| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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| 3. |
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| 4. |
- Ekstrand, Karl, et al.
(författare)
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Malignant tumors of the maxilla : virtual planning and real-time rehabilitation with custom-made R-zygoma fixtures and carbon-graphite fiber-reinforced polymer prosthesis
- 2008
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Ingår i: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 10:1, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oral cancer is a mutilating disease. Because of the expanding application of computer technology in medicine, new methods are constantly evolving. This project leads into a new technology in maxillofacial reconstructive therapy using a redesigned zygoma fixture. PURPOSE: Previous development experiences showed that the procedure was time-consuming and painful for the patients. Frequent episodes of sedation or general anesthetics were required and the rehabilitation is costly. The aim of our new treatment goal was to allow the patients to wake up after tumor surgery with a functional rehabilitation in place. MATERIALS AND METHODS: Stereolithographic models were introduced to produce a model from the three-dimensional computed tomography (CT). A guide with the proposed resection was fabricated, and the real-time maxillectomy was performed. From the postoperative CT, a second stereolithographic model was manufactured and in addition, a stent for the optimal position of the implants. Customized zygoma implants were installed (R-zygoma, Integration AB, Göteborg, Sweden). A fixed construction was fabricated by using a new material based on poly(methylacrylate) reinforced with carbon/graphite fibers and attached to the implants. On the same master cast, a separate obturator was fabricated in permanent soft silicon. RESULTS: The result of this project showed that it was possible to create a virtual plan preoperatively to apply during surgery in order for the patient to wake up functionally rehabilitated. CONCLUSION: From a quality-of-life perspective, it is an advantage to be rehabilitated fast. By using new computer technology, pain and discomfort are less and the total rehabilitation is faster, which in turn reduces days in hospital and thereby total costs.
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| 5. |
- Eliasson, Alf, 1959, et al.
(författare)
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A 5-year prospective clinical study of submerged and nonsubmerged Paragon system implants in the edentulous mandible.
- 2010
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Ingår i: The International journal of prosthodontics. - : Quintessence. - 0893-2174 .- 1139-9791. ; 23:3, s. 231-8
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: The aim of this investigation was to evaluate the clinical outcome of two different surgical protocols in the edentulous mandible: submerged and nonsubmerged. Further, the Paragon dental implant with a titanium plasma-sprayed surface was evaluated. MATERIALS AND METHODS: Twenty-nine consecutively treated patients with 168 implants supporting fixed prostheses were included. All but 3 patients were provided 6 implants, placed via nonsubmerged healing on one side and submerged healing on the other. Data were collected from patient records and radiographs. Twenty-four patients participated in the 5-year clinical follow-up examination. RESULTS: After 5 years, all patients still had their mandibular fixed prostheses in function. Cumulative survival rates were 100% for prostheses and 99.4% for implants. However, 3 implants fractured in 1 patient. One submerged implant was lost before loading but no further implants were lost during follow-up. The radiographic bone loss was small for all implants with a mean of 0.14 mm (standard deviation [SD]: 0.37) at 1 year and 0.42 mm (SD: 0.48) at 5 years for nonsubmerged implants and 0.17 mm (SD: 0.32) at 1 year and 0.51 mm (SD: 0.33) at 5 years for submerged implants. Nineteen implants (including the 3 that fractured) presented annual bone loss exceeding 0.2 mm after the first year, yielding a cumulative success rate of 86.2% after 5 years. CONCLUSION: Single-stage surgery was shown to have the same predictability as two-stage surgery in the anterior edentulous mandible. Paragon implants with a titanium plasma-sprayed surface showed a fracture rate of 2.2% and a success rate of 86.2% after 5 years.
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| 6. |
- Erkapers, Maria, et al.
(författare)
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Patient satisfaction following dental implant treatment with immediate loading in the edentulous atrophic maxilla
- 2011
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Ingår i: International Journal of Oral & Maxillofacial Implants. - 0882-2786 .- 1942-4434. ; 26:2, s. 356-364
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The present study evaluated patient satisfaction using the Oral Health Impact Profile 49 (OHIP-49) questionnaire for patients who received six implants in the severely resorbed maxilla and an implant-supported prosthesis that was delivered within 24 hours after surgery. Materials and Methods: Fifty-one edentulous patients with severe atrophy in the maxilla were included in the study, which was performed at two centers. Six implants were placed in the maxilla and loaded within 24 hours with a provisional restoration. The definitive restorations were delivered 20 to 24 weeks later. Patients were asked to complete the OHIP-49 questionnaire (which includes seven domains representing functional limitation, physical pain, psychologic discomfort, physical disability, psychologic disability, social disability, and handicap) prior to implant placement and on three subsequent occasions. The data were collected and analyzed and OHIP scores were compared over time. Results: Baseline satisfaction scores for the two different centers displayed no statistically significant differences. Treatment resulted in improved total OHIP-49 scores in both centers, with no significant difference between centers. Furthermore, no significant differences were observed in any of the individual pretreatment and posttreatment OHIP-49 domains between centers. All seven domains showed a statistically significant improvement posttreatment. Of the seven domains, social disability and handicap showed the least improvement and had the lowest pretreatment scores, indicating lower significance for these domains compared to the other domains during implant treatment. This study also indicated that domains one to five (functional limitation, physical pain, psychologic discomfort, physical disability, and psychologic disability) are the most important domains in patient satisfaction with implant therapy. Conclusion: Measurement with the OHIP-49 questionnaire displayed that patient satisfaction increases after treatment with a fixed restoration on implants loaded within 24 hours.
