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  • Ahokas, Essi K., et al. (författare)
  • Nocturnal Heart Rate Variability in Women Discordant for Hormonal Contraceptive Use
  • 2023
  • Ingår i: Medicine & Science in Sports & Exercise. - : Ovid Technologies (Wolters Kluwer Health). - 0195-9131 .- 1530-0315. ; 55:7, s. 1342-1349
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The aim of this study was to investigate within-cycle differences in nocturnal heart rate (HR) and heart rate variability (HRV) in naturally menstruating women (NM) and women using combined hormonal contraceptives (CU) or progestin-only hormonal contraceptives (PU).Methods Physically active participants were recruited into three groups: NM (n = 19), CU (n = 11), and PU (n = 12). Participants’ HR and HRV (with Bodyguard 2 HRV monitor), and blood hormones were monitored during one menstrual cycle (MC) (NM-group) or for 4 weeks (CU and PU-groups). Estradiol, progesterone, and luteinizing hormone were analyzed from fasting blood samples collected four times in the NM (M1 = bleeding, M2 = follicular phase, M3 = ovulation, and M4 = luteal phase) and PU groups (M1 = lowest E2; M2 = M1 + 7 days; M3 = M1 + 14 days; M4 = M1 + 21 days) and twice in the CU group (active and inactive pill phases). After every blood sample, nightly HR and HRV were recorded and examined as an average from two nights.Results Hormonal concentrations differed (p < 0.05) between MC phases in the NM- and PU-groups, but not (p ≥ 0.116) between the active and inactive phases in the CU-group. In the NM- and PU-groups, some of the HRV values were higher, while in the NM-group, HR was lower during M2 compared to M3 (p < 0.049) and M4 (p < 0.035). In the CU-group, HRV values (p = 0.014-0.038) were higher, and HR was lower (p = 0.038) in the inactive phase compared to the first week of the active phase.Conclusions The MC and hormonal cycle phases influence autonomic nervous system balance, which is reflected in measurements of nocturnal HR and HRV. This should be considered when monitoring recovery in physically active individuals.
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  • Berner, Logan T., et al. (författare)
  • The Arctic plant aboveground biomass synthesis dataset
  • 2024
  • Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
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  • Gronberg, B. H., et al. (författare)
  • High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial
  • 2021
  • Ingår i: Lancet Oncology. - 1470-2045 .- 1474-5488. ; 22:3, s. 321-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Concurrent chemoradiotherapy is standard treatment for limited stage small-cell lung cancer (SCLC). Twice-daily thoracic radiotherapy of 45 Gy in 30 fractions is considered to be the most effective schedule. The aim of this study was to investigate whether high-dose, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions improves survival. Methods This open-label, randomised, phase 2 trial was done at 22 public hospitals in Norway, Denmark, and Sweden. Patients aged 18 years and older with treatment-naive confirmed limited stage SCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. All participants received four courses of intravenous cisplatin 75 ing/m 2 or carboplatin (area under the curve 5-6 mg/mL x min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m 2 on days 1-3 every 3 weeks. Participants were randomly assigned (1:1) in permuted blocks (sized between 4 and 10) stratifying for ECOG performance status, disease stage, and presence of pleural effusion to receive thoracic radiotherapy of 45 Gy in 30 fractions or 60 Gy in 40 fractions to the primary lung tumour and PET-CT positive lymph node metastases starting 20-28 days after the first chemotherapy course. Patients in both groups received two fractions per day, ten fractions per week. Responders were offered prophylactic cranial irradiation of 25-30 Gy. The primary endpoint, 2-year overall survival, was assessed after all patients had been followed up for a minimum of 2 years. All randomly assigned patients were included in the efficacy analyses, patients commencing thoracic radiotherapy were included in the safety analyses. Follow-up is ongoing. This trial is registered at ClinicalTrials.gov , NCT02041845. Findings Between July 8,2014, and June 6,2018,176 patients were enrolled, 170 of whom were randomly assigned to 60 Gy (n=89) or 45 Gy (n=81). Median follow-up for the primary analysis was 49 months (IQR 38-56). At 2 years, 66 (74.2% [95% CI 63-8-82.9]) patients in the 60 Gy group were alive, compared with 39 (48.1% 136-9-59.51) patients in the 45 Gy group (odds