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1.
  • Mårell, Lena, 1957-, et al. (author)
  • Psychological symptoms and self-image of patients with complaints attributed to dental restorative materials
  • 2019
  • In: Clinical Oral Investigations. - : Springer Berlin/Heidelberg. - 1432-6981 .- 1436-3771. ; 23:6, s. 2805-2811
  • Journal article (peer-reviewed)abstract
    • Objectives: The aim was to study self-image and the level of psychological symptoms in patients with symptoms attributed to their dental restorative materials.Materials and methods: A questionnaire containing questions regarding dental and medical history was answered by 257 participants, one group with local oral symptoms only (LSO), and one group with multi-symptoms (M-S). A reference group was randomly selected from a research database at the Department of Psychology, Umeå University, Sweden. The self-image was assessed using the Structural Analysis of Social Behavior (SASB). Psychological symptoms such as somatization, depression, and anxiety were assessed using the Symptom Check List 90 (SCL-90) and the Global Severity Index (GSI) was used to determine the level of psychological symptoms.Results: SASB showed that the M-S group and the LSO-group scored significantly higher on the Bspontaneous^ and Bpositive self-image^ than the reference group. In the SCL-90, the M-S group scored significantly higher than the LSO-group and the references on the somatization subscales. On depression, anxiety, and the GSI scale, the M-S group scored significantly higher than the reference group.Conclusions: The two subgroups scored significantly higher on the SASB Spontaneous and Positive clusters which indicates that these patients have an excessively positive self-image, are very spontaneous and have an overconfidence in themselves compared to the reference group. In the M-S group there was a clear tendency to somatization, depression, and anxiety and they were more psychologically stressed than the reference group.Clinical relevance: Among the patients with illness attributed to their dental materials, the M-S-patients had a significantly higher level of general psychological distress and somatization than the control group which may lead to mental stress.
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2.
  • Tillberg, Anders, et al. (author)
  • Changes in health over time in patients with symptoms allegedly caused by dental restorative materials
  • 2005
  • In: Community Dentistry and Oral Epidemiology. - : John Wiley & Sons, Inc. - 0301-5661 .- 1600-0528. ; 33:6, s. 427-437
  • Journal article (peer-reviewed)abstract
    • Abstract –  Objectives:  In Sweden, many patients with symptoms allegedly caused by their dental materials have exchanged their restorations, but the effects of the exchange have been insufficiently investigated. Therefore, the aim of the study was to describe the change in health over time for these patients and the hypothesis was that the patients could be divided based on their symptoms and that the ability to recover differs between these groups. Furthermore, we also examined if other factors such as replacement of dental restorative materials and follow-up time had any impact on the perceived health status.Methods:  A questionnaire was sent to 614 patients who had been referred to the School of Dentistry, Umeå, Sweden, with symptoms allegedly caused by dental restorative materials. The response rate was 55%.Results:  The risk of having any further complaints was higher for patients with complex symptoms (P = 0.03) and these patients had exchanged their restorations to a significantly larger extent than the others (P = 0.03). The remaining complaints was more frequent among men (P = 0.02). Exchange of dental restorative materials had no significant impact on the ability to recover completely. However, the patients who had exchanged their restorations completely perceived a significantly larger alleviation of their symptoms than the others (P < 0.01), although the frequency of most of the symptoms had increased.Conclusions:  Patients with complex symptoms had a more unfavorable long-term prognosis concerning persistent complaints than those with localized symptoms only. Furthermore, the results indicate that the patients might experience health improvements after removal of their dental restorative materials. The reason for this improvement, however, is unclear. Further analyses regarding other possible explanations than the ‘odontological/medical’ are needed.
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3.
  • Andersson, Tilde, et al. (author)
  • Common skin bacteria protect their host from oxidative stress through secreted antioxidant RoxP
  • 2019
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
  • Journal article (peer-reviewed)abstract
    • Cutibacterium acnes is an abundant skin commensal with several proposed mutualistic functions. A protein with strong antioxidant activity was recently identified from the C. acnes secretome. This protein, termed RoxP, facilitated aerobic bacterial growth in vitro and ex vivo. As reducing events naturally occurred outside of the bacterial cell, it was further hypothesized that RoxP could also serve to modulate redox status of human skin. The biological function of RoxP was here assessed in vitro and in vivo, through oxidatively stressed cell cultures and through protein quantification from skin affected by oxidative disease (actinic keratosis and basal cell carcinoma), respectively. 16S rDNA amplicon deep sequencing and single locus sequence typing was used to correlate bacterial prevalence to cutaneous RoxP abundances. We show that RoxP positively influence the viability of monocytes and keratinocytes exposed to oxidative stress, and that a congruent concentration decline of RoxP can be observed in skin affected by oxidative disease. Basal cell carcinoma was moreover associated with microbial dysbiosis, characterized by reduced C. acnes prevalence. C. acnes's secretion of RoxP, an exogenous but naturally occurring antioxidant on human skin, is likely to positively influence the human host. Results furthermore attest to its prospective usability as a biopharmaceutical.
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4.
