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  • 301.
    Nyberg, Gusten
    et al.
    Linköping University.
    Mossberg, Karl Hjort
    Umeå university.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Lysholm, Jack
    Linköping University Hospital, Department of Orthopaedic Surgery, Sports and Ttrauma Research Group, Winternet, Bodens sjukhus, Ortopedkliniken, Läkarhuset Hermelinen Luleå, Sjukgymnastiken, Department of Orthopaedics, Surgical and Perioperative Sciences, Umeå University, Department of Orthopaedics, Sunderby Hospital.
    Subsequent traumatic injuries after a concussion in elite ice hockey: A study over 28 years2015In: Current Research: Concussion, Vol. 2, no 3, p. 109-112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Concussion is a frequent injury in contact sports. Following a concussion, balance and neurocognitive function have been shown to be affected for >6 days. OBJECTIVE: To analyze whether athletes who have sustained a concussion are at an increased risk for subsequent traumatic injuries. METHODS: A cohort study was performed to investigate all concussions that were sustained in one Swedish elite hockey club over 28 seasons. All injuries and absences were registered prospectively. Players who sustained a concussion were followed-up for seven, 21 and 42 days with respect to new injuries and were compared with a group of players with knee distortions/knee medial collateral ligament injuries. RESULTS: Players who sustained a cerebral concussion did not have an increased risk for subsequent injuries compared with players who experienced a knee injury; however, concussed athletes experienced significantly more serious subsequent injuries (absence >28 days) within 21 days after return to play. Discussion: The authors were unable to confirm whether players who return to play following a concussion are at a higher risk for subsequent new injuries. However, a significantly increased risk for a severe subsequent injury after a concussion may exist. There may also be a possibly increased risk for subsequent injury among players who sustained >1 concussion during the study period. CONCLUSION: The authors were unable to confirm their hypothesis; however, the possibility of a higher risk for a more serious injury following a concussion requires further study.

  • 302.
    Oyarzun-Ampuero, Felipe
    et al.
    Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago.
    Guerrero, Ariel
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Hassan-Lopez, Natalia
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago.
    Bollo, Soledad
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Corvalan, Alejandro
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Quest, Andrew F G
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Kogan, Marcelo J
    Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago.
    Organic and Inorganic Nanoparticles for Prevention and Diagnosis of Gastric Cancer2015In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 21, no 29, p. 4145-4154Article in journal (Refereed)
    Abstract [en]

    Organic and inorganic nanoparticles show great potential for cancer diagnosis and treatment. Because gastric cancer (GC) represents the second most deadly type of neoplasia worldwide, continued research efforts by scientists and clinicians are essential to improve diagnosis and treatment. This paper reviews significant findings in the area of nanoparticles (organic and inorganic origin) that may aid in prevention and diagnosis of GC. This review focuses in the first section on H. pylori and the connection to GC, highlighting nanoformulations designed to control bacterial growth. The second section evaluates the potential of different imaging techniques (especially using inorganic nanoparticles) in the detection of GC, and the third section summarizes how nanotechnology may be employed in the analytical detection of GC biomarkers (metallic plasmons, electrochemical biosensors and colorimetric sensors). We foresee that the prevention and diagnosis of GC will require the development of complex collaborative studies. Additionally, scientists also need to be tightly connected to industry in order to facilitate upscaling and rapid transfer of promising products to the clinic.

  • 303.
    Oyarzun-Ampuero, Felipe
    et al.
    Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago.
    Vidal, Alejandra
    Instituto de Anatomía Histología y Patología, Universidad Austral de Chile, Valdivia.
    Concha, Miguel
    Instituto de Anatomía Histología y Patología, Universidad Austral de Chile, Valdivia.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab. Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago, Chile.
    Orellana, Sandra
    Instituto de Ciencias Químicas, Universidad Austral de Chile, Isla Teja, Casilla,Valdivia.
    Moreno-Villoslada, Ignacio
    Instituto de Ciencias Químicas, Universidad Austral de Chile, Isla Teja, Casilla,Valdivia.
    Nanoparticles for the Treatment of Wounds2015In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 21, no 29, p. 4329-4341Article in journal (Refereed)
    Abstract [en]

    The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticles, have shown potential therapeutic effects on wound healing. Due to their specific characteristics, nanoparticles such as nanocapsules, polymersomes, solid lipid nanoparticles, and polymeric nanocomplexes are ideal vehicles to improve the effect of drugs (antibiotics, growth factors, etc.) aimed at wound healing. On the other hand, if active excipients are added during the formulation, such as hyaluronate or chitosan, the nanomedicine could significantly improve its potential. In addition, the inclusion of nanoparticles in different pharmaceutical materials may enhance the beneficial effects of the formulations, and allow achieving a better dose control. This paper aims at reviewing significant findings in the area of nanoparticles and wound treatment. Among the reviewed topics, we underline formulations comprising inorganic, polymeric, surfactant self-assembled, and lipid nanosystems. Among the drugs included in the nanoformulations, the paper refers to antibiotics, natural extracts, proteins, and growth factors, among others. Finally, the paper also addresses nanoparticles embedded in secondary vehicles (fibers, dressings, hydrogels, etc.) that could improve their application and/or upgrade the release profile of the active.

  • 304.
    Padrela, Luis
    et al.
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Azevedo, Edmundo Gomes de
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Powder X-ray diffraction method for the quantification of cocrystals in the crystallization mixture2012In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 38, no 8, p. 923-929Article in journal (Refereed)
    Abstract [en]

    Context: The solid state purity of cocrystals critically affects their performance. Thus, it is important to accurately quantify the purity of cocrystals in the final crystallization product.Objective: The aim of this study was to develop a powder X-ray diffraction (PXRD) quantification method for investigating the purity of cocrystals. The method developed was employed to study the formation of indomethacin-saccharin (IND-SAC) cocrystals by mechanochemical methods.Materials and methods: Pure IND-SAC cocrystals were geometrically mixed with 1:1 w/w mixture of indomethacin/saccharin in various proportions. An accurately measured amount (550 mg) of the mixture was used for the PXRD measurements. The most intense, non-overlapping, characteristic diffraction peak of IND-SAC was used to construct the calibration curve in the range 0–100% (w/w). This calibration model was validated and used to monitor the formation of IND-SAC cocrystals by liquid-assisted grinding (LAG).Results: The IND-SAC cocrystal calibration curve showed excellent linearity (R2 = 0.9996) over the entire concentration range, displaying limit of detection (LOD) and limit of quantification (LOQ) values of 1.23% (w/w) and 3.74% (w/w), respectively. Validation results showed excellent correlations between actual and predicted concentrations of IND-SAC cocrystals (R2 = 0.9981).Discussion: The accuracy and reliability of the PXRD quantification method depend on the methods of sample preparation and handling. The crystallinity of the IND-SAC cocrystals was higher when larger amounts of methanol were used in the LAG method.Conclusion: The PXRD quantification method is suitable and reliable for verifying the purity of cocrystals in the final crystallization product.

  • 305.
    Padrela, Luis
    et al.
    Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
    Rodrigues, Miguel A.
    Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
    Tiago, João Tiago
    Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Matos, Henrique A.
    Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
    Azevedo, Edmundo Gomes de
    Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
    Tuning physicochemical properties of theophylline by cocrystallization using the supercritical fluid enhanced atomization technique2014In: Journal of Supercritical Fluids, ISSN 0896-8446, E-ISSN 1872-8162, Vol. 86, p. 129-136Article in journal (Refereed)
    Abstract [en]

    Formation of different micro- to nanosized cocrystals of theophylline is addressed by using the supercritical enhanced atomization (SEA) process. The experimental results presented here help to highlight how to prepare cocrystals of theophylline (TPL), using a supercritical fluid-based technique to accomplish the required physicochemical properties of that active pharmaceutical ingredient (API). The SEA process shows a strong versatility and feasibility towards the formation of highly pure theophylline cocrystals, using tetrahydrofuran as a solvent. The formation of TPL cocrystals with different types of morphology and dissolution behaviour/properties is induced by using different coformers, such as urea, saccharin, gentisic acid, salicylic acid, glutaric acid, sorbic acid, 1-hydroxy-2-naphthoic acid, oxalic acid, maleic acid and nicotinamide. The solubility of each coformer in the dissolution medium of phosphate-buffered saline (pH 7.4 at 25 °C), could determine the dissolving rate behaviour of the produced cocrystals. Consequently, the low-soluble coformers generate TPL cocrystals with a slow-dissolving rate, while the use of highly-soluble coformers produces faster-dissolving TPL cocrystals. Albeit the SEA process operating temperature influences the mean cocrystal particle size, this technique shows a high potential as an effective cocrystal screening tool.