ratio 3.09 [95% CI 1.62-5-89]; p=0-0005). The most common grade 3-4 adverse events were neutropenia (72 [81%] of 89 patients in the 60 Gy group vs 62 181%1 of 77 patients in the 45 Gy group), neutropenic infections (24 [27%] vs 30 [39%1), thrombocytopenia (21 [24%] vs 19 125%1), anaemia (14 [16%] vs 15 120%D, and oesophagitis (19 [21%] vs 14 [18%]). There were 55 serious adverse events in 38 patients in the 60 Gy group and 56 serious adverse events in 44 patients in the 45 Gy group. There were three treatment-related deaths in each group (one neutropenic fever, one aortic dissection, and one pneumonitis in the 60 Gy group; one thrombocytic bleeding, one cerebral infarction, and one myocardial infarction in the 45 Gy group). Interpretation The higher radiotherapy dose of 60 Gy resulted in a substantial survival improvement compared with 45 Gy, without increased toxicity, suggesting that twice-daily thoracic radiotherapy of 60 Gy is an alternative to existing schedules. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
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  • Killingberg, K. T., et al. (författare)
  • Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer
  • 2022
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 166, s. 49-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: In a randomized phase II trial, twice daily (BID) thoracic radiotherapy (TRT) of 60 Gy/40 frac-tions improved survival compared with 45 Gy/30 fractions in limited stage small-cell lung cancer (LS SCLC). Notably, the higher dose did not cause more toxicity. Here we present health related quality of life (HRQoL) reported by the trial participants during the first 2 years.& nbsp;Materials and methods: 170 patients were randomized 1:1 to TRT of 45 Gy or 60 Gy concurrently with cisplatin/etoposide chemotherapy. The 150 patients who commenced TRT and completed a minimum of one HRQoL-questionnaire were included in the present study. Patients reported HRQoL on the European Organization for Research and Treatment of Cancer Core 30 and Lung Cancer 13 Quality of Life Questionnaires. Questionnaires were completed weeks 0, 4 (before TRT), 8 (end of TRT), 12 (response evaluation after chemoradiotherapy) and 16 (end of prophylactic cranial irradiation), then every 10 weeks year one, and every 3 months year two. Primary HRQoL endpoints were dysphagia and dyspnea. A difference in mean score of >= 10 was defined as clinically significant.& nbsp;Results: Maximum dysphagia was reported on week 8, with no significant difference between treatment arms (mean scores 45 Gy: 44.2, 60 Gy: 51.1). The 60 Gy arm had more dysphagia in the convalescence period, but dysphagia scores returned to baseline levels at week 16 in both arms. For dyspnea there were no significant changes, or differences between treatment arms, at any timepoint. There were no significant differences between treatment arms for any other HRQoL-scales.& nbsp;Conclusion: TRT of 60 Gy did not cause significantly higher maximum dysphagia, though patients on the 60 Gy arm reported more dysphagia the first 8 weeks of convalescence. The higher dose was well tolerated and is an attractive alternative to current TRT schedules in LS SCLC.& nbsp;
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  • Lindberg, K., et al. (författare)
  • The HILUS-Trial—a Prospective Nordic Multicenter Phase 2 Study of Ultracentral Lung Tumors Treated With Stereotactic Body Radiotherapy
  • 2021
  • Ingår i: Journal of Thoracic Oncology. - : Elsevier BV. - 1556-0864. ; 16:7, s. 1200-1210
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial for tumors located less than or equal to 1 cm from the proximal bronchial tree with primary end point of local control and secondary end point of toxicity. Methods: Stereotactic body radiation therapy with 7 Gy × 8 was prescribed to the 67% isodose encompassing the planning target volume. The patients were stratified to group A (tumors ≤ 1 cm from the main bronchi and trachea) or group B (all other tumors). Risk factors for treatment-related death were tested in univariate analysis, and a logistic regression model was developed for fatal bronchopulmonary bleeding versus dose to the main bronchi and trachea. Results: A total of 65 patients (group A/group B, n = 39/26) were evaluated. The median distance between the tumor and the proximal bronchial tree was 0 mm (0–10 mm). The 2-year local control was 83%. Grade 3 to 5 toxicity was noted in 22 patients, including 10 cases of treatment-related death (bronchopulmonary hemorrhage, n = 8; pneumonitis, n = 1; fistula, n = 1). Dose to the combined structure main bronchi and trachea and tumor distance to