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  • 151.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Bonnedahl, Jonas
    Linkoping Univ, Dept Clin & Expt Med, SE-58183 Linkoping, Sweden;Kalmar Cty Hosp, Dept Infect Dis, SE-39185 Kalmar, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Dept Clin Microbiol, SE-39185 Kalmar, Sweden.
    Hernandez, Jorge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ramey, Andrew M.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Acquisition and dissemination of cephalosporin-resistant E.coli in migratory birds sampled at an Alaska landfill as inferred through genomic analysis2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 7361Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in bacterial pathogens threatens global health, though the spread of AMR bacteria and AMR genes between humans, animals, and the environment is still largely unknown. Here, we investigated the role of wild birds in the epidemiology of AMR Escherichia coli. Using next-generation sequencing, we characterized cephalosporin-resistant E. coli cultured from sympatric gulls and bald eagles inhabiting a landfill habitat in Alaska to identify genetic determinants conferring AMR, explore potential transmission pathways of AMR bacteria and genes at this site, and investigate how their genetic diversity compares to isolates reported in other taxa. We found genetically diverse E. coli isolates with sequence types previously associated with human infections and resistance genes of clinical importance, including blaCTX-M and blaCMY. Identical resistance profiles were observed in genetically unrelated E. coli isolates from both gulls and bald eagles. Conversely, isolates with indistinguishable core-genomes were found to have different resistance profiles. Our findings support complex epidemiological interactions including bacterial strain sharing between gulls and bald eagles and horizontal gene transfer among E. coli harboured by birds. Results suggest that landfills may serve as a source for AMR acquisition and/or maintenance, including bacterial sequence types and AMR genes relevant to human health.

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  • 152.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Bonnedahl, Jonas
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden;Kalmar Cty Council, Dept Infect Dis, Kalmar, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Res Sect, Dept Dev & Publ Hlth, Kalmar, Sweden.
    Hernandez, Jorge
    Kalmar Cty Hosp, Dept Clin Microbiol, Kalmar, Sweden.
    Reed, John A.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Tibbitts, Lee
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Douglas, David C.
    US Geol Survey, Alaska Sci Ctr, Juneau, AK USA.
    Ramey, Andrew M.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Satellite tracking of gulls and genomic characterization of faecal bacteria reveals environmentally mediated acquisition and dispersal of antimicrobial-resistant Escherichia coli on the Kenai Peninsula, Alaska2019In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 28, no 10, p. 2531-2545Article in journal (Refereed)
    Abstract [en]

    Gulls (Larus spp.) have frequently been reported to carry Escherichia coli exhibiting antimicrobial resistance (AMR E. coli); however, the pathways governing the acquisition and dispersal of such bacteria are not well described. We equipped 17 landfill-foraging gulls with satellite transmitters and collected gull faecal samples longitudinally from four locations on the Kenai Peninsula, Alaska to assess: (a) gull attendance and transitions between sites, (b) spatiotemporal prevalence of faecally shed AMR E. coli, and (c) genomic relatedness of AMR E. coli isolates among sites. We also sampled Pacific salmon (Oncorhynchus spp.) harvested as part of personal-use dipnet fisheries at two sites to assess potential contamination with AMR E. coli. Among our study sites, marked gulls most commonly occupied the lower Kenai River (61% of site locations) followed by the Soldotna landfill (11%), lower Kasilof River (5%) and upper Kenai River (<1%). Gulls primarily moved between the Soldotna landfill and the lower Kenai River (94% of transitions among sites), which were also the two locations with the highest prevalence of AMR E. coli. There was relatively high spatial and temporal variability in AMR E. coli prevalence in gull faeces and there was no evidence of contamination on salmon harvested in personal-use fisheries. We identified E. coli sequence types and AMR genes of clinical importance, with some isolates possessing genes associated with resistance to as many as eight antibiotic classes. Our findings suggest that gulls acquire AMR E. coli at habitats with anthropogenic inputs and subsequent movements may represent pathways through which AMR is dispersed.

  • 153.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, Alaska Sci Ctr, 4210 Univ Dr, Anchorage, AK 99508 USA..
    Woksepp, Hanna
    Kalmar Cty Hosp, Dept Dev & Publ Hlth, S-39185 Kalmar, Sweden.;Linnaeus Univ, Dept Med & Optometry, S-39185 Kalmar, Sweden..
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mohsin, Mashkoor
    Univ Agr Faisalabad, Inst Microbiol, Faisalabad 38040, Pakistan..
    Hasan, Badrul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Anim Bacteriol Sect, Anim Bacteriol Sect Microbial Sci Pests & Dis, Bundoora, Vic, Australia..
    Muzyka, Denys
    Inst Expt & Clin Vet Med, Natl Sci Ctr, UA-61023 Kharkiv, Ukraine..
    Hernandez, Jorge
    Kalmar Cty Hosp, Dept Clin Microbiol, SE-39185 Kalmar, Sweden..
    Aguirre, Filip
    Kalmar Cty Hosp, Dept Clin Microbiol, SE-39185 Kalmar, Sweden..
    Tok, Atalay
    Uppsala Univ, Dept Med Sci, Zoonosis Sci Ctr, SE-75185 Uppsala, Sweden..
    Soderman, Jan
    Linköping Univ, Dept Clin & Expt Med, Lab Med, Linköping, Sweden..
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ramey, Andrew M.
    US Geol Survey, Alaska Sci Ctr, 4210 Univ Dr, Anchorage, AK 99508 USA..
    Bonnedahl, Jonas
    Linköping Univ, Dept Biomed & Clin Sci, S-58183 Linköping, Sweden.;Region Kalmar Cty, Dept Infect Dis, S-39185 Kalmar, Sweden..
    Genomically diverse carbapenem resistant Enterobacteriaceae fromwild birds provide insight into global patterns of spatiotemporal dissemination2022In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 824, article id 153632Article in journal (Refereed)
    Abstract [en]

    Carbapenem resistant Enterobacteriaceae (CRE) are a threat to public health globally, yet the role of the environment in the epidemiology of CRE remains elusive. Given that wild birds can acquire CRE, likely from foraging in anthropogenically impacted areas, and may aid in the maintenance and dissemination of CRE in the environment, a spatiotemporal comparison of isolates from different regions and timepoints may be useful for elucidating epidemiological information. Thus, we characterized the genomic diversity of CRE from fecal samples opportunistically collected from gulls (Larus spp.) inhabiting Alaska (USA), Chile, Spain, Turkey, and Ukraine and from black kites (Milvus migrans) sampled in Pakistan and assessed evidence for spatiotemporal patterns of dissemination. Within and among sampling locations, a high diversity of carbapenemases was found, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), oxacillinase (OXA), and Verona integron Metallo beta-lactamase (VIM). Although the majority of genomic comparisons among samples did not provide evidence for spatial dissemination, we did find strong evidence for dissemination among Alaska, Spain, and Turkey. We also found strong evidence for temporal dissemination among samples collected in Alaska and Pakistan, though the majority of CRE clones were transitory and were not repeatedly detected among locations where samples were collected longitudinally. Carbapenemase-producing hypervirulent K. pneumoniae was isolated from gulls in Spain and Ukraine and some isolates harbored antimicrobial resistance genes conferring resistance to up to 10 different antibiotic classes, including colistin. Our results are consistent with local acquisition of CRE by wild birds with spatial dissemination influenced by intermediary transmission routes, likely involving humans. Furthermore, our results support the premise that anthropogenicallyassociated wild birds may be good sentinels for understanding the burden of clinically-relevant antimicrobial resistance in the local human population.

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  • 154.
    Ahlstrom, Håkan
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Eriksson, Barbro
    Department of Medical Sciences.
    Bergstrom, Mats
    Bjurling, P
    Langstrom, Bengt
    Oberg, Kjell
    Department of Medical Sciences.
    Positron emission tomography in endocrine pancreatic tumors.1995In: Radiology, Vol. 195, p. 333-Article in journal (Refereed)
  • 155.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bergström, M
    Bjurling, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pancreatic neuroendocrine tumors: diagnosis with PET1995In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 195, no 2, p. 333-337Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To evaluate the use of carbon-11-labeled L-dihydroxyphenylalanine (L-DOPA) and hydroxytryptophan (5-HTP) in the diagnosis of pancreatic endocrine tumors with positron emission tomography (PET).