  • 306.
    Padrela, Luis
    et al.
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Rodrigues, Miguel A.
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa, Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
    Tiago, João
    Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Matos, Henrique A.
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa, Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
    Azevedo, Edmundo Gomes de
    Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Insight into the Mechanisms of Cocrystallization of Pharmaceuticals in Supercritical Solvents2015In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 15, no 7, p. 3175-3181Article in journal (Refereed)
    Abstract [en]

    Carbon dioxide has been extensively used as a green solvent medium for the crystallization of active pharmaceutical ingredients (APIs) by replacing harmful organic solvents. This work explores the mechanisms underlying a novel recrystallization method-cocrystallization with supercritical solvent (CSS)-which enables APIs cocrystallization by suspending powders in pure CO2. Six well-known APIs that form cocrystals with saccharin (SAC) were processed by CSS, namely, theophylline (TPL), indomethacin (IND), carbamazepine (CBZ), caffeine (CAF), sulfamethazine (SFZ), and acetylsalicylic acid (ASA). Pure cocrystals were obtained for TPL, IND, and CBZ (with SAC) after 2 h of CSS processing. Convection was revealed to be a determining parameter for successful cocrystallization with high-yield levels. TPL-SAC was selected as a model system to study the cocrystallization kinetics in the gas, supercritical, and liquid phases under different conditions of pressure (8-20 MPa), temperature (30 to 70 degrees C), and convection regimes. The solubility of each substance in CO2 was measured at the selected working conditions. TPL-SAC showed a cocrystallization rate of 2.9% min(-1), two times higher than that of IND-SAC, due to the higher solubility of TPL in CO2. The cocrystallization kinetics was also improved by increasing the CO2 density, showing that cocrystallization was limited by the dissolution of cocrystal formers. Overall, the CSS process has a potential for scale-up as a novel, simple, solvent-free batch process whenever the cocrystal phase is formed in the CO2 media.

  • 307.
    Padrela, Luis
    et al.
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Rodrigues, Miguel A.
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Fernandes, Anabela C.
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Matos, Henrique A.
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Azevedo, Edmundo Gomes de
    Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa.
    Screening for pharmaceutical cocrystals using the supercritical fluid enhanced atomization process2010In: Journal of Supercritical Fluids, ISSN 0896-8446, E-ISSN 1872-8162, Vol. 53, no 1-3, p. 156-164Article in journal (Refereed)
    Abstract [en]

    The supercritical fluid enhanced atomization (SEA) process was used to produce cocrystals of six different active pharmaceutical ingredients (APIs): indomethacin, theophylline, caffeine, sulfamethazine, aspirin and carbamazepine. Micrometric cocrystals using the FDA-approved sweetener saccharin (SAC) as a cocrystal former were produced from ethanol solutions using supercritical CO2 as the atomization enhancing fluid. The corresponding cocrystalline phases were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Particle morphologies and size distributions were analyzed by scanning electron microscopy (SEM) and by aerosizer.The results presented here show the formation of cocrystals of all the APIs selected, evidencing the ability and the potentiality of the SEA technique to generate different pharmaceutical cocrystals. Cocrystal particles produced by SEA had similar mean particle size than those produced by classical grinding methods. Interestingly, a new cocrystal form of theophylline-saccharin (likely with a 1:2 stoichiometry) was obtained by the SEA method that has not been previously reported by traditional screening methods.

  • 308.
    Pandey, Jaya
    et al.
    Physics Department, University of Lucknow.
    Prajapati, Preeti
    Physics Department, University of Lucknow.
    Shimpi, Manishkumar
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Tandon, Poonam
    Physics Department, University of Lucknow.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Srivastava, Anubha
    Physics Department, University of Lucknow.
    Sinha, Kirti
    Physics Department, University of Lucknow.
    Studies of molecular structure, hydrogen bonding and chemical activity of a nitrofurantoin-L-proline cocrystal: a combined spectroscopic and quantum chemical approach2016In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, no 78, p. 74135-74154Article in journal (Refereed)
    Abstract [en]

    Nitrofurantoin (NTF) has been used as an antibacterial drug to treat bacterial infections of the urinary tract. The purpose of this work is to predict the hydrogen bonds (potential synthons) present in the cocrystal of nitrofurantoin-L-proline (NTF-LP) through a computational approach (DFT calculations) and validate using vibrational spectroscopic studies. The present study illustrates the formation and characterization of the cocrystal of NTF-LP. The molecular structure of the NTF-LP cocrystal has been predicted by forming several models on the basis of the hydrogen bonding patterns observed in other NTF cocrystals. A conformational study and potential energy surface scan have been plotted around three flexible bonds of the cocrystal molecule and two stable conformers have been obtained. NBO analysis of the second order perturbation theory of the Fock matrix suggests that interaction n1O(39) → σ*(N13–H21) is responsible for the stabilization of the molecule. Quantum theory of atoms in molecules (QTAIM) explains that all interactions are medium and partially covalent in nature as ∇2ρBCP > 0, HBCP < 0. The molecular electrostatic potential surface (MEPS) of the cocrystal has been visualized for its most electropositive potential in the region of the NH2+ group and most electronegative potential in the vicinity of the COO− group. The HOMO and LUMO energies and electronic charge transfer (ECT) confirms that charge flows from the co-former (LP) to NTF (API). Local reactivity descriptor parameters have been used to predict the reactive sites of the cocrystal and global reactivity descriptor parameters suggest that the cocrystal is softer thus more reactive in comparison to NTF. The experimental and theoretical results support the formation of the cocrystal through the strong hydrogen bond present between the NH group of NTF and carboxylate COO− group of LP and shows that LP is present in the zwitterionic form.

  • 309.
    Pauelsen, Mascha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Jacobson, Inger
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Larsson, Agneta
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Skadepanorama och riskfaktorer inom Flat Track Roller Derby2014In: Svensk idrottsmedicin, ISSN 1103-7652, Vol. 2014, no 1, p. 22-25Article in journal (Other academic)
  • 310.
    Pauelsen, Mascha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehabilitation.
    Nyberg, Gusten
    Department of Radiology, Linköping University Hospital.
    Tegner, Cecilia
    Swedish University of Agricultural Sciences, Uppsala.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Concussion in ice hockey: A Cohort Study Across 29 Seasons2017In: Clinical Journal of Sports Medicine, ISSN 1050-642X, E-ISSN 1536-3724, Vol. 27, no 3, p. 283-287Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to analyse the concussion incidence rate ratios (IRR) across 29 seasons in a Swedish Hockey League team.Design: Cohort study over 29 seasons within one Swedish elite series ice hockey team. Participants: All players who were part of one Swedish elite ice hockey team during the research period gave consent for participation in the study.Independent Variables: Exposure to top level Swedish ice hockey. Main Outcome Measures: Incidence rate ratio for concussion as well as rehabilitation periods due to concussion were calculated and analysed.Results: During the research period, 267 players in total were part of the team. A total of 1638 traumatic injuries were registered of which 162 were concussions. Incidence rates ranged from 0/1,000 games during the first season to 118/1,000 games for the final recorded season. The incidence rate ratio was 1.06 (CI = 1.03-1.10) for the entire research period. A shift towards longer rehabilitation periods was discovered.Conclusions: This study showed a significant increase of concussion incidence rate and a trend towards longer rehabilitation periods due to concussion. Possible risk factors were discussed. Risk behaviour and rehabilitation protocols should be prioritized areas in the research of concussion in ice hockey. 

  • 311.
    Pauelsen, Mascha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Hjärnskakning i hockey: en studie över 29 säsonger2015Conference paper (Other academic)
    Abstract [sv]

    Hockey är en intensiv sport med en stor risk för commotio. Syftet med studien var att analysera förändring i incidensen av commotio över en 29-års period i ett svenskt elit hockeylag. Under åren 1985-2013 gjordes en prospektiv skaderegistrering i laget. Alla skador som föranledde avbrytande eller bortovaro från match/träning registrerades. skadeorsak, -tidpunkt, -mekanism etc. och närvaro på match/träning registrerades i ett skaderegistreringsprogram (ISIS). Skadedefinitionen på commotio var - förutom under första året - densamma över hela perioden och alla diagnoser ställdes av en och samma läkare. Under studieperioden var 267 spelare med i laget. Totalt registrerades 1628 traumatiska skador och av dessa var 162 (10%) commotio. Incidensen av commotio varierade från 0/1000 matcher under första säsongen till 118/1000 matcher under den sista säsongen. De flesta (85%) av commotio inträffade under match. Bortovaron pga commotio ökade från 0 dagar till 10 dagar per commotio (p<0,001) under studieperioden. Denna kohortstudie visar på en ökning av commotio incidensen över en 29 års period. Vidare ökar bortovaron från match/träning tydande på att skadorna blir allvarligare.

