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  • 1. A, Borgström
    et al.
    P, Nerfeldt
    Friberg, Danielle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Questionnaire OSA-18 has poor validity compared to polysomnography in pediatric obstructive sleep apnea.2013In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464Article in journal (Refereed)
  • 2.
    Aagaard, Knut E.
    et al.
    Helsingborg Hosp, Sweden; Lund Univ, Sweden.
    Björnsson, Hanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Lunsjö, Karl
    Helsingborg Hosp, Sweden.
    Frobell, Richard
    Lund Univ, Sweden.
    No differences in histopathological degenerative changes found in acute, trauma-related rotator cuff tears compared with chronic, nontraumatic tears2022In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 30, no 7, p. 2521-2527Article in journal (Refereed)
    Abstract [en]

    Purpose Acute trauma-related rotator cuff tears are believed to have better healing potential than chronic tears due to less degenerative changes of the tendons. However, the histopathological condition of tendons from trauma-related tears is not well investigated. The purpose of this study was to explore specific histopathological features in tendons from acute trauma-related full-thickness rotator cuff tears and to compare them to findings in tendons from nontraumatic, chronic tears. Methods In a prospective cohort study, 62 previously asymptomatic patients [14 women, median age 61 years (range 42-75)] with trauma-related full-thickness rotator cuff tears were consecutively included. Arthroscopic repair was performed within 30 (median, IQR 25-37) days after the injury. During surgery, tissue biopsies were harvested from the supraspinatus tendons in 53 (86%) of the patients. In addition, similar biopsies were harvested from 10 patients undergoing surgery for chronic tears without history of trauma. All tissue samples were examined by a well-experienced pathologist under light microscope. Tendon degeneration was determined using the Bonar score whereas immunostaining was used for proliferation (Ki67), inflammation (CD45), apoptosis (p53) and haemosiderin staining to study traces of bleeding. Results The median (IQR) Bonar score for the acute trauma-related biopsies was 10.5 (7.5-14.5) compared to 11 (5-12.8) for the control group with no statistically significant difference between the groups. No statistically significant between-group difference was found for the inflammatory index whereas tendons from patients with trauma-related full-thickness rotator cuff tears had statistically significantly higher apoptosis [3.1 (0.5-8.9) vs. 0.1 (0-1.5), p = 0.003] and proliferation [4.0 (1.8-6.9) vs. 0.4 (0-2.0), p = 0.001) indices than those undergoing surgery for chronic tears. Positive haemosiderin staining was found in 34% of tissue samples from patients with trauma-related tears compared to 10% in the control group (n.s). Conclusion This study suggests that there is no difference with regard to degenerative changes between supraspinatus tendons harvested from patients with acute, trauma-related rotator cuff tears and patients with nontraumatic, chronic tears.

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  • 3.
    Aagaard, Knut E.
    et al.
    Helsingborg Hosp, Sweden; Lund Univ, Sweden.
    Lunsjo, Karl
    Helsingborg Hosp, Sweden; Lund Univ, Sweden.
    Adolfsson, Lars
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Frobell, Richard
    Lund Univ, Sweden.
    Björnsson Hallgren, Hanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Factors associated with healing failure after early repair of acute, trauma-related rotator cuff tears2023In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 32, no 10, p. 2074-2081Article in journal (Refereed)
    Abstract [en]

    Background: Healing failure after rotator cuff repair is a challenging problem. Acute, trauma-related tears are considered a separate entity and are often treated surgically. The aim of this study was to identify factors associated with healing failure in previously asymp-tomatic patients with trauma-related rotator cuff tears treated with early arthroscopic repair. Methods: This study included 62 consecutively recruited patients (23% women; median age, 61 years; age range, 42-75 years) with acute symptoms in a previously asymptomatic shoulder and a magnetic resonance imaging-verified full-thickness rotator cuff tear after shoulder trauma. All patients were offered, and underwent, early arthroscopic repair, during which a biopsy specimen was har-vested from the supraspinatus tendon and analyzed for signs of degeneration. Of the patients, 57 (92%) completed 1-year follow-up and underwent assessment of repair integrity on magnetic resonance images according to the Sugaya classification. Risk factors for heal-ing failure were investigated using a causal-relation diagram where age, body mass index, tendon degeneration (Bonar score), diabetes mellitus, fatty infiltration (FI), sex, smoking, tear location regarding integrity of the rotator cable, and tear size (number of ruptured tendons and tendon retraction) were included and analyzed. Results: Healing failure at 1 year was identified in 37% of patients (n = 21). A high degree of FI of the supraspinatus muscle (P = .01), a tear location including disruption of rotator cable integrity (P = .01), and old age (P = .03) were associated with healing failure. Tendon degeneration as determined by histopathology was not associated with healing failure at 1-year follow-up (P = .63). Conclusion: Older age, increased FI of the supraspinatus muscle, and a tear including disruption of the rotator cable increased the risk of healing failure after early arthroscopic repair in patients with trauma-related full-thickness rotator cuff tears. Level of evidence: Level I; Prospective Cohort Design; Prognosis Study

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  • 4.
    Aahlin, Eirik K
    et al.
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    von Meyenfeldt, Maarten
    Department of Surgery, University Hospital Maastricht, Maastricht, The Netherlands; NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
    Dejong, Cornelius Hc
    Department of Surgery, University Hospital Maastricht, Maastricht, The Netherlands; NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Surgery, Örebro University Hospital, Örebro; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Fearon, Kenneth C
    Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK .
    Lobo, Dileep N
    Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, National Institute for Health Research, Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, UK .
    Demartines, Nicolas
    Hospital of Lausanne (CHUV), Lausanne, Switzerland .
    Revhaug, Arthur
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    Wigmore, Stephen J
    Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK .
    Lassen, Kristoffer
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    Functional recovery is considered the most important target: a survey of dedicated professionals2014In: Perioperative medicine, ISSN 2047-0525, Vol. 3, article id 3:5Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to survey the relative importance of postoperative recovery targets and perioperative care items, as perceived by a large group of international dedicated professionals.

    Methods: A questionnaire with eight postoperative recovery targets and 13 perioperative care items was mailed to participants of the first international Enhanced Recovery After Surgery (ERAS) congress and to authors of papers with a clear relevance to ERAS in abdominal surgery. The responders were divided into categories according to profession and region.

    Results: The recovery targets 'To be completely free of nausea', 'To be independently mobile' and 'To be able to eat and drink as soon as possible' received the highest score irrespective of the responder's profession or region of origin. Equally, the care items 'Optimizing fluid balance', 'Preoperative counselling' and 'Promoting early and scheduled mobilisation' received the highest score across all groups.

    Conclusions: Functional recovery, as in tolerance of food without nausea and regained mobility, was considered the most important target of recovery. There was a consistent uniformity in the way international dedicated professionals scored the relative importance of recovery targets and care items. The relative rating of the perioperative care items was not dependent on the strength of evidence supporting the items.

  • 5. Aalto, Mikko
    et al.
    Kukka, Antti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, SWEDESD - Sustainability Learning and Research Centre. Gävle sjukhus, Region Gävleborg.
    Elmi, Hassan Abdirahman
    Yared, Solomon
    Viskeraalinen leishmaniaasi tunnistamattomana tappavana tautina: [Visceral leishmaniasis as an unrecognized deadly disease]2023In: Duodecim, ISSN 0012-7183, E-ISSN 2242-3281, Vol. 139, no 11, p. 885-891Article in journal (Refereed)
    Abstract [en]

    Visceral leishmaniasis is a disease caused by Leishmania parasites and transmitted by Phlebotomine sandflies. It affects primarily children and is fatal without treatment but curable with early treatment. Its clinical features are prolonged fever, wasting, hepatosplenomegaly and pancytopenia. Doctors have limited knowledge about its diagnostics. This leads to incorrect diagnoses and deaths, and the disease remains unrecognized. To break this vicious circle, active search of the disease is needed also where environmental factors are conductive to its presence, but it has never been reported. We describe discovering new foci of visceral leishmaniasis in Northern Somalia, Somaliland and Tanzania. 

  • 6.
    Aaltonen, Kristina E.
    et al.
    Lund University, Sweden.
    Rosendahl, Ann H.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Malmstrom, Per
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Hartman, Linda
    Lund University, Sweden; Regional Cancer Centre South, Sweden.
    Ferno, Marten
    Lund University, Sweden.
    Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer2014In: BMC Cancer, E-ISSN 1471-2407, Vol. 14, no 794Article in journal (Refereed)
    Abstract [en]

    Background: Resistance towards endocrine therapy is a great concern in breast cancer treatment and may partly be explained by the activation of compensatory signaling pathways. The aim of the present study was to investigate if the insulin-like growth factor-1 receptor (IGF1R) signaling pathway was activated or deregulated in breast cancer patients and to explore if any of the markers were prognostic, with or without adjuvant tamoxifen. This signaling pathway has been suggested to cause estrogen independent cell growth and thus contribute to resistance to endocrine treatment in estrogen receptor (ER) positive breast cancer. Methods: The protein expression of IGF1R, phosphorylated Mammalian Target of Rapamycin (p-mTOR) and phosphorylated S6 ribosomal protein (p-S6rp) were investigated by immunohistochemistry using tissue microarrays in two patient cohorts. Cohort I (N = 264) consisted of mainly postmenopausal women with stage II breast cancer treated with tamoxifen for 2 years irrespective of ER status. Cohort II (N = 206) consisted of mainly medically untreated, premenopausal patients with node-negative breast cancer. Distant disease-free survival (DDFS) at 5 years was used as end-point for survival analyses. Results: We found that lower IGF1R expression was associated with worse prognosis for tamoxifen treated, postmenopausal women (HR = 0.70, 95% CI = 0.52 - 0.94, p = 0.016). The effect was seen mainly in ER-negative patients where the prognostic effect was retained after adjustment for other prognostic markers (adjusted HR = 0.49, 95% CI = 0.29 - 0.82, p = 0.007). Expression of IGF1R was associated with ER positivity (p less than 0.001) in the same patient cohort. Conclusions: Our results support previous studies indicating that IGF1R positivity reflects a well differentiated tumor with low metastatic capacity. An association between lack of IGF1R expression and worse prognosis was mainly seen in the ER-negative part of Cohort I. The lack of co-activation of downstream markers (p-mTOR and p-S6rp) in the IGF1R pathway suggested that the prognostic effect was not due to complete activation of this pathway. Thus, no evidence could be found for a compensatory function of IGF1R signaling in the investigated cohorts.