    MATERIALS AND METHODS:

    Twenty-two consecutive patients with clinically and biochemically verified pancreatic endocrine tumors were examined with computed tomography (CT) and PET with L-DOPA alone (n = 16) or both C-11-L-DOPA and C-11-5-HTP (n = 6).

    RESULTS:

    Tumor uptake of L-DOPA was found in 11 patients, eight of whom had metastatic disease. Heterogeneity of tracer uptake was noted among different lesions in the same patient (ie, high uptake in some lesions and low uptake in others). Results in patients examined with both L-DOPA and 5-HTP correlated well, but the uptake levels of 5-HTP were higher in two of three patients with positive findings. In two additional patients, CT enabled detection of tumors not detected at PET.

    CONCLUSION:

    The current PET technique can be a valuable complement to CT in demonstration of functional pancreatic endocrine tumors, in particular, glucagonomas, but is less useful in detection of nonfunctional tumors.

  • 156.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bergström, Mats
    Bjurling, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pancreatic Neuroendocrine Tumors: Diagnosis with PET1995In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 195, no 2, p. 333-337Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To evaluate the use of carbon-11-labeled L-dihydroxyphenylalanine (L-DOPA) and hydroxytryptophan (5-HTP) in the diagnosis of pancreatic endocrine tumors with positron emission tomography (PET).

    MATERIALS AND METHODS:

    Twenty-two consecutive patients with clinically and biochemically verified pancreatic endocrine tumors were examined with computed tomography (CT) and PET with L-DOPA alone (n = 16) or both C-11-L-DOPA and C-11-5-HTP (n = 6).

    RESULTS:

    Tumor uptake of L-DOPA was found in 11 patients, eight of whom had metastatic disease. Heterogeneity of tracer uptake was noted among different lesions in the same patient (ie, high uptake in some lesions and low uptake in others). Results in patients examined with both L-DOPA and 5-HTP correlated well, but the uptake levels of 5-HTP were higher in two of three patients with positive findings. In two additional patients, CT enabled detection of tumors not detected at PET.

    CONCLUSION:

    The current PET technique can be a valuable complement to CT in demonstration of functional pancreatic endocrine tumors, in particular, glucagonomas, but is less useful in detection of nonfunctional tumors.

  • 157.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Feltelius, N
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hällgren, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Magnetic resonance imaging of sacroiliac joint inflammation1990In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 33, no 12, p. 1763-1769Article in journal (Refereed)
    Abstract [en]

    A consecutive series of 27 patients with symptoms compatible with sacroiliitis underwent magnetic resonance imaging (MRI) of the sacroiliac joints. The diagnostic sensitivity of MRI was similar to that of computed tomography or conventional radiography. However, MRI seems to have the potential of providing unique information about the disease process in sacroiliitis by demonstrating abnormalities in subchondral bone and periarticular bone marrow. The results of this study suggest that early inflammatory changes in sacroiliitis occur in the subchondral structures of the sacroiliac joints.

  • 158.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Grama, D
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lörelius, L-E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Preoperative localization of endocrine pancreatic tumours by intra-arterial dynamic computed tomography1990In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 31, no 2, p. 171-175Article in journal (Refereed)
    Abstract [en]

    Eleven patients with biochemically confirmed endocrine pancreatic tumours were examined with intra-arterial (i.a.) dynamic computed tomography (CT) and angiography preoperatively. Seven of the patients suffered from the multiple endocrine neoplasia type 1 (MEN-1) syndrome. All patients were operated upon and surgical palpation and ultrasound were the peroperative localization methods. Of the 33 tumours which were found at histopathologic analysis of the resected specimens in the 11 patients, 7 tumours in 7 patients were correctly localized by both i.a. dynamic CT and angiography. Six patients with MEN-1 syndrome had multiple tumours and this group of patients together had 28 tumours, of which 5 (18%) were localized preoperatively by both CT and angiography. I.a. dynamic CT, with the technique used by us, does not seem to improve the localization of endocrine pancreatic tumours, especially in the rare group of MEN-1 patients, as compared with angiography.

  • 159.
    Ahlström, Isabell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Hellström, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Anens, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Reliability of the Swedish version of the Exercise Self-Efficacy Scale (S-ESES): a test-retest study in adults with neurological disease2015In: Physiotherapy Theory and Practice, ISSN 0959-3985, E-ISSN 1532-5040, Vol. 31, no 3, p. 194-199Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the test-retest reliability of the Swedish translated version of the Exercise Self-Efficacy Scale (S-ESES) in people with neurological disease and to examine internal consistency.

    Design: Test-retest study.

    Subjects: A total of 30 adults with neurological diseases including: Parkinson's disease; Multiple Sclerosis; Cervical Dystonia; and Charcot Marie Tooth disease.

    Method: The S-ESES was sent twice by surface mail. Completion interval mean was 16 days apart. Weighted kappa, intraclass correlation coefficient 2,1 [ICC (2,1)], standard error of measurement (SEM), also expressed as a percentage value (SEM%), and Cronbach's alpha were calculated.

    Results: The relative reliability of the test-retest results showed substantial agreement measured using weighted kappa (MD = 0.62) and a very high-reliability ICC (2,1) (0.92). Absolute reliability measured using SEM was 5.3 and SEM% was 20.7. Excellent internal consistency was shown, with an alpha coefficient of 0.91 (test 1) and 0.93 (test 2).

    Conclusion: The S-ESES is recommended for use in research and in clinical work for people with neurological diseases. The low-absolute reliability, however, indicates a limited ability to measure changes on an individual level.

  • 160.
    Ahlström, K.
    et al.
    Anesthesia and Intensive Care Medicine, Sahlgrens University Hospital, Gothenburg, Sweden.
    Biber, B.
    Anesthesia and Intensive Care Medicine, Sahlgrens University Hospital, Gothenburg, Sweden.
    Åberg, A.
    Anesthesia and Intensive Care Medicine, University Hospital of Umeå, Umeå, Sweden.
    Waldenström, A.
    Anesthesia and Intensive Care Medicine, University Hospital of Umeå, Umeå, Sweden.
    Ronquist, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Abrahamsson, P.
    Anesthesia and Intensive Care Medicine, University Hospital of Umeå, Umeå, Sweden.
    Strandén, P.
    Anesthesia and Intensive Care Medicine, University Hospital of Umeå, Umeå, Sweden.
    Johansson, G.
    Anesthesia and Intensive Care Medicine, University Hospital of Umeå, Umeå, Sweden.
    Haney, Michael F.
    Anesthesia and Intensive Care Medicine, University Hospital of Umeå, Umeå, Sweden.
    Metabolic responses in ischemic myocardium after inhalation of carbon monoxide2009In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 53, no 8, p. 1036-1042Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. METHODS: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. RESULTS: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. CONCLUSIONS: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection.

  • 161.
    Ahlström, Tommy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rudberg, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women2009In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 71, no 5, p. 673-678Article in journal (Refereed)
    Abstract [en]

    CONTEXT: In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear.

    OBJECTIVE: To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population.

    DESIGN: We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined.

    RESULTS: The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s-PTH and albumin-corrected s-calcium. Further, positive correlations between plasma calcium and BMI (P = 0.0003), waist circumference (P = 0.0009) and insulin resistance (P = 0.079) were found. PTH and BMI (P < 0.0001), waist circumference (P < 0.0001), systolic blood pressure (P = 0.0034), diastolic blood pressure (P = 0.0008), serum triglycerides (P = 0.0003) and insulin resistance (P = 0.0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0.036) and PTH were negatively correlated.

    CONCLUSIONS: We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.