the main bronchi were important risk factors. Dose modeling revealed minimum dose to the “hottest” 0.2 cc to the structure main bronchi and trachea as the strongest predictor for lethal bronchopulmonary hemorrhage. Conclusions: On the basis of the presented data, 7 Gy × 8, prescribed to the planning target volume-encompassing isodose, should not be used for tumors located within 1 cm from the main bronchi and trachea. Group B-type tumors may be considered for the treatment on the basis of an individual risk-benefit assessment and a maximum dose to the main bronchi and trachea in the order of 70 to 80 Gy (equivalent dose in 2 Gy fractions). © 2021 International Association for the Study of Lung Cancer
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  • Nyman, Gunnar, 1954, et al. (författare)
  • Contact Allergy in Western Sweden to Propolis of Four Different Origins
  • 2020
  • Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 100
  • Tidskriftsartikel (refereegranskat)abstract
    • Propolis, which is produced by honeybees and is used in "natural" products, can cause contact allergy. The composition of propolis varies between regions, but little is known about how this variation affects contact allergenicity. The aims of this study were to investi-gate the frequency of propolis contact allergy in western Sweden, and whether the frequency varies according to the origin of the propolis. Patch-testing was performed using propolis from China, Lithuania, North America, and Sweden in 722 consecutive patients with dermatitis in western Sweden. Frequencies of positive patch-test reactions ranged from 2.4% to 3.6%. There were some, not statistically significant, differences in frequency of contact allergy to the 4 samples of propolis of different origins, with the highest frequency to the sample from China and the lowest frequency to the sample from Sweden. Concomitant positive patch test reactions to plant and fragrance substances in the baseline series were common, most frequently to Myroxylon pereirae resin and colophonium.
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  • Sahin, O, et al. (författare)
  • International Multi-Specialty Expert Physician Preoperative Identification of Extranodal Extension n Oropharyngeal Cancer Patients using Computed Tomography: Prospective Blinded Human Inter-Observer Performance Evaluation
  • 2024
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundExtranodal extension (ENE) is an important adverse prognostic factor in oropharyngeal cancer (OPC) and is often employed in therapeutic decision making. Clinician-based determination of ENE from radiological imaging is a difficult task with high inter-observer variability. However, the role of clinical specialty on the determination of ENE has been unexplored.MethodsPre-therapy computed tomography (CT) images for 24 human papillomavirus-positive (HPV+) OPC patients were selected for the analysis; 6 scans were randomly chosen to be duplicated, resulting in a total of 30 scans of which 21 had pathologically-confirmed ENE. 34 expert clinician annotators, comprised of 11 radiologists, 12 surgeons, and 11 radiation oncologists separately evaluated the 30 CT scans for ENE and noted the presence or absence of specific radiographic criteria and confidence in their prediction. Discriminative performance was measured using accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and Brier score for each physician. Statistical comparisons of discriminative performance were calculated using Mann Whitney U tests. Significant radiographic factors in correct discrimination of ENE status were determined through a logistic regression analysis. Interobserver agreement was measured using Fleiss’ kappa.ResultsThe median accuracy for ENE discrimination across all specialties was 0.57. There were significant differences between radiologists and surgeons for Brier score (0.33 vs. 0.26), radiation oncologists and surgeons for sensitivity (0.48 vs. 0.69), and radiation oncologists and radiologists/surgeons for specificity (0.89 vs. 0.56). There were no significant differences between specialties for accuracy or AUC. Indistinct capsular contour, nodal necrosis, and nodal matting were significant factors in regression analysis. Fleiss’ kappa was less than 0.6 for all the radiographic criteria, regardless of specialty.ConclusionsDetection of ENE in HPV+OPC patients on CT imaging remains a difficult task with high variability, regardless of clinician specialty. Although some differences do exist between the specialists, they are often minimal. Further research in automated analysis of ENE from radiographic images is likely needed.
