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11.
  • Carlsson, Josefine, et al. (author)
  • Suspect and non-target screening of chemicals in clothing textiles by reversed-phase liquid chromatography/hybrid quadrupole-Orbitrap mass spectrometry
  • 2021
  • In: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 414:3, s. 1403-1413
  • Journal article (peer-reviewed)abstract
    • The global manufacturing of clothing is usually composed of multistep processes, which include a large number of chemicals. However, there is generally no information regarding the chemical content remaining in the finished clothes. Clothes in close and prolonged skin contact may thus be a significant source of daily human exposure to hazardous compounds depending on their ability to migrate from the textiles and be absorbed by the skin. In the present study, twenty-four imported garments on the Swedish market were investigated with respect to their content of organic compounds, using a screening workflow. Reversed-phase liquid chromatography coupled to electrospray ionization/high-resolution mass spectrometry was used for both suspect and non-target screening. The most frequently detected compound was benzothiazole followed by quinoline. Nitroanilines with suspected mutagenic and possible skin sensitization properties, and quinoline, a carcinogenic compound, were among the compounds occurring at the highest concentrations. In some garments, the level of quinoline was estimated to be close to or higher than 50,000 ng/g, the limit set by the REACH regulation. Other detected compounds were acridine, benzotriazoles, benzothiazoles, phthalates, nitrophenols, and organophosphates. Several of the identified compounds have logP and molecular weight values enabling skin uptake. This pilot study indicates which chemicals and compound classes should be prioritized for future quantitative surveys and control of the chemical content in clothing as well as research on skin transfer, skin absorption, and systemic exposure. The results also show that the current control and prevention from chemicals in imported garments on the Swedish market is insufficient.
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12.
  • Dezfouli, Mahya, et al. (author)
  • Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies
  • 2020
  • In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
  • Journal article (peer-reviewed)abstract
    • The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.
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13.
  • Ericson, Ulrika, et al. (author)
  • A Health-Conscious Food Pattern Is Associated with Prediabetes and Gut Microbiota in the Malmö Offspring Study
  • 2020
  • In: Journal of Nutrition. - : Elsevier BV. - 0022-3166. ; 150:4, s. 861-872
  • Journal article (peer-reviewed)abstract
    • Background: Diet is a determinant of gut microbiota. Both diet and gut microbiota have been linked to metabolic diseases. Objective: We aimed to examine data-driven food patterns in relation to the prevalence of prediabetes and gut microbiota composition and food pattern-associated bacteria in relation to prediabetes. Methods: Food patterns were extracted using principal component analysis in 1726 individuals (aged 18-71 y, 55% women, mean BMI = 25.5 kg/m2) without diabetes from the population-based Malmö Offspring Study. The gut (fecal) microbiota was analyzed by sequencing the 16S ribosomal RNA gene (V1-V3 region). Prediabetes classification was based on fasting glucose ≥6.0 mmol/L and/or glycated hemoglobin ≥42 mmol/L at baseline and/or type 2 diabetes diagnosis during follow-up (0-3.8 y). Logistic regression was used to investigate cross-sectional associations with prediabetes, and the general linear model to examine associations between food patterns and bacterial genera. Results: Two food patterns, the Health-conscious and the Sugar and High-Fat Dairy patterns, were identified. Adherence to the Health-conscious pattern was associated with a lower prevalence of prediabetes (OR comparing highest quintile with lowest: 0.54; 95% CI: 0.32, 0.92; P-trend = 0.03) and with the abundance of several gut bacterial genera, of which the most robust findings were with a higher abundance of Roseburia and Lachnospira and with a lower abundance of Eubacterium. Roseburia was also associated with a lower prevalence of prediabetes (OR comparing highest quintile with lowest: 0.56; 95% CI: 0.35, 0.92; P-trend = 0.01) and the association between the Health-conscious pattern and prediabetes was attenuated after adjustment for abundance of Roseburia and BMI. Adherence to the Sugar and High-Fat Dairy pattern was associated with a higher prevalence of prediabetes in women (P-trend across food pattern quintiles = 0.03). Conclusions: In this Swedish population-based study, a Health-conscious food pattern showed an inverse association with the prevalence of prediabetes. Potential underlying explanations may involve links between healthy diet and BMI, as well as gut microbiota, especially a higher abundance of Roseburia.
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14.