  • 162. Ahlund, Catherine
    et al.
    Pettersson, Knut
    Lind, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Influence of different types of stressors on the waveform of the peripheral arterial pulse in humans.2003In: Blood Press, ISSN 0803-7051, Vol. 12, no 5-6, p. 291-7Article in journal (Refereed)
  • 163. Ahlund, Catherine
    et al.
    Pettersson, Knut
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pulse wave analysis on fingertip arterial pressure: effects of age, gender and stressors on reflected waves and their relation to brachial and femoral artery blood flow2008In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 28, no 2, p. 86-95Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Analysis of the contour of the arterial pressure pulse (pulse wave analysis; PWA) adds information about arterial stiffness etc., beyond that obtained from absolute pressures. Peripheral pulses normally show an anterograde systolic peak and two reflected peaks: one in systole and one in diastole. The amplitudes and timings of these were estimated from finger pressure recordings in three study groups. We studied the usefulness of continuous digital pressures for PWA. METHODS: First, PWA from intra-arterial (brachial) and non-invasive finger pressure recordings was compared. Secondly, stress-induced (mental arithmetics and cold pressor test) changes in pressure pulse reflection were compared with blood flow changes in brachial and femoral arteries (ultrasound). Thirdly, the influence of age and gender on digital pulse pressures was investigated at rest and during exercise. RESULTS AND CONCLUSION: Pulse wave analysis results from brachial and digital pressures correlated strongly. Stress induced changes in systolic reflection were associated with changes in brachial artery flow patterns, whereas diastolic reflection was associated with femoral artery flow changes. At rest, age increased systolic reflection without affecting diastolic reflection. Exercise increased systolic reflection and reduced diastolic reflection more in older subjects (>40 years) than in younger (<40 years). In conclusion, PWA from continuous, digital pressure recordings is a convenient technique to study the arterial function at rest and during exposure to stressors in broad populations. The two reflected waves are differently regulated, which may indicate different anatomical origin.

  • 164.
    Ahmad, Irma
    et al.
    Örebro Univ, Sch Med Sci, Örebro, Sweden.
    Sandberg, Matilda
    Örebro Univ, Sch Med Sci, Örebro, Sweden.
    Brus, Ole
    Örebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Örebro, Sweden.
    Ekman, Carl Johan
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Stockholm Hlth Care Serv, Stockholm, Sweden.
    Hammar, Åsa
    Univ Bergen, Dept Biol & Med Psychol, Bergen, Norway.;Haukeland Hosp, Div Psychiat, Bergen, Norway.
    Landen, Mikael
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
    Lundberg, Johan
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Stockholm Hlth Care Serv, Stockholm, Sweden.
    Nordanskog, Pia
    Linköping Univ, Ctr Social & Affect Neurosci, Dept Clin & Expt Med, Fac Hlth Sci, Linköping, Sweden.;Reg Ostergotland, Dept Psychiat, Linköping, Sweden.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordenskjold, Axel
    Örebro Univ, Univ Hlth Care Res Ctr, Fac Med & Hlth, Örebro, Sweden.
    Validity of diagnoses, treatment dates, and rating scales in the Swedish national quality register for electroconvulsive therapy2022In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 76, no 2, p. 96-103Article in journal (Refereed)
    Abstract [en]

    Background The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden.

    Aim This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records.

    Materials and methods From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery angstrom sberg Depression Rating Scale between the Q-ECT and the patient record.

    Results A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher.

    Conclusions We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.

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  • 165.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Div Prevent Med, Brigham & Womens Hosp, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Ahluwalia, Tarunveer S.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark.
    Editorial: The Role of Genetic and Lifestyle Factors in Metabolic Diseases2019In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 10, article id 475Article in journal (Other academic)
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  • 166.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Harvard Med Sch, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Arnlov, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, S-14152 Stockholm, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, S-79131 Falun, Sweden..
    Larsson, Susanna C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, S-17177 Stockholm, Sweden.;Uppsala Univ, Dept Surg Sci, Unit Med Epidemiol, S-75185 Uppsala, Sweden..
    Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study2022In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 3, p. 509-, article id 509Article in journal (Refereed)
    Abstract [en]

    Elevated circulating copper levels have been associated with chronic kidney disease (CKD), kidney damage, and decline in kidney function. Using a two sample Mendelian randomization approach where copper-associated genetic variants were used as instrumental variables, genetically predicted higher circulating copper levels were associated with higher CKD prevalence (odds ratio 1.17; 95% confidence interval 1.04, 1.32; p-value = 0.009). There was suggestive evidence that genetically predicted higher copper was associated with a lower estimated glomerular filtration rate and a more rapid kidney damage decline. In conclusion, we observed that elevated circulating copper levels may be a causal risk factor for CKD.

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  • 167.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carrasquilla, Germán
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Langner, Taro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Menzel, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Censin, Jenny C.
    Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK; 7Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
    Sayols-Baixeras, Sergi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Diem
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Mora, Andrés Martínez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Clinical Diabetes and Metabolism, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Genetics of liver fat and volume associate with altered metabolism and whole body magnetic resonance imaging2022In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 77, p. S40-S40Article in journal (Other academic)
  • 168.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Medical School; Harvard T.H. Chan School of Public Health.
    Demler, O. V.
    Sun, Q.
    Moorthy, M. V.
    Li, C.
    Lee, I.-M.
    Ridker, P. M.
    Manson, J. E.
    Hu, F. B.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Chasman, D. I.
    Cheng, S.
    Pradhan, A.
    Mora, S.
    Association of the Mediterranean Diet With Onset of Diabetes in the Women’s Health Study2020In: JAMA Network Open, E-ISSN 2574-3805, Vol. 3, no 11, article id e2025466Article in journal (Refereed)
    Abstract [en]

    Importance  Higher Mediterranean diet (MED) intake has been associated with reduced risk of type 2 diabetes, but underlying biological mechanisms are unclear.

    Objective  To characterize the relative contribution of conventional and novel biomarkers in MED-associated type 2 diabetes risk reduction in a US population.

    Design, Setting, and Participants  This cohort study was conducted among 25 317 apparently healthy women. The participants with missing information regarding all traditional and novel metabolic biomarkers or those with baseline diabetes were excluded. Participants were invited for baseline assessment between September 1992 and May 1995. Data were collected from November 1992 to December 2017 and analyzed from December 2018 to December 2019.

    Exposures  MED intake score (range, 0 to 9) was computed from self-reported dietary intake, representing adherence to Mediterranean diet intake.

    Main Outcomes and Measures  Incident cases of type 2 diabetes, identified through annual questionnaires; reported cases were confirmed by either telephone interview or supplemental questionnaire. Proportion of reduced risk of type 2 diabetes explained by clinical risk factors and a panel of 40 biomarkers that represent different physiological pathways was estimated.

    Results  The mean (SD) age of the 25 317 female participants was 52.9 (9.9) years, and they were followed up for a mean (SD) of 19.8 (5.8) years. Higher baseline MED intake (score ≥6 vs ≤3) was associated with as much as a 30% lower type 2 diabetes risk (age-adjusted and energy-adjusted hazard ratio, 0.70; 95% CI, 0.62-0.79; when regression models were additionally adjusted with body mass index [BMI]: hazard ratio, 0.85; 95% CI, 0.76-0.96). Biomarkers of insulin resistance made the largest contribution to lower risk (accounting for 65.5% of the MED–type 2 diabetes association), followed by BMI (55.5%), high-density lipoprotein measures (53.0%), and inflammation (52.5%), with lesser contributions from branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%), and minimal contribution (≤2%) from hemoglobin A1c. In post hoc subgroup analyses, the inverse association of MED diet with type 2 diabetes was seen only among women who had BMI of at least 25 at baseline but not those who had BMI of less than 25 (eg, women with BMI <25, age- and energy-adjusted HR for MED score ≥6 vs ≤3, 1.01; 95% CI, 0.77-1.33; P for trend = .92; women with BMI ≥25: HR, 0.76; 95% CI, 0.67-0.87; P for trend < .001).

    Conclusions and Relevance  In this cohort study, higher MED intake scores were associated with a 30% relative risk reduction in type 2 diabetes during a 20-year period, which could be explained in large part by biomarkers of insulin resistance, BMI, lipoprotein metabolism, and inflammation.

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  • 169.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Prevent Med Div, Brigham & Womens Hosp, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Fatima, Syeda Sadia
    Aga Khan Univ, Dept Biol & Biomed Sci, Karachi, Pakistan.
    Rukh, Gull
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Smith, Caren E.
    Tufts Univ, Res Ctr Aging, Jean Mayer US Dept Agr, Nutr & Genom Lab, Boston, MA 02111 USA.
    Gene Lifestyle Interactions With Relation to Obesity, Cardiometabolic, and Cardiovascular Traits Among South Asians2019In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 10, article id 221Article, review/survey (Refereed)
    Abstract [en]

    The rapid rise of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) during the last few decades among South Asians has been largely attributed to a major shift in lifestyles including physical inactivity, unhealthy dietary patterns, and an overall pattern of sedentary lifestyle. Genetic predisposition to these cardiometabolic risk factors may have interacted with these obesogenic environments in determining the higher cardiometabolic disease prevalence. Based on the premise that gene-environment interactions cause obesity and cardiometabolic diseases, we systematically searched the literature and considered the knowledge gaps that future studies might ful fill. We identified only seven published studies that focused specifically on gene-environment interactions for cardiometabolic traits in South Asians, most of which were limited by relatively small sample and lack of replication. Some studies reported that the differences in metabolic response to higher physical activity and low caloric diet might be modified by genetic risk related to these cardiometabolic traits. Although studies on gene lifestyle interactions in cardiometabolic traits report significant interactions, future studies must focus on more precise assessment of lifestyle factors, investigation of a larger set of genetic variants and the application of powerful statistical methods to facilitate translatable approaches. Future studies should also be integrated with findings both using mechanistic studies through laboratory settings and randomized clinical trials for clinical outcomes.