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  • 7.
    Aam, Stina
    et al.
    Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, NTNU-Norwegian University of Science and Technology, Trondheim, Norway; Department of Geriatric Medicine, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
    Gynnild, Mari Nordbø
    Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, NTNU-Norwegian University of Science and Technology, Trondheim, Norway; Stroke Unit, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
    Munthe-Kaas, Ragnhild
    Department of Medicine, Vestre Viken Hospital Trust, Bærum Hospital, Drammen, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Saltvedt, Ingvild
    Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, NTNU-Norwegian University of Science and Technology, Trondheim, Norway; Department of Geriatric Medicine, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
    Lydersen, Stian
    Department of Mental Health, Faculty of Medicine and Health Science, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
    Knapskog, Anne-Brita
    Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
    Ihle-Hansen, Hege
    Department of Medicine, Vestre Viken Hospital Trust, Bærum Hospital, Drammen, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
    Ellekjær, Hanne
    Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, NTNU-Norwegian University of Science and Technology, Trondheim, Norway; Stroke Unit, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
    Eldholm, Rannveig Sakshaug
    Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, NTNU-Norwegian University of Science and Technology, Trondheim, Norway; Department of Geriatric Medicine, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
    Fure, Brynjar
    Örebro University, School of Medical Sciences. Department of Internal Medicine, Central Hospital, Karlstad, Sweden.
    The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment: The Nor-COAST Study2021In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 12, article id 678794Article in journal (Refereed)
    Abstract [en]

    Introduction: Post-stroke cognitive impairment (PSCI) is common, but evidence on the impact of vascular risk factors is lacking. We explored the association between pre-stroke vascular risk factors and PSCI and studied the course of PSCI.

    Materials and Methods: Vascular risk factors were collected at baseline in stroke survivors (n = 635). Cognitive assessments of attention, executive function, memory, language, and the Montreal Cognitive Assessment (MoCA) were performed at 3 and/or 18 months post-stroke. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). PSCI was measured with global z; MoCA z-score; and z-score of the four assessed cognitive domains. Mixed-effect linear regression was applied with global z, MoCA z-score, and z-scores of the cognitive domains as dependent variables. Independent variables were the vascular risk factors (hypertension, hypercholesterolemia, smoking, diabetes mellitus, atrial fibrillation, coronary heart disease, previous stroke), time, and the interaction between these. The analyses were adjusted for age, education, and sex. There were between 5 and 25% missing data for the variables for PSCI.

    Results: Mean age was 71.6 years (SD 11.7); 42% were females; and the mean NIHSS score at admittance was 3.8 (SD 4.8). Regardless of vascular risk factors, global z, MoCA, and all the assessed cognitive domains were impaired at 3 and 18 months, with MoCA being the most severely impaired. Atrial fibrillation (AF) was associated with poorer language at 18 months and coronary heart disease (CHD) with poorer MoCA at 18 months (LR =12.80, p = 0.002, and LR = 8.32, p = 0.004, respectively). Previous stroke was associated with poorer global z and attention at 3 and 18 months (LR = 15.46, p < 0.001, and LR = 16.20, p < 0.001). In patients without AF, attention improved from 3 to 18 months, and in patients without CHD, executive function improved from 3 to 18 months (LR = 10.42, p < 0.001, and LR = 9.33, p = 0.009, respectively).

    Discussion: Our findings indicate that a focal stroke lesion might be related to pathophysiological processes leading to global cognitive impairment. The poorer prognosis of PSCI in patients with vascular risk factors emphasizes the need for further research on complex vascular risk factor interventions to prevent PSCI.

  • 8. Aanesen, Arthur
    et al.
    Westerbotn, Margareta
    Sophiahemmet University.
    Prospective study of a Swedish infertile cohort 2005-08: population characteristics, treatments and pregnancy rates2014In: Family Practice, ISSN 0263-2136, E-ISSN 1460-2229, Vol. 31, no 3, p. 290-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We here report on results from a prospective study comprising 380 infertile couples undergoing infertility work-up and various treatments for infertility in our clinic. The aim was to investigate the overall birth rate as a result of different treatments, as well as spontaneous pregnancies.

    METHODS: Three hundred and eighty couples were consecutively included between December 2005 and May 2008. All couples underwent a fertility work-up, including hysterosalpingogram, hormonal characterization, clinical examination, screening for infectious diseases and semen analysis. The mean age of the women at the time of inclusion was 33.2 years. The mean duration of infertility prior to inclusion was 1.8 years. And 46.6% (n = 177) of the women had been pregnant prior to their first visit to the clinic and 30.0% (n = 114) had been pregnant earlier in their present relationship.

    RESULTS: As of November 2010, 57.3% (n = 218) of the women had given birth to a child when they were lost to follow up by the study. Spontaneous conception was observed in 11.3% (n = 43) of the women, 14.5% (n = 64) conceived after intrauterine insemination (IUI), 4.2% (n = 16) conceived after ovarian hyperstimulation and ovulation induction (OH/OI) and 28.4% (n = 113) after in vitro fertilization. There were 280 pregnancies and 58 spontaneous abortions (22.3%) in the group. Mean anti-mullerian hormone significantly correlated with antral follicle count and age and was significantly higher in the subgroup that became pregnant after IUI.

    CONCLUSIONS: Spontaneous pregnancies and IUI + OH/OI contributed significantly to the pregnancies observed in the total population. Predictive factors for pregnancy were anti-mullerian hormone in the group undergoing IUI treatment and in the age group ≥38-duration of infertility. Previous pregnancies, body mass index, estradiol, follicle stimulating hormone or having given birth prior to the infertility period were not predictive of pregnancy for the infertile couples in this study.

  • 9.
    Aanestad, Øystein
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Quantitative electromyographic studies of the perineal muscles in normal subjects and patients suffering from anal or urinary incontinence1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of the study were to characterize the interference pattern in perineal muscles in healthy subjects with the use of quantitative EMG techniques, to evaluate if prostatic surgery had any effect on the interference pattern and furthermore to examine the interference pattern in the perineal muscles in patients suffering from urinary or anal incontinence.

    The interference pattern in the perineal muscles was examined with a computerized analysis, the Turns and Amplitude (T/A) analysis, and the innervation pattern of the muscles was examined with single fiber electromyography measuring the fiber density. Reference values were collected from 30 normal subjects. The patient material consisted of 20 males subjected to transurethral prostatectomy (TUR-P), 10 males who underwent radical retropubic prostatectomy (RRP), 20 patients suffering from anal incontinence and 24 women withurinary incontinence.

    T/A analysis of the interference pattern in the perineal muscles in normal subjects showed a significant increase in number of turns/sec and mean amplitude correlating to increasing force but no age-related changes.

    TUR-P and RRP did effect the innervation of the distal urethral sphincter muscle as shown by increased fiber density indicating a peripheral nerve lesion. T/A analysis did not shown any increased activation of the distal urethral sphincter as a compensation for the loss in bladder neck sphincter function but rather signs of decreasedcentral activation.

    Patients with idiopathic faecal incontinence showed signs of impaired innervation of the external anal sphincter muscle. A decreased interference pattern at maximal contraction indicated a reduced central activation of perineal muscles, in particular for patients with partial rupture of the external anal sphincter muscle. The reduced central activation could play a role for the aetiology of faecal incontinence.

    Patients with urinary stress incontinence also showed signs of impaired innervation of the external anal sphincter muscle as well as reduced interference pattern at maximal contraction and during continuous recording of the EMG activity during cystometry. A reduced central activation of the motor units was predicted as one factor involved in the aetiology.

  • 10.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Mobäck, Caroline
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Jakobsson, Sandra
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Germany.
    Hoffmann, Johannes J. M. L.
    Abbott GmbH and Co KG, Germany.
    Iron depletion in blood donors - Have extended erythrocyte and reticulocyte parameters diagnostic utility?2015In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 53, no 1, p. 76-81Article in journal (Refereed)
    Abstract [en]

    Background: Blood donation is associated with iron depletion, but donor iron status is not usually investigated, as such tests are cumbersome and costly. It would therefore be desirable to have simple, fast and inexpensive tests that give information on a donors risk of developing iron depletion. In a pilot study we investigated whether novel erythrocyte and reticulocyte parameters can serve this goal. Methods: In regular blood donors extended red cell parameters were measured using the Abbott CELL-DYN Sapphire hematology analyzer and conventional biochemical tests of iron status. Donors were compared with a regionally matched group of non-donating controls. Results: In the controls, the reference ranges of extended RBC parameters were well comparable to published data. Donors had significantly more microcytic RBC than controls (median 0.9 vs 0.6%), lower serum ferritin concentration (median 43 vs 91 mg/L) and higher soluble transferrin receptor/ferritin index (median 1.60 vs 1.27). Overall 18-28% of the donors were iron depleted. Moreover, 3.3% of donors had iron-restricted erythropoiesis. Microcytic RBC and reticulocyte mean cell hemoglobin content predicted iron depletion with 70% and 64% sensitivities and specificities of 72% and 78%, respectively. When combined these two parameters increased the sensitivity to 82%. Conclusions: Our results in Swedish blood donors confirm a high prevalence of iron depletion, despite iron supplementation used by about half of the donors. Microcytic RBC and MCHr appeared to be helpful in identifying iron-depleted donors, who might benefit from iron supplementation. We recommend larger prospective investigations in order to confirm and extend the findings of this pilot study. (C) 2015 Elsevier Ltd. All rights reserved.

  • 11.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ochala, Julien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Norman, Holly S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Eriksson, Lars I
    Göransson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Chen, Yi-Wen
    Hoffman, Eric P
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model2011In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 24, p. 1334-1350Article in journal (Refereed)
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

  • 12.
    Aarnio, Mikko
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Visualization of Peripheral Pain Generating Processes and Inflammation in Musculoskeletal Tissue using [11C]-D-deprenyl PET2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An objective visualization and quantification of pain-generating processes in the periphery would alter pain diagnosis and represent an important paradigm shift in pain research. Positron emission tomography (PET) radioligand [11C]-D-deprenyl has shown an elevated uptake in painful inflammatory arthritis and whiplash-associated disorder. However, D-Deprenyl’s molecular binding target and uptake mechanism in inflammation and musculoskeletal injuries are still unknown. The present thesis aimed to gain insight into the mechanisms of D-deprenyl binding and uptake and to verify whether pain-associated sites and inflammation in acute musculoskeletal injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET-computed tomography (PET/CT).

    To identify the D-deprenyl binding target, a high-throughput analysis and competitive radioligand binding studies were performed. D-deprenyl inhibited monoamine oxidase A (MAO-A) activity by 55%, MAO-B activity by 99% and angiotensin-converting enzyme (ACE) by 70%, which identified these enzymes as higher-affinity targets. Furthermore, radioligand receptor binding assays pointed favorably towards the concept of MAO-B as the primary target. To investigate the biochemical characteristics of the binding site, we used radioligand binding assays to assess differences in the binding profile in inflamed human synovial membranes exhibiting varying levels of inflammation. D-deprenyl bound to a single, saturable population of membrane-bound protein in synovial membrane homogenates and the level of inflammation correlated with an increase in D-deprenyl binding affinity.

    To verify whether D-deprenyl can visualize pain-generating processes, patients with musculoskeletal injuries were investigated and followed-up with [11C]-D-deprenyl PET/CT. In the study of eight patients with ankle sprain, the molecular aspects of inflammation and tissue injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. The pain coexisted with increased [11C]-D-deprenyl uptake. In the study of 16 whiplash patients, an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self-rated disability.

    To further evaluate D-Deprenyl’s usefulness as a marker of inflammation, three PET tracers were compared in an animal PET/CT study. Preliminary findings showed that [11C]-D-deprenyl had an almost identical uptake pattern when compared with [11C]-L-deprenyl. The two deprenyl enantiomers showed no signs of specific binding or trapping and therefore may not be useful to study further in models of inflammatory pain, surgical pain, or both.

