D-glucose Stimulates the Na+/K+ Pump in Mouse Pancreatic Islet Cells

To determine the effect of D-glucose on the β-cell Na+/K+ pump, 86Rb+ influx was studied in isolated, -cell-rich islets of Umeå-ob/ob mice in the absence or presence of lmM ouabain. D-glucose (20 mM) stimulated the ouabain-sensitive portion of 86Rb+ influx by 65%, whereas the ouabain-resistant portion was inhibited by 48%. The Na+/K+ ATPase activity in homogenates of islets of Umeå-ob/ob mice or normal mice was determined to search for direct effects of D-glucose. Thus, ouabain-sensitive ATP hydrolysis in islet homogenates was measured in the presence of different D-glucose concentrations. No effect of D-glucose (3–20 mM) was observed in either ob/ob or normal islets at the optimal Na+/K+ ratio for the enzyme (135 mM Na+ and 20 mM K+). Neither D-glucose (3–20 mM) nor L-glucose or 3-O-methyl-D-glucose (20 mM) affected the enzyme activity at a high Na+/K+ ratio (175 mM Na+ and 0.7mM K+). Diphenylhydantoin (150 μM) decreased the enzyme activity at optimal Na+/K+ ratio, whereas 50 μM of the drug had no effect. The results suggest that D-glucose induces a net stimulation the Na+/K+ pump of β-cells in intact islets and that D-glucose does not exert any direct effect on the Na+/K+ ATPase activity

Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry

Background: The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features. Methods: Data prospectively accumulated over a 4-year period in the Swedish Childhood Cancer Registry from patients aged 0-18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%). Results: The time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4-year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis. Conclusion: This study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement.</p

SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts

Acknowledgements We sincerely thank the patients and family members who participated in this study. We would also like to thank Stefan Esher, Umeå University, for help with genealogy, and Anna Westerlund for excellent technical assistance. This work was supported by grants from the FOU, at the Umeå university hospital, and the Medical Faculty at Umeå University. The work at University of Gothenburg was supported by grants from The Swedish Research Council, the Swedish Rheumatism Association, the Royal 80-Year Fund of King Gustav V, ALF/LUA research grant from Sahlgrenska University Hospital in Gothenburg and the Lundberg Foundation. The work at the University of Gothenburg and the University of Aberdeen was supported by Euroclast, a Marie Curie FP7-People-2013-ITN: # 607446.Peer reviewedPublisher PD

Stratification of asthma phenotypes by airway proteomic signatures

© 2019 Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies

V-modulen, en del av en hållbarhetsstrategi

The state of our society is frequently changing. Due to various factors, the pressure of creating a changeable city is high and necessary to adequately supply the needs for its inhabitants. But making these changes and adapt to the fast shifting state of the city is not always physical possible. Young adults and students is a group that often seeks to move to intensely growing city regions. The reason for this is a more promising job market and more attractive educations, but coincidentally the shortage of housing is extremely high in these areas. Thus the market for simple and cheap housing already exists, so the question is how to provide a quick solution for this problem and fill the need? It´s our opinion that a sustainable city must have a stabile action program when these kind of problem, for instants when shortage of housing, occurs. The aim of this study is to create a multifunctional basis structure for a versatility module (V-module), try it virtually and hypothetical in an existing city environment, and investigate how several units together with its surroundings can form a vibrant living situation. Furthermore, the intention is to evaluate the module housing concept as a part of a sustainable city development, and how it could become a part of the city of Malmo’s durability strategy

