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1.
  • Akhi, Shamima N, et al. (författare)
  • Uterine rejection after allogeneic uterus transplantation in the rat is effectively suppressed by tacrolimus.
  • 2013
  • Ingår i: Fertility and sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 99:3, s. 862-870
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate the effects of the immunosuppressant tacrolimus on rejection of a transplanted uterus and on uterine expression of markers of inflammation and implantation. DESIGN: Experimental study. SETTING: University laboratory. ANIMAL(S): Female rats. INTERVENTION(S): Uteri from brown Norway rats were transplanted to Lewis rats, receiving either tacrolimus or no treatment. Sham groups underwent either hemihysterectomy or tacrolimus treatment. MAIN OUTCOME MEASURE(S): Gross morphology, histology, density of T-lymphocytes by immunohistochemistry, and mRNA levels of interleukin (IL)-1α, leukemia inhibitory factor (LIF), galectin-1, CD200, IL-15, interferon-inducible protein-10 (IP-10), and nuclear factor-κB (NF-κB) at 14 days' post-transplantation. RESULT(S): Nontreated uterine grafts showed rejection with necrosis. Sham groups and the tacrolimus-treated transplanted group exhibited normal uterine morphology with low numbers of T-lymphocytes in all uteri except in two out of seven uteri of the tacrolimus-treated transplant group. Uteri of the nontreated transplanted group showed elevated mRNA expression of IL-1α and IP-10 and reduced galectin-1, compared with the tacrolimus-treated transplanted group. There was no difference between any groups concerning uterine expression of LIF, NF-κB, IL-15, and CD200. CONCLUSION(S): Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1α and IP-10 and prevents T-lymphocyte infiltration.
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2.
  • Andersson, Fredrik W., 1974, et al. (författare)
  • Sick listing-Partly a family phenomenon?
  • 2011
  • Ingår i: Journal of Socio-Economics. - : Elsevier BV. - 1053-5357. ; 40:5, s. 496-502
  • Tidskriftsartikel (refereegranskat)abstract
    • Being sick listed is not always identical to being ill; it is rather a behaviour associated with illness. In this paper we have analysed whether there is a higher risk of becoming sick listed if a family member has been sick listed earlier-partly a family phenomenon. This aspect of sick listing has never been investigated before. Our results indicate that an individual's risk of being sick listed in 2007 was higher if he/she had family members who had been sick listed in 2006. This may be a sign for an existing " sick listing culture" -social norms within families. © 2010 Elsevier Inc.
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3.
  • Andersson, Sofia, et al. (författare)
  • Care professional's experiences about using Liverpool Care Pathway in end-of-life care in residential care homes
  • 2018
  • Ingår i: Scandinavian Journal of Caring Sciences. - Hoboken : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 32:1, s. 299-308
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Residential care homes (RCHs) play an important role in end-of-life care, being the most common place of death for elderly people in several European countries. Care pathways such as the Liverpool Care Pathway for the Dying Patient (LCP) are used to improve and ensure quality care at the end of life. There is a lack of scientific evidence supporting the use of care pathways.DESIGN: A descriptive qualitative study.OBJECTIVE: The aim was to describe care professionals' experiences of using the Liverpool Care Pathway for the Dying Patient in the care of dying residents in residential care homes.METHODS: Five focus group interviews and two individual interviews with enrolled nurses (n = 10), Registered Nurses (n = 9) and general practitioners (n = 5) were carried out and analysed using qualitative content analysis.RESULTS: Care professionals expressed that they became confident through a shared approach to care, were supported to tailor the care according to the residents' individual needs, were supported to involve family members in decision-making and care and became more aware of the care environment.CONCLUSION: The results of this study indicate that the LCP might be a useful tool for care professionals in improving end-of-life care in RCHs through increased attention to the goals of care, the individual needs of residents and family involvement.
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4.
  • Andersson, Sofia, et al. (författare)
  • End-of-life care in residential care homes : a retrospective study of the perspectives of family members using the VOICES questionnaire
  • 2017
  • Ingår i: Scandinavian Journal of Caring Sciences. - : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 31:1, s. 72-84
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In Europe, residential care homes (RCHs) are replacing hospitals as the place where death occurs, and they play an important role in end-of-life (EOL) care.OBJECTIVE: The aim was to describe the quality of care during the last 3 months and last 3 days of life of those who died in RCHs as reported by family members. We also investigated whether there were differences in the EOL care of younger patients (<85 years) vs. the oldest old patients (≥85 years) as reported by family members.DESIGN: A retrospective survey design.METHODS: Deaths (n = 189) at 19 RCHs in one municipality in Sweden were included. Family members were sent the VOICES questionnaire 1 month after their elderly relative had died. Descriptive statistics were used.RESULTS: In the last 3 days before death, most family members reported there was enough help with nursing (93%) and personal care (78.5%). Among the family members, 86% were told that the resident was likely to die shortly. Most (94.1%) of residents were reported to have died at their preferred place. No significant difference was found between age groups. Family members also reported that about half of the elderly had pain (46.5%) and 86.4% received treatment; 55.9% had breathlessness and 39.7% received treatment. Breathlessness was significantly (p = 0.01) more common in the younger group, and they were treated more often (p = 0.006) than the oldest old.CONCLUSION: This study revealed an overall positive picture of personal and nursing care and communication. These findings indicate that the quality of EOL care at RCHs is high. Inadequate management was found for symptom relief the last days of life. This suggests that this subject merits further attention by care professionals. To achieve better quality of EOL care at RCHs, we emphasise the importance of systematically working to improve symptom relief.
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5.
  • Andersson, Sofia, 1972-, et al. (författare)
  • End-of-life discussions in residential care homes improves symptom control : a national register study
  • 2024
  • Ingår i: BMJ Supportive & Palliative Care. - : BMJ Publishing Group Ltd. - 2045-435X .- 2045-4368. ; 14:e1, s. e1008-e1015
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In Europe, residential care homes (RCHs) rather than hospitals are the most common care facilities for the older adult and the place where most deaths occur in this age group. There is a lack of knowledge regarding end-of-life (EOL) discussions and how they correlate with symptoms and symptom relief.OBJECTIVE: The aim was to examine the correlation between EOL discussions and symptom occurrence, symptom relief and prescriptions or PRN drugs against symptoms for care home residents.METHODS: All expected deaths at RCHs from 1 October 2015 to 31 December 2016 and registered in the Swedish Register of Palliative Care were included. Univariate and multivariate logistic regression were used to compare the RCH residents, or their family members, who had received documented EOL discussions with a physician (the EOL discussion group) and the non-EOL discussion group.RESULTS: The EOL discussion group (n=17 071) had a higher prevalence of pain, nausea, anxiety, death rattles and shortness of breath reported, compared with the non-EOL discussion group (n=4164). Those with symptoms were more often completely relieved and had more often been prescribed PRN drugs against that symptom in the EOL discussion group. All differences remained significant when adjusting for age, time living in unit and cause of death.CONCLUSION: The results indicate that EOL discussions are correlated with higher prevalence of symptoms, but also with better symptom relief and prescription of symptom drugs PRN when symptomatic. A possible explanation for this is that the EOL discussion can work as an opportunity to discuss symptoms and treatment for symptom relief.
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6.
  • Andersson, Sofia, 1972-, et al. (författare)
  • Factors Associated With Symptom Relief in End-of-Life Care in Residential Care Homes: A National Register-Based Study
  • 2018
  • Ingår i: Journal of Pain and Symptom Management. - : Elsevier BV. - 0885-3924 .- 1873-6513. ; 55:5, s. 1304-1312
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Residential care homes (RCHs) are a common place of death. Previous studies have reported a high prevalence of symptoms such as pain and shortness of breath among residents in the last week of life.& para;& para;Objectives. The aim of the study was to explore the presence of symptoms and symptom relief and identify factors associated with symptom relief of pain, nausea, anxiety, and shortness of breath among RCH residents in end-of-life care.& para;& para;Methods. The data consisted of all expected deaths at RCHs registered in the Swedish Register of Palliative Care (N 22,855). Univariate and multiple logistic regression analyses were conducted.& para;& para;Results. Pain was reported as the most frequent symptom of the four symptoms (68.8%) and the one that most often had been totally relieved (84.7%) by care professionals. Factors associated with relief from at least one symptom were gender; age; time in the RCH; use of a validated pain or symptom assessment scale; documented end-of-life discussions with physicians for both the residents and family members; consultations with other units; diseases other than cancer as cause of death; presence of ulcers; assessment of oral health; and prescribed pro re nata injections for pain, nausea, and anxiety.& para;& para;Conclusion. Our results indicate that use of a validated pain assessment scale, assessment of oral health, and prescribed pro re nata injections for pain, nausea, and anxiety might offer a way to improve symptom relief. These clinical tools and medications should be implemented in the care of the dying in RCHs, and controlled trials should be undertaken to prove the effect. (C) 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
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7.