  • 312.
    Persson, Ann-Sofie
    et al.
    Department of Pharmacy, Uppsala University.
    Ahmed, Hamzah
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Alderborn, Göran
    Department of Pharmacy, Uppsala University.
    Powder compression properties of paracetamol, paracetamol hydrochloride, paracetamol cocrystals and coformers2018In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 107, no 7, p. 1920-1927Article in journal (Refereed)
    Abstract [en]

    The objective was to study the relationship between crystal structure, particle deformation properties and tablet-forming ability for the monoclinic form of paracetamol (PRA), two cocrystals and a salt crystal of PRA in addition to two coformers (oxalic acid and 4,4’-bipyridine). Thus, the structure – property – performance relationship was investigated. Analytical powder compression was used for determination of effective plasticity, as inferred from the Heckel yield pressure and the Frenning parameter, and the elastic deformation was determined from in-die tablet elastic recovery.

    plasticity could not be linked to the crystal lattice structure as crystals containing zig-zag layers displayed similar plasticity as cThe rystals containing slip planes. In addition, crystals containing slip-planes displayed both high and low plasticity.

    The mechanical properties could neither be linked to the tablet-forming ability as the tablet tensile strength, unexpectedly, displayed a tendency to reduce with increased plasticity stiffness. Furthermore, the elastic deformation could not explain the tablet forming ability.

    It was concluded that no relationship between structure – property – performance for paracetamol and its cocrystals and salt could be established. Thus, it was indicated that to establish such a relationship an improved knowledge of crystallographic structure and inter-particle bonding during compaction is needed.

  • 313.
    Poso, Tomi
    et al.
    Sunderby Hospital, Department of Anaesthesiolofy & Intensive Care.
    Kesek, Doris
    Umea University, Department of Surgery & Perioperative Science, Department fo Cardiothorac Anaesthesia.
    Winso, Ola
    Umea University, Department of Surgery & Perioperative Science, Department fo Cardiothorac Anaesthesia.
    Andersson, Staffan
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Volatile rapid sequence induction in morbidly obese patients2011In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 28, no 11, p. 781-787Article in journal (Refereed)
    Abstract [en]

    Background and objective The interest in bariatric surgery is growing. Morbidly obese patients have an increased risk of hypoxia and decreased blood pressure during rapid sequence induction (RSI). Alternate RSI methods that provide cardiovascular and respiratory stability are required. With this in mind, we evaluated a method for volatile RSI in morbidly obese patients. Design Observational study. Methods Thirty-four patients with mean BMI 42.4 kg m(-2) undergoing bariatric surgery (morbidly obese group) and 22 patients with mean BMI 25.6 kg m(-2) as a control group were included in the study. Anaesthesia was induced with sevoflurane, propofol, suxamethonium and alfentanil, designed to avoid respiratory and haemodynamic adverse events and to minimise depressing effect on the brain respiratory centre under ongoing RSI. Peripheral oxygen saturation (SpO(2)) and mean arterial blood pressure were registered before and after endotracheal intubation. In addition, two time periods were measured during RSI: spontaneous breathing time (SBT) and apnoea time. Results We found no significant differences between the groups. No periods of desaturation were detected. SpO(2) was 100% before and after endotracheal intubation in all patients. Mean arterial pressure was maintained at a stable level in both groups. Mean SBT and apnoea time were 65.6 and 45.8 s in the morbidly obese group, and 70.7 and 47.7 s in the control group, respectively.

  • 314.
    Prajapati, Preeti
    et al.
    Physics Department, University of Lucknow.
    Pandey, Jaja
    Physics Department, University of Lucknow.
    Shimpi, Manishkumar
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Srivastava, Anubha
    Physics Department, University of Lucknow.
    Tandon, Poonam
    Physics Department, University of Lucknow.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Sinha, Kirti
    Physics Department, University of Lucknow.
    Combined spectroscopic and quantum chemical studies of ezetimibe2016In: Journal of Molecular Structure, ISSN 0022-2860, E-ISSN 1872-8014, Vol. 1125, p. 193-203Article in journal (Refereed)
    Abstract [en]

    Ezetimibe (EZT) is a hypocholesterolemic agent used for the treatment of elevated blood cholesterol levels as it lowers the blood cholesterol by blocking the absorption of cholesterol in intestine. Study aims to combine experimental and computational methods to provide insights into the structural and vibrational spectroscopic properties of EZT which is important for explaining drug substance physical and biological properties. Computational study on molecular properties of ezetimibe is presented using density functional theory (DFT) with B3LYP functional and 6-311++G(d,p) basis set. A detailed vibrational assignment has been done for the observed IR and Raman spectra of EZT. In addition to the conformational study, hydrogen bonding and molecular docking studies have been also performed. For conformational studies, the double well potential energy curves have been plotted for the rotation around the six flexible bonds of the molecule. UV absorption spectrum was examined in methanol solvent and compared with calculated one in solvent environment (IEF-PCM) using TD-DFT/6-31G basis set. HOMO-LUMO energy gap of both the conformers have also been calculated in order to predict its chemical reactivity and stability. The stability of the molecule was also examined by means of natural bond analysis (NBO) analysis. To account for the chemical reactivity and site selectivity of the molecules, molecular electrostatic potential (MEPS) map has been plotted. The combination of experimental and calculated results provide an insight into the structural and vibrational spectroscopic properties of EZT. In order to give an insight for the biological activity of EZT, molecular docking of EZT with protein NPC1L1 has been done.

  • 315.
    Rao Vuddanda, Parameswara
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Banaras Hindu University, Institute of Technology, Department of Pharmaceutics, Varanasi .
    Chakraborty, Subhashis
    Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi .
    Singh, Sanjay Kumar
    Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh.
    Berberine: A potential phytochemical with multispectrum therapeutic activities2010In: Expert Opinion on Investigational Drugs, ISSN 1354-3784, E-ISSN 1744-7658, Vol. 19, no 10, p. 1297-1307Article in journal (Refereed)
    Abstract [en]

    Importance of the field: The use of traditional medicines of natural origin is being encouraged for the treatment of chronic disorders, as synthetic drugs in such cases may cause unpredictable adverse effects. Berberine, a traditional plant alkaloid, is used in Ayurvedic and Chinese medicine for its antimicrobial and antiprotozoal properties. Interestingly, current clinical research on berberine has revealed its various pharmacological properties and multi-spectrum therapeutic applications. Areas covered in this review: An extensive search in three electronic databases (Unbound Medline, PubMed and ScienceDirect) and internet search engines (Scirus and Google Scholar) were used to identify the clinical studies on berberine, without any time constraints. This review elaborates the recent studies which reveal that with time, the drug has evolved with superior therapeutic activities. In addition, this review will also attract the attention of formulation scientists towards the issues and challenges associated in its drug delivery and the probable approaches that may be explored to help patients reap the maximum benefit of this potentially useful drug. What the reader will gain: A relatively large number of studies discussed here have revealed the possible areas where this phytochemical constituent can exhibit its therapeutic activities in the treatment of chronic ailments or diseases including diabetes, cancer, depression, hypertension and hypercholesterolemia. Take home message: The potential of the drug remains to be harvested by designing a suitable formulation that could overcome its inherent low bioavailability

  • 316.
    Rao Vuddanda, Parameswara
    et al.
    Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh.
    Mishra, Amit Kumar
    Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh.
    Singh, Sanjay
    Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh.
    Singh, Sanjay Kumar
    Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh.
    Development of polymeric nanoparticles with highly entrapped herbal hydrophilic drug using nanoprecipitation technique: An approach of quality by design2015In: Pharmaceutical development and technology (Print), ISSN 1083-7450, E-ISSN 1097-9867, Vol. 20, no 5, p. 579-587Article in journal (Refereed)
    Abstract [en]

    The intention of this study is to achieve higher entrapment efficiency (EE) of berberine chloride (selected hydrophilic drug) using nanoprecipitation technique. The solubility of drug was studied in various pH buffers (1.2-7.2) for selection of aqueous phase and stabilizer. Quality by design (QbD)-based 32 factorial design were employed for optimization of formulation variables; drug to polymer ratio (X1) and surfactant concentration (X2) on entrapment efficiency (EE), particle size (PS) and polydispersity index (PDI) of the nanoparticles. The nanoparticles were subjected to solid state analysis, in vitro drug release and stability study. The aqueous phase and stabilizer selected for the formulations were pH 4.5 phthalate buffer and surfactant F-68, respectively. The formulation (F-6) containing drug to polymer ratio (1:3) and stabilizer (F-68) concentration of 50mM exhibited best EE (82.12%), PS (196.71nm), PDI (0.153). The various solid state characterizations assured that entrapped drug is amorphous and nanoparticles are fairly spherical in shape. In vitro drug release of the F-6 exhibited sustained release with non-Fickian diffusion and stable at storage condition. This work illustrates that the proper selection of aqueous phase and optimization of formulation variables could be helpful in improving the EE of hydrophilic drugs by nanoprecipitation technique