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| 7. |
- Erkapers, Maria, et al.
(författare)
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The influence of immediately loaded implant treatment in the atrophic edentulous maxilla on oral health related quality of life of edentulous patients : 3-year results of a prospective study
- 2017
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Ingår i: Head & Face Medicine. - : Springer Science and Business Media LLC. - 1746-160X. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To evaluate oral health related quality of life (OHQoL) in edentulous patients treated with immediately loaded implants in the maxilla.METHODS: Fifty-one edentulous patients in two centers received six maxillary implants each were loaded within 24 h with provisional restoration. Definitive restoration was delivered 20-24 weeks later. OHQoL was evaluated preoperatively with the Oral Health Impact Profile 49 questionnaire (OHIP-49) and on five subsequent occasions. OHIP-49 includes seven domains representing functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap. A reduction in OHIP scores indicated an improved OHQoL.RESULTS: Forty-five patients reached the three-year follow up. OHQoL improved after treatment. A plateau of OHQoL improvement was observed at 12 months after surgery. The seven domains improved at different pace, 12 weeks to 12 months after treatment. OHIP showed continuously low scores with no significant changes at consecutive visits 12 months to three years after treatment. Dental status with removable prosthesis in the mandible had a negative impact on OHQoL prior to and during treatment, but did not affect OHQoL after permanent restoration was placed. Patients age or gender did not affect OHQoL.CONCLUSIONS: Patients with edentulous maxilla who received prosthetic rehabilitation on immediately loaded implants experienced the highest improved OHQoL 12 months after implant installation. Quality of life related to oral health continued to be high after three years. Edentulous patients with atrophy of the maxilla experience an improved OHQoL after implant treatment with immediate loading protocol.TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00711022 .
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| 8. |
- Glynn, Anders, et al.
(författare)
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PFAS i blod – modellering av exponering via dricksvatten
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med projektet var att undersöka sambandet mellan halter av per- och polyfluorerade alkylsubstanser (PFAS) i dricksvatten (DV) och i serumprover från befolkningsgrupper som druckit PFAS-förorenat DV under lång tid. Målet var att utveckla en populationsmodell där PFAS-halter i serum kan uppskattas från PFAS-halter i DV och exponeringstid för detta DV. I projektet användes redan publicerade resultat från studier av PFAS-halter i serum och DV, omfattande anställda vid Arvidsjaurs flygplats (brunnsvatten), permanent/fritidsboende i närheten av Luleå flygplats (brunnsvatten), permanent/fritidsboende i närheten av Visby flygplats (brunnsvatten), och invånare från Uppsala (kommunalt DV). En grupp vuxna från Karlshamn (kommunalt vatten) fick representera populationer som druckit rent DV. Linjära regressionsanalyser visade starka samband mellan uppmätta PFAS-halter i serum och DV. PFHxS uppvisade den högsta kvoten mellan halt i serum och DV (ca 100), medan PFHxA och PFBS hade kvoter i intervallet 1-2. Skillnaderna i kvoter, som illustrerar hur effektivt PFAS bioackumuleras i kroppen från DV, är relaterad till hur länge olika PFAS stannar i kroppen efter avslutad exponering (halveringstider). PFAS med långa halveringstider (PFOA, PFHxS, PFOS) hade klart högre kvoter, och därmed högre bioackumulering, än PFAS med korta halveringstider (PFHxA, PFBS). I separata regressionsanalyser observerades lägre kvoter mellan PFAS-halt i serum och DV hos kvinnor än hos män, vilket antyder att kvinnor inte bioackumulerar de studerade PFAS från DV i lika hög grad som män. Befolkningen i Sverige exponeras för PFAS från andra källor än DV, vilket leder till bakgrundshalter av PFAS i serum även bland dem som inte druckit förorenat DV. Resultaten från regressionsanalyserna användes för att uppskatta vid vilka halter av PFAS i DV som det med stor sannolikhet går att upptäcka PFAS-halter i serum som ligger över bakgrundshalterna. Dessa PFAS-halter i DV varierade mellan olika PFAS, från ca 50 ng/L för PFOA till ca 100 ng/L för PFOS. Dessa halter ligger mycket högre än de som normalt uppmäts i kommunalt och enskilt DV i Sverige, och representerar halter i starkt förorenade områden. Med den relativt enkla populationsmodell som utvecklats i projektet kan man beräkna hur halterna av PFAS i serum påverkas av PFAS-halterna i