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1.
  • Amare, Azmeraw T, et al. (author)
  • Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
  • 2023
  • In: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
  • Journal article (peer-reviewed)abstract
    • Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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  • Gumulka, M, et al. (author)
  • Nickel exposure when working out in the gym
  • 2015
  • In: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 95:2, s. 247-249
  • Journal article (peer-reviewed)
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  • Isaksson, Marléne, et al. (author)
  • Exclusion of Disperse Orange 3 is possible from the textile dye mix present in the Swedish baseline patch test series. A study by the Swedish Contact Dermatitis Research Group
  • 2022
  • In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 88:1, s. 54-59
  • Journal article (peer-reviewed)abstract
    • Background The textile dye mix (TDM) 6.6% in petrolatum contains Disperse Blue (DB) 35, Disperse Yellow 3, Disperse Orange (DO) 1 and 3, Disperse Red 1 and 17, and DB 106 and 124. The most frequent allergen in TDM-positive patients is DO 3. Around 85% of para-phenylenediamine (PPD)-allergic dermatitis patients have been positive to DO 3. There has been a discussion to exclude DO 3 from TDM 6.6% because of strong simultaneous reactions to TDM and PPD. Objectives To study if DO 3 can be excluded from TDM 6.6%. Methods Patch tests were performed on 1481 dermatitis patients with TDM 6.6%, TDM 7.0% (without DO 3 but the other disperse dyes at 1.0% each), DO 3 1.0%, and PPD 1.0% pet. Results Contact allergy to TDM 6.6% was 3.6% and to TDM 7.0% was 3.0%. All 26 DO 3-positive patients were positive to PPD. The 44 patients positive to TDM 7.0% plus the 13 positive to PPD and TDM 6.6% but negative to TDM 7.0% were 57, outnumbering the 53 positive to TDM 6.6%. Conclusion TDM 7.0% can replace TDM 6.6% in the Swedish baseline series, since TDM 7.0% together with PPD 1.0% will detect patients with textile dye allergy.
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  • Isaksson, Marléne, et al. (author)
  • Suitable test concentration of cobalt and concomitant reactivity to nickel and chromium. A multicentre study from the Swedish Contact Dermatitis Research Group
  • 2021
  • In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 84:3, s. 153-158
  • Journal article (peer-reviewed)abstract
    • Background In Sweden, cobalt chloride 0.5% has been included in the baseline series since the mid-1980s. A recent study from Stockholm showed that cobalt chloride 1% petrolatum (pet.) was more suitable than 0.5%. Cobalt chloride at 1.0% has been patch tested for decades in many European countries and around the world. Objectives To study the suitability of patch testing to cobalt 1.0% vs 0.5% and to analyze the co-occurrence of allergy to cobalt, chromium, and nickel. Results Contact allergy to cobalt was shown in 90 patients (6.6%). Eighty (5.9%) patients tested positive to cobalt 1.0%. Thirty-seven of the 90 patients (41.1%) with cobalt allergy were missed by cobalt 0.5% and 10 (0.7%) were missed by cobalt 1.0% (P < .001). No case of patch test sensitization was reported. Allergy to chromium was seen in 2.6% and allergy to nickel in 13.3%. Solitary allergy to cobalt without nickel allergy was shown in 61.1% of cobalt-positive individuals. Female patients had larger proportions of positive reactions to cobalt (P = .036) and nickel (P < .001) than males. Conclusion The results speak in favor of replacing cobalt chloride 0.5% with cobalt chloride 1.0% pet. in the Swedish baseline series, which will be done 2021.
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  • Matura, M, et al. (author)
  • Selected oxidized fragrance terpenes are common contact allergens
  • 2005
  • In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 52:6, s. 320-328
  • Journal article (peer-reviewed)abstract
    • Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air-exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3% showed a positive reaction to oxidized linalool and 1.1% to the hydroperoxide fraction. About 0.5% of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58% had fragrance-related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.
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  • Andernord, D., et al. (author)
  • Contact allergy to haptens in the Swedish baseline series: Results from the Swedish Patch Test Register (2010 to 2017)
  • 2022
  • In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 86:3, s. 175-188
  • Journal article (peer-reviewed)abstract
    • Background Allergic contact dermatitis has considerable public health impact and causative haptens vary over time. Objectives To report the prevalence of contact allergy to allergens in the Swedish baseline series 2010 to 2017, as registered in the Swedish Patch Test Register. Methods Results and demographic information for patients tested with the Swedish baseline series in 2010 to 2017 were analysed. Results Data for 21 663 individuals (females 69%) were included. Females had significantly more positive patch tests (54% vs 40%). The reaction prevalence rates were highest for nickel sulfate (20.7%), fragrance mix I (7.1%), Myroxylon pereirae (6.9%), potassium dichromate (6.9%), cobalt chloride (6.8%), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; 6.4%), MI (3.7%), colophonium (3.5%), fragrance mix II (3.2%), and formaldehyde (3.2%). Myroxylon pereirae reaction prevalence increased from 5% in 2010 to 9% in 2017 and that for methyldibromo glutaronitrile from 3.1% to 4.6%. MCI/MI and MI reactions decreased in prevalence after 2014. Nickel reaction prevalence decreased among females aged 10 to 19 years. Conclusions Nickel remains the most common sensitizing agent, with reaction prevalence decreasing among females younger than 20 years. The changes in MCI/MI and MI reaction prevalence mirrored those in Europe. The register can reveal changes in contact allergy prevalence over time among patients patch tested in Sweden.