  • 317.
    Rao Vuddanda, Parameswara
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Montenegro-Nicolini, Miguel
    Department of Pharmaceutical Sciences and Technology, University of Chile, Santiago.
    Morales, Javier O.
    Department of Pharmaceutical Sciences and Technology, University of Chile, Santiago.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Effect of plasticizers on the physico-mechanical properties of pullulan based pharmaceutical oral films2017In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 96, p. 290-298Article in journal (Refereed)
    Abstract [en]

    The effect of different plasticizers (glycerol, vitamin E TPGS and triacetin) and their concentrations on the physico-mechanical properties of pullulan based oral films was studied. A full factorial (32) design of experiments was used. Elastic modulus, tensile strength, elongation at break and disintegration time were selected as response variables. Modulated differential scanning calorimeter (MDSC) was used for determining glass transition temperature (Tg) of pullulan films. The surface morphology of films was evaluated by SEM, while ATR-FTIR was used to obtain a molecular level understanding of polymer-plasticizer interactions. The DoE analysis allowed for the modelling of tensile strength and elongation at break. The highest elongations were observed in glycerol at 20% w/w. Majority of the films disintegrated within one minute without significant differences. ATR-FTIR spectra of pullulan alone and different plasticizer blend films show characteristic molecular interactions. The present study concluded that glycerol is suitable plasticizer compared to others for manufacturing pullulan based oral films.

  • 318.
    Rao Vuddanda, Parameswara
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Montenegro-Nicolini, Miguel
    Department of Pharmaceutical Sciences and Technology, University of Chile.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Effect of surfactants and drug load on physico-mechanical and dissolution properties of nanocrystalline tadalafil-loaded oral films2017In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 109, p. 372-380Article in journal (Refereed)
    Abstract [en]

    The aim of the present work was to prepare tadalafil (TDF) nanocrystals-loaded oral polymeric films (OFs) and investigate the effect of hydrophilic surfactants and drug loads on the physico-mechanical and dissolution properties. The nanosuspensions of TDF were prepared by high shear homogenization. HPMC based placebo casting film gel was prepared and mixed with TDF nanosuspensions. Films were casted using an automated film applicator and dried at 60 °C for 45 min. Particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of TDF nanosuspensions were measured in a Zetasizer. The films were characterized using SEM, AFM, DSC, TGA and PXRD. The mechanical properties and in vitro drug release were determined using standard methods. TDF existed in crystalline form and the particles remained in the nano-range in redispersed films. TDF nanocrystals were embedded in the polymeric matrix and the drug loaded films were rough on the surface. Mechanical properties of the films varied with changes in drug load and surfactant. Significant changes in the disintegration times were noticed in films containing surfactants compared to surfactant-free films. About 80% of the drug release was observed between 3 and 30 min. TPGS showed better TDF release from the films at different drug loads

  • 319. Rao Vuddanda, Parameswara
    et al.
    Rajamanickam, Vijayakumar Mahalingam Ahalingam
    Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi.
    Yaspal, Madhu
    Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi.
    Singh, Sanjay Kumar
    Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh.
    Investigations on agglomeration and haemocompatibility of Vitamin E TPGS surface modified berberine chloride nanoparticles2014In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, Vol. 2014, article id 951942Article in journal (Refereed)
    Abstract [en]

    The objective of the present study is to investigate the influence of surface modification on systemic stability of NPs. Vitamin E TPGS (1% w/v) was used for surface modification of berberine chloride nanoparticles. Naked and surface modified NPs were incubated in different SBFs (pH 6.8 and 7.4) with or without bile salts and human plasma. NPs were observed for particle agglomeration and morphology by particle size analyzer and TEM, respectively. The haemocompatibility studies were conducted on developed NPs to evaluate their safety profile. The surface modified NPs were stable compared to naked NPs in different SBFs due to the steric stabilization property of vitamin E TPGS. Particle agglomeration was not seen when NPs were incubated in SBF (pH 6.8) with bile salts. No agglomeration was observed in NPs after their incubation in plasma but particle size of the naked NPs increased due to adhesion of plasma proteins. The TEM images confirmed the particle size results. DSC and FT-IR studies confirmed the coexistence of TPGS in surface modified NPs. The permissible haemolysis, LDH release, and platelet aggregation revealed that NPs were compatible for systemic administration. Thus, the study illustrated that the surface modification is helpful in the maintenance of stability of NPs in systemic conditions

  • 320.
    Risberg, Anitha
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Hormoner och vätskebalans under graviditet, förlossning och postpartum2010Conference paper (Other academic)
  • 321.
    Risberg, Anitha
    et al.
    Department of Nursing and Health Sciences, Mid Sweden University, Ornskoldsvik.
    Larsson, A.
    Olsson, Kerstin
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Lyrenäs, Sven
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Sjöquist, Mats
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Relationship between urinary albumin and albumin/creatinine ratio during normal pregnancy and pre-eclampsia2004In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 64, no 1, p. 17-23Article in journal (Refereed)
    Abstract [en]

    Pre-eclampsia is a serious complication of pregnancy and it is important to detect the condition as early as possible. Albuminuria is an important symptom of pre-eclampsia and repeated urine analyses to screen for the condition are part of the standard antenatal care. The purpose of this study was to investigate whether measurement of the urine albumin/creatinine ratio in spot samples could be a complement to the dipstick method and could reduce the need for 24-h urine collections. Urine samples were collected for 24 h in weeks 12, 24 and 36 of pregnancy from both normotensive women and women who developed hypertension or who had pregnancy-induced hypertension (PIH) when they entered the study. The 24-h albumin excretion was significantly correlated to the albumin/creatinine ratio in all measurements (Pearson correlation coefficient). In week 12, the values were: n = 44, r = 0.964, p < 0.001 (normotensive group) and in the PIH group: n = 8, r = 0.789, p < 0.05. In week 24, the correlation values were r = 1.0 and p < 0.001 in both the normotensive group (n = 41) and in the PIH group (n = 11). In week 36 the correlation values were r = 0.791 and p < 0.001 in the normotensive group (n = 39) and r = 1.0 and p < 0.001 in the PIH group (n = 16). Microalbuminuria was defined as urine albumin excretion higher than 30 mg/24 h and this corresponded to an albumin/creatinine ratio of 2.9. Microalbuminuria was found in three persons in the PIH group and in two persons in the normotensive group. Overt albuminuria (> 300 mg/24 h) was found in one of the 46 normotensive women (2%) and in 3 of the 19 PIH women (16%). In all these women the high albumin values had been detected by using the albumin/creatinine ratio method. In conclusion, it has been found that the albumin excretion in urine correlates significantly to the albumin/creatinine ratio during pregnancy. The urinary albumin/creatinine ratio appears to be a good alternative to the dipstick method and to 24-h urine collections.

  • 322. Risberg, Anitha
    et al.
    Olsson, Kerstin
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Lyrenäs, Sven
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Sjöquist, Mats
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Oxytocin concentration increase and vasopressin concentration decrease in normotensive and hypertensive pregnant women1999Conference paper (Refereed)
  • 323.
    Risberg, Anitha
    et al.
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Olsson, Kerstin
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Lyrenäs, Sven
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Sjöquist, Mats
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Plasma vasopressin, oxytocin, estradiol, and progesterone related to water and sodium excretion in normal pregnancy and gestational hypertension2009Conference paper (Refereed)
  • 324.
    Risberg, Anitha
    et al.
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Olsson, Kerstin
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Lyrenäs, Sven
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Sjöquist, Mats
    Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University.
    Plasma vasopressin, oxytocin, estradiol, and progesterone related to water and sodium excretion in normal pregnancy and gestational hypertension2009In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 88, no 6, p. 639-646Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate associations between plasma oxytocin and vasopressin concentrations and renal water and sodium excretion during normal pregnancy in comparison with gestational hypertension.

    DESIGN:

    A prospective open trial conducted in the 12th, 24th, and 36th weeks of gestation.

    SETTINGS:

    Seven antenatal clinics in Sweden.

    PARTICIPANTS:

    Thirty-seven normotensive women, 15 women with gestational hypertension, and five women with mild preeclampsia.

    MAIN OUTCOME MEASURES:

    Hormones were analyzed with radioimmunoassay. Albumin, osmolality, sodium, and urea were analyzed by routine methods.