  • Andersson, Sofia, 1972-, et al. (författare)
  • Family members' experiences of care of the dying in residential care homes where the Liverpool Care Pathway was used
  • 2018
  • Ingår i: International Journal of Palliative Nursing. - London : Mark Allen Group. - 1357-6321 .- 2052-286X. ; 24:4, s. 194-202
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Residential care homes (RCHs) are increasingly becoming a common place of death for older people. Aim: The aim of this study was to describe family members' experiences of care of the dying in RCHs where the Liverpool care pathway for the dying patient was used. Methods: This study had a descriptive qualitative study design. Fifteen (n=15) individual interviews were analysed using qualitative content analysis. Results: The analysis resulted in three themes: being confident in a familiar and warm atmosphere, being involved vs not being involved in end-of-life (EoL) care, and being consoled by witnessing the health professional's endeavour to relieve suffering. Significance of results: The results indicated that taking part in a care plan seems to increase family members' feelings of involvement in EoL care. This study also highlights the family members' needs for increased possibilities for EoL discussions with the GP.
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8.
  • Andersson, Sofia, 1972- (författare)
  • Vård i livets slutskede på särskilt boende för äldre personer : närstående och vårdpersonals skattade och berättade erfarenheter
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Bakgrund I Europa, blir det allt vanligare att äldre personer dör på särskilt boende i stället för på sjukhus. Särskilda boenden spelar därför en viktig roll när det gäller vård i livets slutskede. Målet med palliativ vård för personer med livshotande sjukdom och deras närstående är att öka livskvaliteten och lindra lidande. Strukturerade vårdplaner såsom Liverpool Care Pathway for care of the dying (LCP) kan vara ett sätt att öka vårdkvaliteten. Det saknas dock forskning om vård i livets slutskede på särskilda boenden när en strukturerad vårdplan har använts.Syfte Det övergripande syftet med avhandlingen var att beskriva vård i livets slutskede på särskilt boende för äldre personer utifrån närstående och vårdpersonals skattade och berättade erfarenheter.Metod Avhandlingen baseras på två kvantitativa (I, II) och två kvalitativa (III, IV) studier. Studie I baseras på frågeformuläret Views of Informal Carers – Evaluation of Services (VOICES) som har besvarats av närstående (n = 189) efter att en anhörig har dött. Data har därefter analyserats med beskrivande och jämförande statistik. Studie II baseras på data om alla förväntade dödsfall (n = 22 855) som registrerats i Svenska palliativregistret (SPR). Dödsfallsenkäten har besvarats av vårdpersonal och svaren har sedan analyserats med beskrivande statistik och univariat och multipel logistisk regressionsanalys. Studie III baseras på fokusgruppsintervjuer och enskilda intervjuer med vårdpersonal. Studie IV baseras på enskilda intervjuer med närstående. Data från studie III och IV har analyserats med hjälp av kvalitativ innehållsanalys.Resultat Resultatet i studie I visar att majoriteten av de närstående skattade att den äldre personen fick tillräcklig hjälp såväl med personlig vård (78,5 %) som med sjukvård (93,0 %) de sista tre dagarna i livet. De närstående (86,2 %) rapporterade att de var informerade om att det var sannolikt att den äldre personen skulle avlida och majoriteten (94,1 %) av de äldre hade avlidit på önskad plats. Resultatet visade dock på hög förekomst av smärta (46,5 %) och andnöd (55,9 %). Det var ingen skillnad mellan åldersgrupperna när det gällde smärta men de äldre < 85 år hade signifikant högre förekomst av andnöd (70,6 %) jämfört med de äldre äldre, ≥ 85 år, (47,5 %). De äldre, < 85 år, hade signifikant oftare symtomlindring för andnöd (53,1 %) jämfört med äldre äldre, ≥ 85 år, (31,8 %).Resultatet i studie II visar hög förekomst av smärta (68,8 %) och ångest (44,0 %). Faktorer associerade med symtomlindring av smärta, illamående, ångest och andnöd var dels att validerat smärtskattningsinstrument hade använts, dels att munhälsan var bedömd. Starkast samband var det mellan symtomlindring av tre symtom (smärta, andnöd och ångest) och att injektioner var förskrivna vid behov.Resultatet i studie III visar att vårdpersonalen upplevde sig tryggare efter implementeringen av LCP genom att de hade fått ett gemensamt förhållningssätt, kände stöd att skräddarsy vården utifrån den döende personens individuella behov, kände stöd att involvera närstående i beslut och i vården samt hade blivit mer medvetna om vårdmiljön.Resultatet i studie IV visar att närstående upplevde sig tryggare i en välbekant och varm atmosfär, att vara kontra inte vara involverad i vård i livets slutskede och att bli tröstade genom att bevittna vårdpersonalens strävan att lindra lidande.Konklusion Resultatet från studierna i den här avhandlingen pekar på hög vårdkvalitet i livets slutskede på särskilt boende genom god omvårdnad, men resultatet pekar också mot förekomst av inadekvat symtomlindring och hög förekomst av smärta, andnöd och ångest de sista dagarna i livet. Det framkom ett tydligt samband mellan ordinerade injektioner vid behov och symtomlindring av smärta, illamående och ångest. Resultatet indikerar även vikten av att använda smärtskattningsinstrument och göra munhälsobedömningar för symtomlindring vid vård i livets slutskede. Således kan ett sätt att öka vårdkvaliteten för döende personer vara att det finns ordinerade injektionsläkemedel vid behov mot vanliga symtom, att använda validerade smärtskattningsinstrument och att göra munhälsobedömningar. Det framkom också att användandet av en standardiserad vårdplan såsom LCP kan vara ett sätt att förbättra vården för de äldre personerna i livets slutskede. Såväl vårdpersonalen som de närstående upplevde stöd av den struktur för bedömningar och vårdaktiviteter som LCP ger. Vårdpersonalen upplevde också stöd i att involvera närstående i vården och i vårdrelaterade beslut.
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9.
  • Back, Erik, et al. (författare)
  • Mucosal blood flow in the remaining rectal stump is more affected by total than partial mesorectal excision in patients undergoing anterior resection : a key to understanding differing rates of anastomotic leakage?
  • 2021
  • Ingår i: Langenbeck's archives of surgery (Print). - : Springer. - 1435-2443 .- 1435-2451. ; 406:6, s. 1971-1977
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Anterior resection is the procedure of choice for tumours in the mid and upper rectum. Depending on tumour height, a total mesorectal excision (TME) or partial mesorectal excision (PME) can be performed. Low anastomoses in particular have a high risk of developing anastomotic leakage, which might be explained by blood perfusion compromise. A pilot study indicated a worse blood flow in TME patients in an open setting. The aim of this study was to further evaluate perianastomotic blood perfusion changes in relation to TME and PME in a predominantly laparoscopic context.METHOD: In this prospective cohort study, laser Doppler flowmetry was used to evaluate the perianastomotic colonic and rectal perfusion before and after surgery. The two surgical techniques were compared in terms of mean differences of perfusion units using a repeated measures ANOVA design, which also enabled interaction analyses between type of mesorectal excision and location of measurement. Anastomotic leakage until 90 days after surgery was reported for descriptive purposes.RESULTS: Some 28 patients were available for analysis: 17 TME and 11 PME patients. TME patients had a reduced blood perfusion postoperatively compared to PME patients in the aboral posterior area (mean difference: -57 vs 18 perfusion units; p = 0.010). An interaction between mesorectal excision type and anterior/posterior location was detected at the aboral level (p = 0.007). Two patients developed a minor leakage, diagnosed after discharge.CONCLUSION: Patients operated on using TME have a decreased blood flow in the aboral posterior quadrant of the rectum postoperatively compared to patients operated on using PME. This might explain differing rates of anastomotic leakage.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02401100.