    This thesis demonstrates that D-deprenyl visualizes painful inflammation in musculoskeletal injuries and that the probable underlying mechanism of [11C]-D-deprenyl uptake is binding to MAO.

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  • 13.
    Aarnio, Pauliina
    et al.
    Univ Tampere, Fac Social Sci Global Hlth & Dev, Kalevantie 4, FI-33014 Tampere, Finland;Univ Tampere, Med Sch, Dept Int Hlth, Tampere, Finland.
    Kulmala, Teija
    Univ Tampere, Med Sch, Child Hlth Res Unit, Tampere, Finland;Univ Tampere, Med Sch, Dept Int Hlth, Tampere, Finland.
    Olsson, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Husband's role in handling pregnancy complications in Mangochi District, Malawi: A call for increased focus on community level male involvement2018In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 16, p. 61-66Article in journal (Refereed)
    Abstract [en]

    Objective: The objective of the current study is to provide information about husbands' role in decision-making and healthcare seeking in cases of pregnancy complications in Mangochi district, Malawi with an analysis of qualitative interviews using the concepts of "capital" and "field" from Bourdieu's social field theory. Study design: Twelve husbands and wives who had experienced pregnancy complications and six key informants from a semi-rural area of Mangochi district were interviewed individually. Thematic analysis was conducted based on the concepts of capital and field in Bourdieu's social field theory. Results: Husbands have significant economic and symbolic capital in decisions about healthcare seeking during instances of pregnancy complications as a result of their roles as father, head of the household and main income earner. Lack of money is the only acceptable reason for husbands to deny their wives healthcare. Husbands have limited access to knowledge of maternal health, which can compromise their decisions about seeking healthcare. Joint decision-making within families can be bypassed to allow for prompt healthcare seeking in emergencies. Conclusions: Husbands are important decision makers regarding seeking healthcare for pregnancy complications because of their economic and symbolic power and despite their limited access to knowledge of maternal health. Maternal healthcare seeking practices would benefit from wives gaining an empowered role as well as improved knowledge of maternal health among husbands.

  • 14.
    Aarnio, Riina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Self-sampling for HPV testing in primary cervical screening: Including clinical and health economic aspects2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Persistent infection with high-risk human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. HPV testing has higher sensitivity for high-grade cervical intraepithelial neoplasia (CIN2+) than cytology, resulting in more effective screening. As HPV testing also offers an opportunity for self-sampling, it could serve as an even more effective and cost-effective method of cervical screening.

    First, we compared repeated self-sampling for HPV testing with Pap smear cytology in detection of CIN2+ in primary cervical screening for women aged 30–49 years (n=36 390). We found a more than twofold higher detection rate of CIN2+ and a fourfold higher detection rate of CIN2 with self-sampling compared with cytology. However, no difference was seen between the arms in the detection rate of CIN3+. It thus seems that CIN is detected at an earlier stage with self-sampling than with cytology, but the impact of this needs to be further explored.

    Second, as management of HPV-positive women with normal cytology results is a challenge, we wanted to evaluate the proportion of cases of histological CIN2+ in these women. In this prospective study we performed LEEP and found that 15% (6/40) of the women had undetected CIN2+. These findings can be used in counseling women about the risk of cervical cancer and helping clinicians in decisions on management.

    Third, we performed a cost-effectiveness analysis on the same study population as in Study I. Self-sampling for HPV testing resulted in a higher participation rate and more detected cases of CIN2+ at a lower cost and was regarded as more cost-effective than Pap smear cytology in cervical screening. These results can guide policy-makers when planning future screening programs.

    Fourth, we compared self-sampling with sampling by medical professionals for HPV testing in detection of CIN2+, using a combination of an FTA card as storage medium and a PCR-based HPV test (hpVIR) in women aged 30–60 years (n=11 951). No difference in the detection rates of histological CIN2+ was found between the arms.

    Taken together, self-sampling resulted in a higher participation rate than sampling by medical professionals in cervical screening and that triage with repeated self-sampling resulted in high compliance and detection rate of CIN2+. As repeated self-sampling for HPV testing was also cost-effective, it could serve as an attractive alternative in the development of future cervical screening programs. More research is needed on how to refine the management of HPV-positive women by self-sampling only.

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  • 15.
    Aarnio, Riina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Isacson, Isabella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sanner, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Gustavsson, Inger M.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+: a randomized study2021In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 148, no 12, p. 3051-3059Article in journal (Refereed)
    Abstract [en]

    Primary screening with human papillomavirus (HPV) test is more effective in reducing cervical cancer incidence than cytology and it also offers the opportunity to self-sample. We conducted a randomized study to compare vaginal self-sampling with cervical sampling by medical professionals for HPV testing concerning prevalence of HPV and detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in primary screening. In total, 11 951 women aged 30-60 years were randomized into two groups, 5961 for self-sampling (SS arm) and 5990 for sampling by medical professionals (SMP arm). Sampling was performed with a RoversViba-brush in the SS arm and a cytobrush in the SMP arm. All samples were applied to an indicating FTA elute card and analyzed for HPV using a clinically validated real-time PCR test (hpVIR). All HPV-positive women performed repeated sampling about 6 months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. The prevalence of HPV in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (P = .255). The prevalence of CIN2+ per 1000 screened women was 17 (43/2466 × 1000) (95%CI 13-24) in the SS arm and 21 (32/1519 × 1000) (95%CI 15-30) in the SMP arm. For CIN3+, the prevalence per 1000 screened women was 14 (35/2466 × 1000) (95%CI 10-20) in the SS arm and 15 (23/1519 × 1000) (95%CI 10-23) in the SMP arm. In conclusion, self-sampling and sampling by medical professionals showed the same prevalence of HPV and detection rate of CIN2+ and CIN3+ in histology.

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  • 16.
    Aarnio, Riina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Wikström, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Gustavsson, Inger M.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Diagnostic excision of the cervix in women over 40 years with human papilloma virus persistency and normal cytology2019In: European journal of obstetrics & gynecology and reproductive biology: X, ISSN 2590-1613, Vol. 3, article id 100042Article in journal (Refereed)
    Abstract [en]

    Objective: Persistent infection with human papillomavirus (HPV) is recognized as the main risk factor of cervical cancer. Investigation via cytology and colposcopy have lower sensitivity than HPV testing in the diagnosis of high-grade cervical intraepithelial neoplasia (CIN2+). Despite normal cytology and colposcopy findings women with persistent HPV infection have an increased risk of CIN2+. The aim of the study was to evaluate the proportion of histologically confirmed CIN2+ in women with persistent HPV infection and normal Pap smears.

    Study design: From April 2013 until March 2016 we prospectively recruited 91 women over 40 years with persistent HPV infection without any abnormalities in cytology. Of these, 40 women attended a gynecological examination including an HPV test, Pap smear, endocervical cytology, colposcopy with biopsies and diagnostic loop electrosurgical excision procedure (LEEP). Biopsy and LEEP samples were subjected to histological examination.

    Results: CIN2+ was verified by histological examination of the LEEP sample in 6/40 (15%) of the women. All the cytological samples were normal and none of the biopsies confirmed CIN2+. Only 19/40 women still had a persistent HPV infection at the study visit. None of the 21/40 women who had cleared their HPV infection at the study visit had CIN2+ in histology of the LEEP sample.

    Conclusions: A persistent HPV infection needs to be monitored despite normal Pap smears, since 6/40 (15%) women older than 40 years, was revealed to have an undiagnosed CIN2+ when LEEP was performed. Counseling women regarding the risk of cervical cancer and the expected effect of an eventual LEEP can help them to make an optimal informed choice.

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  • 17.
    Aarnio, Riina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Östensson, Ellinor
    Karolinska Institutet.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Gustavsson, Inger M.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study2020In: BMC Cancer, E-ISSN 1471-2407, Vol. 20, no 1, article id 645Article in journal (Other academic)
    Abstract [en]

    Background

    Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening.

    Methods

    A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36 390 women aged 30–49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17 997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18 393, Pap smear arm).

    Results

    Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 228 642 vs. € 781 139). 

    Conclusions

    This study projected that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening.

     

  • 18.
    Aarnivala, Henri
    et al.
    Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland..
    Harila-Saari, Arja H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatric oncological and neurological research.
    Niinimaki, Riitta
    Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland..
    Reply to Ian J. Cohen2022In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 30, no 3, p. 1901-1902Article in journal (Other academic)
  • 19.
    Aarnivala, Henri
    et al.
    Univ Oulu, Oulu Univ Hosp, Dept Children & Adolescents, Kajaanintie 52, SF-90220 Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Kajaanintie 52, SF-90220 Oulu, Finland.
    Pokka, Tytti
    Univ Oulu, Oulu Univ Hosp, Dept Children & Adolescents, Kajaanintie 52, SF-90220 Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Kajaanintie 52, SF-90220 Oulu, Finland.
    Soininen, Riina
    Univ Oulu, Oulu Univ Hosp, Dept Children & Adolescents, Kajaanintie 52, SF-90220 Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Kajaanintie 52, SF-90220 Oulu, Finland.
    Mottonen, Merja
    Univ Oulu, Oulu Univ Hosp, Dept Children & Adolescents, Kajaanintie 52, SF-90220 Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Kajaanintie 52, SF-90220 Oulu, Finland.
    Harila-Saari, Arja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Niinimaki, Riitta
    Univ Oulu, Oulu Univ Hosp, Dept Children & Adolescents, Kajaanintie 52, SF-90220 Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Kajaanintie 52, SF-90220 Oulu, Finland.
    Trends in age- and sex-adjusted body mass index and the prevalence of malnutrition in children with cancer over 42 months after diagnosis: a single-center cohort study2020In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 179, no 1, p. 91-98Article in journal (Refereed)
    Abstract [en]

    The adequate nutritional status of pediatric cancer patients is particularly important to enable them to cope with the demands of the disease and its treatment and to maintain normal growth. Malnutrition and obesity have both been associated with reduced survival and increased drug toxicity. We investigated trends in the age- and sex-adjusted body mass index (ISO-BMI) and the prevalence of malnutrition in a Finnish cohort of 139 consecutive children receiving chemotherapy for cancer, with a follow-up period of 42 months after diagnosis. In total, 28% (39/139) of the patients experienced malnutrition (ISO-BMI < 17 or > 10% weight loss), and 12% (16/139) had a nasogastric tube or underwent gastrostomy. Patients with acute or chronic myeloid leukemia (5/10), central nervous system (CNS) tumors (5/13), or solid tumors (13/31) most frequently suffered from malnutrition. There was a significant increase in the ISO-BMI of patients with acute lymphoblastic leukemia (ALL) (+ 2.1 kg/m(2)) and lymphomas (+ 2.4 kg/m(2)) during the first 6 months, and the ISO-BMI of patients with ALL remained higher at 42 months compared to baseline (+ 1.9 kg/m(2)). Conclusion: The cumulative incidence of malnutrition in Finnish pediatric cancer patients is comparable to that reported in other populations. The nutritional status of patients with acute myeloid leukemia, CNS tumors, or solid tumors should be monitored with extra care to facilitate early intervention in the case of impending malnutrition.