    RESULTS:

    Blood pressure was elevated in the hypertensive women and body mass index in mild preeclampsia from week 12. Renal sodium excretion did not differ between groups or weeks and mean renal free water clearance was negative. In normotensive women, the vasopressin concentration was 1.1+/-0.2 (week 12) and 0.7+/-0.1 pmol/L (week 36: p = 0.053). In hypertensive women, vasopressin concentration was 1.7+/-1.0 pmol/L, week 12, and 0.7+/-0.1 pmol/L in week 36 (ns). In normotensive women, oxytocin concentration increased from 23+/-1 pmol/L in week 12 to 48+/-3 pmol/L in week 36 (p<0.001). Corresponding values in hypertensive women were 36+/-11 (week 12) and 55+/-5 pmol/L (week 36: ns). In all groups, plasma estradiol concentration increased. Plasma progesterone increased until week 24 in normotensive and hypertensive women with further increase in normotensive women.

    CONCLUSIONS:

    The low plasma vasopressin and increasing plasma oxytocin concentrations with unchanged water and sodium excretion indicate that oxytocin assists vasopressin in concentrating urine during pregnancy.

  • 325.
    Risberg, Anitha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Sjöquist, Mats
    Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala.
    Wedenberg, Kaj
    The section of womens health, Vasteras Hospital.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University.
    Elevated glucose levels in early puerperium, and association with high cortisol levels during parturition2017In: 38th IUPS World Congress: Rhythms of Life, 2017Conference paper (Refereed)
  • 326.
    Risberg, Anitha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Sjöquist, Mats
    Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala.
    Wedenberg, Kaj
    The section of womens health, Vasteras Hospital.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University.
    Elevated glucose levels in early puerperium, and association with high cortisol levels during parturition2017In: DIP 2017, 2017Conference paper (Refereed)
  • 327.
    Risberg, Anitha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Sjöquist, Mats
    Sveriges Lantbruksuniversitet, Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala.
    Wedenberg, Kaj
    Västerås Hospital.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University.
    Elevated glucose levels in early puerperium, and association with high cortisol levels during parturition2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 4, p. 309-312Article in journal (Refereed)
    Abstract [en]

    Background Gestational diabetes is one of the commonest metabolic problems associated with pregnancy and an accurate diagnosis is critical for the care. Research has shown that pregnant women have high levels of cortisol during the last stage of parturition. As cortisol is a diabetogenic hormone causing increased glucose levels, we wanted to study the association between cortisol and glucose levels during parturition. Materials and methods Glucose and cortisol were analyzed during parturition in 50 females divided according to slow (n = 11) and normal labors (n = 39). Blood samples were analyzed three times during the parturition and four times in the first day after delivery. Glucose levels were also measured once in each trimester. Results In the normal group, the glucose concentration increased from 6.2 (IQR 5.6-8.0) mmol/L in the latency phase to 11.6 (10.0-13.3) mmol/L at aftercare (p < 0.05). After parturition the glucose concentrations decreased gradually. There were significant Spearman rank correlations between glucose and cortisol values. Conclusions The changes associated with birth cause significant elevations of cortisol and glucose around parturition

  • 328.
    Risberg, Anitha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Sjöquist, Mats
    Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala.
    Wedenberg, Kaj
    The section of womens health, Vasteras Hospital.
    Olsson, Ulf
    Department of Economics, Unit of Applied Statistics and Mathematics, Swedish University of Agricultural Sciences, Uppsala .
    Larsson, Anders
    Department of Medical Sciences, Uppsala University.
    Water balance during parturition and early puerperium: a prospective open trial2017In: DIP 2017, 2017Conference paper (Refereed)
  • 329.
    Risberg, Anitha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehabilitation.
    Sjöquist, Mats
    Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala.
    Wedenberg, Kaj
    The section of womens health, Vasteras Hospital.
    Olsson, Ulf
    Department of Economics, Unit of Applied Statistics and Mathematics, Swedish University of Agricultural Sciences, Uppsala .
    Larsson, Anders
    Department of Medical Sciences, Uppsala University.
    Water balance during parturition and early puerperium: a prospective open trial2017In: 38th IUPS World Congress: Rhythms of Life, 2017Conference paper (Refereed)
  • 330.
    Risberg, Anitha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Sjöquist, Mats
    Sveriges Lantbruksuniversitet, Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala.
    Wedenberg, Kaj
    Västerås Hospital.
    Olsson, Ulf
    Department of Economics, Unit of Applied Statistics and Mathematics, Swedish University of Agricultural Sciences, Uppsala.
    Larsson, Anders
    Department of Medical Sciences, Clinical Chemistry, Uppsala University.
    Water balance during parturition and early puerperium: a prospective open trial2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 13-14, p. 837-842Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo investigate how water balance is regulated during labour and 27 h postpartum. Design and methods A prospective open trial with 49 women giving birth vaginally. Ringer-acetate was infused intravenously and combined with epidural analgesia in seven women (fluid group). Intravenous infusions of oxytocin in 5% glucose were given to 12 women (oxytocin group). Thirty women delivered their babies without infusion (nofluid group). Blood and urine samples were collected at arrival, at early stage 1, at early stage 2, and at aftercare, and 9-, 15-, and 27-h postpartum. Plasma osmolality, sodium, cystatin C, vasopressin, oxytocin, urine flow, urine osmolality and urine sodium were measued.ResultsThe oxytocin group had significantly lower plasma osmolality than the nofluid group before parturition, and they had lower plasma sodium concentration at early stage one and two. Plasma vasopressin concentration was low and did not differ between groups or before and after parturition. Water diuresis developed postpartum in all groups. The cystatin C concentration decreased significantly after parturition in the oxytocin and nofluid groups.ConclusionsThe vasopressin levels were suppressed during parturition irrespective of the P-osmolality and the nongravid regulation of water balance had not returned within 27 h postpartum.

  • 331.
    Roos, Eva M.
    et al.
    Unit for Musculoskeletal Function and Physiotherapy, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense.
    Engelhart, Luella
    Health Economics & Outcomes Research, DePuy, Inc., Raynham.
    Ranstam, Jonas
    Department of Orthopedics, Clinical Sciences Lund, Lund University.
    Anderson, Allen F.
    Tennessee Orthopaedic Alliance/The Lipscomb Clinic, Nashville.
    Irrgang, Jay J.
    Department of Orthopedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh.
    Marx, Robert G.
    Hospital for Special Surgery, Weill Cornell Medical College, New York.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Davis, Aileen M.
    Division of Health Care and Outcomes Research and Arthritis and Community Research and Evaluation Unit, Toronto Western Research Institute, and Departments of Physical Therapy, Rehabilitation Science and Health Policy Management and Evaluation, University of Toronto.
    ICRS recommendation document: Patient-reported outcome instruments for use in patients with articular cartilage defects2011In: Cartilage, ISSN 1947-6035, E-ISSN 1947-6043, Vol. 2, no 2, p. 122-136Article in journal (Refereed)
    Abstract [en]

    Objective: The purpose of this article is to describe and recommend patient-reported outcome instruments for use in patients with articular cartilage lesions undergoing cartilage repair interventions. Methods: Nonsystematic literature search identifying measures addressing pain and function evaluated for validity and psychometric properties in patients with articular cartilage lesions. Results: The knee-specific instruments, titled the International Knee Documentation Committee Subjective Knee Form and the Knee injury and Osteoarthritis and Outcome Score, both fulfill the basic requirements for reliability, validity, and responsiveness in cartilage repair patients. A major difference between them is that the former results in a single score and the latter results in 5 subscores. A single score is preferred for simplicity’s sake, whereas subscores allow for evaluation of separate constructs at all levels according to the International Classification of Functioning. Conclusions: Because there is no obvious superiority of either instrument at this time, both outcome measures are recommended for use in cartilage repair. Rescaling of the Lysholm Scoring Scale has been suggested, and confirmatory longitudinal studies are needed prior to recommending this scale for use in cartilage repair. Inclusion of a generic measure is feasible in cartilage repair studies and allows analysis of health-related quality of life and health economic outcomes. The Marx or Tegner Activity Rating Scales are feasible and have been evaluated in patients with knee injuries. However, activity measures require age and sex adjustment, and data are lacking in people with cartilage repair.

  • 332.
    Rutberg, Stina
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Professional tools and a personal touch: experiences of physical therapy of persons with migraine2013In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 35, no 19, p. 1614-1621Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim was to explore the lived experience of physical therapy of persons with migraine. Method: Data were collected by conducting narrative interviews with 11 persons with migraine. Inspired by van Manen, a hermeneutic phenomenological method was used to analyse the experiences of physical therapy which these persons had. Results: Physical therapy for persons with migraine meant making an effort in terms of time and energy to improve their health by meeting a person who was utilising his or her knowledge and skill to help. Being respected and treated as an individual and having confidence in the physical therapist were highlighted aspects. The analysis revealed a main theme, “meeting a physical therapist with professional tools and a personal touch”. The main theme included four sub-themes, “investing time and energy to feel better”, “relying on the competence of the physical therapist”, “wanting to be treated and to become involved as an individual” and “being respected in a trustful relationship”. Conclusions: The therapeutic relationship with the physical therapist is important and the findings of this study can increase awareness about relational aspects of physical therapy and encourage thoughtfulness among physical therapists and other healthcare professionals interacting with persons with migraine. Implications for Rehabilitation •Physical therapists use both professional tools and a personal touch in their interaction with persons with migraine and this article can increase physical therapists’ awareness and encourage thoughtfulness in their professional practice.•Being respected and treated as an individual and having confidence in the physical therapist are important aspects of the therapeutic relationship and indicate a need for patient-centred care.•By making the effort of spending the time and energy required, physical therapy could be a complement or an alternative to medication to ease the consequences of migraine.