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10.
  • Bergh, Johan, 1983-, et al. (författare)
  • Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping
  • 2015
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:14, s. 4489-4494
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite considerable progress in uncovering the molecular details of protein aggregation in vitro, the cause and mechanism of protein-aggregation disease remain poorly understood. One reason is that the amount of pathological aggregates in neural tissue is exceedingly low, precluding examination by conventional approaches. We present here a method for determination of the structure and quantity of aggregates in small tissue samples, circumventing the above problem. The method is based on binary epitope mapping using anti-peptide antibodies. We assessed the usefulness and versatility of the method in mice modeling the neurodegenerative disease amyotrophic lateral sclerosis, which accumulate intracellular aggregates of superoxide dismutase-1. Two strains of aggregates were identified with different structural architectures, molecular properties, and growth kinetics. Both were different from superoxide dismutase-1 aggregates generated in vitro under a variety of conditions. The strains, which seem kinetically under fragmentation control, are associated with different disease progressions, complying with and adding detail to the growing evidence that seeding, infectivity, and strain dependence are unifying principles of neurodegenerative disease.
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11.
  • Bergh, Johan, 1983- (författare)
  • Structural investigation of SOD1 aggregates in ALS : identification of prion strains using anti-peptide antibodies
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative syndrome characterized by progressive degeneration of motor neurons that result in muscle wasting. The symptoms advance gradually to paralysis and eventually death. Most patients suffer from sporadic ALS (sALS) but 10% report a familial predisposition. Mutations in the gene encoding super­oxide dismutase-1 (SOD1) were the first identified cause of ALS. The disease mecha­nism is debated but there is a consensus that mutations in this protein confer a cytotoxic gain of function. SOD1 aggregates in motor neurons are hallmarks of ALS both in patients and in transgenic mouse models expressing a mutated form of human SOD1 (hSOD1). Recently, our group showed that SOD1 aggregates are present also in sALS patients, thus indicating a broader involvement of this protein in ALS. Misfolding and aggregation of SOD1 are dif­ficult to study in vivo since aggregate concentration in the central nervous system (CNS) is exceedingly low. The aim of this thesis was to find a method circumventing this problem to investigate the hSOD1 aggregate structure, distribution and spread in ALS disease.Many studies provide circumstantial evidence that the wild-type hSOD1 protein can be neurotoxic. We developed the first homozygous mouse model that highly overexpresses the wild-type enzyme. These mice developed an ALS-like syndrome and become terminally ill after around 370 days. Motor neuron loss and SOD1 aggregate accumulation in the CNS were observed. This lends further support to the hypothesis of a more general involve­ment of SOD1 in human disease.A panel of polyclonal antibodies covering 90% of the SOD1 protein was developed by our laboratory. These antibodies were shown to be highly specific for misfolded SOD1. Aggre­gated hSOD1 was purified from the CNS of terminally ill hSOD1 mice. Disordered segments in aggregated hSOD1 could be identified with these antibodies. Two aggregate strains with different structural architectures, molecular properties, and growth kinetics, were found using this novel method. The strains, denoted A and B, were also associated with different disease progression. Aggregates formed in vitro were structurally different from these strains. The results gave rise to questions about aggregate development and possible prion-like spread. To investigate this, inoculations of purified strain A and B hSOD1 seeds was performed in lumbar spinal cords of 100-day old mice carrying a hSOD1G85R mutation. Mice seeded with A or B aggregates developed premature signs of ALS and became terminally ill 200 days earlier than mice inoculated with control preparation. Interestingly, a tem­plated spread of aggregates along the neuraxis was concomitantly observed, with strain A and B provoking the buildup of their respective hSOD1 aggregate structure. The phenotypes initiated by the A and B strains differed regarding progression rates, distribution, end-stage aggregate levels, and histopathology. To further establish the importance of hSOD1 aggregates in human disease, purification and inoculation of aggregate seeds from spinal cords of ALS patients and mice carrying the hSOD1G127X mutation were performed. Inoculation of both human and mouse seeds as described above, induced strain A aggregation and premature fatal ALS-like disease.In conclusion, the data presented in this thesis provide a new, straightforward method for characterization of aggregate strains in ALS, and plausibly also in other neurodegen­erative diseases. Two different prion strains of hSOD1 aggregates were identified in mice that resulted in ALS-like disease. Emerging data suggest that prion-like growth and spread of hSOD1 aggregation could be the primary pathogenic mechanism not only in hSOD1 transgenic models, but also in human ALS.
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12.
  • Broecker, Verena, et al. (författare)
  • Reproducibility of Rejection Grading in Uterus Transplantation: A Multicenter Study.
  • 2023
  • Ingår i: Transplantation Direct. - 0041-1337 .- 1534-6080. ; 9:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Diagnosis of rejection after uterus transplantation is based on histopathological examination of ectocervical biopsies. Inflammation at the stromal-epithelial interface is the backbone of the histopathological classification proposed by our group in 2017. However, the reproducibility of this grading scheme has not been tested, and it is unclear whether it covers the full morphological spectrum of rejection.We present a multicenter study in which 5 pathologists from 4 uterus transplantation centers performed 2 rounds of grading on 145 and 48 cervical biopsies, respectively. Three of the centers provided biopsies. Additionally, the presence of perivascular stromal inflammation was recorded. During discussions after the first round, further histological lesions (venous endothelial inflammation and apoptosis) were identified for closer evaluation and added to the panel of lesions to score in the second round. All participants completed a questionnaire to explore current practices in handling and reporting uterus transplant biopsies.Cervical biopsies were commonly performed in all centers to monitor rejection. Intraobserver reproducibility of rejection grading (performed by 1 rater) was excellent, whereas interobserver reproducibility was moderate and did not improve in the second round. Reproducibility of perivascular stromal inflammation was moderate but unsatisfactory for venous endothelial inflammation and apoptosis. All lesions were more frequent in, but not restricted to, biopsies with rejection patterns.Grading of rejection in cervical biopsies is reproducible and applicable to biopsies from different centers. Diagnosis of rejection may be improved by adding further histological lesions to the grading system; however, lesions require rigorous consensus definition.
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13.
  • Broecker, Verena, et al. (författare)
  • Uterus transplantation: Histological findings in explants at elective hysterectomy
  • 2021
  • Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 21:2, s. 798-808
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterus transplantation has enabled women with absolute uterine factor infertility to carry a pregnancy. The first human uterus transplantation trial was initiated in 2013 in Gothenburg, Sweden. It was completed with 7 transplantations with long-term allograft survival and 9 children born from 6 women. In the present study we describe the histopathology of these 7 allografts, which were removed at 22-83 months after transplantation, and compare findings to control cases. Morphological findings in a subset of explants included linear subepithelial inflammation and perivascular stromal inflammation in the cervix, small inflammatory foci in the myometrium, and intimal inflammation in larger arteries. The average number of T cells, B cells, and macrophages was higher in transplants compared to normal controls, but variability was high among transplants. Chronic-active vascular rejection was seen in 2 of 7 transplants, both showed also inflammation in the cervix. Further, the inflammation seen in the cervix reflected the inflammation in the myometrium, suggesting that cervical biopsies are suitable to monitor rejection. However, the degree of inflammation and signs of rejection in explants did not reflect on the possibility to become pregnant in this limited series.
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14.