  • Ankarberg, Emma, et al. (author)
  • Regionala skillnader i intag av persistenta organiska miljögifter hos förstföderskor i Uppsala, Göteborg och Lycksele
  • 2007
  • Reports (other academic/artistic)abstract
    • Under perioden 2000-2006 samlades bröstmjölk in från förstföderskor i Uppsala, Göteborg, Lund och Lycksele. Syftet med studien var att undersöka om det finns några regionala skillnader i halter av polyklorerade bifenyler (PCBer), klorerade pesticider (hexaklorbensen (HCB), ß-hexaklorocyklohexan (ß-HCH), oxyklordan, trans-nonaklor, DDT och DDT-metaboliter) och bromerade flamskyddsmedel (polybromerade difenyletrar (PBDE) och hexabromcyklododekan (HBCD)) i bröstmjölk. Resultaten visade att vissa signifikanta regionala skillnader i halter av de studerade substanserna förelåg. Skillnaderna var dock små, och inga säkra slutsatser om orsaker till skillnaderna kunde dras. Vissa regionala skillnader i halter av organiska miljögifter i livsmedel har också observerats. I en matkorgsstudie utförd 1999 (Darnerud et al. 2006) köptes livsmedel in i fyra olika städer i Sverige (Malmö, Göteborg, Uppsala och Sundsvall), och högre halter av ΣPCB, ΣDDT och ΣPBDE kunde ses i livsmedel från de södra delarna av Sverige i jämförelse med de norra. Denna tendens till nord-sydlig gradient observerades också i en senare matkorgsstudie som utfördes i samma städer 2005 (Ankarberg et al. 2006). Även den omfattande fiskundersökning som utfördes vid Livsmedelsverket 2000-2003 visade på regionala skillnader i halter i vissa fiskarter (NFA 2003). Studien som redovisas i denna rapport syftar till att genom intagsberäkningar undersöka om det finns regionala skillnader i exponering för organiska miljögifter (dioxiner, dioxinlika PCBer, PCB 153 och p,p´-DDE) från mat. Intagsberäkningarna grundas på en kostenkät, ifylld av mödrarna vid bröstmjölksinsamlingen, med frågor gällande konsumtionen av kött, fågel, fisk, mjölkprodukter, vegetabiliskt fett och ägg under året före graviditeten. Haltdata för de studerade substanserna i olika livsmedel hämtades från undersökningar och kontrollprogram vid Livsmedelsverket. De regionala jämförelser som gjordes inkluderade Uppsala, Göteborg och Lycksele. Den kostenkät som användes i Lund skiljde sig åt från de som användes i Uppsala, Göteborg och Lycksele. Resultaten från Lund kunde därför inte användas i denna undersökning. Trots vissa skillnader i konsumtionsmönster mellan de olika regionerna kunde inte några skillnader i intag av miljögifterna påvisas. Det beräknade medianintaget av dioxiner och dioxinlika PCBer varierade mellan 0,9 och 1,2 pg WHO-TEQ/kg kroppsvikt/dag, mellan 1,3 och 1,9 ng/kg kroppsvikt/dag för PCB 153 och mellan 2,5 och 3,5 ng/kg kroppsvikt/dag för 2 p,p´-DDE. Fisk och skaldjur bidrog till den största delen av intaget av WHO-TEQ (52-61 %). Enligt beräkningarna hade 14 % av kvinnorna intagsnivåer som överskred EU’s tolerabla veckointag för dioxiner och dioxinlika PCBer (14 pg WHO-TEQ/kg kroppsvikt/vecka). Livsmedelsverkets konsumtionsråd gällande fet fisk från Östersjön överskreds av 4 % av kvinnorna, och samtliga av dessa åtta individer fanns med bland dem som överskred TWI. Högexponerade individer karaktäriserades generellt av hög konsumtion av fisk och mjölkprodukter. Det finns inte någon tolerabel intagsnivå framtagen för icke dioxinlika PCBer (t.ex. PCB 153), så för dessa var det inte möjligt att göra några jämförelser. Ingen kvinna i studien överskred JECFA’s tolerabla dagliga intagsnivå för DDT-föreningar (10 μg/kg kroppsvikt/dag). En osäkerhet i de beräknade intagsnivåerna är att det är mycket svårt att minnas och korrekt ange sin konsumtion av olika livsmedel under ett år tillbaka. Dessutom är det troligt att konsumtionen av lax från Östersjön är överskattad eftersom det är mycket ovanligt med sådan fisk i butik. De haltdata som använts i beräkningarna är medel- och medianhalter som kommer från olika analysprojekt vid Livsmedelsverket. Dessa halter kan skilja sig åt från de verkliga nivåerna i de livsmedel som kvinnorna konsumerat. Dessutom användes samma haltdata för samtliga kvinnor, och hänsyn togs alltså inte till eventuella regionala skillnader i livsmedelshalter. Trots dessa osäkerheter tyder resultaten på att svenska förstföderskor från olika delar av landet har exponerats för liknande nivåer av de studerade föreningarna. En korrelationsanalys kunde inte påvisa några samband mellan de beräknade intagen av PCB 153 och p,p´-DDE och nivåerna av dessa substanser i bröstmjölk. Detta beror sannolikt till viss del på att bröstmjölkshalterna av persistenta organiska miljögifter speglar den totala exponeringen under livstiden, och inte bara exponeringen under det senaste året.
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5.
  • Bergdahl, Anders (author)
  • Altered vascular responses in experimental congestive heart failure
  • 1999
  • Doctoral thesis (other academic/artistic)abstract
    • Congestive heart failure is accompanied with increased circulatory levels of several vasoregulatory neurotransmitters and hormones which affect the outcome of this disease. In this thesis the blood levels of several vasoactive peptides in humans with congestive heart failure and their effects on the vasculature by the use of an animal model of heart failure were studied. Patients with congestive heart failure had increased levels of noradrenaline (NA), adrenaline (A), neuropeptide Y, atrial natriuretic peptide (ANP) and antidiuretic hormone. The increased levels of ANP and NA correlated to the survival time in patients with congestive hart failure. Increased levels of NA and A were also found in the animal heart failure model. The passive elastic and active contractile capacity of small mesenteric arteries were attenuated in heart failure animals. Ca2+-mediated and KCl -induced contractions were attenuated in heart failure vessels, an effect due to alterations of a-adrenoceptors. The contractile responses of isolated vessel segments to agonists of the sympathetic nervous system were altered, especially the a2- adrenergic receptor, which mediated an attenuated response in several vascular beds, both in vivo and in vitro, in heart failure animals. The sympathetic co-transmitter neuropeptide Y (NPY) enhanced the response to NA in human omental arteries via the Y1 receptor and this receptor was involved in the modulation of the response to endothelin (ET) -1, U46619 and 5-HT in heart failure vessels. NPY-induced potentiation of ET seem to be mediated by a receptor different from the NPY Y1 type. Endothelin was found to be less potent in large conductance arteries in heart failure while the reverse was noted in small mesenteric arteries. The response mediated through the smooth muscle endothelin B receptor was altered since inhibition of this receptor in endothelium-denuded arteries induced a leftward shift of the concentration-response curve in heart failure but not in control animals. The dilatory response to calcitonin gene-related peptide was attenuated in several arterial beds in heart failure rats. It is concluded that the animal model is suitable for studying the effects of neurotransmitters in heart failure and correlates with findings in humans. Further, several receptor alterations are induced which might influence the outcome of this condition.
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6.
  • Bergdahl, Anders, et al. (author)
  • Neuropeptide Y potentiates noradrenaline-induced contraction through the neuropeptide Y Y1 receptor
  • 1996
  • In: European Journal of Pharmacology. - 1879-0712. ; 316:1, s. 59-64
  • Journal article (peer-reviewed)abstract
    • To elucidate which neuropeptide Y receptor subtype is responsible for the neuropeptide Y-induced potentiation of the noradrenaline-evoked contraction in human omental arteries we used antisense oligodeoxynucleotide (Antisense), the new selective neuropeptide Y Y1 receptor antagonist, BIBP3226 {(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginine-amide} and the reverse transcriptase-polymerase chain reaction (RT-PCR). Neuropeptide Y significantly potentiated the noradrenaline-induced contraction in non-incubated vessels (pEC50 6.4 +/- 0.2 vs. 5.9 +/- 0.2) and in vessels incubated with 1 microM Sense oligodeoxynucleotide (Sense) (pEC50 6.0 +/- 0.1 vs. 5.6 +/- 0.2). In vessels incubated with 1 microM Antisense the potentiating effect of neuropeptide Y was completely abolished. BIBP3226 (1 microM) inhibited the neuropeptide Y-induced potentiation in human omental arteries (pEC50 5.8 +/- 0.3 vs. 6.4 +/- 0.2). Finally, messenger RNA for the neuropeptide Y Y1 receptor was detected using RT-PCR. On the basis of our results we conclude that the neuropeptide Y-induced potentiation of the noradrenaline-induced contraction is mediated by the neuropeptide Y Y1 receptor.