  • 333.
    Rutberg, Stina
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Travelling along a road with obstacles: Experiences of managing life to feel well while living with migraine2013In: International Journal of Qualitative Studies on Health and Well-being, ISSN 1748-2623, E-ISSN 1748-2631, Vol. 8Article in journal (Refereed)
    Abstract [en]

    Living a life with migraine can impair one’s sense of feeling well, and migraine is a disorder that is associated with substantial disability. Earlier research on how people manage their migraine has given important insight into these people’s preventive actions and how they handle their attacks, but there is still a lack of knowledge of how persons with migraine manage their lives to feel well from a more holistic viewpoint. Therefore, the aim of this study was to explore lived experiences of managing life to feel well while living with migraine. Nineteen persons with migraine were interviewed. A hermeneuticphenomenological approach was used to explore their lived experiences. The findings reveal that persons with migraine not only used preventive strategies to abort and ease the consequences of migraine but also tried to amplify the good in life through increasing their energy and joy and through reaching peace with being afflicted with migraine. The findings of this study can encourage healthcare providers, as well as persons with migraine, to consider channeling their efforts into strategies aiming to amplify the good in life, including reaching peace of mind despite being afflicted.

  • 334.
    Röijezon, Ulrik
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehabilitation.
    Løvoll, Grunde
    Norwegian Institute for Water Research (NIVA), Section for Environmental Data Science .
    Henriksson, Anders
    Department of Sport and Health Sciences, School of Education, Health and Social Sciences, Dalarna University.
    Tonkonogi, Michail
    Department of Sport and Health Sciences, School of Education, Health and Social Sciences, Dalarna University.
    Lehto, Niklas
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    An Initial Study on the Coordination of Rod and Line Hauling Movements in Distance Fly Casting2017In: Annals of Applied Sport Science, ISSN 2476-4981, Vol. 5, no 2, p. 61-72Article in journal (Refereed)
    Abstract [en]

    Background. The double haul is a unique feature of single-handed fly casting and is used in both fly fishing and fly casting competition. The movement behaviour during the double haul has not been investigated in previous research.

    Objectives. Describe the coordination of the rod and line hauling movements during distance fly casting.

    Methods. Elite fly casters performed distance casting with four different fly rod and fly line set-ups used in fly fishing and fly casting competition. Rod and hauling movements were measured with a 3D motion analysis system.

    Results. The rod and line hauling movements were coordinated in an order whereby peak translational speed of the rod occurs prior to the peak speed of the angular rotation of the rod, and the peak speed of the angular rotation of the rod occurs prior to the peak speed of the line haul. This was consistent for all cast sequences, i.e., the back and forward false casts and the delivery cast, and for all four equipment set-ups, i.e., a shooting-head line cast with a relatively stiff fly rod and a long-belly line cast with three different fly rods with different stiffness and action curves. Results also showed differences in movement coordination between cast sequences and rod and line set-ups.

    Conclusion. Among elite casters, single-handed fly casting with double haul is coordinated in an order of events whereby the peak speed occurs first for the translation of the rod, then for the rotation of the rod and finally for the line haul.

  • 335.
    Rönmark, Eva
    et al.
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN unit, Umeå University.
    Warm, Katja
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, The OLIN Unit, Umeå University; Division of Medicine, The OLIN Unit, Umeå University, Umeå, Sweden.
    Bjerg, Anders Munch
    Department of Women's and Children's Health, Karolinska Institutet.
    Backman, Helena
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, The OLIN Unit, Umeå University.
    Hedman, Linnea
    Luleå University of Technology, Department of Health Sciences, Nursing Care. Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, The OLIN Unit, Umeå University, Umeå, Sweden.
    Lundbäck, Bo
    Krefting Research Centre, Institute of Medicine, University of Gothenburg.
    High incidence and persistence of airborne allergen sensitization up to age 19 years2017In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 72, no 5, p. 723-730Article in journal (Refereed)
    Abstract [en]

    Background

    Longitudinal population-based studies about the natural history of allergic sensitization are rare. The aim was to study incidence and persistence of airborne allergen sensitization up to young adulthood and risk factors for early and late onset of sensitization.

    Methods

    All children aged 7–8 years in two municipalities in Northern Sweden were invited to a parental questionnaire and skin prick tests (SPTs) to ten airborne allergens, and 2148 (88%) participated. The protocol was repeated at age 11–12 and 19 years, and 1516 participated in all three examinations.

    Results

    Prevalence of any positive SPT increased from 20.6% at age 7–8 years to 30.6% at 11–12 years, and 42.1% at 19 years. Animals were the primary sensitizers at age 7–8 years, 16.3%, followed by pollen, 12.4%. Mite and mold sensitization was low. Mean annual incidence of any positive SPT varied between 2.8 and 3.4/100 per year, decreased by age for animal, and was stable for pollen. Sensitization before age 7–8 years was independently associated with family history of allergy, OR 2.1 (95% CI 1.6–2.8), urban living, OR 1.9 (95% CI 1.2–2.9), and male sex, OR 1.3 (95% CI 1.0–1.7), and negatively associated with birth order, OR 0.8 (95% CI 0.7–1.0), and furry animals at home, OR 0.7 (95% CI 0.7–0.9). Incidence after age 11–12 years was associated only with family history of allergy. Multisensitization at age 19 years was significantly associated with early age at sensitization. Remission of sensitization was uncommon.

    Conclusion

    The increasing prevalence of allergic sensitization by age was explained by high incidence and persistence. After age 11–12 years, the factors urban living, number of siblings, and male sex lost their importance.

  • 336.
    Rönnqvist, Mats
    et al.
    Luleå University of Technology, Department of Health Sciences.
    Johansson, Magnus
    Luleå University of Technology, Department of Health Sciences.
    Artificiell Intelligens inom medicinsk bilddiagnostik: En allmän litteraturstudie2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Artificial Intelligence (AI) increasingly comes in to our society and homes. In the field of medical care and radiology, AI will provide an aid for radiologists and radiographers in their professions. Research on AI continues in finding better and more functional algorithms which can achieve that.

    Purpose: The purpose of this literature study is to compile facts about modalities using artificial intelligence as support. Method: The study was conducted as a general literature study, which generated fifteen articles that were quality-reviewed and categorized after analysis. Result: Depending on the date when the articles were written the methods varied concerning how training of AI was performed. It also varied how the images were pre-processed before training. The images need to be processed by noise reduction and segmentation for AI in order to be able to classify the pathological change. That process was facilitated in later versions of AI where all these steps were performed at the same time. Conclusion: Major changes may occur in radiology and the changes are likely to affect everyone in an X-ray ward. The authors can see that the development has just begun and research has to continue for many years to come.

  • 337.
    Sawalha, Sami
    et al.
    Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, SwedenDivision of Respiratory Medicine, Sunderby Hospital, Luleå, Sweden.
    Hedman, Linnea
    Luleå University of Technology, Department of Health Sciences, Nursing Care. Department of Public Health and Clinical Medicine, The OLIN unit, Section of Sustainable Health, Umeå University, Umeå.
    Backman, Helena
    Department of Public Health and Clinical Medicine, The OLIN unit, Section of Sustainable Health, Umeå University, Umeå, .
    Stenfors, Nikolai
    Department of Public Health and Clinical Medicine, The OLIN unit, Section of Sustainable Health, Umeå University, Umeå, .
    Rönmark, Eva
    Department of Public Health and Clinical Medicine, The OLIN unit, Section of Sustainable Health, Umeå University, Umeå, Sweden.
    Lundbäck, Bo
    Krefting Research center, Institution of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Lindberg, Anne
    Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden.
    The impact of comorbidities on mortality among men and women with COPD: report from the OLIN COPD study2019In: Therapeutic Advances in Respiratory Disease, ISSN 1753-4658, Vol. 13, p. 1-10Article in journal (Refereed)
    Abstract [en]

    Background:

    Comorbidities probably contribute to the increased mortality observed among subjects with chronic obstructive pulmonary disease (COPD), but sex differences in the prognostic impact of comorbidities have rarely been evaluated in population-based studies. The aim of this study was to evaluate the impact of common comorbidities, cardiovascular disease (CVD), diabetes mellitus (DM), and anxiety/depression (A/D), on mortality among men and women with and without airway obstruction in a population-based study.