DV. Dessutom kan man beräkna hur PFAS-halterna i serum påverkas av exponeringstiden för det förorenade DV, samt hur halterna minskar i serum efter övergång till rent DV. Som ingångsvärden i modellen användes de bakgrundshalter av PFAS i serum och kvoter mellan serum/DV-halter av PFAS som tagits fram i regressionsanalysen. Dessutom utnyttjades de halveringstider som tagits fram för de som arbetade (och konsumerade PFAS-förorenat DV) vid Luleå flygplats, samt en population vuxna från Canada. I ett test av modellen jämfördes de modellerade halterna av PFOA, PFHxS och PFOS i serum med uppmätta halter i tre populationer från Sverige (Ronneby), Italien (Veneto) och Arnsberg (Tyskland) som druckit förorenat DV under lång tid. Jämförelsen visade att modellen på ett bra sätt uppskattar variationen av halterna i serum i populationen, men att den underskattar medelhalterna, om medianen används vid jämförelsen. Om de modellerade medelvärdena (artimetiskt medelvärde) istället används i jämförelsen med de uppmätta medianerna, ligger de modellerade och uppmätta medel-halterna nära varandra. De observerade skillnaderna kan bero på att den regressionsanalys som användes för att ta fram ingångsvärdena i modellen påverkat fördelningen av värdena på ett sätt som inte helt överensstämmer med fördelningen i de studerade populationerna. Eliminering av PFAS efter övergång till rent DV modellerades också. Som exempel användes haltdata från de Ronnebybor som druckit förorenat DV under lång tid. Som slutpunkt i modelleringen användes den serumhalt som i medeltal representerar ett långsiktigt intag av PFAS i nivå med det tolerabla veckointaget (serumTVI), som EFSA tagit fram i sin senaste riskbedömning. SerumTVI är uppskattat för en summa-halt av PFOA, PFNA, PFHxS och PFOS i serum (6,9 ng PFAS4/ml). Modelleringen pekar mot en stor variation i den tid det tar innan serumTVI nås i en befolkningsgrupp efter byte till rent DV. Den kortaste tiden modellerades till 14 år och den längsta till längre än en livstid. Resultaten i projektet uppmuntrar till fortsatt utveckling av modellen för uppskattning av PFAS-halter i serum från uppmätta halter i DV.
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| 9. |
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| 10. |
- Johanson, G., et al.
(författare)
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Quantitative relationships of perfluoroalkyl acids in drinking water associated with serum concentrations above background in adults living near contamination hotspots in Sweden
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 219
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Tidskriftsartikel (refereegranskat)abstract
- Contaminated drinking water (DW) is a major source of exposure to per- and polyfluoroalkyl substances (PFAS) at locations around PFAS production/use facilities and military airports. This study aimed to investigate quantitative relationships between concentrations in DW and serum of nine perfluoroalkyl acids (PFAAs) in Swedish adult populations living near contamination hotspots. Short-chained (PFPeA, PFHxA, PFHpA, and PFBS) and long-chained PFAAs (PFOA, PFNA, PFDA, PFHxS and PFOS) were measured in DW and serum. We matched DW and serum concentrations for a total of 398 subjects living or working in areas receiving contaminated DW and in one non-contaminated area. Thereafter, linear regression analysis with and without adjustments for co-variates was conducted. This enabled to derive (i) serum concentrations at background exposure (CB) from sources other than local DW exposure (i.e. food, dust and textiles) at 0 ng/L DW concentration, (ii) population-mean PFAA serum:water ratios (SWR) and (iii) PFAA concentrations in DW causing observable elevated serum PFAA concentrations above background variability. Median concentrations of the sum of nine PFAAs ranged between 2.8 and 1790 ng/L in DW and between 7.6 and 96.9 ng/mL in serum. DW concentration was the strongest predictor, resulting in similar unadjusted and adjusted regression coefficients. Mean CB ranged from <0.1 (PFPeA, PFHpA, PFBS) to 5.1 ng/mL (PFOS). Serum concentrations increased significantly with increasing DW concentrations for all PFAAs except for PFPeA with SWRs ranging from <10 (PFHxA, PFHpA and PFBS) to 111 (PFHxS). Observed elevated serum concentrations above background variability were reached at DW concentrations between 24 (PFOA) and 357 ng/L (PFHxA). The unadjusted linear regression predictions agreed well with serum concentrations previously reported in various populations exposed to low and high DW levels of PFOA, PFHxS and PFOS. The quantitative relationships derived herein should be helpful to translate PFAA concentrations in DW to concentrations in serum at the population level.
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