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7.
  • Bergdahl, Anders, et al. (author)
  • The use of DFA/DFAA Analysis for early start up of Assembly System Design
  • 2005
  • In: International Forum on Design for Manufacture and Assembly. - Providence - Warwick, Rhode Island, USA.
  • Conference paper (peer-reviewed)abstract
    • Assembly system design and development is still characterized by uncertainty resulting in increased lead-times in the design and development process and ineffective assembly system solutions. One important reason for this situation is that companies do not use methods for assembly system design and development in the extent needed, simply because there are no methods applicable. Methods developed by academia are still too complicated and not distinct enough, in quantifiable means, concerning the link to assembly system design. In this research four case studies in four different companies have been executed with the objective to find out more about how industry handles assembly system design and if there are possibilities for improvement. The findings in the case studies unambiguously point out that there is a need for a guideline supporting the assembly system design, development and re-design phases. The case studies do also indicate that the information from DFA/DFA2 analysis, valuable for the assembly system design process, is not used within the subsequent assembly system design phase. An assembly system design guideline that uses information and results from the DFA work, together with internal and external demands, would facilitate the assembly system design and development process. This paper will introduce a framework for such a method.
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8.
  • Bergdahl, Basti, et al. (author)
  • Engineering yeast hexokinase 2 for improved tolerance toward xylose-induced inactivation.
  • 2013
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
  • Journal article (peer-reviewed)abstract
    • Hexokinase 2 (Hxk2p) from Saccharomyces cerevisiae is a bi-functional enzyme being both a catalyst and an important regulator in the glucose repression signal. In the presence of xylose Hxk2p is irreversibly inactivated through an autophosphorylation mechanism, affecting all functions. Consequently, the regulation of genes involved in sugar transport and fermentative metabolism is impaired. The aim of the study was to obtain new Hxk2p-variants, immune to the autophosphorylation, which potentially can restore the repressive capability closer to its nominal level. In this study we constructed the first condensed, rationally designed combinatorial library targeting the active-site in Hxk2p. We combined protein engineering and genetic engineering for efficient screening and identified a variant with Phe159 changed to tyrosine. This variant had 64% higher catalytic activity in the presence of xylose compared to the wild-type and is expected to be a key component for increasing the productivity of recombinant xylose-fermenting strains for bioethanol production from lignocellulosic feedstocks.
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9.
  • Bergdahl, Ingvar A., et al. (author)
  • Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes
  • 1997
  • In: Basic and Clinical Pharmacology and Toxicology. - : Wiley. - 0901-9928. ; 81:4, s. 153-158
  • Journal article (peer-reviewed)abstract
    • Over 99% of the lead present in blood is usually found in erythrocytes. To investigate the nature of this selective accumulation of lead in erythrocytes, the specific binding of lead to proteins in human erythrocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal lead-binding protein had a mass of approximately 240 kDa, and adsorption to specific antibodies showed that protein was delta-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocytes was bound primarily to haemoglobin has to be revised. Furthermore, in lead-exposed workers, the percentage of lead bound to ALAD was influenced by a common polymorphism in the ALAD gene. Specifically, in seven carriers of the ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD1 allele whose erythrocytes were matched for blood-lead concentration. The small difference was statistically significant in Wilcoxon matched-pairs signed-rank test (P = 0.03). No ALAD allele-specific difference in ALAD-bound lead was found among 20 unexposed controls. Perhaps the difference in ALAD-bound lead can provide an explanation for the previously reported finding of higher blood-lead levels among carriers of the ALAD2 allele than among ALAD1 homozygotes in lead-exposed populations.
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10.
  • Bergdahl, Lars, 1943, et al. (author)
  • Förankringen till en vågenergiboj i Kattegatt
  • 1981
  • In: Efaringer fra dagens forankringssystemer og krav til morgendagens. Noges sivilingenjörers forening. ; , s. 18-
  • Conference paper (other academic/artistic)abstract
    • Sommaren 1979 genomfördes i sjön Lygnern
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11.
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12.
  • Bergdahl, Lars, 1943, et al. (author)
  • Luftbubbelridå som spärr mot gravitationell och vindgenererad spridning av olja på stagnant vatten
  • 1968
  • Reports (other academic/artistic)abstract
    • Institutionen för vattenbyggnad, Chalmers tekniska högskola, har på uppdrag av AB Atlas Copco utfört en laboratoriemätning av en luftbubbelridås effekivivitet som spärr mot gravitationell och vingenererad spridning av olja på stagnant vatten. Målsättmniongen har varit att försöka bestämma det för erhållande av minimalt oljeläckage erforderliga luftflödet i ridån som funktion av oljans täthet och viskositet vid varierande vind- och vågförhållanden.
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13.
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14.
  • Carlsson, Sigrid, 1982, et al. (author)
  • Effects of surgeon variability on oncologic and functional outcomes in a population-based setting.
  • 2014
  • In: BMC urology. - : Springer Science and Business Media LLC. - 1471-2490. ; 14
  • Journal article (peer-reviewed)abstract
    • Oncologic and functional outcomes after radical prostatectomy (RP) can vary between surgeons to a greater extent than is expected by chance. We sought to examine the effects of surgeon variation on functional and oncologic outcomes for patients undergoing RP for prostate cancer in a European center.
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15.
  • Chatziioannou, Aristotelis, et al. (author)
  • Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Journal article (peer-reviewed)abstract
    • We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.
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16.
  • Espín-Pérez, Almudena, et al. (author)
  • Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs)
  • 2019
  • In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
  • Journal article (peer-reviewed)abstract
    • PCBs are classified as xenoestrogens and carcinogens and their health risks may be sex-specific. To identify potential sex-specific responses to PCB-exposure we established gene expression profiles in a population study subdivided into females and males. Gene expression profiles were determined in a study population consisting of 512 subjects from the EnviroGenomarkers project, 217 subjects who developed lymphoma and 295 controls were selected in later life. We ran linear mixed models in order to find associations between gene expression and exposure to PCBs, while correcting for confounders, in particular distribution of white blood cells (WBC), as well as random effects. The analysis was subdivided according to sex and development of lymphoma in later life. The changes in gene expression as a result of exposure to the six studied PCB congeners were sex- and WBC type specific. The relatively large number of genes that are significantly associated with PCB-exposure in the female subpopulation already indicates different biological response mechanisms to PCBs between the two sexes. The interaction analysis between different PCBs and WBCs provides only a small overlap between sexes. In males, cancer-related pathways and in females immune system-related pathways are identified in association with PCBs and WBCs. Future lymphoma cases and controls for both sexes show different responses to the interaction of PCBs with WBCs, suggesting a role of the immune system in PCB-related cancer development.
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17.