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  • 170.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kennedy, Beatrice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. School of Medical Sciences, Örebro University, Örebro, Sweden.
    Ganna, Andrea
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. The George Institute for Global Health, Sydney, Australia.
    Ärnlöv, Johan
    Division of and Primary Care, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet; School of Health and Social Studies, Dalarna University.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Magnusson, Patrik KE
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Larsson, Susanna C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden..
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study2022In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 71, no 2, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.

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  • 171.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Ctr Lipid Metabol, 900 Commonwealth Ave, Boston, MA 02215 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02215 USA.
    Moorthy, M. Vinayaga
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Ctr Lipid Metabol, 900 Commonwealth Ave, Boston, MA 02215 USA.
    Demler, Olga, V
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02215 USA.
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02215 USA.
    Ridker, Paul M.
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02215 USA.
    Chasman, Daniel, I
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA.
    Mora, Samia
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Ctr Lipid Metabol, 900 Commonwealth Ave, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02215 USA.
    Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet2018In: JAMA Network Open, E-ISSN 2574-3805, Vol. 1, no 8, article id e185708Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations.

    OBJECTIVE To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population.

    DESIGN, SETTING, AND PARTICIPANTS Using a prospective cohort design, baseline MED intake was assessed in 25 994 initially healthy US women in theWomen's Health Study who were followed up to 12 years. Potential mediating effects of a panel of 40 biomarkers were evaluated, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small-molecule metabolites, and clinical factors. Baseline study information and samples were collected between April 30, 1993, and January 24, 1996. Analyses were conducted between August 1, 2017, and October 30, 2018.

    EXPOSURES Intake of MED is a 9-category measure of adherence to a Mediterranean dietary pattern. Participants were categorized into 3 levels based on their adherence to the MED.

    MAIN OUTCOMES AND MEASURES Incident CVD confirmed through medical records and the proportion of CVD risk reduction explained by mediators.

    RESULTS Among 25 994women (mean [SD] age, 54.7 [7.1] years), those with low, middle, and upper MED intakes composed 39.0%, 36.2%, and 24.8% of the study population and experienced 428 (4.2%), 356 (3.8%), and 246 (3.8%) incident CVD events, respectively. Compared with the reference group who had low MED intake, CVD risk reductions were observed for the middle and upper groups, with respective HRs of 0.77 (95% CI, 0.67-0.90) and 0.72 (95% CI, 0.61-0.86) (P for trend < .001). The largest mediators of the CVD risk reduction of MED intake were biomarkers of inflammation (accounting for 29.2% of the MED-CVD association), glucose metabolism and insulin resistance (27.9%), and body mass index (27.3%), followed by blood pressure (26.6%), traditional lipids (26.0%), high-density lipoprotein measures (24.0%) or very low-density lipoprotein measures (20.8%), with lesser contributions from low-density lipoproteins (13.0%), branched-chain amino acids (13.6%), apolipoproteins (6.5%), or other small-molecule metabolites (5.8%).

    CONCLUSIONS AND RELEVANCE In this study, higher MED intake was associated with approximately one-fourth relative risk reduction in CVD events, which could be explained in part by known risk factors, both traditional and novel.

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  • 172.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard Med Sch, Div Prevent Med, Boston, MA USA.
    Mora, Samia
    Harvard Med Sch, Div Prevent Med, Boston, MA USA;Harvard Med Sch, Cardiovasc Div, Boston, MA USA;Harvard Med Sch, Ctr Lipid Metabol, Boston, MA USA.
    Ridker, Paul M.
    Harvard Med Sch, Div Prevent Med, Boston, MA USA;Harvard Med Sch, Cardiovasc Div, Boston, MA USA;Harvard Med Sch, Ctr Lipid Metabol, Boston, MA USA.
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Network Med, Boston, MA USA.
    Chasman, Daniel I.
    Harvard Med Sch, Div Prevent Med, Boston, MA USA.
    Gene-Based Elevated Triglycerides and Type 2 Diabetes Mellitus Risk in the Women's Genome Health Study2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 1, p. 97-106Article in journal (Refereed)
    Abstract [en]

    Objective- Higher triglyceride (TG) is a risk factor for incident type 2 diabetes mellitus (T2DM), but paradoxically, genetic susceptibility for higher TG has been associated with lower T2DM risk. There is also evidence that the genetic association may be modified by baseline TG. Whether such associations can be replicated and the interaction is selective for certain TG-rich lipoprotein particles remains to be explored.

    Approach and Results-Cox regression involving TG, TG-rich lipoprotein particles, and genetic determinants of TG was performed among 15 813 participants with baseline fasting status in the WGHS (Women's Genome Health Study), including 1453 T2DM incident cases during a mean 18.6 (SD= 5.3) years of follow-up. A weighted, 40-single-nucleotide polymorphism TG genetic risk score was inversely associated with incident T2DM (hazard ratio [95% CI], 0.66 [0.580.75]/ 10-TG risk alleles; P< 0.0001) with adjustment for baseline body mass index, HDL (high-density lipoprotein) cholesterol, and TG. TG-associated risk was higher among individuals in the low compared with the high 40-singlenucleotide polymorphism TG genetic risk score tertile (hazard ratio [95% CI], 1.98 [1.83-2.14] versus 1.68 [1.58-1.80] per mmol/L; P-interaction = 0.0007). In TG-adjusted analysis, large and medium but not small TG-rich lipoprotein particles were associated with higher T2DM incidence for successively lower 40-single-nucleotide polymorphism TG genetic risk score tertiles, P-interaction = 0.013, 0.012, and 0.620 across tertiles, respectively.

    Conclusions-Our results confirm the previous observations of the paradoxical associations of TG with T2DM while focusing attention on the larger TG-rich lipoprotein particle subfractions, suggesting their importance in clinical profiling of T2DM risk.

  • 173. Ahmad, Shafqat
    et al.
    Rukh, Gull
    Varga, Tibor V.
    Ali, Ashfaq
    Kurbasic, Azra
    Shungin, Dmitry
    Ericson, Ulrika
    Koivula, Robert W.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ganna, Andrea
    Qi, Qibin
    Stancakova, Alena
    Sandholt, Camilla H.
    Elks, Cathy E.
    Curhan, Gary
    Jensen, Majken K.
    Tamimi, Rulla M.
    Allin, Kristine H.
    Jorgensen, Torben
    Brage, Soren
    Langenberg, Claudia
    Aadahl, Mette
    Grarup, Niels
    Linneberg, Allan
    Pare, Guillaume
    Magnusson, Patrik K. E.
    Pedersen, Nancy L.
    Boehnke, Michael
    Hamsten, Anders
    Mohlke, Karen L.
    Pasquale, Louis T.
    Pedersen, Oluf
    Scott, Robert A.
    Ridker, Paul M.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Laakso, Markku
    Hansen, Torben
    Qi, Lu
    Wareham, Nicholas J.
    Chasman, Daniel I.
    Hallmans, Goran
    Hu, Frank B.
    Renstrom, Frida
    Orho-Melander, Marju
    Franks, Paul W.
    Gene x Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry2013In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 7, p. e1003607-Article in journal (Refereed)
    Abstract [en]

    Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

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  • 174.
    Ahmadi, Zainab
    et al.
    Lund Univ, Fac Med, Dept Clin Sci Lund, Resp Med & Allergol, Lund, Sweden..
    Igelström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Åsenlöf: Physiotheraphy.
    Sandberg, Jacob
    Lund Univ, Fac Med, Dept Clin Sci Lund, Resp Med & Allergol, Lund, Sweden..
    Sundh, Josefin
    Örebro Univ, Sch Med Sci, Dept Resp Med, Örebro, Sweden..
    Sköld, Magnus
    Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Resp Med & Allergy, Stockholm, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Blomberg, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med, Sect Med, Umeå, Sweden..
    Bornefalk, Hans
    Hans Bornefalk AB, Vallentuna, Sweden..
    Bornefalk Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Ekström, Magnus
    Lund Univ, Fac Med, Dept Clin Sci Lund, Resp Med & Allergol, Lund, Sweden..
    Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease2022In: ERJ Open Research, E-ISSN 2312-0541, Vol. 8, no 1, article id 00460-2021Article in journal (Refereed)
    Abstract [en]

    Background The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease. Methods Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramer's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure. Results In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramer's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramer's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramer's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes. Conclusion In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.