  • Brännström, Andreas, et al. (författare)
  • Kite Aerial Photography - Hué
  • 2014
  • Bok (populärvet., debatt m.m.)abstract
    • The Kite Aerial Photography - Hué project started with the intention from Mattias Ericsson and me Micael Norberg to work artistically on a jointly project with students from di erent art schools and from di erent cultures. We had an idea of building bridges both artistically and culturally. We traveled to Hué in Vietnam in order to explore new ways to collaborate and  nd new artistic meth- ods. We wanted to use kites and send our cameras up in the air to make aerial pictures. We tried to  nd a way to control events and by that also control our artistic outcome and understanding. But in the The Kite Aerial Photography project we had no control. The weather controlled our kites. The place and the language controlled what we knew and understood. What was left was to look into ourself and negate a compromise. The leftovers became documentations of an experience.And now I am looking back at those events, wondering what really happened. I am using words, trying to create an image of my memories and of my experience - hot air, smells and noise. Experi- ences I can’t communicate fully in words. You as a viewer will never feel them and I will only remember them. We will also remember di erently. Every participant have their own image ofwhat happened during those days in Hué. The feeling of being di erent, not understanding and being an outsider made us all meet ourselves in di erent ways. We believed that language would build bridges of understanding, and maybe it did. But here we are now. A long time has passed since we returned from Hué. What we have left are images and memories. I remember smells and emotions and in this state between memory and fact a tension is created. A juxtaposition of con ict- ing feelings. I look at the photographs now with a new understanding. We tried to move out of our comfort-zone looking for the unseen, the enigma, where memory and re ection becomes a liminal state. I now realize that knowledge is not fact or truth, but a state that we can call ”not knowing”. A state which for me is the very basic for understanding, and by that becoming the very essence of art.
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15.
  • Brännström, Johan, et al. (författare)
  • Defect internalization and tyrosine kinase activation in Aire deficient antigen presenting cells exposed to Candida albicans antigens
  • 2006
  • Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 121:3, s. 265-273
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with Autoimmune polyendocrine syndrome type I (APS I) present with multiple endocrine failures due to organ-specific autoimmune disease, thought to be T-cell-mediated. Paradoxically, APS I patients suffer from chronic mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus and in antigen presenting cells in the periphery. T cells from Aire deficient mice and men displayed an enhanced proliferative response against Candida antigen in vitro, suggesting that Aire deficient T cells are competent in recognizing Candida albicans. In contrast, monocytes from APS I patients displayed a decreased and delayed internalization of zymosan. Furthermore, Candida antigen activated monocytes from APS I patients show decreased and altered phoshotyrosine kinase activation. In conclusion, Aire deficient APCs have a defect receptor mediated internalization of Candida which affects kinase activation, likely altering the innate Candida immune response.
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16.
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17.
  • Brännström, Margareta, et al. (författare)
  • Effectiveness of the Liverpool care pathway for the dying in residential care homes: An exploratory, controlled before-and-after study
  • 2016
  • Ingår i: Palliative Medicine. - : SAGE Publications. - 0269-2163 .- 1477-030X. ; 30:1, s. 54-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Clinical pathways aim to ensure that individuals receive appropriate evidence-based care and interventions, with the Liverpool Care Pathway for the Dying Patient focusing on end of life. However, controlled studies of the Liverpool Care Pathway for the Dying Patient, particularly outside of cancer settings, are lacking. Aim: To compare the effects of the Liverpool Care Pathway for the Dying Patient and usual care on patients' symptom distress and well-being during the last days of life, in residential care homes. Design: Exploratory, controlled before-and-after study. During a 15-month baseline, usual care was carried out in two areas. During the following 15-months, usual care continued in the control area, while residential care home staff implemented Liverpool Care Pathway for the Dying Patient use in the intervention area. The intervention was evaluated by family members completing retrospective symptom assessments after the patient's death, using the Edmonton Symptom Assessment System and Views of Informal Carers - Evaluation of Services. Settings/participants: Patients who died at all 19 residential care homes in one municipality in Sweden. Results: Shortness of breath (estimate=-2.46; 95% confidence interval=-4.43 to -0.49) and nausea (estimate=-1.83; 95% confidence interval=-3.12 to -0.54) were significantly reduced in Edmonton Symptom Assessment System in patients in the intervention compared to the control area. A statistically significant improvement in shortness of breath was also found on the Views of Informal Carers - Evaluation of Services item (estimate=-0.47; 95% confidence interval=-0.85 to -0.08). Conclusion: When implemented with adequate staff training and support, the Liverpool Care Pathway for the Dying Patient may be a useful tool for providing end-of-life care of elderly people at the end of life in non-cancer settings.
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18.
  • Brännström, Margareta, et al. (författare)
  • Healthcare professionals' experiences of video consultations in palliative care in rural areas : an intervention study in community care
  • 2024
  • Ingår i: BMC Health Services Research. - : BioMed Central (BMC). - 1472-6963. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The population is aging, leading to an increased need for palliative care and end-of-life care. There is a lack of research on the use of video consultations for knowledge transfer between specialist and general palliative care. The aim of this study was to describe healthcare professionals’ experiences of video consultations in palliative care in community homecare and nursing homes in rural areas.Methods: Individual interviews (n = 11) were conducted with five community nurses, one occupational therapist, two specialist palliative nurses, and three specialist palliative care physicians. The data were analysed using reflexive thematic analysis.Results: The analysis identified three themes: feeling comfortable with increased availability of specialist expertise; seeing each other facilitates communication; and being supported by physically present care professionals is essential.Conclusion: HCPs suggest that video consultations are an effective way to increase access to specialist palliative care and provide more equal care to patients with palliative care needs in rural community care.
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19.
  • Brännström, Mats, 1958, et al. (författare)
  • Live birth after robotic-assisted live donor uterus transplantation.
  • 2020
  • Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 99:9, s. 1222-1229
  • Tidskriftsartikel (refereegranskat)abstract
    • The proof-of-concept of uterus transplantation, as a treatment for absolute uterine factor infertility, came with the first live birth after uterus transplantation, which took place in Sweden in 2014. This was after a live donor procedure, with laparotomy in both donor and recipient. In our second, ongoing trial we introduced a robotic-assisted laparoscopic surgery of the donor to develop minimal invasive surgery for this procedure. Here, we report the surgery and pregnancy behind the first live birth from that trial.In the present study, within a prospective observational study, a 62-year-old mother was the uterus donor and her 33-year-old daughter with uterine absence as part of the Mayer-Rokitansky-Küster-Hauser syndrome, was the recipient. Donor surgery was mainly done by robotic-assisted laparoscopy, involving dissections of the utero-vaginal fossa, arteries and ureters. The last part of surgery was by laparotomy. Recipient laparotomy included vascular anastomoses to the external iliac vessels. Data relating to in vitro fertilization, surgery, follow up, obstetrics and postnatal growth are presented.Three in vitro fertilization cycles prior to transplantation gave 12 cryopreserved embryos. The surgical time of the donor in the robot was 360minutes, according to protocol. The durations for robotic surgery for dissections of the utero-vaginal fossa, arteries and ureters were 30, 160 and 84minutes, respectively. The remainder of donor surgery was by laparotomy. Recipient surgery included preparations of the vaginal vault, three end-to-side anastomoses (one arterial, two venous) on each side to the external iliacs and fixation of the uterus. Ten months after transplantation, one blastocyst was transferred and resulted in pregnancy, which proceeded uneventfully until elective cesarean section in week 36+1 . A healthy boy (Apgar 9-10-10) was delivered. Follow up of child has been uneventful for 12months.This is the first report of a live birth after use of robotic-assisted laparoscopy in uterus transplantation and is thereby a proof-of-concept of use of minimal invasive surgery in this new type of transplantation.
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20.
  • Brännström, Mats, 1958, et al. (författare)
  • Livebirth after uterus transplantation.
  • 2015
  • Ingår i: Lancet. - 1474-547X. ; 385:9968, s. 607-616
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported.
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21.
  • Brännström, Mats, 1958, et al. (författare)
  • One uterus bridging three generations: first live birth after mother-to-daughter uterus transplantation
  • 2016
  • Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 106:2, s. 261-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To determine whether a uterus from the mother of a woman with absolute uterine factor infertility can be transplanted to daughter and carry a pregnancy with delivery of a healthy child. Patient(s): Twenty eight-year-old woman with uterine agenesis, her male partner, and her 50-year-old mother. Intervention(s): In vitro fertilization with embryo cryopreservation before live donor uterus transplantation (UTx). Induction immunosuppression. Embryo transfer 12 months after UTx, pregnancy controls, delivery, and hysterectomy. Main Outcome Measure(s): Results of IVF-ET, parameters of pregnancy/birth, and surgical data of transplantation/cesarean section/hysterectomy. Result(s): Two IVF cycles before UTx resulted in 10 cryopreserved embryos. Donor surgery included hysterectomy with vascular pedicles of uterine vessels and proximal vessels up to and including parts of internal iliacs. Recipient surgery was by bilateral vascular connections to external iliacs, vaginal-vaginal anastomosis, and uterine fixation. Pregnancy occurred at the first single ET, and the pregnancy proceeded uneventfully until gestational week 34, when the patient developed cholestasis with intense pruritus. Cesarean section was performed at 34+6, with delivery of a healthy boy (weight 2,335 g). Hysterectomy was performed 3.5 months after delivery. The weight of the healthy child at 12 months was 9.3 kg. Grandmother (uterus donor) and mother are in good health 3 years after UTx. Conclusion(s): This is the first report of a live birth after mother-to-daughter UTx, and it also represents the second birth ever after human UTx. (C) 2016 by American Society for Reproductive Medicine.