  • Georgiadis, Panagiotis, et al. (author)
  • Omics for prediction of environmental health effects : Blood leukocyte-based cross-omic profiling reliably predicts diseases associated with tobacco smoking.
  • 2016
  • In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
  • Journal article (peer-reviewed)abstract
    • The utility of blood-based omic profiles for linking environmental exposures to their potential health effects was evaluated in 649 individuals, drawn from the general population, in relation to tobacco smoking, an exposure with well-characterised health effects. Using disease connectivity analysis, we found that the combination of smoking-modified, genome-wide gene (including miRNA) expression and DNA methylation profiles predicts with remarkable reliability most diseases and conditions independently known to be causally associated with smoking (indicative estimates of sensitivity and positive predictive value 94% and 84%, respectively). Bioinformatics analysis reveals the importance of a small number of smoking-modified, master-regulatory genes and suggest a central role for altered ubiquitination. The smoking-induced gene expression profiles overlap significantly with profiles present in blood cells of patients with lung cancer or coronary heart disease, diseases strongly associated with tobacco smoking. These results provide proof-of-principle support to the suggestion that omic profiling in peripheral blood has the potential of identifying early, disease-related perturbations caused by toxic exposures and may be a useful tool in hazard and risk assessment.
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18.
  • Gerdtsson, Axel, et al. (author)
  • Initial surveillance in men with marker negative clinical stage IIA non-seminomatous germ cell tumours
  • 2024
  • In: BJU INTERNATIONAL. - : John Wiley & Sons. - 1464-4096 .- 1464-410X.
  • Journal article (peer-reviewed)abstract
    • Objectives To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. Patients and methods Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. Results Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. Conclusions Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.
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19.
  • Gerdtsson, Axel, et al. (author)
  • Unilateral or Bilateral Retroperitoneal Lymph Node Dissection in Nonseminoma Patients with Postchemotherapy Residual Tumour? Results from RETROP, a Population-based Mapping Study by the Swedish Norwegian Testicular Cancer Group
  • 2022
  • In: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 5:2, s. 235-243
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection. OBJECTIVE: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm. DESIGN, SETTING, AND PARTICIPANTS: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured. RESULTS AND LIMITATIONS: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients. CONCLUSIONS: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection. PATIENT SUMMARY: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer.
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20.
  • Glynn, Anders, et al. (author)
  • Regional differences in levels of chlorinated and brominated pollutants in mother's milk from primiparous women in Sweden.
  • 2011
  • In: Environment international. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 37:1, s. 71-9
  • Journal article (peer-reviewed)abstract
    • Early life exposure to halogenated persistent organic pollutants, such as polychlorinated biphenyls (PCBs), the DDT metabolite p,p'-dichlorodiphenyldichloroethane (p,p'-DDE), polybrominated diphenylethers (PBDEs), and hexabromocyclododecane (HBCD), may affect human health. We determined if there are regional differences in mother's milk levels of these compounds in Sweden. In year 2000-2004, milk was sampled from 204 randomly recruited primiparas from four regions of Sweden. Levels of the compounds were measured by gas chromatography with dual electron-capture detectors. Women were recruited at delivery in three hospitals located in urban areas in southern and central Sweden (Lund, Gothenburg and Uppsala), and in one hospital located in a more rural area in northern Sweden (Lycksele). Information about dietary habits and medical/life-style factors were collected by questionnaires. Among PCB congeners, CB 153, CB 138 and CB 180 showed the highest median concentrations (18-48 ng/g mother's milk lipid), whereas more than 50% of the women had CB 52, CB 101, CB 114, and CB 157 levels below the LOQ (0.3-1.5 ng/g lipid). Median p,p'-DDE levels were in the range of 46-78 ng/g lipid. BDE 47 showed the highest median concentrations (1-2 ng/g lipid) among the brominated compounds, whereas more than 50% of the women had levels of BDE 28, BDE 66, BDE 138, BDE 154, and HBCD below the LOQ (0.05-0.10 ng/g lipid). Regional differences in median organohalogen compound concentrations were small, less than 2-fold. Lycksele women generally had the lowest levels of Σmono-and Σdi-ortho PCBs, mainly due to a lower average age. In contrast, these women had higher tetra- to penta-brominated PBDE levels, but no diet or life-style factor could explain this finding. Wide ranges of PBDEs and HBCD levels (up to 200-fold) were found, especially in the Lycksele area. The highest levels of PBDE were in the range of average levels found in mother's milk from North America, suggesting that food may not be the only source of exposure to PBDEs among some individuals.
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21.
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22.
  • Holmgren, Anders, et al. (author)
  • Troponin T but not C-reactive protein is associated with future surgery for aortic stenosis : a population based nested case-referent study
  • 2020
  • In: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 7:2
  • Journal article (peer-reviewed)abstract
    • Aims: High-sensitivity troponin T (hs-TnT) and high-sensitivity C reactive protein (hs-CRP) may convey prognostic information in patients with aortic stenosis (AS). This study evaluated if hs-TnT and hs-CRP associate with myocardial mass, and risk of future surgery for AS.Methods: In total, 336 patients (48% women) with surgery for AS with previous participation in large population surveys were identified. Preoperatively, myocardial mass and the presence of coronary artery disease (CAD) were assessed. Two matched referents were allocated for each case, and hs-TnT and hs-CRP were determined in stored plasma from the baseline survey. Conditional logistic regression analysis was used to estimate the risk (OR (95% CI)) related to one (natural logarithm) SD increase in hs-TnT and hs-CRP. Kaplan-Mayer and Cox regression analyses were used to evaluate time to surgery.Results: Median age (IQR) was 59.8 (10.3) years at survey, and median time between survey and surgery was 10.9 (9.3) years. Hs-TnT was independently associated with surgery for AS (1.24 (1.06–1.44)) irrespective of CAD, whereas Hs-CRP was not (1.05 (0.90–1.22)). Elevated hs-TnT levels at survey associated with shorter time to surgery (p<0.001), and with increased myocardial mass (p=0.002). Hs-CRP did not associate with time to surgery or with myocardial mass.Conclusions: Hs-TnT—but not hs-CRP—was associated with increased risk of—and shorter time to—future surgery for AS. Hs-TnT associated with myocardial mass at surgery which indicates that hs-TnT could be a potential biomarker for determining intervention.
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23.
