| 1. |
- Andersson, Linda, 1973, et al.
(författare)
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PLD1 and ERK2 regulate cytosolic lipid droplet formation
- 2006
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Ingår i: J Cell Sci. ; 119:Pt 11, s. 2246-57
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Tidskriftsartikel (refereegranskat)abstract
- We have previously uncovered roles for phospholipase D (PLD) and an unknown cytosolic protein in the formation of cytosolic lipid droplets using a cell-free system. In this report, PLD1 has been identified as the relevant isoform, and extracellular signal-regulated kinase 2 (ERK2) as the cytosolic protein. Increased expression of PLD1 increased lipid droplet formation whereas knockdown of PLD1 using siRNA was inhibitory. A role for ERK2 in basal lipid droplet formation was revealed by overexpression or microinjection, and ablation by siRNA knockdown or pharmacological inhibition. Similar manipulations of other Map kinases such as ERK1, JNK1 or JNK2 and p38alpha or p38beta were without effect. Insulin stimulated the formation of lipid droplets and this stimulation was inhibited by knockdown of PLD1 (by siRNA) and by inhibition or knockdown (by siRNA) of ERK2. Inhibition of ERK2 eliminated the effect of PLD1 on lipid droplet formation without affecting PLD1 activity, suggesting that PLD1 functions upstream of ERK2. ERK2 increased the phosphorylation of dynein which increased the amount of the protein on ADRP-containing lipid droplets. Microinjection of antibodies to dynein strongly inhibited the formation of lipid droplets, demonstrating that dynein has a central role in this formation. Thus dynein is a possible target for ERK2.
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| 2. |
- Asp, Lennart, 1965, et al.
(författare)
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Role of ADP ribosylation factor 1 in the assembly and secretion of ApoB-100-containing lipoproteins
- 2005
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Ingår i: Arterioscler Thromb Vasc Biol. - 1524-4636. ; 25:3, s. 566-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated the role of ADP ribosylation factor 1 (ARF1) in the assembly of very-low-density lipoproteins (VLDLs). METHODS AND RESULTS: The dominant-negative ARF1 mutant, T31N, decreased the assembly of apoB-100 VLDL 1 (Svedberg floatation units [Sf] 60 to 400) by 80%. The decrease coincided with loss of coatamer I (COPI) from the Golgi apparatus and inhibition of anterograde transport, as demonstrated by time-lapse studies of the vesicular stomatitis virus G protein. The VLDL 1 assembly was also completely inhibited at 15 degrees C. Thus, the antegrade transport is essential for the assembly of VLDL 1. Intracellular localization of N-acetylgalactosaminyl transferase 2 indicated that the Golgi apparatus was at least partly intact when the VLDL assembly was inhibited. Transient transfection with phospholipase D 1 increased the assembly of VLDL 1 and VLDL 2 (Sf 20 to 60). Overexpression of ARF1 in stably transfected McA-RH7777 cells increased the secretion of VLDL 2 but not of VLDL 1, which was dependent on the availability of oleic acid. Secretion of VLDL 1 increased with increasing amounts of oleic acid, and VLDL 2 secretion decreased simultaneously. CONCLUSIONS: Overexpression of ARF1 increased the assembly of VLDL 2 but not of VLDL 1, whose production was dependent on both anterograde transport and the availability of fatty acids.
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| 3. |
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| 4. |
- Flynn, Traci, 1973, et al.
(författare)
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A longitudinal study of hearing and middle ear status of individuals with cleft palate with and without additional malformations/syndromes.