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22.
  • Brännström, Mats, 1958, et al. (författare)
  • Outcome of Recipient Surgery and 6-Month Follow-Up of the Swedish Live Donor Robotic Uterus Transplantation Trial.
  • 2020
  • Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017-2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one family friend. Donor surgery was by robotic-assisted laparoscopy. Recipient surgery was by laparotomy and vascular anastomoses to the external iliacs. The duration (median (ranges)) of recipient surgery, blood loss, measured (left/right) uterine artery blood flow after reperfusion, and length of hospital stay were 5.15 h (4.5-6.6), 300 mL (150-600), 43.5 mL/min (20-125)/37.5 mL/min (10-98), and 6 days (5-9), respectively. Postoperative uterine perfusion evaluated by color Doppler showed open anastomoses but restricted blood distribution in two cases. Repeated cervical biopsies in these two cases initially showed ischemia and, later, necrosis. Endometrial growth was not seen, and hysterectomy was later performed, with pathology showing partly viable myometrium and fibrosis but necrosis towards the cavity. The other six patients acquired regular menstrual cyclicity. Surgery was performed in two patients to correct vaginal stenosis. Reversible rejection episodes were seen in two patients. In conclusion, the rate of viable uterine grafts during the initial 6-months of the present study (75%) leaves room for improvement in the inclusion/exclusion criteria of donors and in surgical techniques. Initial low blood flow may indicate subsequent graft failure.
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23.
  • Brännström, Mattias, et al. (författare)
  • Predicting board strength by X-ray scanning of logs : the impact of different measurement concepts
  • 2007
  • Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 22:1, s. 60-70
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to compare the individual board strength predictions from an X-ray log scanner by using either two or four X-ray directions. The benefit of applying traceability between log and board was also studied. In total, 119 Norway spruce [Picea abies (L.) Karst.] sawlogs were scanned by an X-ray log scanner at the log sorting station of a sawmill and sawn into two centre pieces per log. Individual board traceability was enabled by following the rotational position of the log in the scanner and at the succeeding sawing. All boards were graded by a commercial strength grading machine before destructive testing was done. The resulting data were used to derive variables for building multivariate partial least squares strength prediction models. In the modelling a hierarchical modelling approach was used, where annual ring width, dry density and elasticity were also modelled. For all concepts studied the models' fit was similar. Only minor benefits could be found when using four directions and traceability compared with two directions and no traceability. One conclusion is that the result for traceability, from four directions in particular, is more sensitive for the interior knot reconstruction result. The strength prediction was on the same R2 level as for the strength grading machine
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24.
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25.
  • Brännström, Mattias, et al. (författare)
  • Predicting the strength of sawn wood by tracheid laser scattering
  • 2008
  • Ingår i: BioResources. - 1930-2126. ; 3:2, s. 437-451
  • Tidskriftsartikel (refereegranskat)abstract
    • An industrial laser light scattering scanner, designed to detect the spiral grain angle of logs by the light scattering along the grain, was used on two large samples of Norway spruce (Picea abies (var. Karst)) in various sawn dimensions (approximately 750 pieces). Additional measurements were made by other techniques, such as X-ray scanning, resonance frequency measurement, and various manual measurements. The strength properties of the boards were measured by destructive testing in four-point bending according to European standard. Multivariate methods (PLS) were used to model the relationship between the bending strength of the board (MOR) and the measurements. Based only on the output from the simple tracheid scattering equipment, a model for MOR achieved an R² exceeding 0.3. Combinations with average density or outer shape parameters from log scanning resulted in R² 0.4 and 0.3 respectively, although these parameters alone only accounted for R² 0.2. The results can be used to increase the understanding of strength in wood and in an improved industrial strength-grading process.
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26.
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27.
  • Brännström, Mattias, et al. (författare)
  • Rear end collision mitigation system for an automotive vehicle : patent pending
  • 2006
  • Patent (populärvet., debatt m.m.)abstract
    • The present invention relates to a system (1) and method for autonomous rear impact mitigation in a host vehicle (2) having a brake system (4) and a steering system (5). The relative motion parameters between the host vehicle (2) and a second vehicle (11) behind the host vehicle (2) are established. While the host vehicle (2) has a positive velocity, the brake system (4) of the host vehicle (2) is selectively activated based on the determined relative motion parameters.
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28.
  • Brännström, Mats, 1958, et al. (författare)
  • Reproductive, obstetric, and long-term health outcome after uterus transplantation: results of the first clinical trial
  • 2022
  • Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 118:3, s. 576-585
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). Design: Prospective. Setting: University hospital. Patient(s): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. Intervention(s): In vitro fertilization was performed with embryo transfer (ET) of day 2 or day 5 embryos in natural cycles. Pregnancies and growth trajectory of the children born were observed. Health-related quality of life, psychosocial outcome, and medical health of donors and recipients were evaluated by questionnaires. Main Outcome Measure(s): The results of in vitro fertilization, pregnancies, growth of children, and long-term health of patients were reported. Result(s): Six women delivered nine infants, with three women giving birth twice (cumulative birth rates of 86% and 67% in surgically successful and performed transplants, respectively). The overall clinical pregnancy rate (CPR) and live birth rate (LBR) per ET were 32.6% and 19.6%, respectively. For day 2 embryos, the CPR and LBR per ET were 12.5% and 8.6%, respectively. For day 5 embryos, the CPR and LBR per ET were 81.8% and 45.4%, respectively. Fetal growth and blood flow were normal in all pregnancies. Time of delivery (median in full pregnancy weeks + days [ranges]) by cesarean section and weight deviations was 35 + 3 (31 + 6 to 38 + 0) and -1% (-13% to 23%), respectively. Three women developed preeclampsia and four neonates acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. Measures of long-term health in both donors and recipients were noted to be favorable. When UTx resulted in a birth, scores for anxiety, depression, and relationship satisfaction were reassuring for both the donors and recipients. Conclusion(s): The results of this first complete UTx trial show that this is an effective infertility treatment, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for donors and recipients. Clinical Trial Registration Number: NCT02987023.
  •  
29.
  • Brännström, Mats, 1958, et al. (författare)
  • The first clinical uterus transplantation trial: a six-month report.
  • 2014
  • Ingår i: Fertility and sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 101:5, s. 1228-1236
  • Tidskriftsartikel (refereegranskat)abstract
    • To report the 6-month results of the first clinical uterus transplantation (UTx) trial. This type of transplantation may become a treatment of absolute uterine-factor infertility (AUFI).
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30.
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31.
  • Brännström, Margareta, et al. (författare)
  • Unequal care for dying patients in Sweden : a comparative registry study of deaths from heart disease and cancer
  • 2012
  • Ingår i: European Journal of Cardiovascular Nursing. - : Elsevier. - 1474-5151 .- 1873-1953. ; 11:4, s. 454-459
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Swedish Palliative Registry is a nationwide quality registry aimed at facilitating improvement in end-of-life care. The goal is for the registry to list and report quality indicators related to care during the last week of life in all cases expected death in Sweden.AIM: To examine the quality of care during the last week of life as reported to the registry for patients with heart disease compared to those with cancer.METHOD: A retrospective registry study.RESULTS: Patients dying of heart disease compared to those dying from cancer had more shortness of breath, fewer drugs prescribed as needed against the usual symptoms and often died alone. Furthermore, they and their close relatives received less information about the imminence of death and bereavement follow-up was less common. The healthcare personnel were less aware of the heart disease patients' symptoms and less often knew about where they wished to die.CONCLUSION: Great differences were found in registered end-of-life care suggesting that the care given to patients with heart disease and cancer was unequal even after adjustment for age, sex and setting at the time of death. If our observational findings are confirmed in future studies there is obviously a need for new models for end-of-life management in order to facilitate the provision of equal care to dying patients regardless of diagnosis.