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  • Engfeldt, Malin, et al. (author)
  • Can patch testing with methylchloroisothiazolinone/methylisothiazolinone be optimized using a new diagnostic mix? - A multicenter study from the Swedish Contact Dermatitis Research Group
  • 2020
  • In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 82:5, s. 283-289
  • Journal article (peer-reviewed)abstract
    • Background Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and methylisothiazolinone (MI) are tested to detect contact allergy to these isothiazolinones. Objectives To study if an aqueous patch test preparation with MCI and MI in a mix of 0.015% and 0.2%, respectively, detects more contact allergies than the commonly used preparations of MCI/MI in 0.02% aq. and MI in 0.2% aq. Methods A total of 1555 patients with dermatitis in five Swedish dermatology departments were tested consecutively with MCI/MI 0.215% aq., MCI/MI 0.02% aq., and MI 0.2% aq. Results The share of contact allergy to MCI/MI 0.215% aq., MCI/MI 0.02% aq., and MI 0.2% aq. varied in the test centers between 7.9% and 25.9%, 3.2% and 10.3%, and 5.8% and 12.3%, respectively. MCI/MI 0.215% aq. detected significantly more patch-test positive individuals than both MCI/MI 0.02% aq. (P < .001) and MI 0.2% aq. (P < .001), as well as either one of MCI/MI and MI (P < .001). In the patients only reacting to MCI/MI 0.215% aq., 57.7% were recorded as having a dermatitis that was explained or aggravated by exposure to either MCI/MI or MI. Conclusion The results speak in favor of replacing the preparations MCI/MI 0.02% aq. and MI 0.2% aq. with MCI/MI 0.215% aq. as the screening substance in the Swedish baseline series, which has been implemented in 2020.
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  • Engfeldt, Malin, et al. (author)
  • Patch Testing with a New Composition of Mercapto Mix: A Multi-centre Study by the Swedish Contact Dermatitis Research Group
  • 2019
  • In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 99:11, s. 960-963
  • Journal article (peer-reviewed)abstract
    • This study investigated whether more patients with contact allergies were detected by patch testing with mercapto mix with a higher concentration of 2-mercaptobenzothiazolinone (MBT) than the commonly used mercapto mix. A total of 3,143 dermatitis patients in 5 Swedish dermatology departments were patch-tested with 3 mercapto test preparations: MBT 2.0% petrolatum (pet.); mercapto mix 2.0% pet.; and mercapto mix 3.5% pet. Positive reactions to these mercapto mixes varied between 0-0.50%, 0-0.93%, and 0-1.4%, respectively, in the 5 centres. Numerically, mercapto mix 3.5% pet. detected all positive patients and more patch-test positive patients than did the 2 other substances, but the difference was not statistically significant. The authors recommend replacing mercapto mix 2.0% pet. in the Swedish baseline series with mercapto mix 3.5% pet., since the latter also detected those patients who would have been missed because MBT 2.0% is not included in the Swedish baseline series.
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  • Johansen, Jeanne D., et al. (author)
  • European Society of Contact Dermatitis guideline for diagnostic patch testing : recommendations on best practice
  • 2015
  • In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 73:4, s. 195-221
  • Research review (peer-reviewed)abstract
    • The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
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  • Kittel-Schneider, Sarah, et al. (author)
  • Non-mental diseases associated with ADHD across the lifespan : Fidgety Philipp and Pippi Longstocking at risk of multimorbidity?
  • 2022
  • In: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 132, s. 1157-1180
  • Research review (peer-reviewed)abstract
    • Several non-mental diseases seem to be associated with an increased risk of ADHD and ADHD seems to be associated with increased risk for non-mental diseases. The underlying trajectories leading to such brain-body co-occurrences are often unclear - are there direct causal relationships from one disorder to the other, or does the sharing of genetic and/or environmental risk factors lead to their occurring together more frequently or both? Our goal with this narrative review was to provide a conceptual synthesis of the associations between ADHD and non-mental disease across the lifespan. We discuss potential shared pathologic mechanisms and genetic background and treatments in co-occurring diseases. For those co-occurrences for which published studies with sufficient sample sizes exist, meta-analyses have been published by others and we discuss those in detail. We conclude that non-mental diseases are common in ADHD and vice versa and add to the disease burden of the patient across the lifespan. Insufficient attention to such co-occurring conditions may result in missed diagnoses and suboptimal treatment in the affected individuals.
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  • Ramzy, Ahmad G., et al. (author)
  • Isothiocyanates are important as haptens in contact allergy to chloroprene rubber
  • 2017
  • In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 177:2, s. 522-530
  • Journal article (peer-reviewed)abstract
    • Background Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate. Objectives To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates. Methods Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates. Results All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2-1200 nmol cm(-2). At 35 degrees C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission. Conclusions Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.
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