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  • 175.
    Ahmadi, Zainab
    et al.
    Univ Lund Hosp, Div Resp Med & Allergol, Dept Clin Sci, SE-22100 Lund, Sweden..
    Lundstrom, Staffan
    Stockholms Sjukhem Fdn, Palliat Care Serv, Stockholm, Sweden.;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala Univ, Dept Med Sci Resp Med & Allergol, Uppsala, Sweden..
    Strang, Peter
    Stockholms Sjukhem Fdn, Palliat Care Serv, Stockholm, Sweden.;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Currow, David C.
    Flinders Univ S Australia, Discipline Serv, Adelaide, SA 5001, Australia.;Flinders Univ S Australia, Palliat Serv, Adelaide, SA 5001, Australia.;Flinders Univ S Australia, Support Serv, Adelaide, SA 5001, Australia..
    Ekström, Magnus
    Univ Lund Hosp, Div Resp Med & Allergol, Dept Clin Sci, SE-22100 Lund, Sweden.;Flinders Univ S Australia, Discipline Serv, Adelaide, SA 5001, Australia.;Flinders Univ S Australia, Palliat Serv, Adelaide, SA 5001, Australia.;Flinders Univ S Australia, Support Serv, Adelaide, SA 5001, Australia..
    End-of-life care in oxygen-dependent COPD and cancer: a national population-based study2015In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 46, no 4, p. 1190-1193Article in journal (Refereed)
  • 176.
    Ahmadi, Zainab
    et al.
    Univ Lund Hosp, Dept Clin Sci, Div Resp Med & Allergol, SE-22100 Lund, Sweden..
    Wysham, Nicholas G.
    Duke Univ, Duke Clin Res Inst, Ctr Learning Hlth Care, Div Pulm Allergy & Crit Care,Dept Med, Durham, NC USA..
    Lundstrom, Staffan
    Stockholms Sjukhem Fdn, Palliat Care Serv, Stockholm, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Currow, David C.
    Flinders Univ S Australia, Dept Discipline Palliat & Support Serv, Adelaide, SA 5001, Australia..
    Ekstrom, Magnus
    Univ Lund Hosp, Dept Clin Sci, Div Resp Med & Allergol, SE-22100 Lund, Sweden.;Flinders Univ S Australia, Dept Discipline Palliat & Support Serv, Adelaide, SA 5001, Australia..
    End-of-life care in oxygen-dependent ILD compared with lung cancer: a national population-based study2016In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 71, no 6, p. 510-516Article in journal (Refereed)
    Abstract [en]

    Rationale: Advanced fibrosing interstitial lung disease (ILD) is often progressive and associated with a high burden of symptoms and poor prognosis. Little is known about the symptom prevalence and access to palliative care services at end of life (EOL).

    Objectives: Compare prevalence of symptoms and palliative treatments between patients dying with oxygen-dependent ILD and patients dying of lung cancer.

    Methods: Nationwide registry-based cohort study of patients with oxygen-dependent ILD and patients with lung cancer who died between 1 January 2011 and 14 October 2013. Prevalence of symptoms and treatments during the last seven days of life were compared using data in Swedish Registry of Palliative Care.

    Measurements and main results: 285 patients with ILD and 10 822 with lung cancer were included. In ILD, death was more likely to be 'unexpected' (15% vs 4%), less likely to occur in a palliative care setting (17% vs 40%) and EOL discussions with the patients (41% vs 59%) were less common than in lung cancer. Patients with ILD suffered more from breathlessness (75% vs 42%) while patients with lung cancer had more pain (51% vs 73%) (p<0.005 for all comparisons). Patients with ILD had more unrelieved breathlessness, pain and anxiety. The survival time from initiation of oxygen therapy in ILD was a median 8.4 months (IQR 3.4-19.2 months).

    Conclusions: Patients with ILD receive poorer access to specialist EOL care services and experience more breathlessness than patients with lung cancer. This study highlights the need of better EOL care in oxygen-dependent ILD.

  • 177.
    Ahmadpour, Doryaneh
    et al.
    Chalmers Univ Technol, Dept Biol & Biol Engn, Gothenburg, Sweden.;Motala Hosp, Inst Neurol, Dept Med Specialists, Motala, Sweden..
    Kristoffersson, Anna
    Motala Hosp, Inst Neurol, Dept Med Specialists, Motala, Sweden..
    Fredrikson, Mats
    Linkoping Univ, Forum Ostergotland, Linkoping, Sweden..
    Huang-Link, Yumin
    Linkoping Univ Hosp, Dept Neurol, Linkoping, Sweden..
    Eriksson, Anne
    Motala Hosp, Inst Med, Dept Med Specialists, Motala, Sweden..
    Iacobaeus, Ellen
    Karolinska Inst, Dept Clin Neurosci, Div Neurol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology. Linkoping Univ Hosp, Dept Neurol, Linkoping, Sweden.;Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Haghighi, Sara
    Motala Hosp, Inst Neurol, Dept Med Specialists, Motala, Sweden.;Linkoping Univ Hosp, Dept Neurol, Linkoping, Sweden..
    Inventory study of an early pandemic COVID-19 cohort in South-Eastern Sweden, focusing on neurological manifestations2023In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 1, article id e0280376Article in journal (Refereed)
    Abstract [en]

    BackgroundNeurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection.The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county of ostergotland in southeastern Sweden. MethodsThis is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. ResultsSeventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. ConclusionNeurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.

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    FULLTEXT01
  • 178. Ahmed, A A
    et al.
    Ahmed, M
    Theodorsson, E
    Nordlind, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Expression of CGRP in Leishmania major murine cutaneous leishmaniasis.1998In: Neurosci Lett, Vol. 246, p. 149-Article in journal (Refereed)
  • 179. Ahmed, A A
    et al.
    Nordlin, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Schultzberg, M
    Brakenhoff, J
    Bristulf, J
    Novick, D
    Svenson, S B
    Azizi, M
    Liden, S
    Immunohistochemical studies of proinflammatory cytokines and their receptors in hair follicles of normal human skin.1996In: Acta Derm Venereol (Stockh), Vol. 76, p. 348-Article in journal (Refereed)
  • 180. Ahmed, A A
    et al.
    Nordlind, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Hedblad, M
    Lagerholm, B
    Schultzberg, M
    Liden, S
    Interleukin (IL)-1 alpha- and -1 beta-, IL-6-, and tumor necrosis factor-alpha-like immunoreactivities in human common and dysplastic nevocellular nevi and malignant melanoma.1995In: Am J Dermatopathol, Vol. 17, p. 222-Article in journal (Refereed)
  • 181. Ahmed, A A
    et al.
    Nordlind, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Schultzberg, M
    Liden, S
    Immunohistochemical localization of IL-1 alpha- and -1 beta, IL-6-, and tumor necrosis factor-alpha-like immunoreactivities in human apocrine glands.1995In: Arch Derm Res, Vol. 287, p. 764-Article in journal (Refereed)
  • 182. Ahmed, A A
    et al.
    Wahbi, A H
    Nordlind, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Kharazmi, A
    Sundquist, K G
    Liden, S
    In vitro Leishmania major promastigote-induced macrophage migration is modulated by sensory and autonomic neuropeptides.1998In: Scand J Immunol, Vol. 48, p. 79-Article in journal (Refereed)
  • 183. Ahmed, A
    et al.
    Ahmed, M
    Theordsson, E
    Nordlind, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Neuropeptide Y concentrations in experimental Leishmania major cutaneous leishmaniasis1998In: NeuroReport, Vol. 9, p. 3271-Article in journal (Refereed)
  • 184. Ahmed, A
    et al.
    Nordlind, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Soderstrom, S
    Department of Neuroscience.
    Liden, S
    Differential expression of nerve growth factor in Leishmania major murine cutaneous leishmaniasis.1998In: Acta Derm.-Venereol. (Stockh), Vol. 78, p. 87-Article in journal (Refereed)
  • 185. Ahmed, AA
    et al.
    Mutt, V
    Nordlind, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Modulating effects of sensory and autonomic neuropeptides on spontaneous and Leishmania major-induced murine splenocyte proliferation and cytokine secretion.1999In: Immunopharmacol Immunotoxicol, Vol. 21, p. 507-Article in journal (Refereed)
  • 186.
    Ahmed, Degmo Said
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Wande, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ryden, Ingvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Quantitative determination of cerebrospinal fluid bilirubin on a high throughput chemistry analyzer2009In: Clinical laboratory, ISSN 1433-6510, Vol. 55, no 7-8, p. 283-288Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Subarachnoid hemorrhage is a condition with high rates of mortality and morbidity. The diagnosis requires an urgent cerebral computed tomography scan and also a lumbar puncture if the scan fails to demonstrate intracranial blood. In Sweden the cerebrospinal fluid (CSF) is analyzed by spectrophotometric scanning for the presence of hemoglobin and bilirubin. The aim of the study was to develop a quantitative diazo reagent based analysis of cerebrospinal fluid bilirubin as a replacement for spectrophotometric scanning. METHODS: The CSF bilirubin assay on an Architect C8000 chemistry analyzer was compared with spectrophotometry using patient samples. RESULTS: The method correlates with spectrophotometry, has a good linearity and precision. CONCLUSIONS: Quantitative bilirubin measurement offers shorter turnaround times, simplifies the interpretation of the results and reduces work load in comparison with spectrophotometry.