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  • 20. Aarseth, Espen
    et al.
    Bean, Anthony M.
    Boonen, Huub
    Carras, Michelle Colder
    Coulson, Mark
    Das, Dimitri
    Deleuze, Jory
    Dunkels, Elza
    Umeå University, Faculty of Social Sciences, Department of applied educational science.
    Edman, Johan
    Ferguson, Christopher J.
    Haagsma, Maria C.
    Bergmark, Karin Helmersson
    Hussain, Zaheer
    Jansz, Jeroen
    Kardefelt-Winther, Daniel
    Kutner, Lawrence
    Markey, Patrick
    Nielsen, Rune Kristian Lundedal
    Prause, Nicole
    Przybylski, Andrew
    Quandt, Thorsten
    Schimmenti, Adriano
    Starcevic, Vladan
    Stutman, Gabrielle
    Van Looy, Jan
    Van Rooij, Antonius J.
    Scholars' open debate paper on the World Health Organization ICD-11 Gaming Disorder proposal2017In: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 6, no 3, p. 267-270Article in journal (Other academic)
    Abstract [en]

    Concerns about problematic gaming behaviors deserve our full attention. However, we claim that it is far from clear that these problems can or should be attributed to a new disorder. The empirical basis for a Gaming Disorder proposal, such as in the new ICD-11, suffers from fundamental issues. Our main concerns are the low quality of the research base, the fact that the current operationalization leans too heavily on substance use and gambling criteria, and the lack of consensus on symptomatology and assessment of problematic gaming. The act of formalizing this disorder, even as a proposal, has negative medical, scientific, public-health, societal, and human rights fallout that should be considered. Of particular concern are moral panics around the harm of video gaming. They might result in premature application of diagnosis in the medical community and the treatment of abundant false-positive cases, especially for children and adolescents. Second, research will be locked into a confirmatory approach, rather than an exploration of the boundaries of normal versus pathological. Third, the healthy majority of gamers will be affected negatively. We expect that the premature inclusion of Gaming Disorder as a diagnosis in ICD-11 will cause significant stigma to the millions of children who play video games as a part of a normal, healthy life. At this point, suggesting formal diagnoses and categories is premature: the ICD-11 proposal for Gaming Disorder should be removed to avoid a waste of public health resources as well as to avoid causing harm to healthy video gamers around the world.

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  • 21.
    Aarts, Clara
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Exclusive breastfeeding-Does it make a difference?: A longitudinal, prospective study of daily feeding practices, health and growth in a sample of Swedish infants2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The concept of exclusive breastfeeding in relation to daily feeding practices and to health and growth of infants in an affluent society was examined. In a descriptive longitudinal prospective study 506 mother-infant pairs were followed from birth through the greater part of the first year. Feeding was recorded daily, and health and growth were recorded fortnightly.

    Large individual variations were seen in breastfeeding patterns. A wide discrepancy between the exclusive breastfeeding rates obtained from "current status" data and data "since birth" was found.

    Using a strict definition of exclusive breastfeeding from birth and taking into account the reasons for giving complementary feeding, the study showed that many exclusively breastfed infants had infections early in life, the incidence of which increased with age, despite continuation of exclusive breastfeeding. However, truly exclusively breastfed infants seem less likely to suffer infections than infants who receive formula in addition to breast milk. Increasing formula use was associated with an increasing likelihood of suffering respiratory illnesses. The growth of exclusively breastfed infants was similar to that of infants who were not exclusively breastfed.

    The health of newborn infants during the first year of life was associated with factors other than feeding practices alone. Some of these factors may be prenatal, since increasing birth weight was associated with an increasing likelihood of having respiratory symptoms, even in exclusively breastfed infants. However, exclusive breastfeeding was shown to be beneficial for the health of the infant even in an affluent society.

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  • 22.
    Aas, Kirsti
    et al.
    Consultant Urological Surgeon and Associate Professor, Akershus University Hospital, Norway; Faculty of Medicine, University of Oslo, Norway.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Consultant Urological Surgeon and Associate Professor, Norrlands University Hospital, Umeå, Sweden.
    Long-term patient follow-up should be routinely implemented in radiotherapy units to detect late adverse effects after cancer treatment2023In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 58, p. 30-31Article in journal (Other academic)
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  • 23.
    Aasa, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Norrlandsklinikens hälsocentral, Umeå, Sweden.
    Berglund, Lars
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Michaelson, Peter
    Luleå Tekniska Universitet, Institutionen för hälsovetenskap, Avdelningen för hälsa och rehabilitering, Fysioterapi.
    Aasa, Ulrika
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Individualized low-load motor control exercises and education versus a high-load lifting exercise and education to improve activity, pain intensity, and physical performance in patients with low back pain: a randomized controlled trial2015In: Journal of Orthopaedic and Sports Physical Therapy, ISSN 0190-6011, E-ISSN 1938-1344, Vol. 45, no 2, p. 77-85Article in journal (Refereed)
    Abstract [en]

    Study Design Randomized controlled trial. Background Low back pain is a common disorder. Patients with low back pain frequently have aberrant and pain-provocative movement patterns that often are addressed with motor control exercises. Objective To compare the effects of low-load motor control (LMC) exercise and those of a high-load lifting (HLL) exercise. Methods Seventy participants with recurrent low back pain, who were diagnosed with nociceptive mechanical pain as their dominating pain pattern, were randomized to either LMC or HLL exercise treatments. Participants were offered 12 treatment sessions over an 8-week period. All participants were also provided with education regarding pain mechanisms. Methods Participants were assessed prior to and following treatment. The primary outcome measures were activity (the Patient-Specific Functional Scale) and average pain intensity over the last 7 days (visual analog scale). The secondary outcome measure was a physical performance test battery that included 1 strength, 3 endurance, and 7 movement control tests for the lumbopelvic region. Results Both interventions resulted in significant within-group improvements in pain intensity, strength, and endurance. The LMC group showed significantly greater improvement on the Patient-Specific Functional Scale (4.2 points) compared with the HLL group (2.5 points) (P<.001). There were no significant between-group differences in pain intensity (P = .505), strength, and 1 of the 3 endurance tests. However, the LMC group showed an increase (from 2.9 to 5.9) on the movement control test subscale, whereas the HLL group showed no change (from 3.9 to 3.1) (P<.001). Conclusion An LMC intervention may result in superior outcomes in activity, movement control, and muscle endurance compared to an HLL intervention, but not in pain intensity, strength, or endurance.

  • 24.
    Aasa, Jenny
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Granath, Fredrik
    Törnqvist, Margareta
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Cancer risk estimation of glycidol based on rodent carcinogenicity studies, a multiplicative risk model and in vivo dosimetry2019In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 128, p. 54-60Article in journal (Refereed)
    Abstract [en]

    Here we evaluate a multiplicative (relative) risk model for improved cancer risk estimation of genotoxic compounds. According to this model, cancer risk is proportional to the background tumor incidence and to the internal dose of the genotoxic compound. Furthermore, the relative risk coefficient per internal dose is considered to be approximately the same across tumor sites, sex, and species. In the present study, we demonstrate that the relative risk model is valid for cancer risk estimation of glycidol, a common food contaminant. Published tumor data from glycidol carcinogenicity studies in mice and rats were evaluated in combination with internal dose estimates from hemoglobin adduct measurements in blood from mice and rats treated with glycidol in short-term studies. A good agreement between predicted and observed tumor incidence in responding sites was demonstrated in the animals, supporting a relative risk coefficient that is independent of tumor site, sex, and species. There was no significant difference between the risk coefficients for mice (5.1% per mMh) and rats (5.4% per mMh) when considering internal doses of glycidol. Altogether, this mechanism-based risk model gives a reliable risk coefficient, which then was extrapolated to humans considering internal dose, and background cancer incidence.

  • 25. Aasa, M
    et al.
    Dellborg, M
    Herlitz, Johan
    [external].
    Svensson, L
    Grip, L
    Risk Reduction for Cardiac Events After Primary Coronary Intervention Compared With Thrombolysis for Acute ST-Elevation Myocardial Infarction (Five-Year Results of the Swedish Early Decision Reperfusion Strategy [SWEDES] Trial)2010In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 106, no 12, p. 1685-1691Article in journal (Refereed)
    Abstract [en]

    Primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction compares favorably to thrombolysis. In previous studies the benefit has been restricted to the early postinfarction period with no additional risk decrease beyond this period. Long-term outcome after use of third-generation thrombolytics and modern adjunctive pharmaceutics in the 2 treatment arms has not been investigated. This study was conducted to compare 5-year outcome after updated regimens of PPCI or thrombolysis. Patients with ST-elevation myocardial infarction were randomized to enoxaparin and abciximab followed by PPCI (n = 101) or enoxaparin followed by reteplase (n = 104), with prehospital initiation of therapy in 42% of patients. Data on survival and major cardiac events were obtained from Swedish national registries after 5.3 years. PPCI resulted in a better outcome with respect to the composite of death or recurrent myocardial infarction (hazard ratio 0.54, confidence interval 0.31 to 0.95) compared to thrombolysis. This was attributed to a significant decrease in cardiac deaths (hazard ratio 0.16, confidence interval 0.04 to 0.74). The difference evolved continuously over the 5-year follow-up. After adjustment for covariates, a significant benefit remained with respect to cardiac death or recurrent infarction but not for the composite of total survival or recurrent myocardial infarction (p = 0.07). The observed differences were not seen in patients in whom therapy was initiated in the prehospital phase. In conclusion, PPCI in combination with enoxaparin and abciximab compares favorably to thrombolysis in combination with enoxaparin with a risk decrease that stretches beyond the early postinfarction period. Prehospital thrombolysis may, however, match PPCI in long-term outcome.

  • 26.
    Aasa, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lundell, Sara
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Aasa, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Norrlandskliniken, Umeå, Sweden.
    Westerståhl, Maria
    Institutionen för laboratoriemedicin, Karolinska institutet.
    Physical Activity Might Be of Greater Importance for Good Spinal Control Than If You Have Had Pain or Not: A Longitudinal Study2015In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 40, no 24, p. 1926-1933Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN: Longitudinal design. A cohort followed in 3 waves of data collection.

    OBJECTIVE: The aim of the study was to describe the relationships between the performance of 2 tests of spinal control at the age of 52 years and low back pain, physical activity level, and fitness earlier in life, as well as to describe the cross-sectional relationships between these measures.

    SUMMARY OF BACKGROUND DATA: Altered spinal control has been linked to pain; however, other stimuli may also lead to inability to control the movements of the spine.

    METHODS: Participants answered questions about physical activity and low back pain, and performed physical fitness tests at the age of 16, 34, and 52 years. The fitness test battery included tests of endurance in the back and abdominal muscles, a submaximal bicycle ergometer test to estimate maximal oxygen uptake, and measurements of hip flexion, thoracic spine flexibility, and anthropometrics. Two tests were aggregated to a physical fitness index. At the age of 52, also 2 tests of spinal control, the standing Waiter's bow (WB) and the supine double leg lower (LL) were performed.

    RESULTS: Logistic regression analyses showed that higher back muscle endurance at the age of 34 years could positively predict WB performance at 52 years and higher physical fitness at the age of 34 could positively predict LL performance at 52 years. Regarding cross-sectional relationships, an inability to perform the WB correctly was associated with lower physical fitness, flexibility and physical activity, and larger waist circumference. An inability to correctly perform the LL was associated with lower physical fitness. One-year prevalence of pain was not significantly associated with WB or LL test performance.