  • Farrell, Mary, et al. (author)
  • Effect of AMY1 copy number variation and various doses of starch intake on glucose homeostasis : data from a cross-sectional observational study and a crossover meal study
  • 2021
  • In: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 16, s. 1-12
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Copy number (CN) variation (CNV) of the salivary amylase gene (AMY1) influences the ability to digest starch and may influence glucose homeostasis, obesity and gut microbiota composition. Hence, the aim was to examine the association of AMY1 CNV with fasting glucose, BMI, and gut microbiota composition considering habitual starch intake and to investigate the effect of AMY1 CNV on the postprandial response after two different starch doses.METHODS: The Malmö Offspring Study (n = 1764, 18-71 years) was used to assess interaction effects between AMY1 CNV (genotyped by digital droplet polymerase chain reaction) and starch intake (assessed by 4-day food records) on fasting glucose, BMI, and 64 gut bacteria (16S rRNA sequencing). Participants with low (≤ 4 copies, n = 9) and high (≥ 10 copies, n = 10) AMY1 CN were recruited for a crossover meal study to compare postprandial glycemic and insulinemic responses to 40 g and 80 g starch from white wheat bread.RESULTS: In the observational study, no overall associations were found between AMY1 CNV and fasting glucose, BMI, or gut microbiota composition. However, interaction effects between AMY1 CNV and habitual starch intake on fasting glucose (P = 0.03) and BMI (P = 0.05) were observed, suggesting inverse associations between AMY1 CNV and fasting glucose and BMI at high starch intake levels and positive association at low starch intake levels. No associations with the gut microbiota were observed. In the meal study, increased postprandial glucose (P = 0.02) and insulin (P = 0.05) were observed in those with high AMY1 CN after consuming 40 g starch. This difference was smaller and nonsignificant after consuming 80 g starch.CONCLUSIONS: Starch intake modified the observed association between AMY1 CNV and fasting glucose and BMI. Furthermore, depending on the starch dose, a higher postprandial glucose and insulin response was observed in individuals with high AMY1 CN than in those with low AMY1 CN.TRIAL REGISTRATION: ClinicalTrials.gov , NCT03974126 . Registered 4 June 2019-retrospectively registered.
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15.
  • Fors, Andreas, 1977, et al. (author)
  • Effects of a person-centred approach in a school setting for adolescents with chronic pain-The HOPE randomized controlled trial
  • 2020
  • In: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 24:8, s. 1598-1608
  • Journal article (peer-reviewed)abstract
    • Background Chronic pain among adolescents is common but effective interventions applicable in a school setting are rare. Person-centred care (PCC) is a key factor in improving health by engaging persons as partners in their own care. Methods In this randomized controlled trial, a total of 98 adolescents in secondary school or upper secondary school (aged 14 - 21 years) with chronic pain were randomly assigned to a PCC intervention or standard school healthcare. In the intervention group a pain management programme, based on a PCC approach, comprising four face-to-face sessions with a school nurse over a period of 5 weeks was added to standard school healthcare. The main outcome measure was self-efficacy in daily activities (SEDA scale) and rating scales for pain intensity and pain impact were used as secondary outcome measures. Results At the follow-up, no significant differences were found between the groups in the SEDA scale (p = .608) or in the rating scales for pain intensity (p = .261) and pain impact (p= .836). In the sub-group analysis, a significant improvement in the SEDA scale was detected at the secondary school in favour of the PCC intervention group (p = .021). Conclusion In this pain management programme based on a PCC approach, we found no effect in the total sample, but the programme showed promising results to improve self-efficacy in daily activities among adolescents at secondary school. Significance This study evaluates the effects of a pain management programme based on a PCC approach in a school setting addressing adolescents at upper secondary and secondary schools with chronic pain. No overall effects were shown, but results illustrate that the intervention improved self-efficacy in adolescents at secondary school. Implementation of a PCC approach in a school setting may have the potential to improve self-efficacy in daily activities for adolescents with chronic pain at secondary school.
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16.
  • Haraldson, Philip, et al. (author)
  • Botulinum Toxin A as a Treatment for Provoked Vestibulodynia A Randomized Controlled Trial
  • 2020
  • In: Obstetrics and Gynecology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0029-7844 .- 1873-233X. ; 136:3, s. 524-532
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To evaluate pain reduction after two injections of 50 units botulinum toxin A compared with placebo for provoked vestibulodynia. METHODS: We conducted a double-blinded, placebo-controlled randomized trial of 50 units botulinum toxin A or placebo injected in the bulbocavernosus muscles twice, 3 months apart, in women with provoked vestibulodynia. Primary outcome was self-reported dyspareunia or pain at tampon use on a visual analog scale (VAS, 0-100). Secondary outcomes were pain at weekly tampon insertion (VAS score), reduction of pelvic floor hypertonicity (measured with a vaginal manometer), adverse events, and sexual function and distress. A sample size of 38 participants for each group was calculated to achieve a statistical power of 80% based on an effect size of 20 VAS units (0-100) (mean score range 56-76 +/- 31 SD). RESULTS: Between May 2016 and June 2018, 124 women with provoked vestibulodynia were assessed, and 88 were randomized to botulinum toxin A (BTA group, n=44) or placebo (placebo group, n=44). Primary outcome showed a lower but statistically nonsignificant pain rating by 7 VAS units (95% CI -15.0 to 0.4) in the BTA group compared with the placebo group. Secondary results showed a significant decrease in pain at weekly tampon insertion by 11 VAS units (95% CI -16.6 to 6.0) with botulinum toxin A injection. The vaginal manometer measured lower maximum contraction strength by 7 mm Hg (95% CI -12.7 to -2.4) and lower 10-second endurance strength by 4 mm Hg (95% CI -7.72 to -1.16) in the BTA group compared with the placebo group. No changes were observed for sexual function and distress, but there was a significant increase in women attempting vaginal intercourse in the BTA group (0.27, 95% CI 0.06-0.48). No severe adverse events were reported. CONCLUSION: Twice-repeated injections of 50 units of botulinum toxin A in women with provoked vestibulodynia did not reduce dyspareunia or pain at tampon use, but secondary outcomes suggested positive effects of the treatment.