  •  
32.
  • Brännström, Mats, 1958, et al. (författare)
  • Uterus transplantation: A Rapidly Expanding Field
  • 2018
  • Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 102:4, s. 569-577
  • Forskningsöversikt (refereegranskat)abstract
    • Uterus transplantation (UTx) has been successfully introduced as a treatment option for women with absolute uterine factor infertility (AUFI). AUFI representing approximately 3% to 5% of the female general population is linked to either congenital uterine agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome), major congenital uterine malformation (hypoplastic uterus, fraction of bicornuate/unicornuate uterus), a surgically absent uterus, or an acquired condition (intrauterine adhesions, leiomyoma) linked to uterine malfunction that causes implantation failure or defect placentation. The world's first clinical uterus transplant was performed in 2000. However, a hysterectomy became necessary shortly after the surgery due to uterine necrosis. In 2011, a group in Turkey reported on a surgically successful deceased donor transplant; however, this procedure has, to date, not resulted in a healthy live birth, the ultimate goal of UTx. Building on an extensive experimental background in various animal models, including primates, the Gothenburg group led by Brannstrom reported on the first delivery of a healthy baby in a recipient of a live donor UTx in 2014. This event did not only show the feasibility of UTx, it also helped defining relevant areas of clinical and basic research. Use of a gestational surrogate carrier, is, at least in theory, an alternative for a woman with AUFI seeking genetic motherhood. However, in the clear majority of countries worldwide, gestational surrogacy is not practiced based on legal, ethical, or religious concerns. Of note, the overwhelming majority of surveyed women in the United Kingdom, a country which permits surrogacy, preferred UTx over gestational surrogacy and adoption. Moreover, randomly selected women of fertile age in Sweden preferred UTx over gestational surrogacy. A recent large survey in Japan with more than 3000 participants revealed that UTx had a twofold higher acceptance rate compared with gestational surrogacy. In a recent US survey exploring the potential of donating vascularized composite allografts, uterus donation achieved the highest priority. Thus, the acceptance of UTx as infertility treatment for women with AUFI is high, although the procedure remains in its infancy. Here, we provide an update of clinical activities, summarize achievements and challenges, and submit areas of research interests.
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33.
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34.
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35.
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36.
  • Bugaytsova, Jeanna, et al. (författare)
  • pH regulated H. pylori adherence : implications for persistent infection and disease
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.
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37.
  • Dahm-Kähler, Pernilla, 1964, et al. (författare)
  • Transplantation of the uterus in sheep: methodology and early reperfusion events.
  • 2008
  • Ingår i: The journal of obstetrics and gynaecology research. - : Wiley. - 1341-8076 .- 1447-0756. ; 34:5, s. 784-93
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: Uterine transplantation is developing into a clinical treatment for uterine factor infertility. An animal model with a similar uterus size and vessels to humans and with pregnancy extending over several months would be beneficial for research on uterine transplantation. The aim of this study was to develop and evaluate autotransplantation of the sheep uterus to an orthotopic position in the pelvis. METHODS: Female sheep (n=7) were subjected to laparotomy with the uterus and its vascular supply and drainage being surgically isolated. The excised uterus was kept ex vivo at +4 degrees C for 60 min and then autotransplanted with vascular end-to-side anastomoses to the external iliac vessels. The effects of uterine blood-reperfusion were assessed by measurements of pCO(2), pO(2), lactate and pH in uterine venous blood. Uterine contractility and histology was assessed after 3 h of reperfusion. RESULTS: Reperfusion of blood was observed in five out of seven transplanted uteri. The pCO(2)/pO(2)-ratio and the lactate level were initially elevated but decreased and became normal after 60 min. After 3 h of reperfusion there was a visible tissue blood flow and spontaneous uterine contractions were seen. Histological analysis revealed a mild inflammation, but no edema or stasis. CONCLUSIONS: This study demonstrates that the sheep uterus can successfully be autotransplanted to an orthotopic position with novel vascular connections. This model is suitable for future experiments studying long-term results concerning uterine viability and pregnancy using a transplanted uterus of similar size to the human uterus.
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38.
  • Ekhtiari Bidhendi, Elaheh, et al. (författare)
  • Mutant superoxide dismutase aggregates from human spinal cord transmit amyotrophic lateral sclerosis
  • 2018
  • Ingår i: Acta Neuropathologica. - : Springer. - 0001-6322 .- 1432-0533. ; 136:6, s. 939-953
  • Tidskriftsartikel (refereegranskat)abstract
    • Motor neurons containing aggregates of superoxide dismutase 1 (SOD1) are hallmarks of amyotrophic lateral sclerosis (ALS) caused by mutations in the gene encoding SOD1. We have previously reported that two strains of mutant human (h) SOD1 aggregates (denoted A and B) can arise in hSOD1-transgenic models for ALS and that inoculation of such aggregates into the lumbar spinal cord of mice results in rostrally spreading, templated hSOD1 aggregation and premature fatal ALS-like disease. Here, we explored whether mutant hSOD1 aggregates with prion-like properties also exist in human ALS. Aggregate seeds were prepared from spinal cords from an ALS patient carrying the hSOD1G127Gfs*7 truncation mutation and from mice transgenic for the same mutation. To separate from mono-, di- or any oligomeric hSOD1 species, the seed preparation protocol included ultracentrifugation through a density cushion. The core structure of hSOD1G127Gfs*7 aggregates present in mice was strain A-like. Inoculation of the patient- or mouse-derived seeds into lumbar spinal cord of adult hSOD1-expressing mice induced strain A aggregation propagating along the neuraxis and premature fatal ALS-like disease (p < 0.0001). Inoculation of human or murine control seeds had no effect. The potencies of the ALS patient-derived seed preparations were high and disease was initiated in the transgenic mice by levels of hSOD1G127Gfs*7 aggregates much lower than those found in the motor system of patients carrying the mutation. The results suggest that prion-like growth and spread of hSOD1 aggregation could be the primary pathogenic mechanism, not only in hSOD1 transgenic rodent models, but also in human ALS.
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39.
  • Ekhtiari Bidhendi, Elaheh, et al. (författare)
  • Two superoxide dismutase prion strains transmit amyotrophic lateral sclerosis-like disease
  • 2016
  • Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 126:6, s. 2249-2253
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is an adult-onset degeneration of motor neurons that is commonly caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Both patients and Tg mice expressing mutant human SOD1 (hSOD1) develop aggregates of unknown importance. In Tg mice, 2 different strains of hSOD1 aggregates (denoted A and B) can arise; however, the role of these aggregates in disease pathogenesis has not been fully characterized. Here, minute amounts of strain A and B hSOD1 aggregate seeds that were prepared by centrifugation through a density cushion were inoculated into lumbar spinal cords of 100-day-old mice carrying a human SOD1 Tg. Mice seeded with A or B aggregates developed premature signs of ALS and became terminally ill after approximately 100 days, which is 200 days earlier than for mice that had not been inoculated or were given a control preparation. Concomitantly, exponentially growing strain A and B hSOD1 aggregations propagated rostrally throughout the spinal cord and brainstem. The phenotypes provoked by the A and B strains differed regarding progression rates, distribution, end-stage aggregate levels, and histopathology. Together, our data indicate that the aggregate strains are prions that transmit a templated, spreading aggregation of hSOD1, resulting in a fatal ALS-like disease.
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40.
  • Elfman, Lena, et al. (författare)
  • Detection of Horse Allergen around a Stable
  • 2008
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 145:4, s. 269-276
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Integrating horse stables with built-up areas may lead to conflicts. Dispersion of horse allergen may become a health risk for allergic people. The aim was to measure the dispersion of horse allergen around a stable, considering wind speed and direction and vegetation. The disturbance of staff at a workplace nearby a stable was investigated. Methods: Air sampling was performed around a stable (32 horses) at distances of 50-500 m in all directions. Sampling was done with a pump and an IOM sampler. Samples were collected at 50 points during all seasons. Horse allergen levels were determined using ELISA. Disturbance by horses was studied with a questionnaire handed to the employees in an office near the stable. Results: The median horse allergen level at the stable entrance was 316 U/m3, in the horse fields 40 U/m3 and in the whole source area 16 U/m3, which declined to <2 U/m3 at about 50 m from the source area. Downwind of the prevailing winds low levels of horse allergen (2-4 U/m3) could sometimes be detected at up to 500 m. The staff, including those allergic to horses, managed to tolerate horses close to the workplace. Conclusions: At low winds horse allergen spread in ambient air about 50 m from the stable and horse fields. At higher winds low allergen levels were sometimes found in open areas up to 500 m from the source area. These levels were similar to those found in the office after moving away from the stable area. The employees did not report more symptoms of allergy or asthma while working close to the stable compared to after the move.