    CONCLUSION: An active life resulting in higher physical fitness is related to better spinal control in middle-aged men and women. This further strengthens the importance of physical activity throughout the life span.

    LEVEL OF EVIDENCE: 3.

  • 27.
    Aasa, Ulrika
    et al.
    Umeå universitet.
    Wiitavaara, Birgitta
    University of Gävle, Faculty of Health and Occupational Studies, Department of Occupational and Public Health Sciences, Occupational health science. University of Gävle, Centre for Musculoskeletal Research.
    Personalens hälsa och arbetsmiljö2016In: Prehospital akutsjukvård / [ed] Björn-Ove Suserud, Lars Lundberg, Stockholm: Liber, 2016, 2, p. 72-79Chapter in book (Other academic)
  • 28.
    Aase, Audun
    et al.
    Norwegian Institute Public Heatlh, Norway.
    Hajdusek, Ondrej
    Academic Science Czech Republic, Czech Republic.
    Oines, Oivind
    Norwegian Vet Institute, Norway.
    Quarsten, Hanne
    Sorlandet Hospital Health Enterprise, Norway.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Herstad, Tove K.
    Norwegian Institute Public Heatlh, Norway.
    Kjelland, Vivian
    University of Agder, Norway; Sorlandet Hospital Health Enterprise, Norway.
    Sima, Radek
    Academic Science Czech Republic, Czech Republic.
    Jalovecka, Marie
    Academic Science Czech Republic, Czech Republic.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Aaberge, Ingeborg S.
    Norwegian Institute Public Heatlh, Norway.
    Validate or falsify: Lessons learned from a microscopy method claimed to be useful for detecting Borrelia and Babesia organisms in human blood2016In: INFECTIOUS DISEASES, ISSN 2374-4235, Vol. 48, no 6, p. 411-419Article in journal (Refereed)
    Abstract [en]

    Background A modified microscopy protocol (the LM-method) was used to demonstrate what was interpreted as Borrelia spirochetes and later also Babesia sp., in peripheral blood from patients. The method gained much publicity, but was not validated prior to publication, which became the purpose of this study using appropriate scientific methodology, including a control group. Methods Blood from 21 patients previously interpreted as positive for Borrelia and/or Babesia infection by the LM-method and 41 healthy controls without known history of tick bite were collected, blinded and analysed for these pathogens by microscopy in two laboratories by the LM-method and conventional method, respectively, by PCR methods in five laboratories and by serology in one laboratory. Results Microscopy by the LM-method identified structures claimed to be Borrelia- and/or Babesia in 66% of the blood samples of the patient group and in 85% in the healthy control group. Microscopy by the conventional method for Babesia only did not identify Babesia in any samples. PCR analysis detected Borrelia DNA in one sample of the patient group and in eight samples of the control group; whereas Babesia DNA was not detected in any of the blood samples using molecular methods. Conclusions The structures interpreted as Borrelia and Babesia by the LM-method could not be verified by PCR. The method was, thus, falsified. This study underlines the importance of doing proper test validation before new or modified assays are introduced.

  • 29.
    Aasebö, Kristine Ö.
    et al.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mezheyeuski, Artur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Eide, Geir Egil
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Ctr Clin Res, Bergen, Norway.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sorbye, Halfdan
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients2019In: Cancer Medicine, E-ISSN 2045-7634, Vol. 8, no 7, p. 3623-3635Article in journal (Refereed)
    Abstract [en]

    Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted.

    Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated.

    Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005).

    Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).

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  • 30. Aasebø, Kristine
    et al.
    Bruun, Jarle
    Bergsland, Christian H
    Nunes, Luís
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eide, Geir Egil
    Pfeiffer, Per
    Dahl, Olav
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lothe, Ragnhild A
    Sorbye, Halfdan
    Prognostic role of tumour-infiltrating lymphocytes and macrophages in relation to MSI, CDX2 and BRAF status: a population-based study of metastatic colorectal cancer patients2022In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 126, no 1, p. 48-56Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tumour-infiltrating CD3, CD8 lymphocytes and CD68 macrophages are associated with favourable prognosis in localised colorectal cancer, but the effect in metastatic colorectal cancer (mCRC) is not established.

    METHODS: A Scandinavian population-based cohort of non-resectable mCRC patients was studied. Tissue microarrays (n = 460) were stained with CD3, CD8 and CD68 using fluorescence-based multiplex immunohistochemistry. Associations with clinicopathological variables, overall survival (OS) and progression-free survival were estimated.

    RESULTS: Two-thirds of microsatellite instable (MSI) and one-fourth of microsatellite stable (MSS) tumours displayed the highest quartile density of CD8. For CD3 high vs low cases, median OS was 20 vs 16 months (HR: 0.76, 95% CI: 0.59, 0.76, p = 0.025) with 3-year OS of 27 vs 13%. For CD68 high vs low cases, median OS was 23 vs 15 months (HR: 0.69, 95% CI: 0.54, 0.88, p = 0.003) with 3-year OS of 28 vs 12%. MSI, BRAF mutation and CDX2 loss were negative prognostic markers independent of tumour immune infiltration.

    CONCLUSIONS: In mCRC, high lymphocyte infiltration was found in proportions of MSI and MSS tumours-potential subgroups of immunotherapy response. Tumour-infiltrating CD3 lymphocytes and CD68 macrophages were associated with median and long-term survival. MSI was a significant negative prognostic marker despite high immunogenicity.

  • 31.
    Aaseth, Jan
    et al.
    Innlandet Hosp Trust, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Alehagen, Urban
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Coenzyme Q(10) supplementation - In ageing and disease2021In: Mechanisms of Ageing and Development, ISSN 0047-6374, E-ISSN 1872-6216, Vol. 197, article id 111521Article in journal (Refereed)
    Abstract [en]

    Coenzyme Q(10) (CoQ(10)) is an essential component of the mitochondrial electron transport chain. It is also an antioxidant in cellular membranes and lipoproteins. All cells produce CoQ(10) by a specialized cytoplasmatic-mitochondrial pathway. CoQ(10) deficiency can result from genetic failure or ageing. Some drugs including statins, widely used by inter alia elderly, may inhibit endogenous CoQ(10) synthesis. There are also chronic diseases with lower levels of CoQ(10) in tissues and organs. High doses of CoQ(10) may increase both circulating and intracellular levels, but there are conflicting results regarding bioavailability. Here, we review the current knowledge of CoQ(10) biosynthesis and primary and acquired CoQ(10) deficiency, and results from clinical trials based on CoQ(10) supplementation. There are indications that supplementation positively affects mitochondrial deficiency syndrome and some of the symptoms of ageing. Cardiovascular disease and inflammation appear to be alleviated by the antioxidant effect of CoQ(10). There is a need for further studies and well-designed clinical trials, with CoQ(10) in a formulation of proven bioavailability, involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ(10) treatment in neurodegenerative disorders, as well as in metabolic syndrome and its complications.

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  • 32.
    Aaseth, Jan
    et al.
    Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, N-2624 Lillehammer, Norway.
    Alexander, Jan
    Norwegian Institute of Public Health, P.O. Box 222, N-0213 Oslo, Norway.
    Alehagen, Urban
    Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
    Tinkov, Alexey
    IM Sechenov First Moscow State Medical University (Sechenov University), Bolshaya Pirogovskaya St., 2-4, 119146 Moscow, Russia.
    Skalny, Anatoly
    IM Sechenov First Moscow State Medical University (Sechenov University), Bolshaya Pirogovskaya St., 2-4, 119146 Moscow, Russia.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Crisponi, Guido
    Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato-Cagliari, Italy.
    Nurchi, Valeria Marina
    Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato-Cagliari, Italy.
    The Aging Kidney-As Influenced by Heavy Metal Exposure and Selenium Supplementation2021In: Biomolecules, E-ISSN 2218-273X, Vol. 11, no 8, article id 1078Article in journal (Refereed)
    Abstract [en]

    The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50-60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance.

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  • 33.
    Aaseth, Jan
    et al.
    Innlandet Hosp, Norway; Inland Norway Univ Appl Sci, Norway.
    Ellefsen, Stian
    Inland Norway Univ Appl Sci, Norway.
    Alehagen, Urban
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sundfor, Tine M.
    Oslo Univ Hosp, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Diets and drugs for weight loss and health in obesity: An update2021In: Biomedicine and Pharmacotherapy, ISSN 0753-3322, E-ISSN 1950-6007, Vol. 140, article id 111789Article, review/survey (Refereed)
    Abstract [en]

    Numerous combinations of diets and pharmacological agents, including lifestyle changes, have been launched to treat obesity. There are still ambiguities regarding the efficacies of different approaches despite many clinical trials and the use of animal models to study physiological mechanisms in weight management and obesity comorbidities, Here, we present an update on promising diets and pharmacological aids. Literature published after the year 2005 was searched in PubMed, Medline and Google scholar. Among recommended diets are low-fat (LF) and low-carbohydrate (LC) diets, in addition to the Mediterranean diet and the intermittent fasting approach, all of which presumably being optimized by adequate contents of dietary fibers. A basic point for weight loss is to adopt a diet that creates a permanently negative and acceptable energy balance, and prolonged dietary adherence is a crucial factor. As for pharmacological aids, obese patients with type 2 diabetes or insulin resistance seem to benefit from LC diet combined with a GLP-1 agonist, e.g. semaglutide, which may improve glycemic control, stimulate satiety, and suppress appetite. The lipase inhibitor orlistat is still used to maintain a low-fat approach, which may be favorable e.g. in hypercholesterolemia. The bupropion-naltrexone-combination appears promising for interruption of the vicious cycle of addictive over-eating. Successful weight loss seems to improve almost all biomarkers of obesity comorbidities. Until more support for specific strategies is available, clinicians should recommend an adapted lifestyle, and when necessary, a drug combination tailored to individual needs and comorbidities. Different diets may change hormonal secretion, gut-brain signaling, and influence hunger, satiety and energy expenditure. Further research is needed to clarify mechanisms and how such knowledge can be used in weight management.

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  • 34.
    Aaseth, Jan O.
    et al.
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Alehagen, Urban
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Opstad, Trine Baur
    Oslo Univ Hosp Ullevaal, Norway; Univ Oslo, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Vitamin K and Calcium Chelation in Vascular Health2023In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 12, article id 3154Article, review/survey (Refereed)
    Abstract [en]

    The observation that the extent of artery calcification correlates with the degree of atherosclerosis was the background for the alternative treatment of cardiovascular disease with chelator ethylenediamine tetraacetate (EDTA). Recent studies have indicated that such chelation treatment has only marginal impact on the course of vascular disease. In contrast, endogenous calcium chelation with removal of calcium from the cardiovascular system paralleled by improved bone mineralization exerted, i.e., by matrix Gla protein (MGP) and osteocalcin, appears to significantly delay the development of cardiovascular diseases. After post-translational vitamin-K-dependent carboxylation of glutamic acid residues, MGP and other vitamin-K-dependent proteins (VKDPs) can chelate calcium through vicinal carboxyl groups. Dietary vitamin K is mainly provided in the form of phylloquinone from green leafy vegetables and as menaquinones from fermented foods. Here, we provide a review of clinical studies, addressing the role of vitamin K in cardiovascular diseases, and an overview of vitamin K kinetics and biological actions, including vitamin-K-dependent carboxylation and calcium chelation, as compared with the action of the exogenous (therapeutic) chelator EDTA. Consumption of vitamin-K-rich foods and/or use of vitamin K supplements appear to be a better preventive strategy than EDTA chelation for maintaining vascular health.