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  • Akaberi, Dario, et al. (författare)
  • Targeting the NS2B-NS3 protease of tick-borne encephalitis virus with pan-flaviviral protease inhibitors
  • 2021
  • Ingår i: Antiviral Research. - : Elsevier. - 0166-3542 .- 1872-9096. ; 190
  • Tidskriftsartikel (refereegranskat)abstract
    • Tick-borne encephalitis (TBE) is a severe neurological disorder caused by tick-borne encephalitis virus (TBEV), a member of the Flavivirus genus. Currently, two vaccines are available in Europe against TBEV. However, TBE cases have been rising in Sweden for the past twenty years, and thousands of cases are reported in Europe, emphasizing the need for antiviral treatments against this virus. The NS2B-NS3 protease is essential for flaviviral life cycle and has been studied as a target for the design of inhibitors against several well-known flaviviruses, but not TBEV. In the present study, Compound 86, a known tripeptidic inhibitor of dengue (DENV), West Nile (WNV) and Zika (ZIKV) proteases, was predicted to be active against TBEV protease using a combination of in silico techniques. Further, Compound 86 was found to inhibit recombinant TBEV protease with an IC50 = 0.92 mu M in the in vitro enzymatic assay. Additionally, two more peptidic analogues were synthetized and they displayed inhibitory activities against both TBEV and ZIKV proteases. In particular, Compound 104 inhibited ZIKV protease with an IC50 = 0.25 mu M. These compounds represent the first reported inhibitors of TBEV protease to date and provides valuable information for the further development of TBEV as well as pan-flavivirus protease inhibitors.
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  • Björklund Carlstedt, Anita, 1953-, et al. (författare)
  • Older workers and extended working life - Managers' experiences and age management
  • 2024
  • Ingår i: Work. - : IOS Press. - 1051-9815 .- 1875-9270.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In 2020 the Swedish Government started a gradual raising of the retirement age, but employers have been silent on the issue. Little is known about whether and how they reflect on what it will mean for their organization, or whether they already have, or are going to, make arrangements in order to facilitate and motivate older workers to stay longer.OBJECTIVE: The aim of this study was to explore and describe managers' experiences of older workers and age management in connection with the increase of the retirement age in Sweden.METHODS: Data was collected through semi-structured interviews with fourteen managers from a broad set of organizations in the public and private sectors, and from the Middle and East of Sweden. The transcribed material was analysed in line with qualitative content analysis.RESULTS: The analysis ended up in seven main categories with associated sub-categories: Older Workers, Retirement Ages, Transition Initiatives, Competence Transfer, Competence Development, Increased Retirement Ages, Knowledge Gaps.CONCLUSION: Our findings reveal that there is an ambivalence in addressing the issue of age among the interviewed managers, what we have interpreted and labelled as "silent age discrimination", and it was shown that they do not have elaborated strategies for age management.
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  • Delanaye, Pierre, et al. (författare)
  • Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil, and Africa
  • 2022
  • Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 38:1, s. 106-118
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A new Chronic Kidney Disease Epidemiology equation without race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared to the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts.METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France, (n = 4429, including 964 Black Europeans), from Brazil (n = 100), and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed.RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73m², and accuracy within 30% of 86.9 and 87.4, respectively versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value ( = concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans, and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males.CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated, population-specific Q-values presents the best performance in the whole age range in the European and African populations included in this study.