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41.
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42.
  • Forsberg, Karin, et al. (författare)
  • Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients
  • 2010
  • Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 5:7, s. e11552-
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations in CuZn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) and are found in 6% of ALS patients. Non-native and aggregation-prone forms of mutant SOD1s are thought to trigger the disease. Two sets of novel antibodies, raised in rabbits and chicken, against peptides spaced along the human SOD1 sequence, were by enzyme-linked immunosorbent assay and an immunocapture method shown to be specific for denatured SOD1. These were used to examine SOD1 in spinal cords of ALS patients lacking mutations in the enzyme. Small granular SOD1-immunoreactive inclusions were found in spinal motoneurons of all 37 sporadic and familial ALS patients studied, but only sparsely in 3 of 28 neurodegenerative and 2 of 19 non-neurological control patients. The granular inclusions were by confocal microscopy found to partly colocalize with markers for lysosomes but not with inclusions containing TAR DNA binding protein-43, ubiquitin or markers for endoplasmic reticulum, autophagosomes or mitochondria. Granular inclusions were also found in carriers of SOD1 mutations and in spinobulbar muscular atrophy (SBMA) patients and they were the major type of inclusion detected in ALS patients homozygous for the wild type-like D90A mutation. The findings suggest that SOD1 may be involved in ALS pathogenesis in patients lacking mutations in the enzyme.
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43.
  • Fransson, Moa, et al. (författare)
  • Mesenchymal stromal cells supportendothelial cell interactions in anintramuscular islet transplantation model
  • 2015
  • Ingår i: Regenerative Medicine Research. - : Springer Science and Business Media LLC. - 2050-490X. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Mesenchymal stromal cells (MSC) have been under investigation for a number of therapies andhave lately been in focus as immunosuppressive actors in the field of transplantation. Herein we haveextended our previously published in vitro model of MSC-islets in an experimental setting of islettransplantation to the abdominal muscle.Human islets coated with luciferase-GFP transduced human MSC were transplanted to the abdomen muscletissue of NOD-scid ILR2γnull mice and cellular interactions were investigated by confocal microscopy.Results:The MSC reduced fibrotic encapsulation and facilitated endothelial cell interactions. In particular, weshow a decreased fraction of αSMA expressing fibrotic tissue surrounding the graft in presence of MSC-isletscompared to islets solely distributed into the muscle tissue. Also, in the presence of MSC, human isletendothelial cells migrated from the center of the graft out into the surrounding tissue forming chimeric bloodvessels with recipient endothelial cells. Further, in the graft periphery, MSC were seen interacting with infiltratingmacrophages.Conclusions:Here, in our experimental in vivo model of composite human islets and luciferase-GFP-transducedhuman MSC, we enable the visualization of close interactions between the MSC and the surrounding tissue. In thismodel of transplantation the MSC contribute to reduced fibrosis and increased islet endothelial cell migration.Furthermore, the MSC interact with the recipient vasculature and infiltrating macrophages.
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44.
  • Graffmo, Karin S., et al. (författare)
  • Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis
  • 2013
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:1, s. 51-60
  • Tidskriftsartikel (refereegranskat)abstract
    • A common cause of amyotrophic lateral sclerosis (ALS) is mutations in the gene encoding superoxide dismutase-1. There is evolving circumstantial evidence that the wild-type protein can also be neurotoxic and that it may more generally be involved in the pathogenesis of ALS. To test this proposition more directly, we generated mice that express wild-type human superoxide dismutase-1 at a rate close to that of mutant superoxide dismutase-1 in the commonly studied G93A transgenic model. These mice developed an ALS-like syndrome and became terminally ill after around 370 days. The loss of spinal ventral neurons was similar to that in the G93A and other mutant superoxide dismutase-1 models, and large amounts of aggregated superoxide dismutase-1 were found in spinal cords, but also in the brain. The findings show that wild-type human superoxide dismutase-1 has the ability to cause ALS in mice, and they support the hypothesis of a more general involvement of the protein in the disease in humans.
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45.
  • Groth, Klaus, et al. (författare)
  • Cyclosporine A exposure during pregnancy in mice: effects on reproductive performance in mothers and offspring.
  • 2010
  • Ingår i: Human reproduction. - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 25:3, s. 697-704
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Pregnancies after organ transplantation and under immunosuppressive treatment are associated with slightly elevated risks for obstetric and post-natal complications but can usually be managed well. However, little is known about the effects of intrauterine exposure (IUE) to immunosuppressants in the growing and adult offspring. One major issue is the potentially negative effects of immunosuppressive medication on reproduction. This study investigates the effect of exposure during pregnancy to the most commonly used immunosuppressant in organ transplantation, cyclosporine A (CsA), on the reproductive outcome in mothers and offspring. METHODS Female C57CBA-F1 mice received 0, 10, 20 or 30 mg/kg bodyweight of CsA daily by subcutaneous mini-osmotic pumps during mating and pregnancy. Blood concentrations of CsA, implantation rates, resorption rates and fetal weights were analysed. In addition, female and male mice exposed to CsA in utero were mated to unexposed partners and pregnancy outcomes were analysed. RESULTS Direct maternal exposure to CsA at high doses reduced implantation rates and fetal survival. IUE to CsA reduced adolescent growth but did not affect fertility, although a reduction in birthweight was seen in offspring of females exposed to CsA in utero. CONCLUSIONS CsA exposure during pregnancy correlates with impaired reproductive outcome, but offspring fertility is not affected. The cause of reduction in adolescent weight gain and low birthweight in offspring of females exposed to CsA in utero need further investigation.
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46.
  • Groth, Klaus, et al. (författare)
  • Effects of immunosuppression by cyclosporine A on allogenic uterine transplant in the rat.
  • 2012
  • Ingår i: European journal of obstetrics, gynecology, and reproductive biology. - : Elsevier BV. - 1872-7654 .- 0301-2115. ; 163:1, s. 97-103
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE(S): : Research on uterine transplantation (UTx) is conducted in preparation for its introduction in the human as a treatment for absolute uterine factor infertility. A major area of research in experimental animals is to ascertain that immunosuppressants that will be used at UTx do not negatively affect the potential of the uterus to implant an embryo and to carry a pregnancy to term. This study investigates the effects on a uterine transplant in the rat of the calcineurin inhibitor, cyclosporine A (CsA), on uterine morphology and expression patterns of some mediators involved in implantation/inflammation. STUDY DESIGN: : Donor rats were of Brown Norway strain and recipients were of Lewis strain. The uterus was transplanted to an orthotopic site by vascular anastomosis. The recipients were given CsA (10mg/kg) sc once daily or no CsA until they were sacrificed at postoperative day 7. Syngenic transplanted Lewis rats were used as controls. Uteri were analyzed regarding histology, immunohistochemistry against T-cells and mRNA levels of the implantation/inflammation-related markers leukaemia inhibitory factor (LIF), galectin-1, CD200, interleukin (IL)-1α, and IL-15. RESULT(S): : There was pronounced inflammation with abundance of CD8-lymphocytes in uterine grafts of non-CsA-treated animals and only mild inflammation in treated animals. The uterine mRNA levels of IL-1α were decreased after CsA in comparison to uteri of non-treated transplanted animals. The mRNA levels of galectin-1 were decreased in the rejected uteri and were higher in the CsA-treated. The levels of mRNA of IL-15 were lower in the syngenic transplanted group compared to the CsA-treated transplanted. There was no difference between the groups concerning mRNA levels of CD200, or LIF, with wide variation of the levels of the two latter mediators in all groups. CONCLUSION(S): : Cyclosporine A suppresses rejection of an allogenic rat uterine transplant, with normalization of mRNA levels of the proinflammatory cytokine IL-1α and the glycan-binding protein galectin-1.