  • 187.
    Ahmed, Fozia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Estrogen and its receptors in adipose tissue from women and men: Associations with age, adiposity and type 2 diabetes2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Obesity and its complications, such as insulin resistance and type 2 diabetes (T2D), are leading causes of morbidity and mortality globally. Adipose tissue is important for whole-body homeostasis, functioning as an energy storage reservoir and an endocrine organ. Estrogens mediate their effects through estrogen receptor alpha (ESR1) and beta (ESR2) and contribute to sex and menopause-related differences in body fat distribution. Moreover, estrogens can be produced from androgens in the adipose tissue by the enzyme aromatase. The overall aim of this thesis was to investigate the role of estrogen and estrogen signalling in human adipose tissue and their association with age, adiposity, and insulin resistance. 

    In Paper I, we assessed ESR1 and ESR2 gene expression in subcutaneous adipose tissue (SAT) from pre- and postmenopausal women, and investigated the effects of estradiol on adipocyte glucose uptake. We found that ESR2 gene expression was higher in postmenopausal women than premenopausal women. Moreover, in late, but not pre- or early postmenopausal women, estradiol incubation reduced basal and insulin-stimulated glucose uptake, which corresponded to an increase in ESR2 gene expression levels. The inhibiting effect of estradiol on adipocyte glucose uptake was prevented using an ESR2 antagonist. 

    Subsequently, in Paper II we assessed the role of ESR2 in SAT lipid and glucose metabolism and preadipocyte differentiation. ESR2 expression in SAT was inversely correlated with markers of central adiposity and positively correlated with markers of lipid accumulation. Moreover, ESR2 knockdown impaired subcutaneous preadipocyte differentiation and glucose utilization. 

    In Paper III, we focused on adipocyte lipolysis in women, which is regulated, in part, by catecholamines. OCT3, which mediates catecholamine transport into adipocytes, where they can be degraded, was increased in SAT with age, and higher in postmenopausal women than premenopausal women. Moreover, its expression was negatively associated with markers of insulin resistance and ex vivo lipolysis. Estradiol incubation of SAT downregulated OCT3 gene expression, which may explain lower OCT3 gene expression in premenopausal compared to postmenopausal women. 

    In Paper IV, we focused on the role of aromatase and estradiol in SAT from men. We found that aromatase expression was higher in SAT from men with obesity and T2D compared to subjects without obesity and T2D, respectively, and was positively associated with markers of central obesity and markers of insulin resistance. Contrastingly, ESR1 expression in SAT was lower in men with obesity and T2D compared to subjects without obesity and T2D, respectively, and negatively associated with markers of obesity and insulin resistance. ESR2 expression was higher in SAT from men with T2D compared to men without T2D. Estradiol reduced insulin-stimulated glucose uptake, however, neither testosterone, nor aromatase inhibition, altered adipocyte glucose uptake. 

    In this thesis, we found that estrogen has important metabolic effects in adipose tissue, including regulating lipid accumulation, glucose uptake capacity, and catecholamine transport. Overall, our findings suggest that estrogen and estrogen receptors may have an important role in age-, menopausal- and sex-dependent differences in body fat distribution, and may serve as potential targets for the prevention and treatment obesity and insulin resistance. 

    List of papers
    1. Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women
    Open this publication in new window or tab >>Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women
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    2022 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, no 5, p. E1879-E1889Article in journal (Refereed) Published
    Abstract [en]

    Context: Reduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood.

    Objective: This work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes.

    Methods: Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits.

    Results: ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage.

    Conclusion: E2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.

    Place, publisher, year, edition, pages
    ENDOCRINE SOC, 2022
    Keywords
    estradiol, adipose tissue, menopause, insulin resistance, type 2 diabetes
    National Category
    Endocrinology and Diabetes Obstetrics, Gynecology and Reproductive Medicine
    Identifiers
    urn:nbn:se:uu:diva-483563 (URN)10.1210/clinem/dgac042 (DOI)000764767300001 ()35084504 (PubMedID)
    Funder
    DiabetesfondenEU, Horizon 2020, H2020-MSCA-ITN-721236EXODIAB - Excellence of Diabetes Research in SwedenErnfors FoundationP.O. Zetterling FoundationSwedish Society for Medical Research (SSMF)Novo Nordisk
    Available from: 2022-09-08 Created: 2022-09-08 Last updated: 2024-03-22Bibliographically approved
    2. ESR2 expression in subcutaneous adipose tissue is related to body fat distribution in women, and knockdown impairs preadipocyte differentiation
    Open this publication in new window or tab >>ESR2 expression in subcutaneous adipose tissue is related to body fat distribution in women, and knockdown impairs preadipocyte differentiation
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    2022 (English)In: Adipocyte, ISSN 2162-3945, E-ISSN 2162-397X, Vol. 11, no 1, p. 434-447Article in journal (Refereed) Published
    Abstract [en]

    Oestrogen receptor 2 (ESR2) expression has been shown to be higher in subcutaneous adipose tissue (SAT) from postmenopausal compared to premenopausal women. The functional significance of altered ESR2 expression is not fully known. This study investigates the role of ESR2 for adipose tissue lipid and glucose metabolism. SAT biopsies were obtained from 44 female subjects with or without T2D. Gene expression of ESR2 and markers of adipose function and metabolism was assessed. ESR2 knockdown was performed using CRISPR/Cas9 in preadipocytes isolated from SAT of females, and differentiation rate, lipid storage, and glucose uptake were measured. ESR2 expression was inversely correlated with measures of central obesity and expression of some fatty acid oxidation markers, and positively correlated with lipid storage and glucose transport markers. Differentiation was reduced in ESR2 knockdown preadipocytes. This corresponded to reduced expression of markers of differentiation and lipogenesis. Glucose uptake was reduced in knockdown adipocytes. Our results indicate that ESR2 deficiency in women is associated with visceral adiposity and impaired subcutaneous adipocyte differentiation as well as glucose and lipid utilization. High ESR2 expression, as seen after menopause, could be a contributing factor to SAT expansion. This may support a possible target to promote a healthy obesity phenotype.

    Place, publisher, year, edition, pages
    Informa UK Limited, 2022
    Keywords
    Adipocytes, adipogenesis, CRISPR, cas9, lipid metabolism, obesity, insulin resistance, type 2 diabetes
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-483752 (URN)10.1080/21623945.2022.2102116 (DOI)000842634400001 ()35856485 (PubMedID)
    Funder
    Diabetesfonden, DIA2021-661EU, Horizon 2020, H2020-MSCA-ITN -721236EXODIAB - Excellence of Diabetes Research in SwedenErnfors FoundationP.O. Zetterling FoundationSwedish Society for Medical Research (SSMF)AstraZenecaNovo Nordisk, NNF20OC0063864Agnes and Mac Rudberg Foundation
    Available from: 2022-09-05 Created: 2022-09-05 Last updated: 2024-03-22Bibliographically approved
    3. Increased OCT3 Expression in Adipose Tissue With Aging: Implications for Catecholamine and Lipid Turnover and Insulin Resistance in Women
    Open this publication in new window or tab >>Increased OCT3 Expression in Adipose Tissue With Aging: Implications for Catecholamine and Lipid Turnover and Insulin Resistance in Women
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    2023 (English)In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 165, no 1, article id bqad172Article in journal (Refereed) Published
    Abstract [en]

    Background Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women.Methods SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed.Results OCT3 mRNA and protein levels in SAT increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist to hip ratio, and circulating lipids (eg, triglycerides).Conclusion OCT3 mRNA and protein levels in SAT increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging.