Höjt minimimått på gös ger ökad avkastning i fisket

Gös är insjöfiskets viktigaste art. Beståndsvårdande åtgärder som ökar och stabiliserar avkastningen av gös är därför viktiga för fisket. Eftersom minimimåttet på gös i de stora sjöarna länge varit 40 cm har göshonor kunnat beskattas innan de nått könsmognad (vid ca 41-44 cm). Ett ökat minimimått borde ge en stabilare och större rekrytering på sikt. Samtidigt borde ett höjt minimimått direkt innebära att avkastningen ökar eftersom den naturliga dödligheten för gös kring 40 cm är liten. På ett halvt år tillväxer gös av denna storlek normalt 5 cm. Från 1 juli år 2001 höjdes därför minimimåttet på gös till 45 cm och minsta tillåtna maska (sträckt maska) sattes till 120 mm i Hjälmaren. I Mälaren bibehölls fortsatt 40 cm minimimått och minsta maska 100 mm, även om en ändring nu förväntas även här. Medelfångsten i Hjälmaren ökade från 59 ton per år perioden 1996-2000 till 153 ton per år perioden 2001-2007. Ökningen var således 174 %. I Mälaren var motsvarande fångster 132 ton den första perioden och 142 ton den senare, en svag ökning med 7,5 %. Statistiskt kunde det beläggas att förändringen i Hjälmaren var avsevärt större än förväntat utgående från utvecklingen i Mälaren. Eftersom de båda sjöarnas avkastning följt varandra under en lång tid före ändringen av fiskebestämmelserna var det sannolikt dessa som orsakat den höga avkastningen i Hjälmaren åren 2001-2007. Det årliga infiskade värdet av gös i Hjälmaren har ökat från cirka 2 miljoner kr (dagens penningvärde) åren 1996-2000 till 6,8 miljoner kronor åren 2001-2007, dvs. med 4,8 miljoner kronor. Indikationer hittills tyder också på att den biologiska mångfalden bevaras och gösfisket i Hjälmaren har kunnat miljöcertifieras (Marine Stewardship Council) som det första sötvattensfisket i världen. Samtidigt har ett antal nya, unga yrkesfiskare rekryterats in i yrket. Det rekommenderas att ett minimimått på minst 45 cm används för gös i insjöar och utefter våra kuster framöver.Regionala inventeringsrapporter import från MDP 2015-05</p

Lupus anticoagulants in two children-bleeding due to nonphospholipid-dependent antiprothrombin antibodies.

We describe two children with significant bleeding: one with multiple ecchymoses and the other with scrotal bleeding. In both patients, the activated partial thromboplastin time (APTT) was prolonged, with positivity for lupus anticoagulants (LA). However, the Owren prothrombin time (PT), usually insensitive for LA, was also prolonged. The presence of LA is associated with diverse clinical manifestations, with most patients being asymptomatic while others present venous or arterial thrombosis. Bleeding in conjunction with LA is rare and it is unusual to see prolongation of the Owren PT assay due to LA. An extended laboratory investigation of one of the patient's plasma revealed not only LA but also a specific nonphospholipid-dependent antiprothrombin antibody causing an acquired hypoprothrombinemia. Conclusion: It is likely that the low prothrombin activity and not the LA caused the bleeding. The bleeding signs and symptoms in both patients subsided when the PT was normalized, although the prolonged APTT and the LA remained

Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors : A study of the Swedish Childhood Cancer Registry

BACKGROUND: The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features.METHODS: Data prospectively accumulated over a 4-year period in the Swedish Childhood Cancer Registry from patients aged 0-18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%).RESULTS: The time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4-year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis.CONCLUSION: This study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement

Are Incidental Gallbladder Cancers Missed with a Selective Approach of Gallbladder Histology at Cholecystectomy?

Background: Incidental gallbladder cancer (IGBC) is an unexpected finding when a cholecystectomy is performed upon a benign indication, and the use of routine or selective histological analysis of gallbladder specimen is still debated. The aim of this study was to investigate whether the proportion of submitted gallbladder specimens for pathological investigation influences the proportion of IGBC found, and what possible factors preoperatively or perioperatively could influence the selection process. Methods: All cholecystectomies between January 2007 and September 2014 registered in the Swedish Registry of Gallstone Surgery and ERCP (GallRiks) were included. Proportion of histological analysis was divided into four subgroups (0–25%, >25–50%, >50–75%, >75–100%). Results: A total of 81,349 cholecystectomies were registered, and 36,010 (44.3%) gallbladder specimens were sent for histological analysis. A total of 213 cases of IGBC were discovered, which constituted 0.26% of all cholecystectomies performed and 0.59% of the number of gallbladder specimens sent for histological analysis. Hospitals submitting >75–100% of the gallbladder specimens had significantly more IGBC/1000 cholecystectomies performed (p = 0.003). Hospitals with the most selective approach had a significantly higher proportion of IGBC/1000 gallbladders that were sent for histological analysis (p < 0.001). Factors such as higher age (p < 0.001), female gender (p = 0.048) and macroscopic cholecystitis (p < 0.001) were more common in gallbladder specimens from hospitals that had a selective approach to histological analysis. Conclusion: A routine approach to histological analysis in cholecystectomies with a benign indication for surgery can uncover a higher proportion of IGBC cases. When a selective approach is used, risk factors should be taken into account