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  • Ercan, Ayse Bahar, et al. (författare)
  • Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
  • 2024
  • Ingår i: The Lancet Oncology. - 1470-2045. ; 25:5, s. 668-682
  • Tidskriftsartikel (refereegranskat)abstract
    • Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
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  • Loid, P, et al. (författare)
  • Case report: A novel de novo IGF2 missense variant in a Finnish patient with Silver-Russell syndrome
  • 2022
  • Ingår i: Frontiers in pediatrics. - : Frontiers Media SA. - 2296-2360. ; 10, s. 969881-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Silver-Russell syndrome (SRS, OMIM 180860) is a rare imprinting disorder characterized by intrauterine and postnatal growth restriction, feeding difficulties in early childhood, characteristic facial features, and body asymmetry. The molecular cause most commonly relates to hypomethylation of the imprinted 11p15.5 IGF2/H19 domain but remains unknown in about 40% of the patients. Recently, heterozygous paternally inherited pathogenic variants in IGF2, the gene encoding insulin-like growth factor 2 (IGF2), have been identified in patients with SRS. We report a novel de novo missense variant in IGF2 (c.122T &gt; G, p.Leu41Arg) on the paternally derived allele in a 16-year-old boy with a clinical diagnosis of SRS. The missense variant was identified by targeted exome sequencing and predicted pathogenic by multiple in silico tools. It affects a highly conserved residue on a domain that is important for binding of other molecules. Our finding expands the spectrum of disease-causing variants in IGF2. Targeted exome sequencing is a useful diagnostic tool in patients with negative results of common diagnostic tests for SRS.
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  • Lundin, J., et al. (författare)
  • Using 360-degree videos for virtual reality exposure in CBT for panic disorder with agoraphobia : A feasibility study
  • 2022
  • Ingår i: Behavioural and Cognitive Psychotherapy. - : Cambridge University Press (CUP). - 1352-4658 .- 1469-1833. ; 50:2, s. 158-170
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cognitive behavioural therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PDA). However, implementation of some of the procedures involved, particularly in vivo exposure, can be time consuming and taxing for routine health care services. CBT with exposure taking place in virtual reality (VR-CBT) is a more time-efficient option and has shown promising results in the treatment of PDA. However, VR-CBT requires expensive equipment and appropriate virtual environments, which historically has been costly and cumbersome to produce. Thus, access to VR-CBT has been sparse in regular care environments. Aims: The aim of this study was to investigate whether VR-CBT using filmed virtual environments produced with a low-cost 360-degree film camera can be a feasible and acceptable treatment for PDA when implemented in a primary care context. Method: This was an open feasibility trial with a within-group design, with assessments conducted at pre-test, post-test, and 6-month follow-up. Participants (n = 12) received a 10-12 week treatment programme of VR-CBT and PDA-related symptoms were assessed by the primary outcome measure The Mobility Inventory for Agoraphobia (MIA) and the Panic-Disorder Severity Scale-Self Rated (PDSS-SR). Results: The results showed that treatment satisfaction was high and participants were significantly improved on PDA-related measures at post-treatment and at 6-month follow-up with large effect sizes (Cohen's d range = 1.46-2.82). All 12 participants completed the treatment. Conclusions: These findings suggest that VR-CBT with 360-degree video virtual environments delivered to primary care patients with PDA is feasible, acceptable, and potentially efficacious. 