    Place, publisher, year, edition, pages
    Oxford University Press, 2023
    Keywords
    OCT3, adipose tissue, estradiol, aging, T2D
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-518092 (URN)10.1210/endocr/bqad172 (DOI)001111781700001 ()37972266 (PubMedID)
    Funder
    AstraZeneca
    Available from: 2024-01-03 Created: 2024-01-03 Last updated: 2024-03-22Bibliographically approved
    4. Increased aromatase expression in subcutaneous adipose tissue from men with obesity and type 2 diabetes: a link between estrogen signalling and insulin resistance
    Open this publication in new window or tab >>Increased aromatase expression in subcutaneous adipose tissue from men with obesity and type 2 diabetes: a link between estrogen signalling and insulin resistance
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-524958 (URN)
    Available from: 2024-03-22 Created: 2024-03-22 Last updated: 2024-04-03
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  • 188.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Vranic, Milica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    ESR2 expression in subcutaneous adipose tissue is related to body fat distribution in women, and knockdown impairs preadipocyte differentiation2022In: Adipocyte, ISSN 2162-3945, E-ISSN 2162-397X, Vol. 11, no 1, p. 434-447Article in journal (Refereed)
    Abstract [en]

    Oestrogen receptor 2 (ESR2) expression has been shown to be higher in subcutaneous adipose tissue (SAT) from postmenopausal compared to premenopausal women. The functional significance of altered ESR2 expression is not fully known. This study investigates the role of ESR2 for adipose tissue lipid and glucose metabolism. SAT biopsies were obtained from 44 female subjects with or without T2D. Gene expression of ESR2 and markers of adipose function and metabolism was assessed. ESR2 knockdown was performed using CRISPR/Cas9 in preadipocytes isolated from SAT of females, and differentiation rate, lipid storage, and glucose uptake were measured. ESR2 expression was inversely correlated with measures of central obesity and expression of some fatty acid oxidation markers, and positively correlated with lipid storage and glucose transport markers. Differentiation was reduced in ESR2 knockdown preadipocytes. This corresponded to reduced expression of markers of differentiation and lipogenesis. Glucose uptake was reduced in knockdown adipocytes. Our results indicate that ESR2 deficiency in women is associated with visceral adiposity and impaired subcutaneous adipocyte differentiation as well as glucose and lipid utilization. High ESR2 expression, as seen after menopause, could be a contributing factor to SAT expansion. This may support a possible target to promote a healthy obesity phenotype.

    Download full text (pdf)
    fulltext
  • 189.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kamble, Prasad G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Vranic, Milica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sarsenbayeva, Assel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kristofi, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Almby, Kristina E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women2022In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, no 5, p. E1879-E1889Article in journal (Refereed)
    Abstract [en]

    Context: Reduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood.

    Objective: This work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes.

    Methods: Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits.

    Results: ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage.

    Conclusion: E2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.

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  • 190.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Laterveer, Rutger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Mathioudaki, Argyri
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hornbrinck, Edvin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Patsoukaki, Vagia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Increased aromatase expression in subcutaneous adipose tissue from men with obesity and type 2 diabetes: a link between estrogen signalling and insulin resistanceManuscript (preprint) (Other academic)
  • 191.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Inst Savoir Montfort, 1E103,713 Montreal Rd, Ottawa, ON K1K 0T2, Canada.;Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada..
    Pereira, Maria João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Aguer, Celine
    Inst Savoir Montfort, 1E103,713 Montreal Rd, Ottawa, ON K1K 0T2, Canada.;Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada.;Univ Ottawa, Fac Hlth Sci, Sch Human Kinet, Ottawa, ON K1N 6N5, Canada.;Univ Ottawa, Fac Hlth Sci, Interdisciplinary Sch Hlth Sci, Ottawa, ON K1N 6N5, Canada..
    Bisphenols and the Development of Type 2 Diabetes: The Role of the Skeletal Muscle and Adipose Tissue2021In: Environments, E-ISSN 2076-3298, Vol. 8, no 4, article id 35Article, review/survey (Refereed)
    Abstract [en]

    Bisphenol A (BPA) and bisphenol S (BPS) are environmental contaminants that have been associated with the development of insulin resistance and type 2 diabetes (T2D). Two organs that are often implicated in the development of insulin resistance are the skeletal muscle and the adipose tissue, however, seldom studies have investigated the effects of bisphenols on their metabolism. In this review we discuss metabolic perturbations that occur in both the skeletal muscle and adipose tissue affected with insulin resistance, and how exposure to BPA or BPS has been linked to these changes. Furthermore, we highlight the possible effects of BPA on the cross-talk between the skeletal muscle and adipose tissue.

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  • 192.
    Ahmed, Fozia
    et al.
    Inst Savoir Montfort Rech, 1E103,713 Montreal Rd, Ottawa, ON K1K 0T2, Canada; Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Sarsenbayeva, Assel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Aguer, Céline
    Inst Savoir Montfort Rech, 1E103,713 Montreal Rd, Ottawa, ON K1K 0T2, Canada; Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada; Univ Ottawa, Fac Hlth Sci, Sch Human Kinet, Ottawa, ON, Canada; Univ Ottawa, Fac Hlth Sci, Interdisciplinary Sch Hlth Sci, Ottawa, ON, Canada.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    The effects of bisphenol A and bisphenol S on adipokine expression and glucose metabolism in human adipose tissue2020In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 445, article id 152600Article in journal (Refereed)
    Abstract [en]

    Purpose

    The environmental endocrine disruptors, bisphenol A (BPA) and bisphenol S (BPS) are associated with the development of type 2 diabetes. We aim to study the effects of BPA or BPS exposure on adipokine expression in human adipose tissue and on adipocyte glucose uptake.

    Methods

    Human subcutaneous adipose tissue was treated for 24 or 72 h with environmentally-relevant and supraphysiological concentrations of BPA or BPS (1–104 nM). Following exposure, gene expression of proinflammatory cytokines, adipokines, and estrogen receptors was measured in adipose tissue. Glucose uptake and the insulin signalling pathway were analyzed in isolated adipocytes following adipose tissue culture with BPA for 24 h.

    Results

    Adipose tissue treated with BPA for 24 h had reduced expression of the proinflammatory genes (IL6, IL1B, TNFA) and adipokines (ADIPOQ, FABP4). BPA and BPS had no effect on the expression of other proinflammatory genes (IL33), adipokines (LEP), or receptors (ESR1, ESR2) after 72-h exposure. Adipose tissue treated with environmentally-relevant concentrations of BPA for 24 h had reduced insulin-stimulated glucose uptake, without altered gene and protein levels of key insulin signalling pathway markers.

    Conclusions

    We found that human adipose tissue treated with environmentally-relevant concentrations of BPA for 24 h, but not BPS, reduced expression of proinflammatory genes and adipokines. Furthermore, BPA reduced glucose uptake in adipocytes independently of insulin signalling. Such mechanisms can contribute to the development of insulin resistance associated with BPA exposure.

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  • 193.
    Ahmed, Fozia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Vranic, Milica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Mathioudaki, Argyri
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Patsoukaki, Vagia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Increased OCT3 Expression in Adipose Tissue With Aging: Implications for Catecholamine and Lipid Turnover and Insulin Resistance in Women2023In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 165, no 1, article id bqad172Article in journal (Refereed)
    Abstract [en]

    Background Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women.Methods SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed.Results OCT3 mRNA and protein levels in SAT increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist to hip ratio, and circulating lipids (eg, triglycerides).Conclusion OCT3 mRNA and protein levels in SAT increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging.