  • 35.
    Aass, Lisbeth Kjelsrud
    et al.
    Department of Health Sciences, Faculty of Medicine and Health Sciences (MH), Norwegian University of Science and Technology (NTNU), Gjøvik, Norway.
    Skundberg-Kletthagen, Hege
    Department of Health Sciences, Faculty of Medicine and Health Sciences (MH), Norwegian University of Science and Technology (NTNU), Gjøvik, Norway.
    Schröder, Agneta
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Health Sciences, Faculty of Medicine and Health Sciences (MH), Norwegian University of Science and Technology (NTNU), Gjøvik, Norway.
    Moen, Øyfrid Larsen
    Department of Health Sciences, Faculty of Medicine and Health Sciences (MH), Norwegian University of Science and Technology (NTNU), Gjøvik, Norway.
    It's Not a Race, It's a Marathon!: Families Living with a Young Adult Suffering from Mental Illness2021In: Issues in Mental Health Nursing, ISSN 0161-2840, E-ISSN 1096-4673, Vol. 42, no 1, p. 15-23Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to explore families' perceptions of everyday life when living with a young adult suffering from mental illness. Findings include: 1) Families balance between letting go and enabling the young adult to become independent while remaining close to help him/her complete education, work and have a social life. 2) Young adults try to deal with symptoms of mental illness by themselves and not be a burden, although longing for family members to understand them and the situation. 3) Healthcare professionals still hold back information although young adults have consented to giving family members insight.

  • 36. Aavik, Einari
    et al.
    Lumivuori, Henri
    Leppänen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Wirth, Thomas
    Hakkinen, Sanna-Kaisa
    Braesen, Jan-Hinrich
    Beschorner, Ulrich
    Zeller, Thomas
    Braspenning, Maarten
    van Criekinge, Wim
    Makinen, Kimmo
    Yla-Herttuala, Seppo
    Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 16, p. 993-U23Article in journal (Refereed)
    Abstract [en]

    Aims Genetics can explain just above 10% of the observed heritability in cardiovascular diseases. Epigenetics is about to provide some further explanations, but the information needed for that is in the accumulation phase. Genome-wide DNA methylation analysis has revealed thousands of genes, which are epigenetically differentially regulated in atherosclerotic plaques. Our results point to an additional level of complexity that needs to be integrated into the aetiology of atherogenesis.We conducted a genome-wide analysis to identify differentially methylated genes in atherosclerotic lesions. Methods DNA methylation at promoters, exons and introns was identified by massive parallel sequencing. Gene expression was analysed by microarrays, qPCR, immunohistochemistry and western blots. Results Globally, hypomethylation of chromosomal DNA predominates in atherosclerotic plaques and two-thirds of genes showing over 2.5-fold differential in DNA methylation are up-regulated in comparison to healthy mammary arteries. The imprinted chromatin locus 14q32 was identified for the first time as an extensively hypomethylated area in atherosclerosis with highly induced expression of miR127, -136, -410, -431, -432, -433 and capillary formation-associated gene RTL1. The top 100 list of hypomethylated promoters exhibited over 1000-fold enrichment for miRNAs, many of which mapped to locus 14q32. Unexpectedly, also gene body hypermethylation was found to correlate with stimulated mRNA expression. Conclusion Significant changes in genomic methylation were identified in atherosclerotic lesions. The most prominent gene cluster activated via hypomethylation was detected at imprinted chromosomal locus 14q32 with several clustered miRNAs that were up-regulated. These results suggest that epigenetic changes are involved in atherogenesis and may offer new potential therapeutic targets for vascular diseases.

  • 37. Aayesh,
    et al.
    Bilal Qureshi, Muhammad
    Afzaal, Muhammad
    Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences.
    Shuaib Qureshi, Muhammad
    Gwak, Jeonghwan
    Fuzzy-Based Automatic Epileptic Seizure Detection Framework2022In: Computers, Materials and Continua, ISSN 1546-2218, E-ISSN 1546-2226, Vol. 70, no 3, p. 5601-5630Article in journal (Refereed)
    Abstract [en]

    Detection of epileptic seizures on the basis of Electroencephalogram (EEG) recordings is a challenging task due to the complex, non-stationary and non-linear nature of these biomedical signals. In the existing literature, a number of automatic epileptic seizure detection methods have been proposed that extract useful features from EEG segments and classify them using machine learning algorithms. Some characterizing features of epileptic and non-epileptic EEG signals overlap; therefore, it requires that analysis of signals must be performed from diverse perspectives. Few studies analyzed these signals in diverse domains to identify distinguishing characteristics of epileptic EEG signals. To pose the challenge mentioned above, in this paper, a fuzzy-based epileptic seizure detection model is proposed that incorporates a novel feature extraction and selection method along with fuzzy classifiers. The proposed work extracts pattern features along with time-domain, frequency domain, and non-linear analysis of signals. It applies a feature selection strategy on extracted features to get more discriminating features that build fuzzy machine learning classifiers for the detection of epileptic seizures. The empirical evaluation of the proposed model was conducted on the benchmark Bonn EEG dataset. It shows significant accuracy of 98% to 100% for normal vs. ictal classification cases while for three class classification of normal vs. inter-ictal vs. ictal accuracy reaches to above 97.5%. The obtained results for ten classification cases (including normal, seizure or ictal, and seizure-free or inter-ictal classes) prove the superior performance of proposed work as compared to other state-of-the-art counterparts.

  • 38. Aazh, Hashir
    et al.
    Knipper, Marlies
    Danesh, Ali A.
    Cavanna, Andrea E.
    Andersson, Linus
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Paulin, Johan
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Schecklmann, Martin
    Heinonen-Guzejev, Marja
    Moore, Brian C. J.
    Insights from the Third International Conference on Hyperacusis: Causes, Evaluation, Diagnosis, and Treatment2018In: Noise & Health, ISSN 1463-1741, E-ISSN 1998-4030, Vol. 20, no 95, p. 162-170Article in journal (Refereed)
    Abstract [en]

    Background: Hyperacusis is intolerance of certain everyday sounds that causes significant distress and impairment in social, occupational, recreational, and other day-to-day activities. 

    Objective: The aim of this report is to summarize the key findings and conclusions from the Third International Conference on Hyperacusis.

    Topics covered: The main topics discussed comprise (1) diagnosis of hyperacusis and audiological evaluations, (2) neurobiological aspect of hyperacusis, (3) misophonia, (4) hyperacusis in autism spectrum disorder, (5) noise sensitivity, (6) hyperacusis-related distress and comorbid psychiatric illness, and (7) audiologist-delivered cognitive behavioral therapy for hyperacusis.

    Conclusions: Implications for research and clinical practice are summarised.

  • 39.
    Abad-Gurumeta, A.
    et al.
    Dept Anaesthesia, Hosp Univ la Paz, Madrid, Spain.
    Ripolles-Melchor, J.
    Dept Anaesthesia, Hosp Univ Infanta Leonor, Univ Complutense Madrid, Madrid, Spain.
    Casans-Frances, R.
    Dept Anaesthesia, Hosp Clin Univ Lozano Blesa, Zaragoza, Spain.
    Espinosa, A.
    Dept Anaesthesia, Örebro University Hospital, Örebro, Sweden.
    Martinez-Hurtado, E.
    Dept Anaesthesia, Hosp Univ Infanta Leonor, Univ Complutense Madrid, Madrid, Spain.
    Fernandez-Perez, C.
    Dept Consultant Prevent Med & Publ Hlth, Univ Complutense Madrid, Madrid, Spain.
    Ramirez, J. M.
    Dept Colorectal Surg, Univ Zaragoza, Zaragoza, Spain.
    Lopez-Timoneda, F.
    Hosp Clin San Carlos, Dept Anaesthesia, Univ Complutense Madrid, Madrid, Spain.
    Calvo-Vecino, J. M.
    Hosp Univ Infanta Leonor, Dept Anaesthesia, Univ Complutense Madrid, Madrid, Spain.
    A systematic review of sugammadex vs neostigmine for reversal of neuromuscular blockade2015In: Anaesthesia, ISSN 0003-2409, E-ISSN 1365-2044, Vol. 70, no 12, p. 1441-1452Article, review/survey (Refereed)
    Abstract [en]

    We reviewed systematically sugammadex vs neostigmine for reversing neuromuscular blockade. We included 17 randomised controlled trials with 1553 participants. Sugammadex reduced all signs of residual postoperative paralysis, relative risk (95% CI) 0.46 (0.29-0.71), p=0.0004 and minor respiratory events, relative risk (95% CI) 0.51 (0.32-0.80), p=0.0034. There was no difference in critical respiratory events, relative risk (95% CI) 0.13 (0.02-1.06), p=0.06. Sugammadex reduced drug-related side-effects, relative risk (95% CI) 0.72 (0.54-0.95), p=0.02. There was no difference in the rate of postoperative nausea or the rate of postoperative vomiting, relative risk (95% CI) 0.94 (0.79-1.13), p=0.53, and 0.87 (0.65-1.17), p=0.36 respectively.