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17.
  • Havervall, Sebastian, et al. (author)
  • Antibody responses after a single dose of ChAdOx1 nCoV-19 vaccine in healthcare workers previously infected with SARS-CoV-2
  • 2021
  • In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 70
  • Journal article (peer-reviewed)abstract
    • Background: Recent reports demonstrate robust serological responses to a single dose of messenger RNA (mRNA) vaccines in individuals previously infected with SARS-CoV-2. Data on immune responses following a single-dose adenovirus-vectored vaccine expressing the SARS-CoV-2 spike protein (ChAdOx1 nCoV-19) in individuals with previous SARS-CoV-2 infection are however limited, and current guidelines recommend a two-dose regimen regardless of preexisting immunity. Methods: We compared RBD-specific IgG and RBD-ACE2 blocking antibodies against SARS-CoV-2 wild type and variants of concern following two doses of the mRNA vaccine BNT162b2 in SARS-CoV-2 naive healthcare workers (n=65) and a single dose of the adenovector vaccine ChAdOx1 nCoV-19 in 82 healthcare workers more than (n=45) and less than (n=37) 11 months post mild SARS-CoV-2 infection at time of vaccination. Findings: The post-vaccine levels of RBD-specific IgG and neutralizing antibodies against the SARS-CoV-2 wild type and variants of concern including Delta lineage 1.617.2 were similar or higher in participants receiving a single dose of ChAdOx1 nCoV-19 vaccine post SARS-CoV-2 infection (both more than and less than 11 months post infection) compared to SARS-CoV-2 naive participants who received two doses of BNT162b2 vaccine. Interpretation: Our data support that a single dose ChAdOx1 nCoV-19 vaccine that is administered up to at least 11 months post SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen. (C) 2021 The Author(s). Published by Elsevier B.V.
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18.
  • Hellstrand, Sophie, et al. (author)
  • Dietary Data in the Malmö Offspring Study : Reproducibility, Method Comparison and Validation against Objective Biomarkers
  • 2021
  • In: Nutrients. - : MDPI AG. - 2072-6643. ; 13:5
  • Journal article (peer-reviewed)abstract
    • Irregular dietary intakes impairs estimations from food records. Biomarkers and method combinations can be used to improve estimates. Our aim was to examine reproducibility from two assessment methods, compare them, and validate intakes against objective biomarkers. We used the Malmö Offspring Study (55% women, 18-71 y) with data from a 4-day food record (4DFR) and a short food frequency questionnaire (SFFQ) to compare (1) repeated intakes (n = 180), (2) intakes from 4DFR and SFFQ (n = 1601), and (3) intakes of fatty fish, fruits and vegetables, and citrus with plasma biomarkers (n = 1433) (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid [CMPF], β-carotene and proline betaine). We also combined 4DFR and SFFQ estimates using principal component analysis (PCA). Moderate correlations were seen between repeated intakes (4DFR median ρ = 0.41, SFFQ median ρ = 0.59) although lower for specific 4DFR-items, especially fatty/lean fish (ρ ≤ 0.08). Between-method correlations (median ρ = 0.33) were higher for intakes of overall food groups compared to specific foods. PCA scores for citrus (proline betaine ρ = 0.53) and fruits and vegetables (β-carotene: ρ = 0.39) showed the highest biomarker correlations, whereas fatty fish intake from the SFFQ per se showed the highest correlation with CMPF (ρ = 0.46). To conclude, the reproducibility of SFFQ data was superior to 4DFR data regarding irregularly consumed foods. Method combination could slightly improve fruit and vegetable estimates, whereas SFFQ data gave most valid fatty fish intake.
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19.
  • Hellström, Ann, 1959, et al. (author)
  • Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants
  • 2021
  • In: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. OBJECTIVE To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. MAIN OUTCOMES AND MEASURES Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. RESULTS A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. CONCLUSIONS AND RELEVANCE This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
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20.
  • Hellström, Ann, 1959, et al. (author)
  • Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity A Randomized Clinical Trial
  • 2021
  • In: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 175:4, s. 359-367
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). OBJECTIVE To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 27 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. INTERVENTIONS Infants received either supplementation with an enteral oil providing AA (100mg/kg/d) and DHA (50mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcomewas severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. RESULTS A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P =.02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P <.001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P =.03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. CONCLUSIONS AND RELEVANCE This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
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