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  • Ndreu, Lorena, 1990-, et al. (författare)
  • Investigation into Propolis Components Responsible for Inducing Skin Allergy : Air Oxidation of Caffeic Acid and Its Esters Contribute to Hapten Formation
  • 2023
  • Ingår i: Chemical Research in Toxicology. - 0893-228X .- 1520-5010. ; 36:6, s. 859-869
  • Tidskriftsartikel (refereegranskat)abstract
    • Propolis is a resin-like material produced by bees fromthe budsof poplar and cone-bearing trees and is used in beehive construction.Propolis is a common additive in various biocosmetics and health-relatedproducts, despite the fact that it is a well-known cause of contactallergy. Caffeic acid and its esters have been the primary suspectsbehind the sensitization potency of propolis-induced contact allergy.However, the chemical structures of the protein adducts formed betweenthese haptens and skin proteins during the process of skin sensitizationremain unknown. In this study, the reactivity of three main contactallergens found in propolis, namely, caffeic acid (CA), caffeic acid1,1-dimethylallyl ester (CAAE), and caffeic acid phenethyl ester (CAPE),was investigated. These compounds were initially subjected to thekinetic direct peptide reactivity assay to categorize the sensitizationpotency of CA, CAAE, and CAPE, but the data obtained was deemed toounreliable to confidently classify their skin sensitization potentialbased on this assay alone. To further investigate the chemistry involvedin generating possible skin allergy-inducing protein adducts, modelpeptide reactions with CA, CAAE, and CAPE were conducted and analyzedvia liquid chromatography-high-resolution mass spectrometry.Reactions between CA, CAAE, and CAPE and a cysteine-containing peptidein the presence of oxygen, both in closed and open systems, were monitoredat specific time points. These studies revealed the formation of twodifferent adducts, one corresponding to thiol addition to the & alpha;,& beta;-unsaturatedcarbonyl region of the caffeic structure and the second correspondingto thiol addition to the catechol, after air oxidation to o-quinone.Observation of these peptide adducts classifies these compounds asprehaptens. Interestingly, no adduct formation was observed when thesame reactions were performed under oxygen-free conditions, highlightingthe importance of air oxidation processes in CA, CAAE, and CAPE adductformation. Additionally, through NMR analysis, we found that thioladdition occurs at the C-2 position in the aromatic ring of the CAderivatives. Our results emphasize the importance of air oxidationin the sensitization potency of propolis and shed light on the chemicalstructures of the resultant haptens which could trigger allergic reactionsin vivo.
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  • Ndreu, L., et al. (författare)
  • Investigation into Propolis Components Responsible for Inducing Skin Allergy: Air Oxidation of Caffeic Acid and Its Esters Contribute to Hapten Formation
  • 2023
  • Ingår i: Chemical Research in Toxicology. - 0893-228X. ; 36:6, s. 859-869
  • Tidskriftsartikel (refereegranskat)abstract
    • Propolis is a resin-like material produced by bees fromthe budsof poplar and cone-bearing trees and is used in beehive construction.Propolis is a common additive in various biocosmetics and health-relatedproducts, despite the fact that it is a well-known cause of contactallergy. Caffeic acid and its esters have been the primary suspectsbehind the sensitization potency of propolis-induced contact allergy.However, the chemical structures of the protein adducts formed betweenthese haptens and skin proteins during the process of skin sensitizationremain unknown. In this study, the reactivity of three main contactallergens found in propolis, namely, caffeic acid (CA), caffeic acid1,1-dimethylallyl ester (CAAE), and caffeic acid phenethyl ester (CAPE),was investigated. These compounds were initially subjected to thekinetic direct peptide reactivity assay to categorize the sensitizationpotency of CA, CAAE, and CAPE, but the data obtained was deemed toounreliable to confidently classify their skin sensitization potentialbased on this assay alone. To further investigate the chemistry involvedin generating possible skin allergy-inducing protein adducts, modelpeptide reactions with CA, CAAE, and CAPE were conducted and analyzedvia liquid chromatography-high-resolution mass spectrometry.Reactions between CA, CAAE, and CAPE and a cysteine-containing peptidein the presence of oxygen, both in closed and open systems, were monitoredat specific time points. These studies revealed the formation of twodifferent adducts, one corresponding to thiol addition to the & alpha;,& beta;-unsaturatedcarbonyl region of the caffeic structure and the second correspondingto thiol addition to the catechol, after air oxidation to o-quinone.Observation of these peptide adducts classifies these compounds asprehaptens. Interestingly, no adduct formation was observed when thesame reactions were performed under oxygen-free conditions, highlightingthe importance of air oxidation processes in CA, CAAE, and CAPE adductformation. Additionally, through NMR analysis, we found that thioladdition occurs at the C-2 position in the aromatic ring of the CAderivatives. Our results emphasize the importance of air oxidationin the sensitization potency of propolis and shed light on the chemicalstructures of the resultant haptens which could trigger allergic reactionsin vivo.