- 2014
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Ingår i: The Cleft Palate-Craniofacial Journal. - : SAGE Publications. - 1055-6656 .- 1545-1569. ; 51:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe and compare the middle ear status and hearing sensitivity in adolescence with isolated cleft palate plus additional malformations and/or syndromes with those with only an isolated cleft palate. Design: Retrospective and longitudinal. Two groups of individuals with isolated cleft palate were compared. Participants: A cohort of individuals born over 4 years in the western region of Sweden. The cohort was divided into one group with isolated cleft palate (n = 31; ICP) and one group with isolated cleft palate plus additional malformations and/or syndromes (n = 37; ICP+). Methods: Middle ear status and hearing thresholds were collected from the medical records at 7, 10, 13, and 16 years of age, examined, and compared within and between groups over time. Results: The ICP+ group demonstrated a significantly higher prevalence of abnormal middle ear status and elevated hearing thresholds as compared with the ICP group. As the individuals aged, the prevalence of abnormal middle ear status decreased. The hearing levels in both groups decreased in the low to middle frequencies as individuals aged; however, the hearing in the high frequencies did not. Conclusions: Individuals with cleft palate need to be followed routinely for middle ear status and hearing thresholds to ensure optimal audiological rehabilitation, with particular attention to those with additional malformations and/or syndromes.
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| 5. |
- Fredriksson, Sofie, 1983, et al.
(författare)
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Preschool teachers have an increased risk of hearing-related symptoms and report more occupational noise exposure compared to randomly selected women
- 2016
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Ingår i: Occupational Health: Think Globally, Act Locally, EPICOH 2016, September 4–7, 2016, Barcelona, Spain. Occupational & Environmental Medicine. ; 73:A191
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Noise-induced hearing disorder has been thoroughly studied among workers in industry-like settings, but less so in female-dominated occupations. In Sweden, noise-related occupational disease among women are reported most frequently in the education sector. We analysed questionnaires from 4,932 women with preschool teacher’s degree who have worked in preschool compared to 5,065 randomly selected women without preschool work-history (response rate 51% vs. 38%). The age range was 24–71 in both cohorts (mean 46 [SD 11] among preschool teachers and 51 [11] among controls). Prevalence and prevalence ratio in age-strata and Mantel-Haenszel pooled risk were calculated for hearing-related symptoms. Noise exposure was compared between the cohorts. A 5% level of significance was applied. Occupational noise exposure and noise annoyance were significantly more common among teachers than controls: 75% vs.31% and 69% vs.26%, respectively. Still, significantly fewer teachers used hearing protection: 3% vs. 4%. Prevalence of hearing-related symptoms was much higher among teachers than controls: sound-induced auditory fatigue (71% [95% CI: 70–72] vs. 31% [30–32]), difficulty perceiving speech (46% [45–47] vs. 26% [25–27] and hyperacusis (38% [37–39] vs. 18% [17–19] and slightly higher for hearing loss (19% [18–20] vs. 17% [6–18] and tinnitus (19% [18–20] vs. 15% [14–16]. Teachers had a twofold risk of sound-induced auditory fatigue (PR-MH 2.2 [95% CI: 2.1–2.3] and hyperacusis (PR-MH 2.1 [1.9–2.2] compared to controls, when adjusted for age. The risk was also increased for difficulty perceiving speech (PR-MH 1.8 [1.7–1.9], tinnitus (PR-MH 1.4 [1.3–1.6] and hearing loss (PR-MH 1.4 [1.3–1.5]. Mean age of onset was significantly lower among teachers for all symptoms, except for hyperacusis (p = 0.902). Leisure-noise was significantly more common among controls. Family history of hearing loss did not differ (p = 0.411). The study is the first to show that preschool teachers have an increased risk of hearing-related symptoms, which may be caused by the work environment.
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| 6. |
- Fredriksson, Sofie, 1983, et al.
(författare)
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The Impact of Occupational Noise Exposure on Hyperacusis: a Longitudinal Population Study of Female Workers in Sweden.