    Methods:

    All subjects with airway obstruction [forced expiratory volume in 1 second (FEV1)/(forced) vital capacity ((F)VC) <0.70, n = 993] were, together with age- and sex-matched referents, identified after examinations of population-based cohorts in 2002–2004. Spirometric groups: normal lung function (NLF) and COPD (post-bronchodilator FEV1/(F)VC <0.70) and additionally, LLN-COPD (FEV1/(F)VC <lower limit of normal). Mortality data was collected until December 2015.

    Results:

    In COPD, the prevalence of CVD and DM was higher in men, whereas the prevalence of A/D was higher in women. The cumulative mortality was significantly higher in COPD than NLF, and higher in men than women in both groups. Among women with COPD, CVD and A/D but not DM increased the risk of death independent of age, body mass index, smoking habits, and disease severity, whereas among men DM and A/D but not CVD increased the risk for death. When the LLN criterion was applied, the pattern was similar.

    Conclusion:

    There were sex-dependent differences regarding the impact of comorbidities on prognosis in COPD. Even though the prevalence of CVD was higher in men, the impact of CVD on mortality was higher in women, and despite higher prevalence of A/D in women, the impact on mortality was similar in both sexes.

  • 338.
    Schenström, Ola
    et al.
    Primärvården, Luleå.
    Lindqvist, Anna-Karin
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Ett liv i balans2003Report (Other (popular science, discussion, etc.))
  • 339.
    Selberg, Stina
    et al.
    The OLIN Studies, Norrbotten County Council, Luleå.
    Hedman, Linnea
    Luleå University of Technology, Department of Health Sciences, Nursing Care. The OLIN Studies, Norrbotten County Council, Luleå. Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, The OLIN unit, Umeå University, Umeå.
    Jansson, Sven-Arne
    Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, The OLIN unit, Umeå University, Umeå.
    Backman, Helena
    The OLIN Studies, Norrbotten County Council, Luleå. Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, The OLIN unit, Umeå University, Umeå.
    Stridsman, Caroline
    Luleå University of Technology, Department of Health Sciences, Medical Science. Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Asthma control and acute health care visits among young adults with asthma: A population‐based study2019In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648Article in journal (Refereed)
    Abstract [en]

    Aims

    To study asthma control and acute health care visits among young adults with asthma.

    Background

    Despite the access to effective treatment and nursing interventions, poor asthma control is still common among individuals with asthma. However, studies describing clinical characteristics among young adults with asthma are rare.

    Design

    A population‐based cohort study.

    Methods

    In 2015, as a part of the OLIN pediatric cohort I (recruited in 1996 at age 7‐8yr), N=2291 young adults (27‐28 yr) completed a postal questionnaire survey including questions on asthma and respiratory symptoms. Of these, N=280 (12%) were identified as having current asthma and were further studied.

    Results

    Of those with current asthma, women reported respiratory symptoms and smoking to a greater extent than men. Approximately one‐fourth had uncontrolled asthma and acute health care visits due to asthma was reported by 15% of women and 8% of men. Uncontrolled asthma was associated with smoking, lower educational level, use of reliever treatment most days and acute health care visits. Acute health care visits due to asthma were associated with periodic use of regular controller treatment also after adjustment for uncontrolled asthma.

    Conclusion

    The result indicate poor adherence to asthma treatment which may lead to decreased asthma control and acute health care visits.

    Impact

    Most young adults with asthma are diagnosed and treated in primary care, ideally in a team with a nurse. The main findings highlight the need for evidenced‐based nursing interventions, contributing to a more efficient asthma management in primary care.

  • 340.
    Sepp, Hanna
    et al.
    Kristianstad University, Department of Behavioural Sciences.
    Wiklund, Maria Lennernäs
    Department of Medical Sciences, Nutrition, Uppsala University.
    Abrahamsson, Lillemor
    Department of Domestic Sciences, Uppsala University.
    Preschool children's meal patterns analysed using the Food-Based Classification of Eating Episodes model2006In: Scandinavian Journal of Food and Nutrition, ISSN 1748-2976, E-ISSN 1748-2984, Vol. 50, no 3, p. 131-138Article in journal (Refereed)
    Abstract [en]

    Background: Because of changing food habits that may influence nutritional status it is important, especially in children, reproducibly to describe and analyse the timing and frequency of eating and the composition of different types of eating episodes. Objective: To describe eating patterns of 3-5-year-old Swedish preschool children by analysing 7 day food records using the Food-Based Classification of Eating Episodes (FBCE) model. Design: Food intakes were categorized into four types of "meals" and four types of "snacks", according to their food profile. Complete 7 day weighed and estimated food records for 109 children were processed and analysed. Results: On weekdays the children ate significantly more frequently than on weekend days, having 5.6 and 5.2 eating episodes per day, respectively. More eating episodes were classified as "meals" on weekdays than on weekend days: 72% and 60%, respectively. On average for the whole week, 43% of the daily energy intake was derived from "complete meals" (CM) and 34% from "incomplete meals" (IM). CM contributed significantly more energy and more nutrients, except for calcium, than did IM. In low-quality snacks (LS), sucrose contributed with about one-third of the energy content and the nutrient density was low. Conclusions: The qualitative FBCE model verified nutritional characteristics of the children's diet previously found in the same cohort by the traditional dietary assessment methods. Processing of the dietary data by the model to show the prevalence and temporal distribution of eating episodes appears to be an applicable tool for nutritional screening of children's eating patterns

  • 341.
    Shahim, Pashtun
    et al.
    Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Adiutori, Rocco
    Queen Mary University of London.
    Ladenson, Jack H.
    Washington University School of Medicine, St. Louis, Missouri.
    Macy, Elizabeth H.
    Washington University School of Medicine, St. Louis, Missouri.
    Crimmins, Dan
    Washington University School of Medicine, St. Louis, Missouri.
    Mattsson, Niklas
    UCSF, San Francisco, California.
    Giovannoni, Gavin
    Queen Mary University of London.
    Kallberg, Birgitta
    Sahlgrenska University Hospital, Mölndal.
    Blennow, Kaj
    Sahlgrenska Academy, University of Gothenburg, Mölndal.
    Kuhne, Jens
    Blizard Institute, London.
    Zetterberg, Henrik
    Sahlgrenska Academy, University of Gothenburg, Mölndal.
    Serum neurofilament light protein and visin-like protein-1 in concussed professional ICE hockey players2014In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 10, no 4 uppl., p. P655-Article in journal (Refereed)
  • 342.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Gren, Magnus
    Institute of Neuroscience and Physiology / The Sahlgrenska Academy, Gothenburg.
    Liman, Victor
    Institute of Neuroscience and Physiology / The Sahlgrenska Academy, Gothenburg.
    Andreasson, Ulf
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg.
    Norgren, Niklas
    UmanDiagnostics, Umeå.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Mattsson, Niklas
    Clinical Memory Research Unit, Lund University.
    Andreassen, Niels
    Department of NVS, Karolinska Institute, Center for Alzheimer Research.
    Öst, Martin
    Institute of Clinical Sciences / Sahlgrenska Academy, Gothenburg.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal.
    Nellgård, Bengt
    Institute of Clinical Sciences / Sahlgrenska Academy, Gothenburg.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Serum neurofilament light protein predicts clinical outcome in traumatic brain injury2016In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 12, no 7 Suppl., p. P896-P897Article in journal (Refereed)
  • 343.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Gren, Magnus
    Institute of Neuroscience and Physiology / The Sahlgrenska Academy, Gothenburg.
    Liman, Victor
    Institute of Neuroscience and Physiology / The Sahlgrenska Academy, Gothenburg.
    Andreasson, Ulf
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg.
    Norgren, Niklas
    UmanDiagnostics, Umeå.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Mattsson, Niklas
    Clinical Memory Research Unit, Lund University.
    Andreassen, Niels
    Department of NVS, Karolinska Institute, Center for Alzheimer Research.
    Öst, Martin
    Institute of Clinical Sciences / Sahlgrenska Academy, Gothenburg.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal.
    Nellgård, Bengt
    Institute of Clinical Sciences / Sahlgrenska Academy, Gothenburg.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Serum neurofilament light protein predicts clinical outcome in traumatic brain injury2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 36791Article in journal (Refereed)
    Abstract [en]

    Axonal white matter injury is believed to be a major determinant of adverse outcomes following traumatic brain injury (TBI). We hypothesized that measurement of neurofilament light protein (NF-L), a protein found in long white-matter axons, in blood samples, may serve as a suitable biomarker for neuronal damage in TBI patients. To test our hypotheses, we designed a study in two parts: i) we developed an immunoassay based on Single molecule array technology for quantification of NF-L in blood, and ii) in a proof-of-concept study, we tested our newly developed method on serial serum samples from severe TBI (sTBI) patients (n = 72) and controls (n = 35). We also compared the diagnostic and prognostic utility of NF-L with the established blood biomarker S100B. NF-L levels were markedly increased in sTBI patients compared with controls. NF-L at admission yielded an AUC of 0.99 to detect TBI versus controls (AUC 0.96 for S100B), and increased to 1.00 at day 12 (0.65 for S100B). Importantly, initial NF-L levels predicted poor 12-month clinical outcome. In contrast, S100B was not related to outcome. Taken together, our data suggests that measurement of serum NF-L may be useful to assess the severity of neuronal injury following sTBI.