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23.
  • Nyman, A., et al. (författare)
  • Speech and Language in 5-year-olds with Different Neurological Disabilities and the Association between Early and Later Consonant Production Speech/Language in Neurological Disabilities
  • 2021
  • Ingår i: Developmental Neurorehabilitation. - : Informa UK Limited. - 1751-8423 .- 1751-8431. ; 24:6, s. 408-417
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary aim was to describe speech and language abilities in a clinical group of verbal 5-year-old children diagnosed with neurological disability (ND) in infancy, and the secondary aim was to trace precursors to consonant production at age 5 years (T2) in data from 12 to 22 months (T1). The participants (n = 11, with Down syndrome (DS), cerebral palsy, and chromosomal deletion syndromes) were tested with a battery of speech and language tests. Consonant production at T2 was compared to data on consonant use at T1. At T2, two participants had age appropriate speech and language and another three had age-appropriate speech, but low results on language tests. The remaining six participants had severe speech and language difficulties. Participants with DS had significantly lower results on consonant production measures. An association between consonant production at T1 and T2 for participants with DS indicates that number of different true consonants might be a predictive measure when evaluating young children with DS.
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24.
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25.
  • Nyman, Elin, et al. (författare)
  • Perturbation biology links temporal protein changes to drug responses in a melanoma cell line
  • 2020
  • Ingår i: PloS Computational Biology. - : PUBLIC LIBRARY SCIENCE. - 1553-734X .- 1553-7358. ; 16:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer cells have genetic alterations that often directly affect intracellular protein signaling processes allowing them to bypass control mechanisms for cell death, growth and division. Cancer drugs targeting these alterations often work initially, but resistance is common. Combinations of targeted drugs may overcome or prevent resistance, but their selection requires context-specific knowledge of signaling pathways including complex interactions such as feedback loops and crosstalk. To infer quantitative pathway models, we collected a rich dataset on a melanoma cell line: Following perturbation with 54 drug combinations, we measured 124 (phospho-)protein levels and phenotypic response (cell growth, apoptosis) in a time series from 10 minutes to 67 hours. From these data, we trained time-resolved mathematical models that capture molecular interactions and the coupling of molecular levels to cellular phenotype, which in turn reveal the main direct or indirect molecular responses to each drug. Systematic model simulations identified novel combinations of drugs predicted to reduce the survival of melanoma cells, with partial experimental verification. This particular application of perturbation biology demonstrates the potential impact of combining time-resolved data with modeling for the discovery of new combinations of cancer drugs.
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26.
  • Pottel, Hans, et al. (författare)
  • Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex
  • 2023
  • Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 388:4, s. 333-343
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUNDThe accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C–based EKFC equation would increase the accuracy of estimated GFR is unknown.METHODSWe used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.RESULTSOn the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83+0.005×(age–50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.CONCLUSIONSThe EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations.
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27.
  • Pottel, Hans, et al. (författare)
  • Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex
  • 2023
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 388:4, s. 333-343
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C–based EKFC equation would increase the accuracy of estimated GFR is unknown.MethodsWe used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.ResultsOn the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83+0.005×(age–50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.ConclusionsThe EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.)
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28.