  • Hou, Mingyan, et al. (author)
  • Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure
  • 1999
  • In: Life Sciences. - 1879-0631. ; 65:11, s. 1195-1206
  • Journal article (peer-reviewed)abstract
    • We wanted to study the expression of P2-receptors at the mRNA-level in the heart and if it is affected by congestive heart failure (CHF). To quantify the P2 receptor mRNA-expression we used a competitive RT-PCR protocol which is based on an internal RNA standard. The P2 receptor mRNA-expression was quantified in hearts from CHF rats and compared to sham-operated rats. Furthermore, the presence of receptor mRNA was studied in the myocardium from patients with heart failure. In the sham operated rats the G-protein coupled P2Y-receptors were expressed at a higher level than the ligand gated ion-channel receptor (P2X1). Among the P2Y-receptors the P2Y6-receptor was most abundantly expressed (P2Y6 > P2Y1 > P2Y2 = P2Y4 > P2X1). A prominent change was seen for the P2X1- and P2Y2-receptor mRNA levels which were increased 2.7-fold and 4.7-fold respectively in the myocardium from the left ventricle of CHF-rats. In contrast, the P2Y1-, P2Y4- and P2Y6-receptor mRNA levels were not significantly altered in CHF rats. In human myocard the P2X1-, P2Y1-, P2Y2-, P2Y6- and P2Y11-receptors were detected by RT-PCR in both right and left atria and ventricles, while the P2Y4-receptor band was weak or absent. In conclusion, most of the studied P2-receptors were expressed in both rat and human hearts. Furthermore, the P2X1- and P2Y2-receptor mRNA were upregulated in CHF, suggesting a pathophysiological role for these receptors in the development of heart failure.
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24.
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25.
  • Kenger, Patrick, et al. (author)
  • Modular Product Verifications Based on Design for Assembly
  • 2005
  • In: International Forum on Design for Manufacture and Assembly. - Providence - Warwick, Rhode Island, USA.
  • Conference paper (peer-reviewed)abstract
    • The desire to conquer markets through advanced product design and trendy business strategies are still predominant approaches in industry today. In fact, product development has acquired an ever more central role in the strategic planning of companies, and it has extended its influence to R&D funding levels as well. It is not surprising that many national R&D project frameworks within the EU today are dominated by product development topics, leaving production engineering, robotics, and systems on the sidelines. The reasons may be many but, unfortunately, the link between product development and the production processes they cater for are seldom treated in depth. The issue dealt with in this article relates to how product development is applied in order to attain the required production quality levels a company may desire, as well as how one may counter assembly defects and deviations through quantifiable design approaches.It is recognized that product verifications (tests, inspections, etc.) are necessary, but the application of these tactics often result in lead-time extensions and increased costs. Modular architectures improve this by simplifying the verification of the assembled product at module level. Furthermore, since Design for Assembly (DFA) has shown the possibility to identify defective assemblies, it may be possible to detect potential assembly defects already in the product and module design phase. The intention of this paper is to discuss and describe the link between verifications of modular architectures, defects and design for assembly. The paper is based on literature and case studies; tables and diagrams are included with the intention of increasing understanding of the relation between poor designs, defects and product verifications.
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26.
  • Kenger, Patrik, et al. (author)
  • Product verification and defect repair - status and considerations
  • 2004
  • In: 2nd International Precision Assembly Seminar, IPAS. - Bad Hofgastein, Austria.
  • Conference paper (peer-reviewed)abstract
    • Product verifications have become a cost-intensive and time-consuming aspect of modern electronics production, but with the onset of an ever-increasing miniaturisation, these aspects will become even more cumbersome. One may also go as far as to point out that certain precision assembly, such as within the biomedical sector, is legally bound to have 0 defects within production. Since miniaturisation and precision assembly will soon become a part of almost any product, the verifications phases of assembly need to be optimised in both functionality and cost. Another aspect relates to the stability and robustness of processes, a pre-requisite for flexibility. Furthermore, as the re-engineering cycle becomes ever more important, all information gathered within the ongoing process becomes vital. In view of these points, product, or process verification may be assumed to be an important and integral part of precision assembly. In this paper, product verification is defined as the process of determining whether or not the products, at a given phase in the life-cycle, fulfil the established specifications. Since the product is given its final form and function in the assembly, the product verification normally takes place somewhere in the assembly line which is the focus for this paper.
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27.
  • Krauskopf, Julian, et al. (author)
  • Blood Transcriptome Response to Environmental Metal Exposure Reveals Potential Biological Processes Related to Alzheimer's Disease
  • 2020
  • In: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 8
  • Journal article (peer-reviewed)abstract
    • Alzheimer's disease (AD) is a neurodegenerative disease which is manifested by a progressive and irreversible decline of cognition, memory loss, a shortened attention span, and changes in personality. Aging and genetic pre-dispositions, particularly the presence of a specific form of apolipoprotein E (APOE), are main risk factors of sporadic AD; however, a large body of evidence has shown that multiple environmental factors, including exposure to toxic metals, increase the risk for late onset AD. Lead (Pb) and cadmium (Cd) are ubiquitous toxic metals with a wide range of applications resulting in global distribution in the environment and exposure of all living organisms on earth. In addition to being classified as carcinogenic (Cd) and possibly carcinogenic (Pb) to humans by the International Agency for Research on Cancer, both compounds disrupt metal homeostasis and can cause toxic responses at the cellular and organismal levels. Pb toxicity targets the central nervous system and evidence for that has emerged also for Cd. Recent epidemiological studies show that both metals possibly are etiological factors of multiple neurodegenerative diseases, including Alzheimer's disease (AD). To further explore the association between metal exposure and AD risk we applied whole transcriptome gene expression analysis in peripheral blood leukocytes (PBLs) from 632 subjects of the general population, taken from the EnviroGenomarkers project. We used linear mixed effect models to associate metal exposure to gene expression after adjustment for gender, age, BMI, smoking, and alcohol consumption. For Pb exposure only few associations were identified, including a downregulation of the human eukaryotic translation initiation factor 5 (eIF5). In contrast, Cd exposure, particularly in males, revealed a much stronger transcriptomic response, featuring multiple pathways related to pathomolecular mechanisms of AD, such as endocytosis, neutrophil degranulation, and Interleukin-7 signaling. A gender stratified analysis revealed that the Cd responses were male-specific and included a downregulation of the APOE gene in men. This exploratory study revealed novel hypothetical findings which might contribute to the understanding of the neurotoxic effects of chronic Pb and Cd exposure and possibly improve our knowledge on the molecular mechanisms linking metal exposure to AD risk.
  •  
28.
  • Krauskopf, Julian, et al. (author)
  • MicroRNA profile for health risk assessment : environmental exposure to persistent organic pollutants strongly affects the human blood microRNA machinery
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Journal article (peer-reviewed)abstract
    • Persistent organic pollutants (POPs) are synthetic chemical substances that accumulate in our environment. POPs such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) have been classified as carcinogenic to humans and animals. Due to their resistance to biodegradation humans are still exposed to these compounds worldwide. We aim to evaluate the miRNA and transcriptomic response of a human population exposed to POPs. The miRNA and transcriptomic response was measured in blood of healthy subjects by microarray technology and associated with the serum concentrations of six PCB congeners, DDE (a common DDT metabolite), and HCB. A total of 93 miRNA levels appeared significantly associated with the POP-exposure (FDR < 0.05). The miRNA profile includes four tumor suppressor miRNAs, namely miR-193a-3p, miR-152, miR-31-5p and miR-34a-5p. Integration of the miRNA profile with the transcriptome profile suggests an interaction with oncogenes such as MYC, CCND1, BCL2 and VEGFA. We have shown that exposure to POPs is associated with human miRNA and transcriptomic responses. The identified miRNAs and target genes are related to various types of cancer and involved in relevant signaling pathways like wnt and p53. Therefore, these miRNAs may have great potential to contribute to biomarker-based environmental health risk assessment.