- 2021
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Ingår i: Ear and Hearing. - 1538-4667. ; 43:4, s. 1366-1377
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to assess the risk of hyperacusis in relation to occupational noise exposure among female workers in general, and among women working in preschool specifically.A retrospective longitudinal study was performed. Survey data were collected in 2013 and 2014 from two cohorts: randomly selected women from the population in region Västra Götaland, Sweden, and women selected based on having received a preschool teacher degree from universities in the same region. The final study sample included n = 8328 women born between 1948 and 1989. Occupational noise exposure was objectively assigned to all time periods from the first to the last reported occupation throughout working life, using the Swedish Job-Exposure Matrix (JEM) with three exposure intervals: <75 dB(A), 75 to 85 dB(A), and >85 dB(A). The JEM assigns preschool teachers to the 75 to 85 dB(A) exposure interval. The outcome hyperacusis was assessed by self-report using one question addressing discomfort or pain from everyday sounds. In the main analysis, a hyperacusis event was defined by the reported year of onset, if reported to occur at least a few times each week. Additional sensitivity analyses were performed using more strict definitions: (a) at least several times each week and (b) every day. The risk (hazard ratio, HR) of hyperacusis was analyzed in relation to years of occupational noise exposure, using survival analysis with frailty regression modeling accounting for individual variation in survival times which reflect, for example, noise exposure during years prior to onset. Occupational noise exposure was defined by the occupation held at year of hyperacusis onset, or the occupation held at the survey year if no event occurred. Models were adjusted for confounders including age, education, income, family history of hearing loss, and change of jobs due to noise.In total, n = 1966 hyperacusis events between 1960 and 2014 were analyzed in the main analysis. A significantly increased risk of hyperacusis was found among women working in any occupation assigned to the 75 to 85 dB(A) noise exposure group [HR: 2.6, 95% confidence interval (CI): 2.4-2.9], compared with the reference group <75 dB(A). The risk was tripled among preschool teachers specifically (HR: 3.4, 95% CI: 3.0-3.7), with the crude Kaplan-Meier curve showing a higher rate of onset early in the working life in preschool teachers compared with all the other exposure groups. The risk was increased, but not statistically significant in the main analysis, for the highest exposure group >85 dB(A), where only six hyperacusis events were identified (HR: 1.4, 95% CI: 0.6-3.1). In the sensitivity analysis, where hyperacusis was defined as occurring every day, the HR was significant also in the highest exposure group (HR: 3.8, 95% CI: 1.4-10.3), and generally slightly higher in the other exposure groups compared to the main analysis.This study indicates increased risk of hyperacusis already below the permissible occupational noise exposure limit in Sweden (85 dB LAeq,8h) among female workers in general, and in particular among preschool teachers. Prospective studies and less wide exposure intervals could confirm causal effects and assess dose-response relationships, respectively, although this study at present suggest a need for risk assessment, improved hearing prevention measures, and noise abatement measures in occupations with noise levels from 75 dB(A). The results could also have implications for management of occupational disability claims.
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| 7. |
- Fredriksson, Sofie, 1983, et al.
(författare)
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Validating self-reporting of hearing-related symptoms against pure-tone audiometry,otoacoustic emission, and speech audiometry
- 2016
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1499-2027 .- 1708-8186. ; 55:8, s. 454-62
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To validate self-reported hearing-related symptoms among personnel exposed to moderately high occupational noise levels at an obstetrics clinic. Design: Sensitivity, specificity, and predictive values were calculated for questionnaire items assessing hearing loss, tinnitus, sound sensitivity, poor hearing, difficulty perceiving speech, and sound-induced auditory fatigue. Hearing disorder was diagnosed by pure-tone audiometry, distortion Product otoacoustic emissions, and HINT (Hearing In Noise Test). Study sample: Fifty-five female obstetrics personnel aged 22–63 participated; including 26 subjects reporting hearing loss, poor hearing, tinnitus, or sound sensitivity, and 29 randomly selected subjects who did not report these symptoms. Results: The questionnaire item assessing sound-induced auditory fatigue had the best combination of sensitivity 85% (95% CIs 56 to 100%)and specificity 70% (95% CIs 55 to 84%) for hearing disorder diagnosed by audiometry or otoacoustic emission. Of those reporting sound-induced auditory fatigue 71% were predicted to have disorder diagnosed by otoacoustic emission. Participants reporting any hearing-related symptom had slightly worse measured hearing. Conclusions: We suggest including sound-induced auditory fatigue in questionnaires for identification of hearing disorder among Healthcare personnel, though larger studies are warranted for precise estimates of diagnostic performance. Also, more specific and accurate hearing tests are needed to diagnose mild hearing disorder.
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| 8. |
- Fredriksson, Sofie, 1983, et al.