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  • 194. Ahmed, Fozia Z.
    et al.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Bloom, Heather
    Cooper, Christopher
    Ellis, Christopher
    Goette, Andreas
    Greenspon, Arnold J.
    Love, Charles J.
    Johansen, Jens Brock
    Philippon, Francois
    Tarakji, Khaldoun G.
    Holbrook, Reece
    Sherfesee, Lou
    Xia, Ying
    Seshadri, Swathi
    Lexcen, Daniel R.
    Krahn, Andrew D.
    Use of healthcare claims to validate the Prevention of Arrhythmia Device Infection Trial cardiac implantable electronic device infection risk score2021In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 23, no 9, p. 1446-1455Article in journal (Refereed)
    Abstract [en]

    AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims.

    METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell's C-statistic for the PADIT score and history of prior CIED infection was 0.76.

    CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.

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  • 195.
    Ahn, Chut Min
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Sandler, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Wegener, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Saldeen, Tom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Effect of indomethacin on thrombin-induced pulmonary edema in the rat1995In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 100, no 2, p. 125-135Article in journal (Refereed)
    Abstract [en]

    The preventive effect of indomethacin on thrombin-induced pulmonary edema was studied in rats. Administration of thrombin caused a significant increase in lung weight, wet weight to dry weight ratio (WW/DW), and relative lung water content. During infusion of thrombin, mean pulmonary artery pressure rose and mean systemic artery pressure fell, PaO2 decreased progressively and there was a continuous rise in pH and PaCO2.

    An inhibitor of cyclooxygenase, indomethacin, at a dose of 1 mg/kg body weight, induced a significant further increase in lung weight (p<0.05), and a tendency towards an increase in WW/DW and water content compared with animals given thrombin alone. Treatment with indomethacin, however, counteracted the elevated pulmonary artery pressure occurring in the early phase after thrombin infusion, but not that in the late phase. Systemic artery pressure was not affected by indomethacin. The increases in pH and PaCO2 after thrombin infusion were attenuated and remained stable almost at baseline level after indomethacin administration. Indomethacin did not prevent the hypoxemia induced by thrombin infusion.

    In conclusion, although indomethacin prevented the early increase in pulmonary artery pressure due to thrombin and the decrease in pH and the increase in PaCO2, it caused lung vascular permeability to protein to increase more than with thrombin alone.

  • 196.
    Ahn, C.M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Sandler, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Wegener, T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Saldeen, Tom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Effect of ibuprofen on thrombin-induced pulmonary edema in the rat1994In: Pulmonary pharmacology, ISSN 0952-0600, Vol. 7, no 6, p. 393-399Article in journal (Refereed)
    Abstract [en]

    The effect of ibuprofen on thrombin-induced pulmonary edema was studied in rats. Thrombin infusion produced a significant increase in lung weight, wet weight/dry weight ratio and relative lung water content, a rise in mean pulmonary arterial pressure and a fall in mean systemic arterial pressure. It also caused a progressive decrease in PaO2 and a continuous increase in pH and PaCO2. Administration of either the S-isomer or R-isomer of ibuprofen at doses of 5 mg/kg body weight prior to thrombin infusion resulted in significant reduction in lung weight, wet weight/dry weight ratio and water content. The wet weight/dry weight ratio and the water content were somewhat lower after infusion of the S-isomer than of the R-isomer. Ibuprofen diminished the thrombin-induced increase in mean pulmonary arterial pressure and attenuated the early and late decrease in mean systemic arterial pressure caused by thrombin. Ibuprofen also stabilized thrombin-induced impairments in PaO2, PaCO2 and pH. The results thus indicate that ibuprofen effectively counteracts hemodynamic changes, stabilizes impairments in arterial blood gas variables and attenuates the increase in lung vascular permeability to protein with pulmonary edema caused by thrombin. The results also indicate a substantial R to S chiral inversion of ibuprofen in vivo in the rat.

  • 197.
    Ahnoff, Martin
    et al.
    Univ Gothenburg, Dept Chem Mol Biol, SE-41296 Gothenburg, Sweden.;Denator AB, Gothenburg, Sweden..
    Cazares, Lisa H.
    US Army Med Res Inst Infect Dis, Mol & Translat Sci, Frederick, MD 21702 USA.;US Army Med Res & Mat Command, DoD Biotechnol High Performance Comp Software App, Telemed & Adv Technol Res Ctr, Ft Detrick, MD 21702 USA..
    Sköld, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Denator AB, Gothenburg, Sweden.;Uppsala Univ, Dept Med Sci Canc Pharmacol & Computat Med, Uppsala, Sweden..
    Thermal inactivation of enzymes and pathogens in biosamples for MS analysis2015In: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 7, no 15, p. 1885-1899Article, review/survey (Refereed)
    Abstract [en]

    Protein denaturation is the common basis for enzyme inactivation and inactivation of pathogens, necessary for preservation and safe handling of biosamples for downstream analysis. While heat-stabilization technology has been used in proteomic and peptidomic research since its introduction in 2009, the advantages of using the technique for simultaneous pathogen inactivation have only recently been addressed. The time required for enzyme inactivation by heat (approximate to 1 min) is short compared with chemical treatments, and inactivation is irreversible in contrast to freezing. Heat stabilization thus facilitates mass spectrometric studies of biomolecules with a fast conversion rate, and expands the chemical space of potential biomarkers to include more short-lived entities, such as phosphorylated proteins, in tissue samples as well as whole-blood (dried blood sample) samples.

  • 198. Ahrens, Richard
    et al.
    Waddell, Amanda
    Seidu, Luqman
    Blanchard, Carine
    Carey, Rebecca
    Forbes, Elizabeth
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilson, Tara
    Cohen, Elizabeth
    Stringer, Keith
    Ballard, Edgar
    Munitz, Ariel
    Xu, Huan
    Lee, Nancy
    Lee, James J.
    Rothenberg, Marc E.
    Denson, Lee
    Hogan, Simon P.
    Intestinal Macrophage/Epithelial Cell-Derived CCL11/Eotaxin-1 Mediates Eosinophil Recruitment and Function in Pediatric Ulcerative Colitis2008In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 181, no 10, p. 7390-7399Article in journal (Refereed)
    Abstract [en]

    Clinical studies have demonstrated a link between the eosinophil-selective chemokines, eotaxins (eotaxin-1/CCL11 and eotaxin-2/CCL24), eosinophils, and the inflammatory bowel diseases, Crohn's disease and ulcerative colitis (UC). However, the cellular source and individual contribution of the eotaxins to colonic eosinophilic accumulation in inflammatory bowel diseases remain unclear. In this study we demonstrate, by gene array and quantitative PCR, elevated levels of eotaxin-1 mRNA in the rectosigmoid colon of pediatric UC patients. We show that elevated levels of eotaxin-1 mRNA positively correlated with rectosigmoid eosinophil numbers. Further, colonic eosinophils appeared to be degranulating, and the levels positively correlated with disease severity. Using the dextran sodium sulfate (DSS)-induced intestinal epithelial injury model, we show that DSS treatment of mice strongly induced colonic eotaxin-1 and eotaxin-2 expression and eosinophil levels. Analysis of eosinophil-deficient mice defined an effector role for eosinophils in disease pathology. DSS treatment of eotaxin-2(-/-) and eotaxin-1/2(-/-) mice demonstrated that eosinophil recruitment was dependent on eotaxin-1. In situ and immunofluorescence analysis-identified eotaxin-1 expression was restricted to intestinal F4/80(+)CD11b(+) macrophages in DSS-induced epithelia] injury and to CD68(+) intestinal macrophages and the basolateral compartment of intestinal epithelial cells in pediatric UC. These data demonstrate that intestinal macrophage and epithelial cell-derived eotaxin-1 plays a critical role in the regulation of eosinophil recruitment in colonic eosinophilic disease such as pediatric UC and provides a basis for targeting the eosinophil/eotaxin-1 axis in UC.

  • 199. Ahrén, B
    et al.
    Skogseid, Britt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin tumörbiologi.
    Endokrina tumörer i mag-tarmkanalen och pancreas2005In: Endokrinology, Liber , 2005Chapter in book (Refereed)
  • 200. Ahrén, Bo
    et al.
    Simonsson, Erik
    Larsson, Hillevi
    Landin-Olsson, Mona
    Torgeirsson, Hlin
    Jansson, Per-Anders
    Sandqvist, Madeléne
    Båvenholm, Peter
    Efendic, Suad
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Dickinson, Sheila
    Holmes, David
    Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.2002In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 25, no 5, p. 869-75Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.

    RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).

    RESULTS: Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.

    CONCLUSIONS: We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.

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