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29.
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30.
  • Kristenson, Margareta, 1950-, et al. (author)
  • Ultrasound determined carotid and femoral atherosclerosis in Lithuanian and Swedish men : The LiVicordia study
  • 2000
  • In: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 151:2, s. 501-508
  • Journal article (peer-reviewed)abstract
    • Coronary heart disease mortality is four times higher in Lithuanian compared to Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear transducer) and staff, we compared the amount of atherosclerosis in carotid and femoral arteries in 100 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Linköping, Sweden. Atherosclerotic plaques were more abundant in Vilnius men compared to Linköping men (53 versus 28% in the common carotid artery, 73 versus 37% in the common femoral artery, P<0.001 for both). Plaques were thicker and more extended in arteries of Vilnius men, and an ultrasound atherosclerosis score was higher in both carotid and femoral arteries (P<0.001 for all). More Vilnius men had a maximal intima-media thickness of the common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid artery was higher in Vilnius men (P<0.001). In a linear regression model of the pooled material, after adjustment for city was made, smoking, systolic blood pressure, low density lipoprotein cholesterol and β-carotene (inversely) significantly contributed to a high total ultrasound score (r2=0.32). These findings show that the higher coronary mortality noted in Lithuanian men goes together with a higher prevalence of early peripheral atherosclerosis.
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31.
  • Lignell, Sanna, et al. (author)
  • Regionala skillnader i halter av persistenta organiska miljögifter i bröstmjölk från förstföderskor i Uppsala, Göteborg, Lund och Lycksele
  • 2005
  • Reports (other academic/artistic)abstract
    • Under perioden 2000-2004 samlades bröstmjölk in från förstföderskor i Uppsala, Göteborg, Lund och Lycksele. Syftet med studien var att undersöka om det finns några regionala skillnader i halter av polyklorerade bifenyler (PCBer), klorerade pesticider/metaboliter (hexaklorbensen (HCB), ß-hexaklorocyklohexan (ß-HCH), oxyklordan, trans-nonaklor, DDT och DDT-metaboliter) och bromerade flamskyddsmedel (polybromerade difenyletrar (PBDE) och hexabromcyklododekan (HBCD)) i bröstmjölk. Resultaten från studien kommer att användas vid riskvärdering av miljöföroreningar i livsmedel, samt vid riskvärdering av spädbarns exponering under fosterstadiet och amningsperioden. Efter justering för faktorer som är kända för att påverka halten av organiska miljöföroreningar i bröstmjölk (ålder, BMI (body mass index), viktsuppgång under graviditet etc.) kunde vissa signifikanta regionala skillnader i halter av de studerade substanserna observeras. Skillnaderna var dock små, och inga säkra slutsatser om orsaker till skillnaderna kan dras. De justerade geometriska medelhalterna av vissa PCB-kongener i bröstmjölk var något lägre i Göteborg och högre i Lund och Lycksele jämfört med Uppsala. Den största skillnaden visades för CB 167, vars justerade medelhalt var två gånger högre i Lund jämfört med Göteborg. Även för de klorerade pesticiderna var skillnaderna i medelhalter mellan de olika regionerna små. De justerade medelhalterna av ß-HCH, trans-nonaklor och p,p’-DDT var något lägre i bröstmjölk från kvinnor i Göteborg jämfört med Uppsala och den justerade medelhalten av ß-HCH var högre i Lund jämfört med Uppsala. Generellt observerades tendenser till en Uformad syd-nord trend, med de högsta halterna av PCBer och klorerade pesticider i Lund och Lycksele och lägre halter i Göteborg och Uppsala. Orsakerna till dessa regionala skillnader är fortfarande oklara. Små skillnader i halter av PBDE i de olika regionerna kunde visas. Den största skillnaden observerades för BDE 99, vars justerade medelhalt var 72% högre i Lycksele jämfört med Lund. För BDE 47, 99, 100 och 153 påvisades en signifikant positiv syd-nord trend. Studien är inte tillräckligt omfattande för att orsakerna till denna trend ska kunna identifieras. Inga regionala skillnader i halter av HBCD i bröstmjölk kunde observeras.
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32.
  • Ljungberg, Johan, et al. (author)
  • Lipoprotein(a) and the Apolipoprotein B/A1 Ratio Independently Associate With Surgery for Aortic Stenosis Only in Patients With Concomitant Coronary Artery Disease
  • 2017
  • In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 6:12
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Aortic stenosis (AS) has different clinical phenotypes, including AS with or without concomitant coronary artery disease (CAD). It is unknown whether these phenotypes share the same risk factors. In particular, lipoprotein(a) [Lp(a)] and apolipoproteins (Apo) are associated with AS, but it is unknown whether these associations differ among phenotypes. In this prospective analysis we examined the impact of Lp(a) and Apo in subgroups of patients with AS.METHODS AND RESULTS: We identified 336 patients (mean age at survey 56.7 years, 48% female) who underwent surgery for AS after a median 10.9 years (interquartile range 9.3 years), participants in 1 of 3 large population surveys. For each patient, 2 matched referents were allocated. Lp(a) and Apo were analyzed in the baseline samples. Uni- and multivariable logistic regression analyses were used to estimate risks related to a 1 (ln) standard deviation increase in Lp(a) and the ratio of Apo B to Apo A1 (Apo B/A1 ratio). High levels of Lp(a) predicted surgery for AS in 203 patients with concomitant CAD (odds ratio [95% confidence intervals]) (1.29 [1.07-1.55]), but not in 132 patients without CAD (1.04 [0.83-1.29]) in the fully adjusted model. Similarly, a high Apo B/A1 ratio predicted surgery in patients with concomitant CAD (1.43 [1.16-1.76]) but not in those without CAD (0.87 [0.69-1.10]).CONCLUSIONS: High levels of Lp(a) and a high Apo B/A1 ratio were associated with surgery for AS in patients with concomitant CAD but not in those with isolated AS. This finding may lead to a new avenue of research for targeted risk factor interventions in this population.
  •  
33.
  • Ljungberg, Johan, et al. (author)
  • Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis
  • 2019
  • In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 79:7, s. 524-530
  • Journal article (peer-reviewed)abstract
    • Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR(cystatin C) and eGFR(creatinine) and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR(cystatin C) and eGFR(creatinine). A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFR(cystatin C) and eGFR(creatinine) was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.
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34.
  • Ljungberg, Johan, et al. (author)
  • Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement
  • 2018
  • In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 138:6
  • Journal article (peer-reviewed)abstract
    • Background: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights. Methods: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study. Results: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease. Conclusions: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.
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35.