  • 40.
    Abadie, V.
    et al.
    Hop Univ Necker, Paris, France..
    Bohorquez, D.
    Vall Hebron, Barcelona, Spain..
    Bulstrode, N. W.
    Great Ormond St Hosp Sick Children, London, England..
    Davies, Gareth
    Hakelius, Malin
    Uppsala Univ Hosp, Uppsala, Sweden..
    Ong, J.
    Great Ormond St Hosp Sick Children, London, England..
    Mathijssen, I. M. J.
    Erasmus MC, Rotterdam, Netherlands..
    Matos, E.
    Santa Maria Hosp, Lisbon, Portugal..
    Mazzoleni, F.
    San Gerardo Hosp, Monza, Italy..
    van der Molen, A. Mink
    Utrecht Med Ctr, Utrecht, Netherlands..
    Muradin, M.
    Utrecht Med Ctr, Utrecht, Netherlands..
    Neovius, E.
    Karolinska Hosp, Stockholm, Sweden..
    Piacentile, K.
    San Bortolo Hosp Vicenza, Vicenza, Italy..
    Redondo, M.
    Hosp 12 Octobre, Madrid, Spain..
    Vuola, P.
    Helsinki Univ Hosp, Helsinki, Finland..
    Wolvius, E. B.
    Erasmus MC, Rotterdam, Netherlands..
    Reinert, Siegmar
    Plast Operationen, Klin & Poliklin Mund Kiefer & Gesichtschirurg, Tubingen, Germany..
    Murray, Dylan
    Childrens Univ Hosp, Craniofacial Team, Temple St, Dublin, Ireland.;Karolinska Inst, Plast Surg & ENT, Stockholm, Sweden..
    Peterson, Petra
    Hens, Greet
    Katholieke Univ Leuven, Dept Neurowetenschappen, Leuven, Belgium..
    Schachner, P.
    Sivertsen, A.
    Irvine, W. F. E.
    Qualicura, Breda, Netherlands..
    Welling-van Overveld, L. F. J.
    Qualicura, Breda, Netherlands..
    van Breugel, M.
    Utrecht Med Ctr, Utrecht, Netherlands..
    van Schalkwijk, K.
    Utrecht Med Ctr, Utrecht, Netherlands..
    Verhey, E.
    Utrecht Med Ctr, Utrecht, Netherlands..
    Khan, A.
    Great Ormond St Hosp Sick Children, London, England..
    Baillie, L.
    Great Ormond St Hosp Sick Children, London, England..
    Bishop, N.
    Great Ormond St Hosp Sick Children, London, England..
    Hillyar, C. R. T.
    Great Ormond St Hosp Sick Children, London, England..
    Koudstaal, M. J.
    Erasmus MC, Rotterdam, Netherlands..
    van de lande, L.
    Great Ormond St Hosp Sick Children, London, England..
    Nibber, A.
    Great Ormond St Hosp Sick Children, London, England..
    Panciewicz, N.
    Great Ormond St Hosp Sick Children, London, England..
    Ramjeeawan, A.
    Great Ormond St Hosp Sick Children, London, England..
    Bouter, A.
    Erasmus MC, Rotterdam, Netherlands..
    El Ghoul, K.
    Erasmus MC, Rotterdam, Netherlands..
    Logjes, B.
    Erasmus MC, Rotterdam, Netherlands..
    van der Plas, P.
    Erasmus MC, Rotterdam, Netherlands..
    Kats, J.
    Erasmus MC, Rotterdam, Netherlands..
    Weissbach, E.
    Erasmus MC, Rotterdam, Netherlands..
    van Veen-van der Hoek, M.
    Erasmus MC, Rotterdam, Netherlands..
    Bittermann, A. J. N.
    Utrecht Med Ctr, Utrecht, Netherlands..
    van den Boogaard, M-JH.
    Coenraad, S.
    Utrecht Med Ctr, Utrecht, Netherlands..
    Dulfer, K.
    Erasmus MC, Rotterdam, Netherlands..
    Joosten, K.
    Erasmus MC, Rotterdam, Netherlands..
    Lachmeijer, A. M. A.
    Utrecht Med Ctr, Utrecht, Netherlands..
    Muradin, M. S. M.
    Utrecht Med Ctr, Utrecht, Netherlands..
    Peters, N. C. J.
    Erasmus MC, Rotterdam, Netherlands..
    Pleumeekers, M.
    Erasmus MC, Rotterdam, Netherlands..
    de Veye, H. Swanenburg
    Utrecht Med Ctr, Utrecht, Netherlands..
    European Guideline Robin Sequence An Initiative From the European Reference Network for Rare Craniofacial Anomalies and Ear, Nose and Throat Disorders (ERN-CRANIO)2024In: The Journal of Craniofacial Surgery, ISSN 1049-2275, E-ISSN 1536-3732, Vol. 35, no 1, p. 279-361Article in journal (Refereed)
    Abstract [en]

    A European guideline on Robin Sequence was developed within the European Reference Network for rare and/ or complex craniofacial anomalies and ear, nose, and throat disorders. The guideline provides an overview of optimal care provisions for patients with Robin Sequence and recommendations for the improvement of care.

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  • 41.
    Abadpour, Shadab
    et al.
    Oslo University Hospital, Oslo, Norway.
    Halvorsen, Bente
    Oslo University Hospital, Oslo, Norway.
    Sahraoui, Afaf
    University of Oslo, Oslo, Norway.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Aukrust, Pål
    Oslo University Hospital, Oslo, Norway.
    Scholz, Hanne
    Oslo University Hospital, Oslo, Norway.
    Interleukin-22 reverses human islet dysfunction and apoptosis triggered by hyperglycemia and LIGHT2018In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 60, no 3, p. 171-183Article in journal (Refereed)
    Abstract [en]

    Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22. The effect of HG + LIGHT impairing glucose stimulated insulin secretion was reversed by IL-22. The harmful effect of HG + LIGHT on human islet function seemed to involve enhanced endoplasmic reticulum stress evidenced by up-regulation of p-IRE1α and BiP, elevated secretion of pro-inflammatory cytokines (IL-6, IL-8, IP-10 and MCP-1) and the pro-coagulant mediator tissue factor (TF) release and apoptosis in human islets, whereas all these effects were at least partly reversed by IL-22. Our findings suggest that IL-22 could counteract the harmful effects of LIGHT/hyperglycemia on human islet cells and potentially support the strong protective effect of IL-22 on impaired islet function and survival.

  • 42.
    Abadpour, Shadab
    et al.
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway.;Univ Oslo, Inst Basic Med Sci, Ctr Excellence, Hybrid Technol Hub, Oslo, Norway..
    Tyrberg, Bjorn
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Schive, Simen W.
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway..
    Huldt, Charlotte Wennberg
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Gennemark, Peter
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;Univ Linköping, Dept Biomed Engn, Linköping, Sweden..
    Ryberg, Erik
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Ryden-Bergsten, Tina
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Smith, David M.
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;AstraZeneca, BioPharmaceut R&D, Discovery Sci, Hit Discovery, Cambridge, England..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Skrtic, Stanko
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden..
    Scholz, Hanne
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway.;Univ Oslo, Inst Basic Med Sci, Ctr Excellence, Hybrid Technol Hub, Oslo, Norway..
    Winzell, Maria Sorhede
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function2020In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, no 7, p. 1355-1367Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Inflammatory signals and increased prostaglandin synthesis play a role during the development of diabetes. The prostaglandin D-2 (PGD(2)) receptor, GPR44/DP2, is highly expressed in human islets and activation of the pathway results in impaired insulin secretion. The role of GPR44 activation on islet function and survival rate during chronic hyperglycaemic conditions is not known. In this study, we investigate GPR44 inhibition by using a selective GPR44 antagonist (AZ8154) in human islets both in vitro and in vivo in diabetic mice transplanted with human islets. Methods Human islets were exposed to PGD(2) or proinflammatory cytokines in vitro to investigate the effect of GPR44 inhibition on islet survival rate. In addition, the molecular mechanisms of GPR44 inhibition were investigated in human islets exposed to high concentrations of glucose (HG) and to IL-1 beta. For the in vivo part of the study, human islets were transplanted under the kidney capsule of immunodeficient diabetic mice and treated with 6, 60 or 100 mg/kg per day of a GPR44 antagonist starting from the transplantation day until day 4 (short-term study) or day 17 (long-term study) post transplantation. IVGTT was performed on mice at day 10 and day 15 post transplantation. After termination of the study, metabolic variables, circulating human proinflammatory cytokines, and hepatocyte growth factor (HGF) were analysed in the grafted human islets. Results PGD(2) or proinflammatory cytokines induced apoptosis in human islets whereas GPR44 inhibition reversed this effect. GPR44 inhibition antagonised the reduction in glucose-stimulated insulin secretion induced by HG and IL-1 beta in human islets. This was accompanied by activation of the Akt-glycogen synthase kinase 3 beta signalling pathway together with phosphorylation and inactivation of forkhead box O-1and upregulation of pancreatic and duodenal homeobox-1 and HGF. Administration of the GPR44 antagonist for up to 17 days to diabetic mice transplanted with a marginal number of human islets resulted in reduced fasting blood glucose and lower glucose excursions during IVGTT. Improved glucose regulation was supported by increased human C-peptide levels compared with the vehicle group at day 4 and throughout the treatment period. GPR44 inhibition reduced plasma levels of TNF-alpha and growth-regulated oncogene-alpha/chemokine (C-X-C motif) ligand 1 and increased the levels of HGF in human islets. Conclusions/interpretation Inhibition of GPR44 in human islets has the potential to improve islet function and survival rate under inflammatory and hyperglycaemic stress. This may have implications for better survival rate of islets following transplantation.

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  • 43.
    Abadpour, Shadab
    et al.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Tyrberg, Bjorn
    AstraZeneca, Sweden.
    Schive, Simen W.
    Oslo Univ Hosp, Norway.
    Wennberg Huldt, Charlotte
    AstraZeneca, Sweden.
    Gennemark, Peter
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. AstraZeneca, Sweden.
    Ryberg, Erik
    AstraZeneca, Sweden.
    Ryden-Bergsten, Tina
    AstraZeneca, Sweden.
    Smith, David M.
    AstraZeneca, Sweden; AstraZeneca, England.
    Korsgren, Olle
    Uppsala Univ, Sweden.
    Skrtic, Stanko
    AstraZeneca, Sweden; Univ Gothenburg, Sweden.
    Scholz, Hanne
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Winzell, Maria Sorhede
    AstraZeneca, Sweden.
    Inhibition of the prostaglandin D-2-GPR44/DP2 axis improves human islet survival and function2020In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, no 7, p. 1355-1367Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Inflammatory signals and increased prostaglandin synthesis play a role during the development of diabetes. The prostaglandin D-2 (PGD(2)) receptor, GPR44/DP2, is highly expressed in human islets and activation of the pathway results in impaired insulin secretion. The role of GPR44 activation on islet function and survival rate during chronic hyperglycaemic conditions is not known. In this study, we investigate GPR44 inhibition by using a selective GPR44 antagonist (AZ8154) in human islets both in vitro and in vivo in diabetic mice transplanted with human islets. Methods Human islets were exposed to PGD(2) or proinflammatory cytokines in vitro to investigate the effect of GPR44 inhibition on islet survival rate. In addition, the molecular mechanisms of GPR44 inhibition were investigated in human islets exposed to high concentrations of glucose (HG) and to IL-1 beta. For the in vivo part of the study, human islets were transplanted under the kidney capsule of immunodeficient diabetic mice and treated with 6, 60 or 100 mg/kg per day of a GPR44 antagonist starting from the transplantation day until day 4 (short-term study) or day 17 (long-term study) post transplantation. IVGTT was performed on mice at day 10 and day 15 post transplantation. After termination of the study, metabolic variables, circulating human proinflammatory cytokines, and hepatocyte growth factor (HGF) were analysed in the grafted human islets. Results PGD(2) or proinflammatory cytokines induced apoptosis in human islets whereas GPR44 inhibition reversed this effect. GPR44 inhibition antagonised the reduction in glucose-stimulated insulin secretion induced by HG and IL-1 beta in human islets. This was accompanied by activation of the Akt-glycogen synthase kinase 3 beta signalling pathway together with phosphorylation and inactivation of forkhead box O-1and upregulation of pancreatic and duodenal homeobox-1 and HGF. Administration of the GPR44 antagonist for up to 17 days to diabetic mice transplanted with a marginal number of human islets resulted in reduced fasting blood glucose and lower glucose excursions during IVGTT. Improved glucose regulation was supported by increased human C-peptide levels compared with the vehicle group at day 4 and throughout the treatment period. GPR44 inhibition reduced plasma levels of TNF-alpha and growth-regulated oncogene-alpha/chemokine (C-X-C motif) ligand 1 and increased the levels of HGF in human islets. Conclusions/interpretation Inhibition of GPR44 in human islets has the potential to improve islet function and survival rate under inflammatory and hyperglycaemic stress. This may have implications for better survival rate of islets following transplantation.