  • 344.
    Shahim, Pashtun
    et al.
    Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Linemann, Thomas
    Nordic Bioscience Biomarkers & Research, Neurodegenerative Diseases, Herlev.
    Inecki, Dilek
    Nordic Bioscience Biomarkers & Research, Neurodegenerative Diseases, Herlev.
    Karsdal, Morten Asser
    Nordic Bioscience Biomarkers & Research, Neurodegenerative Diseases, Herlev.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska Academy, University of Gothenburg, Mölndal.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Zetterberg, Henrik
    Sahlgrenska Academy, University of Gothenburg, Mölndal, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Henriksen, Kim
    Nordic Bioscience Biomarkers & Research, Neurodegenerative Diseases, Herlev.
    Serum tau fragments predict return to play in concussed professional ice hockey players2016In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, no 22, p. 1995-1999Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The diagnosis of sports-related concussion is mainly based on subjective clinical symptoms and neuropsychological tests. Thus, reliable brain injury biomarkers to assess when it is safe to return to play are highly desirable. The overall objective of this study was to evaluate the utility of two newly described tau fragments for diagnosis and prognosis of sports-related concussions Materials and Methods: This multicenter prospective cohort study involved all 12 teams of the top professional ice hockey league in Sweden. A total of 288 players consented to participate in the study. Thirty-five players sustained concussions, of whom 28 underwent repeated blood samplings at 1, 12, 36, and 144 hours after the trauma, or when the player returned to play (7- > 90 days). RESULTS: There was no significant increase in the levels of tau-A in post-concussion samples compared with preseason values. However, serum levels of tau-C were significantly higher in post-concussion samples compared with preseason. Further, levels of Tau-A correlated with the duration of post-concussive symptoms. DISCUSSION: Tau-A in serum, which is newly discovered biomarker, could be used to predict when it is safe to return to play after a sports-related concussion.

  • 345.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Mattsson, Niklas
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Macy, Elizabeth H.
    Washington University School of Medicine, St. Louis, Missouri.
    Crimmins, Dan
    Washington University School of Medicine, St. Louis, Missouri.
    Ladenson, Jack H.
    Washington University School of Medicine, St. Louis, Missouri.
    Zetterberg, Henrik
    Sahlgrenska Academy, University of Gothenburg, Mölndal, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska Academy, University of Gothenburg, Mölndal.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Serum visinin-like protein-1 in concussed professional ice hockey players2015In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 29, no 7-8, p. 872-876Article in journal (Refereed)
    Abstract [en]

    Primary objective: Visinin-like protein-1 (VILIP-1) has shown potential utility as a biomarker for neuronal injury in cerebrospinal fluid. This study investigated serum VILIP-1 as a diagnostic and prognostic marker in sports-related concussion. Methods: This multi-centre prospective cohort study involved the 12 teams of the professional ice hockey league in Sweden. A total of 288 players consented to participate in the study. Thirty-five players sustained concussions, of whom 28 underwent repeated blood samplings at 1, 12, 36 and 144 hours after the trauma or when the player returned to play (7-90 days). Main outcomes and results: The highest levels of VILIP-1 were measured 1 hour after concussion and the levels decreased during rehabilitation, reaching a minimum level at the 36-hour sampling. However, the levels of serum VILIP-1 at 1 hour after concussion were not significantly higher than pre-season baseline values. Serum levels of VILIP-1 1 hour post-concussion did not correlate with the number of days for the concussion symptoms to resolve. Further, serum levels of VILIP-1 increased after a friendly game in players who were not concussed. Conclusions: These results provide evidence that serum VILIP-1 may not be a useful biomarker for diagnosis and prognosis of sports-related concussion.

  • 346.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal.
    Cerebrospinal fluid biomarkers of neuronal injury in chronic traumatic brain injury2016In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 12, no 7 Suppl., p. P1056-Article in journal (Refereed)
  • 347.
    Shahim, Pashtun
    et al.
    Department of Neurology, Washington University School of Medicine, St. Louis, MO.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Broady, David L.
    Washington University School of Medicine, St. Louis, MO.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal.
    Astroglial activation and altered amyloid metabolism in human repetitive concussive traumatic brain injury2017In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, no 7 (Suppl), p. P216-P217Article in journal (Refereed)
  • 348.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Gustafsson, Bengt
    Capio Artro Clinic, Stockholm.
    Gren, Magnus
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Ärlig, Johan
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Olsson, Martin
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Lehto, Niklas
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Engström, Åsa
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Höglund, Kina
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Portelius, Erik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury2016In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 73, no 11, p. 1308-1315Article in journal (Refereed)
    Abstract [en]

    Importance:

    Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury.

    Objective:

    To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury.

    Design, Settings, and Participants:

    A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging.

    Main Outcomes and Measures:

    Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid.

    Results:

    A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05).

    Conclusions and Relevance:

    Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy.

  • 349.
    Shahim, Pashtun
    et al.
    University of Gothenburg, Sahlgrenska Academy, Institute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, Gothenburg, Sweden. Sahlgrens University Hospital, Neurochem Lab, Molndal, Sweden.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Marklund, Niklas
    Department of Neurology, Skåne University Hospital, Lund University, Sweden.
    Blennow, Kaj
    University of Gothenburg, Sahlgrenska Academy, Institute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, Gothenburg, Sweden. Sahlgrens University Hospital, Neurochem Lab, Molndal, Sweden.
    Zetterberg, Henrik
    University of Gothenburg, Sahlgrenska Academy, Institute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, Gothenburg, Sweden. Sahlgrens University Hospital, Neurochem Lab, Molndal, Sweden. UCL Institute of Neurology, Queen Square. UK Dementia Research Institute.
    Neurofilament light and tau as blood biomarkers for sports-related concussion2018In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, no 20, p. e1780-e1788Article in journal (Refereed)
    Abstract [en]

    Objective To compare neurofilament light (NfL) and tau as blood-based biomarkers for acute sports-related concussion (SRC) and determine whether their concentrations at different time points after the injury are associated with prolonged time to return to play (RTP).

    Methods A total of 288 professional hockey players were followed longitudinally from September 1, 2012, to April 30, 2015. Data collection and biomarker analyses were conducted between 2015 and 2017. Associations were tested between blood concentrations of NfL and tau, and RTP time. Serum concentrations of S100B and neuron-specific enolase (NSE) were also measured for comparison.

    Results Of 288 players, 105 sustained an SRC. Of these, 87 underwent blood sampling 1, 12, 36, and 144 hours after SRC and at the RTP time point. Serum NfL concentrations 1, 12, 36, and 144 hours after SRC were related to prolonged RTP time, and could separate players with RTP >10 days from those with RTP ≤10 days (area under the receiver operating characteristic curve [AUROC] 0.82). Also, serum NfL 144 hours after SRC discriminated players who resigned from the game due to persistent postconcussion symptoms (PCS) from those who returned to play (AUROC 0.89). Plasma tau 1 hour after SRC was related to RTP but less strongly than NfL, while S100B and NSE showed no such associations.

    Conclusion Serum NfL outperformed tau, S100B, and NSE as a biomarker for SRC. From a clinical standpoint, serum NfL may be useful to identify individuals at risk of prolonged PCS, and may aid in biomarker-informed decisions with regard to when RTP should be considered.

  • 350.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Marklund, Niklas
    Uppsala university, Department of Neuroscience and Neurosurgery.
    Höglund, Kina
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Portelius, Erik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Astroglial activation and altered amyloid metabolism in human repetitive concussion2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 15, p. 1400-1407Article in journal (Refereed)
    Abstract [en]

    Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood–brain barrier (BBB) impairment.

    Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25–12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio).

    Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS >1 year. Athletes with PCS >1 year had higher RPQ scores and number of concussions than athletes with PCS <1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS >1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of Aβ40 and Aβ42 than controls. The CSF:serum albumin ratio was unaltered.

    Conclusions: This study suggests that PCS may be associated with biomarker evidence of astroglial activation and β-amyloid (Aβ) dysmetabolism in the brain. There was no clear evidence of Aβ deposition as Aβ40 and Aβ42 were reduced in parallel. The CSF:serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS.

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