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47.
  • Groth, Klaus, et al. (författare)
  • Rejection of allogenic uterus transplant in the mouse: time-dependent and site-specific infiltration of leukocyte subtypes
  • 2009
  • Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 24:11, s. 2746-54
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Animal models of uterus transplantation are being developed ahead of a possible treatment for absolute uterus infertility in women. Our knowledge of inflammatory cell involvement in acute rejection of a uterus transplant is limited; therefore, we examined the pattern of invasion of leukocyte subtypes into an allogeneic uterus transplant. METHODS: The uterus and its vasculature were removed from BALB/c mice and transplanted into C57Bl/6 recipient mice at a heterotopic position, with the native uterus left in situ. Both uteri were removed on post-operative day 2 (D2, n = 5), D5 (n = 5) and D10 (n = 6). Immunohistochemistry for neutrophilic granulocytes, macrophages, cytotoxic CD8(+) T-cells, CD4(+) T-helper cells and B-cells was performed and cell density was evaluated in both myometrium and endometrium. RESULTS: Neutrophil density was increased in graft versus native uteri at D5 and D10 in myometrium and D10 in endometrium, and in endometrium was higher in the D5 than D2 graft (all P < 0.05). Infiltration of macrophages occurred from D2 in myometrium and from D5 in endometrium (P < 0.05, graft versus native). Density of CD8(+) cytotoxic T-cells increased in the graft versus native uteri at D5 in both uterine layers and for the graft versus D2 density (P < 0.01). In contrast, CD4(+) T-helper cells increased only transiently in graft endometrium at D5 (P < 0.05). Overall CD19(+) B-cell density was low, with no time-dependent changes in graft myometrium or endometrium. CONCLUSIONS: Acute rejection of an allogeneic uterus transplant in the mouse involves influx of predominately neutrophils, macrophages, CD8(+) T-cells and CD4(+) T-cells between D2 and D5 post-operatively.
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48.
  • Hambraeus, Johan, et al. (författare)
  • Cost-effectiveness of Radiofrequency Denervation for Zygapophyseal Joint Pain
  • 2021
  • Ingår i: Pain Physician. - : NLM (Medline). - 1533-3159 .- 2150-1149. ; 24:8, s. E1205-E1218
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chronic pain is a leading cause of disability. Radiofrequency denervation (RFD) is effective when performed according to guidelines for patients with correctly diagnosed zygapophyseal joint pain (ZJP). However, the cost-effectiveness of this method has not been fully explored.OBJECTIVE: The aim of this study was to analyze whether RFD is cost-effective for ZJP from a societal perspective.STUDY DESIGN: Cost effectiveness study based on an observational study.SETTING: An interventional pain management clinic in central Sweden.METHODS: Patients - This cost-effectiveness study was performed for all patients (n = 873) assessed between 2010 and 2016 at a specialized interventional pain clinic in Sweden. Those diagnosed with ZJP (n = 331, 37.9%) were treated with RFD and followed up for 1 year after the RFD. Using data collected from national registers, we determined the health care costs, medication costs, the patients' time and travel costs, and the patients' ability to work. The effects of RFD on quality-adjusted life years (QALY) and cost/QALY gained were calculated.RESULTS: On average, patients reported very low health-related quality of life (HRQoL; EQ-5D index: 0.212). After RFD, HRQoL increased significantly to 0.530 (P < 0.0001). Drug consumption and specialized health care consumption were reduced by 54% and 81%, respectively, and the cost/QALY gained from a societal perspective was 221,324 Swedish krona (USD ~26,008). The sensitivity analysis showed that the treatment was cost-effective in all scenarios evaluated, using the patients as their own controls. The cost/QALY gained from a health care perspective was 72,749 Swedish krona (USD ~8,548).LIMITATIONS: The results are based on data collected at one center. The results need to be compared with those from pain rehabilitation programs and should be confirmed using data from other centers.CONCLUSIONS: Patients referred for RFD in Sweden report extremely low HRQoL. HRQoL significantly increased following RFD in patients with ZJP. Medications and health care consumption decreased after RFD. RFD was cost-effective, and the sensitivity analysis yielded stable results in different scenarios. Therefore, RFD is a cost-effective treatment that meets the Swedish National Board of Health and Welfare criteria for a high priority treatment.TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT01835704) with Protocol ID SE-Dnr-2012-446-31M-1.  https://clinicaltrials.gov/ct2/show/NCT01835704.
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49.
  • Hambraeus, Johan, 1959- (författare)
  • Interventional pain management focused on zygapophysial joint pain : a health-economic evaluation
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The pain-system is a central mechanism in our life. Chronic pain is one of the major causes of impaired health-related quality of life according to the World Health Organization’s “Global Burden of Disease”-studies. Zygapophysial joint pain has been shown to account for the pain in 30% - 50% of patients with chronic pain. There are several well-established, evidence-based methods to treat zygapophysial joint pain in the cervical and lumbar regions.This thesis originates from this and starts by exploring whether the treatment of zygapophysial joint pain can improve health-related quality of life. This thesis describes methods for the diagnosis and treatment of zygapophysial joint pain in the thoracic region that can be applied to the treatment of all pain-foci localized to the zygapophysial joints. I show that the health-related quality of life was significantly improved after treatment, and that the clinical methods used for treating thoracic pain were similar to the methods that have been established previously for cervical and lumbar pain.In order to better understand the patients’ experiences we performed qualitative interviews with patients who underwent diagnostic tests and treatments. The overall theme revealed by these interviews was that of empowerment, in which the patients were empowered by the process of diagnostic tests and treatments.The next question was whether the method was cost-effective or not. In the first cost-effectiveness analysis, the patients served as their own controls and we evaluated the results against the limits set by the Swedish national board of health and welfare. The results showed that it was cost-effective in the moderate to low range.Finally, we compared the treatment to the “gold standard” for pain management in Sweden; i.e.pain rehabilitation. We mimicked a randomized controlled trial by using propensity score weighting to compare 254 patients agains 15,357 patients registered in the Swedish National Register of Pain Rehabilitation. The results showed that interventional pain management was cost-effective in the moderate (12 months after treatment) to low (≥24 months after) range whereas pain rehabilitation was in the very high range (after 12 months) and became cost-effective in the high range after 24 months of treatment. Currently, interventional pain management accounts for just 2% of all specialized pain management procedures in Sweden. If this could be increased to 25%, it may be possible to save 106 million SEK annually, while simultaneously gain 14 quality adjusted life years of health. If an interventional pain assessment is performed early in the process, treatable patients could be directed toward interventional treatment and away from interdisciplinary pain management programs, with the potential for further reductions in costs. 
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50.
  • Hellström, Mats, et al. (författare)
  • Towards the development of a bioengineered uterus : Comparison of different protocols for rat uterus decellularization
  • 2014
  • Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 10:12, s. 5034-5042
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterus transplantation (UTx) may be the only possible curative treatment for absolute uterine factor infertility, which affects 1 in every 500 females of fertile age. We recently presented the 6-month results from the first clinical UTx trial, describing nine live-donor procedures. This routine involves complicated surgery and requires potentially harmful immune suppression to prevent rejection. However, tissue engineering applications using biomaterials and stem cells may replace the need for a live donor, and could prevent the required immunosuppressive treatment. To investigate the basic aspects of this, we developed a novel whole-uterus scaffold design for uterus tissue engineering experiments in the rat. Decellularization was achieved by perfusion of detergents and ionic solutions. The remaining matrix and its biochemical and mechanical properties were quantitatively compared from using three different protocols. The constructs were further compared with native uterus tissue composition. Perfusion with Triton X-100/dimethyl sulfoxide/H2O led to a compact, weaker scaffold that showed evidence of a compromised matrix organization. Sodium deoxycholate/dH2O perfusion gave rise to a porous scaffold that structurally and mechanically resembled native uterus better. An innovative combination of two proteomic analyses revealed higher fibronectin and versican content in these porous scaffolds, which may explain the improved scaffold organization. Together with other important protocol-dependent differences, our results can contribute to the development of improved decellularization protocols for assorted organs. Furthermore, our study shows the first available data on decellularized whole uterus, and creates new opportunities for numerous in vitro and in vivo whole-uterus tissue engineering applications.
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