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  • 44.
    Abalo, Kossi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden..
    Ekberg, Sara
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden..
    Eloranta, Sandra
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden..
    Pahnke, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.
    Albertsson-Lindblad, Alexandra
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, Lund, Sweden..
    Jerkeman, Mats
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, Lund, Sweden..
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden..
    Secondary malignancies among mantle cell lymphoma patients2023In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 195, article id 113403Article in journal (Refereed)
    Abstract [en]

    Purpose:

    With modern treatments, mantle cell lymphoma (MCL) patients more frequently experience long-lasting remission resulting in a growing population of long-term survivors. Follow-up care includes identification and management of treatment-related late-effects, such as secondary malignancies (SM). We conducted a populationbased study to describe the burden of SM in MCL patients.

    Methods:

    All patients with a primary diagnosis of MCL, aged >= 18 years and diagnosed between 2000 and 2017 in Sweden were included along with up to 10 individually matched population comparators. Follow-up was from twelve months after diagnosis/matching until death, emigration, or December 2019, whichever occurred first. Rates of SM among patients and comparators were estimated using the Anderson-Gill method (accounting for repeated events) and presented as hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age at diagnosis, calendar year, sex, and the number of previous events.

    Results:

    Overall, 1 452 patients and 13 992 comparators were followed for 6.6 years on average. Among patients, 230 (16%) developed at least one SM, and 264 SM were observed. Relative to comparators, patients had a higher rate of SM, HRadj= 1.6 (95%CI:1.4-1.8), and higher rates were observed across all primary treatment groups: the Nordic-MCL2 protocol, R-CHOP, R-bendamustine, ibrutinib, lenalidomide, and R-CHOP/Cytarabine. Compared to Nordic-MCL2, treatment with R-bendamustine was independently associated with an increased risk of SM, HRadj= 2.0 (95%CI:1.3-3.2). Risk groups among patients were those with a higher age at diagnosis (p < 0.001), males (p = 0.006), and having a family history of lymphoma (p = 0.009). Patients had preferably higher risk of melanoma, other neoplasms of the skin and other hematopoietic and lymphoid malignancies.

    Conclusions:

    MCL survivors have an increased risk of SM, particularly if treated with R-bendamustine. The intensive treatments needed for long-term remissions are a concern, and transition to treatment protocols with sustained efficacy but with a lower risk of SM is needed.

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  • 45. Abarca-Goméz, Leandra
    et al.
    Abdeen, Ziad A
    Abdul Hamid, Zargar
    Abu-Rmeileh, Niveen M
    Acosta-Cazares, Benjamin
    Acuin, Cecilia
    Adams, Robert J
    Aekplakorn, Wichai
    Forsner, Maria
    Dalarna University, School of Education, Health and Social Studies, Caring Science/Nursing.
    Ezzati, Majid
    Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults.2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, no 10113, p. 2627-2642Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults.

    METHODS: We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity).

    FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0·01 kg/m2 per decade; 95% credible interval -0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (-0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50-1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to 5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8% (6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6) among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese.

    INTERPRETATION: The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults.

    FUNDING: Wellcome Trust, AstraZeneca Young Health Programme.

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  • 46.
    Abat, F.
    et al.
    Department of Orthopaedic Sports Medicine, ReSport Clinic, Passeig Fabra i Puig 47, Barcelona, Spain.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports Medicine. Alfredson Tendon Clinic Inc, Umeå, Sweden; Pure Sports Medicine Clinic, ISEH, UCLH, London, United Kingdom.
    Cucchiarini, M.
    Molecular Biology, Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr Bldg 37, Homburg/Saar, Germany.
    Madry, H.
    Lehrstuhl für Experimentelle Orthopädie und Arthroseforschung, Universität des Saarlandes, Gebäude 37, Kirrbergerstr 1, Homburg, Germany.
    Marmotti, A.
    Department of Orthopaedics and Traumatology, San Luigi Gonzaga Hospital, Orbassano, University of Turin, Turin, Italy.
    Mouton, C.
    Department of Orthopedic Surgery, Clinique d’Eich-Centre Hospitalier de Luxembourg, 76, rue d’Eich, Luxembourg, Luxembourg.
    Oliveira, J.M.
    3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, GMR, Barco, Portugal; ICVS/3B’s - PT Government Associate Laboratory, Braga, Guimarães, Portugal.
    Pereira, H.
    3B’s Research Group University of Minho, ICVS/3B’s–PT Government Associate Laboratory, Braga, Guimarães, Portugal; Orthopedic Department Centro Hospitalar Póvoa de Varzim, Vila do Conde, Portugal; Ripoll y De Prado Sports Clinic – FIFA Medical Centre of Excellence, Madrid, Murcia, Spain.
    Peretti, G.M.
    IRCCS Istituto Ortopedico Galeazzi, Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
    Romero-Rodriguez, D.
    Department of Physical Therapy and Sports Rehabilitation, ReSport Clinic Barcelona, Barcelona, Spain; EUSES Sports Science, University of Girona, Girona, Spain.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stephen, J.
    Fortius Clinic, 17 Fitzhardinge St, London, United Kingdom; The Biomechanics Group, Department of Mechanical Engineering, Imperial College, London, United Kingdom.
    van Bergen, C.J.A.
    Department of Orthopedic Surgery, Amphia Hospital Breda, Breda, Netherlands.
    de Girolamo, L.
    Orthopaedic Biotechnology Laboratory, Galeazzi Orthopaedic Institute, Milan, Italy.
    Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part I: biology, biomechanics, anatomy and anexercise-based approach2017In: Journal of Experimental Orthopaedics, E-ISSN 2197-1153, Vol. 4, no 1, article id 18Article, review/survey (Refereed)
    Abstract [en]

    Chronic tendinopathies represent a major problem in the clinical practice of sports orthopaedic surgeons, sports doctors and other health professionals involved in the treatment of athletes and patients that perform repetitive actions. The lack of consensus relative to the diagnostic tools and treatment modalities represents a management dilemma for these professionals. With this review, the purpose of the ESSKA Basic Science Committee is to establish guidelines for understanding, diagnosing and treating this complex pathology.

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  • 47. Abat, Ferran
    et al.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine.
    Campos, Jocelio
    Planells, Gabriel
    Torras, Jordi
    Madruga-Parera, Marc
    Rodriguez-Baeza, Alfonso
    Ultrasound-guided versus blind interventions in patellar tendon lesions: a cadaveric study2021In: Skeletal Radiology, ISSN 0364-2348, E-ISSN 1432-2161, Vol. 50, no 5, p. 967-972Article in journal (Refereed)
    Abstract [en]

    Purpose: The present study aims to analyze the accuracy of injections aimed to hit the proximal and depth part of the patellar tendon "target point" in patellar tendinopathy, comparing ultrasound-guided or non-ultrasound-guided (blind) injections.

    Methods: A cadaver randomized study was carried out. Injections were performed under ultrasound control, as well as blinded. There were 26 knees from fresh cadavers and injections were placed by 26 practitioners with experience in the use of musculoskeletal ultrasound and injection treatment. Each participant performed 6 ultrasound-guided and 6 blind punctures in different cadaveric specimens. This provided 312 injections that were analyzed in 2 different anatomical cuts, thus providing a database of 624 measurements for statistical analysis.

    Results: Statistically significant differences were observed (p < 0.0001) in the distance from the target point between the ultrasound-guided and the non-guided infiltrations. The "unguided" injections were considered to have been performed on average 10 mm away from the target point compared to the "ultrasound-guided" injections. The ultrasound-guided injections obtained an accuracy of 74.36% while the "non-ultrasound-guided" injections obtained an accuracy of 11.54% (p < 0.0001).

    Conclusion: The use of ultrasound to guide the positioning of injections on the dorsal side of the proximal patellar tendon had a significantly higher accuracy compared to blind injections. The finding provides knowledge of importance for injection treatment.

  • 48.
    Abate, E.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. University of Gondar, Ethiopia.
    Elias, D.
    University of Southern Denmark, Denmark.
    Getachew, A.
    University of Gondar, Ethiopia.
    Alemu, S.
    University of Gondar, Ethiopia.
    Diro, E.
    University of Gondar, Ethiopia.
    Britton, S.
    Karolinska Hospital, Sweden.
    Aseffa, A.
    Armauer Hansen Research Institute, Ethiopia.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Kalmar County Hospital, Sweden.
    Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial2015In: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 45, no 2-3, p. 133-140Article in journal (Refereed)
    Abstract [en]

    Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400 mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (Delta TB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-gamma, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (Delta TB score: 5.6 +/- 2.9 for albendazole versus 5.9 +/- 2.5 for placebo, P = 0.59). The albendazole-treated group showed a decline in eosinophil cells (P = 0.001) and IL-10 (P = 0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2 +/- 8.5 kg versus 8.2 +/- 8.7 kg, P = 0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. (C) 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  • 49.
    Abate Waktola, Ebba Abate
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. EPHI, Ethiopia.
    Blomgran, Robert
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Lerm, Maria
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Belayneh, Meseret
    Univ Addis Abeba, Ethiopia.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Stendahl, Olle
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Schön, Thomas
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Kalmar County Hospital, Kalmar, Sweden.
    Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 3126Article in journal (Refereed)
    Abstract [en]

    Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.

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  • 50.
    Abawi, Akram
    et al.
    Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Samano, Ninos
    Örebro University Hospital. Örebro University, School of Medical Sciences. University Health Care Research Centre.
    Five-Year Follow-Up After Transcatheter Aortic Valve Implantation in Patients with Severe Aortic Stenosis and Concomitant Coronary Artery Disease: A Single-Center Experience2023In: Brazilian Journal of Cardiovascular Surgery, ISSN 0102-7638, E-ISSN 1678-9741, Vol. 39, no 1, article id e20220461Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There is no consensus on the impact of coronary artery disease in patients undergoing transcatheter aortic valve implantation. Therefore, the objective of this study was, in a single-center setting, to evaluate the five-year outcome of transcatheter aortic valve implantation patients with or without coronary artery disease.

    METHODS: All transcatheter aortic valve implantation patients between 2009 and 2019 were included and grouped according to the presence or absence of coronary artery disease. The primary endpoint, five-year all-cause mortality, was evaluated using Cox regression adjusted for age, sex, procedure years, and comorbidities. Comorbidities interacting with coronary artery disease were evaluated with interaction tests. In-hospital complications was the secondary endpoint.

    RESULTS: In total, 176 patients had aortic stenosis and concomitant coronary artery disease, while 170 patients had aortic stenosis only. Mean follow-up was 2.2±1.6 years. There was no difference in the adjusted five-year all-cause mortality between transcatheter aortic valve implantation patients with and without coronary artery disease (hazard ratio 1.00, 95% confidence interval 0.59-1.70, P=0.99). In coronary artery disease patients, impaired renal function, peripheral arterial disease, or ejection fraction < 50% showed a significant interaction effect with higher five-year all-cause mortality. No significant differences in complications between the groups were found.

    CONCLUSION: Five-year mortality did not differ between transcatheter aortic valve implantation patients with or without coronary artery disease. However, in patients with coronary artery disease and impaired renal function, peripheral arterial disease, or ejection fraction < 50%, we found significantly higher five-year all-cause mortality.

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