  • Malmsjö, Malin, et al. (author)
  • Congestive heart failure induces downregulation of P2X1-receptors in resistance arteries
  • 1999
  • In: Cardiovascular Research. - 1755-3245. ; 43:1, s. 219-227
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Congestive heart failure (CHF) is accompanied by enhanced peripheral sympathetic nerve activity, increased vascular resistance and impaired peripheral blood flow. Besides noradrenaline and neuropeptide Y, the sympathetic nervous system also releases ATP, which has contractile effects mediated by different subtypes of P2-receptors on the vascular smooth muscle cells. The present study was designed to examine postsynaptic changes of the contractile responses to ATP and other extracellular nucleotides in CHF. METHODS: CHF was induced by left coronary artery ligation resulting in a reproducible myocardial infarction in Sprague-Dawley rats. Contractile responses were examined in cylindrical segments of aorta and the mesenteric artery after endothelium removal. To determine if an altered response was regulated on the transcriptional level, competitive reverse transcription polymerase chain reaction (RT-PCR) was used to estimate the amount of P2X1-receptor mRNA. RESULTS: ATP, which is both a P2X1- and a P2Y-receptor agonist, induced a weaker contraction in the mesenteric artery from CHF as compared to sham operated rats. A decrease in both potency and maximum contraction was shown for the selective P2X1-receptor agonist, alpha beta-MeATP, in the mesenteric artery (pEC50 = 6.04 vs. 5.76, Cmax = 57% vs. 33%, sham vs. CHF operated rats), but not in the aorta. Competitive RT-PCR also revealed decreased P2X1-receptor mRNA levels in CHF operated rats in the mesenteric artery (9106 x 10(3) vs. 714 x 10(3) molecules/microgram, sham vs. CHF operated rats), while it remained unaltered in the aorta. To study the P2Y-receptor induced contractile effects, the P2X1-receptors were first desensitised with alpha beta-MeATP (10(-5) M for 8 min). After P2X1-receptors desensitisation, UTP and UDP induced strong contractions in both the mesenteric artery and in the aorta, while ATP and ADP were much less effective. These contractions were not altered by CHF, indicating that vascular contraction mediated by P2Y-receptors are unaffected by CHF. CONCLUSION: CHF induces downregulation of P2X1-receptor stimulated contraction in the mesenteric artery depending on decreased mRNA synthesis for the receptor, while the P2Y-receptor activity remains unchanged. Downregulation of P2X1-receptors appears to be specific for peripheral resistance arteries. This may represent a compensatory response to enhanced peripheral sympathetic nerve activity and increased vascular resistance in CHF.
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36.
  • Malmsjö, Malin, et al. (author)
  • Enhanced acetylcholine and P2Y-receptor stimulated vascular EDHF-dilatation in congestive heart failure
  • 1999
  • In: Cardiovascular Research. - 1755-3245. ; 43:1, s. 200-209
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Congestive heart failure (CHF) is accompanied by impaired peripheral blood flow and endothelial dysfunction with decreased release of nitric oxide (NO). Strong evidence supports the existence of another vasodilatory substance, endothelium derived hyperpolarising factor (EDHF), which has not previously been studied in CHF. METHOD: CHF was induced by left coronary artery ligation resulting in a reproducible myocardial infarction in Sprague Dawley rats. Vasodilatory responses to acetylcholine and extracellular nucleotides (ATP, ADP beta S, ADP and UTP) were examined in cylindrical segments of the mesenteric artery, precontracted with noradrenaline. The combined NO- and EDHF-dilatation (after inhibition of cyclo-oxygenase pathways) was called "total dilatation", as indomethacin had only minor effects in this system. NO-dilatation was studied in segments pretreated with indomethacin and the potassium channel inhibitors charybdotoxin (10(-7.5) M) and apamin (10(-6) M), while EDHF-dilatations were studied in the presence of indomethacin (10(-5) M) and L-NOARG (10(-3.5) M). RESULTS: EDHF-dilatations in CHF were strongly up-regulated for ACh (36% vs. 73%; sham vs. CHF operated rats), ADP beta S (10% vs. 42%), ADP (0% vs. 21%) and UTP (3% vs. 35%). These dilatations were abolished by a combination of charybdotoxin and apamin, confirming that they were mediated by EDHF. The NO-dilatations on the other hand were down-regulated in CHF as compared to sham operated rats for ACh (93% vs. 76%; sham vs. CHF operated rats), ADP beta S (61% vs. 37%). ADP (60% vs. 30%), ATP (49% vs. 34%) and UTP (65% vs. 47%), while a minor decrease was seen in the total dilatation for ACh (87% vs. 75%; sham vs. CHF operated rats), ADP beta S (47% vs. 42%), ADP (59% vs. 39%), ATP (52% vs. 39%) and UTP (59% vs. 44%). CONCLUSION: In this model of non-atherosclerotic CHF there was a minor decrease in the total dilatation and a marked down-regulation of the NO-mediated dilatation, while the EDHF-dilatation was up-regulated. Increased EDHF-activity in CHF may represent a compensatory response to decreased NO-activity to preserve endothelial function and tissue perfusion.
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37.
  • Mårell, Lena, 1957- (author)
  • A multidisciplinary study of patients with signs or symptoms attributed to dental restorative materials
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • Anxiety for adverse health effects attributed to dental restorative materials especially dentalamalgam, have been discussed extensively off and on the last 30 years. The possible health effect ofamalgam and health effect of replacements of amalgam, have been extensively studied but theresults are inconclusive and the etiology of the reactions are not entirely elucidated. Furthermore,the question of psychological influence on symptoms attributed to dental restorative materials hasbeen raised and need further examination.The aims of this thesis were to describe the change in health over time for patient with symptomsattributed to their dental materials and to determine whether replacement of their dentalrestorative materials had any impact on their perceived health. Furthermore, to determine anddescribe the personality, self-image, level of psychological symptoms and stress among thesepatients and compare the results with those of healthy controls. Finally, to evaluate regression ofLichenoid Contact Reactions and Oral lichen Planus after replacement of the dental materials.A questionnaire was mailed to 614 patients that had been referred to the School of Dentistry, Umeå,Sweden with symptoms attributed to dental materials. Among these patients a subgroup with orallichen also underwent a clinical examination at follow-up.The result showed that patients with complex symptoms had a more unfavorable long-termprognosis concerning persistent complaints than those with local symptoms only. The oralsymptoms had decreased between baseline and follow-up and the general symptoms had increased.The increase in general symptoms was contradictory since many patients experienced healthimprovement after removal of their dental restorative materials. Concerning personality thepatients was characterized mainly by high persistence and by high fatigability and asthenia as wellas psychosocially learned high self-acceptance. Regarding self-image, both patients with LocalSymptoms Only and patients with Multi Symptoms, scored significantly higher on "spontaneous"and "positive self-image" than the reference group. The Multi symptoms group scored significantlyhigher on psychological symptoms compared to the reference group. However, the Local symptomsgroup did not differ from the references. The remission of oral lesions was after an exchange ofdental materials was seen to a greater extent in patients with Lichenoid Contact Reaction than inpatients with Oral Lichen Planus. Regarding psychological parameters, there were no significantdifferences between the groups.In conclusion symptoms related to dental restorative materials seem to be multi-factorial wheredental, medical, social, and psychological factors may be involved. Patient with complex symptomshave a more unfavorable prognosis than patient with local symptoms only. Patient with symptomsself-related to their dental materials may feel improvement in general health after an exchange ofdental materials. The group of patients seems to represent personalities that could be vulnerable inthe demanding modern society, and the various mental and somatic symptoms can be interpretedas attributed to dental fillings. Patients with Local Symptoms or Multi Symptoms are equalconcerning self-image, they are impulsive with an elevated positive self-image, that can result indifficulties in setting limits. Thus in combination with high demands may result in mental stress.The Multi Symptoms group was more psychologically stressed than the group with Local SymptomsOnly and the references. Therefore, before an exchange of dental materials is commenced inpatients with oral lichenoid lesions, a correct diagnosis is needed.