  • Robinne, Francois-Nicolas, et al. (författare)
  • Scientists' warning on extreme wildfire risks to water supply
  • 2021
  • Ingår i: Hydrological Processes. - : John Wiley & Sons. - 0885-6087 .- 1099-1085. ; 35:5
  • Tidskriftsartikel (refereegranskat)abstract
    • 2020 is the year of wildfire records. California experienced its three largest fires early in its fire season. The Pantanal, the largest wetland on the planet, burned over 20% of its surface. More than 18 million hectares of forest and bushland burned during the 2019-2020 fire season in Australia, killing 33 people, destroying nearly 2500 homes, and endangering many endemic species. The direct cost of damages is being counted in dozens of billion dollars, but the indirect costs on water-related ecosystem services and benefits could be equally expensive, with impacts lasting for decades. In Australia, the extreme precipitation ("200 mm day-1 in several location") that interrupted the catastrophic wildfire season triggered a series of watershed effects from headwaters to areas downstream. The increased runoff and erosion from burned areas disrupted water supplies in several locations. These post-fire watershed hazards via source water contamination, flash floods, and mudslides can represent substantial, systemic long-term risks to drinking water production, aquatic life, and socio-economic activity. Scenarios similar to the recent event in Australia are now predicted to unfold in the Western USA. This is a new reality that societies will have to live with as uncharted fire activity, water crises, and widespread human footprint collide all-around of the world. Therefore, we advocate for a more proactive approach to wildfire-watershed risk governance in an effort to advance and protect water security. We also argue that there is no easy solution to reducing this risk and that investments in both green (i.e., natural) and grey (i.e., built) infrastructure will be necessary. Further, we propose strategies to combine modern data analytics with existing tools for use by water and land managers worldwide to leverage several decades worth of data and knowledge on post-fire hydrology.
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29.
  • Tribukait, B, et al. (författare)
  • Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer
  • 2023
  • Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988–1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.
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30.
  • Waller, K. Persson, et al. (författare)
  • Intramammary infections and risk factors in freshly calved heifers in dairy herds
  • 2023
  • Ingår i: Journal of Dairy Science. - : Elsevier. - 0022-0302 .- 1525-3198. ; 106:11, s. 7893-7907
  • Tidskriftsartikel (refereegranskat)abstract
    • Subclinical mastitis can be common among freshly calved heifers (FCH), but the prevalence differs between herds possibly due to variation in risk factors. The aims of this observational study were to identify differences in occurrence of IMI in FCH between herds with documented good or not so good first parity udder health based on cow SCC (CSCC) in early lactation, and to study herd differences in animal factors important for udder health such as udder and hock skin lesions and animal cleanliness. Three groups of herds were included, those with high proportion of FCH with low (≤75,000 cells/ml) CSCC at the first 2 milk recordings after calving (LL), herds with high proportion of FCH with high (>100,000 cells/ml) CSCC at the first and low CSCC at the second recording (HL), and herds with high proportion of FCH with high CSCC at both recordings (HH). Thirty-one herds (13 LL, 11 HL, 15 HH) were visited 3 times during a 12-mo period for observation of cleanliness and hock lesions, and sampling of udder/teat skin using swab cloths of milk-fed calves, early pregnant heifers and late pregnant heifers. In 25 (9 LL, 9 HL, 7 HH) udder quarter samples from colostrum and milk on d 3-4 after calving were taken by the farmers from FCH during one year. The farmers also provided information on calving (individual or group), use of restraint and oxytocin at milking, and presence of teat and udder skin lesions. Bacterial growth in swab samples and quarter samples was investigated by culturing, and a selection of isolates was genotyped using whole genome sequencing (WGS). Cleanliness, hock and udder skin lesions other than udder-thigh dermatitis, and growth of bacteria in swab samples did not differ between herd groups. It was more common that FCH from LL herds, compared with FCH in HH and HL herds, calved in a group of animals. Use of restraint at milking was more common in LL herds than in HH herds while presence of udder-thigh dermatitis was lowest in LL herds. Specific infection was found in 14% of 5,593 quarter samples from 722 FCH. The most common IMI was S. chromogenes. Growth of S. simulans was more common in HH than in LL and HL herds. In colostrum samples, S. haemolyticus was more common in HL and HH than in LL herds. The proportion of quarters with the same specific infection at both samplings was higher in HH than in LL herds and tended to be higher in HH than in HL herds. The proportion of quarters with S. chromogenes IMI at both samplings tended to differ between herd groups and was highest in HH herds. WGS found the same sequence type of S. chromogenes and S. aureus in both samples in almost all quarters with the same infection at both samplings. The differences in IMI between herd groups were in line with the higher SCC in HH herds. The reasons for the predominance of S. chromogenes IMI in FCH need further studies.
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