up-to-date evaluation of the evidence for these intravesical treatments.publishedVersio

The levels of IL-6 and soluble IL-33R are increased in the renal vein during surgery for clear cell renal cell carcinoma

Purpose The main aim was to map serum levels of IL-1/IL-6 family cytokines and relevant receptors from serum samples taken across treatment in patients with Renal Cell Carcinoma (RCC). Additionally, we explored the possible interactions between these measurements, immunohistochemistry and intratumoral blood flow. Methods We included 40 patients undergoing open surgery for renal tumors. Blood samples were collected before, during (taken simultaneously from a peripheral site and the renal vein (RV) before clamping) and after surgery. Samples were analyzed for IL-6, IL-27, IL-31, OSM, TNF-α, serum (s)-gp130, s-IL-6Rα, s-IL-33R, IL-1Rα and VEGF. All 35 RCC tumors were histologically subtyped as clear cell (CCRCC), papillary or chromophobe. Immunohistochemistry for the CCRCC group included expression of IL-6/IL-6R. Intratumoral blood flow was determined by calculating intratumoral contrast enhancement on preoperative computerized tomography (CT) imaging. Results In the CCRCC patients, the intraoperative RV concentration of IL-6 was significantly higher than in both the preoperative and postoperative samples (p = 0.005 and p = 0.032, respectively). Furthermore, the intraoperative ratio showed significantly higher levels of IL-6 in the RV than in the simultaneously drawn peripheral sample. Immunohistochemistry showed general expression of IL-6 (23/24) in both tumor cells and the vasculature (20/23). Moreover, s-IL-6R was expressed in tumor cells in 23/24 studied patients. Increased blood flow in the CCRCC tumors predicted increased IL-6 levels in the RV (p < 0.001). The other cytokines and receptors showed an overall stability across the measurements. However, the intraoperative ratios of IL-33R and gp130 showed significantly higher levels in the RV. Conclusion Serum levels of IL-6 increased during surgery. Intraoperative IL-6 and s-IL-33R values were higher in the RV compared to the periphery, suggesting secretion from the tumor or tumor microenvironment itself. Supportive of this is an almost general expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature in the tumor microenvironment. Other studied cytokines/receptors were remarkably stable across all measurements.publishedVersio

Management of Bladder Pain Syndrome (BPS): A Practical Guide

Bladder pain syndrome (BPS) is a prevalent and pervasive disease. The physical and psychological sequelae can be very burdensome for the patient, and the condition represents a real challenge for the clinician as well. With no simple pathognomonic test, finding harmony in navigating patient care can be demanding. Diagnosis and management rely upon a multidisciplinary and holistic approach. Treatment options include conservative measures and pharmacotherapies as well as bladder instillation therapies. Ultimately, surgery may be offered but only in cases of refractory disease. This article offers a pragmatic guide for clinicians managing this challenging disease.publishedVersio

Conceptual System Dynamics and Agent-Based Modelling Simulation of Interorganisational Fairness in Food Value Chains: Research Agenda and Case Studies

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)System dynamics and agent-based simulation modelling approaches have a potential as tools to evaluate the impact of policy related decision making in food value chains. The context is that a food value chain involves flows of multiple products, financial flows and decision making among the food value chain players. Each decision may be viewed from the level of independent actors, each with their own motivations and agenda, but responding to externalities and to the behaviours of other actors. The focus is to show how simulation modelling can be applied to problems such as fairness and power asymmetries in European food value chains by evaluating the outcome of interventions in terms of relevant operational indicators of interorganisational fairness (e.g., profit distribution, market power, bargaining power). The main concepts of system dynamics and agent-based modelling are introduced and the applicability of a hybrid of these methods to food value chains is justified. This approach is outlined as a research agenda, and it is demonstrated how cognitive maps can help in the initial conceptual model building when implemented for specific food value chains studied in the EU Horizon 2020 VALUMICS project. The French wheat to bread chain has many characteristics of food value chains in general and is applied as an example to formulate a model that can be extended to capture the functioning of European FVCs. This work is to be further progressed in a subsequent stream of research for the other food value chain case studies with different governance modes and market organisation, in particular, farmed salmon to fillet, dairy cows to milk and raw tomato to processed tomato.Peer reviewedFinal Published versio

Rules and regulations for a pregnant endourologist: the European perspective

Introduction Working in surgery while pregnant is challenging. Navigating this period safely is of paramount importance. Anecdotal observation suggests that there exists great variation among European nations in regard to maternity leave and radiation safety. The aim of this article was to gain insight into policy patterns and variations across Europe regarding these issues. Methods A series of core question items was distributed to representatives across 12 nations Austria, Belgium, Germany, Greece, Iceland, Italy, Netherlands, Norway, Poland, Republic of Ireland, Spain and the United Kingdom). Results The total number of weeks with full pay ranged from as little as 4 weeks in Belgium to 32 and Iceland. All countries included in this study give the option of additional weeks beyond the initial period, however at reduced pay. Some offer unpaid leave beyond this. Only 5/12 countries had a specific policy on when the pregnant surgeon should come off the on-call rota. Only Austria, Italy and Poland stipulate a requirement for the pregnant clinician to be replaced or be completely exempt in cases involving radiation. Only Germany, Iceland, Norway and Poland highlight the need to limit radiation dose in the first trimester. Beyond this, Germany alone provides written guidance for reduction in gown weight and along with Poland, display arguably the most forward-thinking approach to resting. Conclusion There is a marked range in maternal leave policies across Europe. There also exists a lack of universal guidance on radiation safety for the pregnant urologist. There is urgent need for this void to be addressed.publishedVersio