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38.
  • Mårell, Lena, et al. (author)
  • Regression of oral lichenoid lesions after replacement of dental restorations
  • 2014
  • In: Journal of Oral Rehabilitation. - : Wiley-Blackwell. - 1365-2842 .- 0305-182X. ; 41:5, s. 381-391
  • Journal article (peer-reviewed)abstract
    • The aim of the study was to determine the prognosis and to evaluate the regression of lichenoid contact reactions (LCR) and oral lichen planus (OLP) after replacement of dental restorative materials suspected as causing the lesions. Forty-four referred patients with oral lesions participated in a follow-up study that was initiated an average of 6years after the first examination at the Department of Odontology, i.e. the baseline examination. The patients underwent odontological clinical examination and answered a questionnaire with questions regarding dental health, medical and psychological health, and treatments undertaken from baseline to follow-up. After exchange of dental materials, regression of oral lesions was significantly higher among patients with LCR than with OLP. As no cases with OLP regressed after an exchange of materials, a proper diagnosis has to be made to avoid unnecessary exchanges of intact restorations on patients with OLP.
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39.
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40.
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41.
  • Schmidt, Viktor, et al. (author)
  • Epidemiology, treatment, and mortality of 3,983 scapula fractures from the Swedish fracture register
  • 2024
  • In: Journal of shoulder and elbow surgery. - : Elsevier. - 1058-2746 .- 1532-6500.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Scapula fractures are relatively uncommon, accounting for <1% of all fractures and approximately 3-5% of shoulder girdle fractures. This study comprehensively describes the epidemiology, fracture classification, treatment, and mortality associated with scapula fractures within a large adult Swedish population.METHODS: This observational study included all patients ≥18 years old at the time of injury with a scapula fracture (ICD S42.1) registered in the Swedish Fracture Register between March 2011 and June 2020. Variables studied were age, sex, and injury mechanism, including energy level, fracture classification, associated fractures, treatment, and mortality.RESULTS: We included 3,930 patients (mean age 58 years, SD 18, 64% men) with 3,973 scapula fractures. Some 22% of the fractures were caused by high-energy trauma and 21% had at least one associated fracture. High energy-injuries were most common in glenoid neck (44%) and scapular body (35%) fractures. However, same-level falls were the most common cause of glenoid rim (62%) and intra-articular glenoid (55%) fractures. Clavicle fractures (9%) and proximal humerus fractures (5%) were the most commonly associated fractures. The most common fracture types were the glenoid rim (n=1,289, 32%) and scapular body (n=1,098, 28%) fractures. Nonoperative treatment was performed in 81% of patients. Glenoid rim and intra-articular glenoid fractures were treated operatively in over 30% of cases. The mortality rate for the whole cohort was 4% at 1 year.CONCLUSIONS: Scapula fractures are predominately sustained by men. High energetic injuries and associated fractures are present in one in five patients. Nonoperative treatment is chosen in four of five patients, but for some fracture types one in three undergo surgery.
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42.
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43.
  • Söfteland, John M., 1977, et al. (author)
  • Longevity of anti-spike and anti-nucleocapsid antibodies after COVID-19 in solid organ transplant recipients compared to immunocompetent controls.
  • 2022
  • In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 22:4, s. 1245-1252
  • Journal article (peer-reviewed)abstract
    • Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG-antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n=65) were matched with controls (n=65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG-antibodies against N- and S-antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1-month P=0.007, 3-months P<0.001, 6-months P=0.019 and 9-months P=0.021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at one month (p=0.005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.
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44.
  • Thor, Anna, et al. (author)
  • Primary retroperitoneal lymph node dissection as treatment for low-volume metastatic seminoma in a population-based cohort : the Swedish Norwegian testicular cancer group experience
  • 2024
  • In: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 65, s. 13-19
  • Journal article (peer-reviewed)abstract
    • Background and objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy.Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS).Key findings and limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13–24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16–30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4–14). PFS was 90% (95% confidence interval: 0.86–1) and OS was 100% at 24 mo.Conclusions and clinical implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity.Patient summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden.
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45.
  • Wennberg, Maria, et al. (author)
  • Mercury concentrations in pregnant women in circumpolar Sweden (Kiruna)
  • 2018
  • Reports (other academic/artistic)abstract
    • High exposure to mercury have been found in populations living in circumpolar areas, due to high consumption of sea food and accumulation of mercury closer to the north pole. The developing fetus is especially sensitive to effects of mercury. Exposure to mercury has previously been examined in pregnant women in Sweden, but not in pregnant women residing in Sweden north of the polar circle.In the years 2015-2016, mercury was measured in whole blood from 51 pregnant women living in the city of Kiruna in circumpolar Sweden, taking part in an international comparison between eight circumpolar countries. This report presents the Swedish results on mercury concentrations and associations with some exposure determinants. Also, compliance to dietary advice on fish consumption, appointed to fertile women, was examined.The median concentration of total-Hg in whole blood was 0.40 μg/L (min, max; <0.40, 1.88) among the 51 pregnant women in Kiruna. This is similar or lower compared to concentrations of mercury in pregnant women in other parts of Sweden. None of the women in the study had concentrations of mercury that are considered as dangerous.Mercury concentrations were associated with total fish consumption but not to consumption of predatory fish, known to be higher in mercury. All of the women in the study had knowledge about dietary advice on fish consumption. One woman exceeded the recommended consumption of predatory fish, limited due to risk of high mercury content, but this woman did not have high concentrations of mercury. While the vast majority of women thus followed the recommendations of not eating too much polluted fish, only 15 % of the women reported sufficient fish consumption to comply with the dietary advice (2-3 times/week).In conclusion, pregnant women in circumpolar Sweden have low exposure to mercury, and do not deviant from pregnant women in other parts of Sweden. Knowledge about dietary advice on fish consumption appointed to fertile women is very good. The public health concern though, is that pregnant women in circumpolar Sweden do not eat enough fish.
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