(författare)
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Working in preschool increases the risk of hearing-related symptoms: a cohort study among Swedish women
- 2019
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 92:8, s. 1179-90
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Tidskriftsartikel (refereegranskat)abstract
- © 2019, The Author(s). Purpose: To assess whether working in preschools increases the risk of hearing-related symptoms and whether age, occupational noise, and stressful working conditions affect the risk. Methods: Questionnaire data on hearing-related symptoms were analysed in women aged 24–65 (4718 preschool teachers, and 4122 randomly selected general population controls). Prevalence and risk ratio (RR) of self-reported hearing loss, tinnitus, difficulty perceiving speech, hyperacusis and sound-induced auditory fatigue were assessed by comparing the cohorts in relation to age and self-reported occupational noise and stressful working conditions (effort–reward imbalance and emotional demands). RR was calculated using log-binomial regression models adjusted for age, education, income, smoking, hearing protection, and leisure noise. Incidence rates and incidence rate ratios (IRR) were calculated for retrospectively reported onset of all symptoms except sound-induced auditory fatigue. Results: Compared to the controls, preschool teachers had overall more than twofold RR of sound-induced auditory fatigue (RR 2.4, 95% confidence interval 2.2–2.5) and hyperacusis (RR 2.3, 2.1–2.5) and almost twofold for difficulty perceiving speech (RR 1.9, 1.7–2.0). Preschool teachers had a threefold IRR of hyperacusis (IRR 3.1, 2.8–3.4) and twofold for difficulty perceiving speech (IRR 2.4, 2.2–2.6). Significantly although slightly less increased RR and IRR were observed for hearing loss and tinnitus. RR and IRR were generally still increased for preschool teachers when stratified by age and occupational exposure to noise and stress. Conclusions: This large cohort study showed that working as preschool teacher increases the risk of self-reported hearing-related symptoms, indicating a need of preventative measures.
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| 9. |
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| 10. |
- Laxdal, Gauti, 1966, et al.
(författare)
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Outcome and risk factors after anterior cruciate ligament reconstruction: a follow-up study of 948 patients
- 2005
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Ingår i: Arthroscopy. - : Elsevier BV. - 1526-3231. ; 21:8, s. 958-964
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of the study was to assess the outcome and risk factors after anterior cruciate ligament (ACL) reconstruction in a large group of patients. TYPE OF STUDY: Case series. METHODS: Included in this retrospective study were 948 patients (323 female, 625 male) with a symptomatic unilateral ACL rupture, who underwent arthroscopic reconstruction using patellar tendon autograft and interference screw fixation at 3 Swedish hospitals. The median age of the patients at the time of the index operation was 26 years (range, 14 to 53 years). The patients underwent surgery at a median of 12 months (range, 0.5 to 360 months) after their injury. Independent physiotherapists performed the follow-up examinations at a median of 32 months (range, 21 to 117 months) postoperatively. RESULTS: Of the 948 patients, 550 (58%) underwent meniscal surgery before, during, or after the ACL reconstruction. The median Tegner activity level was 8 (range, 2-10) before injury, 3 (range, 0-9) preoperatively, and 6 (range, 1-10) at follow-up (P < .0001 preoperative v follow-up). At follow-up, the median Lysholm score was 90 points (range, 14-100), the median KT-1000 anterior side-to-side laxity difference was 1.5 mm (range, -6 to 13 mm), and the median 1-leg hop test quotient was 95% (0% to 167%) compared with the contralateral normal side. At follow-up, 69.3% of the patients were classified as normal or nearly normal according to the International Knee Documentation Committee evaluation system. However, 36% of the patients were unable to or had severe problems performing the knee-walking test. Inferior results correlated with increased time period between the index injury and reconstruction and concomitant joint damage found at the index operation. CONCLUSIONS: Overall, the results were good after ACL reconstruction using patellar tendon autograft and interference screw fixation. Concomitant joint damage and a long time period between the injury and reconstruction are major risk factors for inferior outcome after ACL reconstruction. LEVEL OF EVIDENCE: Level IV, case series.
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