| 631. |
- Stukenborg, J. -B., et al.
(författare)
-
Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy
- 2018
-
Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 33:9, s. 1677-1683
-
Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue? SUMMARY ANSWER: Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease. WHAT IS KNOWN ALREADY: Cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is a proposed clinical option for fertility restoration in children. The key clinical consideration behind this approach is a sufficient quantity of healthy cryopreserved spermatogonia. However, since most boys with malignancies start therapy with agents that are not potentially sterilizing, they will have already received some chemotherapy before testicular tissue cryopreservation is considered. STUDY DESIGN, SIZE, DURATION: We examined histological sections of prepubertal testicular tissue to elucidate whether chemotherapy exposure or primary diagnosis affects spermatogonial quantity. Quantity of spermatogonia per transverse tubular cross-section (S/T) was assessed in relation to treatment characteristics and normative reference values in histological sections of paraffin embedded testicular tissue samples collected from 32 consecutive boy patients (aged 6.3 +/- 3.8 [mean +/- SD] years) between 2014 and 2017, as part of the NORDFERTIL study, and in 14 control samples (from boys aged 5.6 +/- 5.0 [mean +/- SD] years) from an internal biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Prepubertal boys in Sweden, Finland and Iceland who were facing treatments associated with a very high risk of infertility, were offered the experimental procedure of testicular cryopreservation. Exclusion criteria were testicular volumes > 10 ml and high bleeding or infection risk. There were 18 patients with a diagnosis of malignancy and 14 patients a nonmalignant diagnosis. While 20 patients had the testicular biopsy performed 1-45 days after chemotherapy, 12 patients had not received any chemotherapy. In addition, 14 testicular tissue samples of patients with no reported testicular pathology, obtained from the internal biobank of the Department of Pathology at Karolinska University Hospital, were included as control samples in addition to reference values obtained from a recently published meta-analysis. The quantity of spermatogonia was assessed by both morphological and immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The main finding was a significant reduction in spermatogonial cell counts in boys treated with alkylating agents or with hydroxyurea for sickle cell disease. The mean S/T values in boys exposed to alkylating agents (0.2 +/- 0.3, n = 6) or in boys with sickle cell disease and exposed to hydroxyurea (0.3 +/- 0.6, n = 6) were significantly lower (P = 0.003 and P = 0.008, respectively) than in a group exposed to non-alkylating agents or in biobank control samples (1.7 +/- 1.0, n = 8 and 4.1 +/- 4.6, n = 14, respectively). The mean S/T values of the testicular tissue samples included in the biobank control group and the patient group exposed to nonalkylating agents were within recently published normative reference values. LIMITATIONS, REASONS FOR CAUTION: Normal testicular tissue samples included in this study were obtained from the internal biobank of Karolinska University Hospital. Samples were considered normal and included in the study if no testicular pathology was reported in the analysed samples. However, detailed information regarding previous medical treatments and testicular volumes of patients included in this biobank were not available. WIDER IMPLICATIONS OF THE FINDINGS: This study summarizes, for the first time, spermatogonial quantity in a prepubertal patient cohort just before and after potentially sterilizing treatments. Boys facing cancer and cytotoxic therapies are regarded as the major group who will benefit from novel fertility preservation techniques. There are no previous reports correlating spermatogonial quantity to cumulative exposure to alkylating agents and anthracyclines (non-alkylating agents) and no information about the timing of cytotoxic exposures among this particular patient cohort. For prepubertal boys in whom fertility preservation is indicated, testicular tissue should be obtained before initiation of chemotherapy with alkylating agents, whilst for those with sickle cell disease and treated with hydroxyurea, this approach to fertility preservation may not be feasible. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from The Swedish Childhood Cancer Foundation (PR2016-0124; TJ2016-0093; PR2015-0073, TJ2015-0046) (J.-B.S. and K.J.), the Jane and Dan Olssons Foundation (2016-33) (J.-B.S.), the Finnish Cancer Society (K.J.), the Foundation for Paediatric Research (J.-B.S.), Kronprinsessan Lovisas Forening For Barnasjukvard/Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Vare Foundation for Paediatric Cancer Research (K.J.) and the Swedish Research Council (2012-6352) (O.S.). R.T.M. was supported by a Wellcome Trust Fellowship (09822). J.P.A.-L. and M.K. were supported by the ITN Marie Curie program 'Growsperm' (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest.
|
|
| 632. |
- Thacher, Jesse D., et al.
(författare)
-
Occupational noise exposure and risk of incident stroke: a pooled study of five Scandinavian cohorts
- 2022
-
Ingår i: OCCUPATIONAL AND ENVIRONMENTAL MEDICINE. - : BMJ. - 1351-0711 .- 1470-7926. ; 79:9, s. 594-601
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To investigate the association between occupational noise exposure and stroke incidence in a pooled study of five Scandinavian cohorts (NordSOUND). Methods We pooled and harmonised data from five Scandinavian cohorts resulting in 78 389 participants. We obtained job data from national registries or questionnaires and recoded these to match a job-exposure matrix developed in Sweden, which specified the annual average daily noise exposure in five exposure classes (L-Aeq8h): <70, 70-74, 75-79, 80-84, >= 85 dB(A). We identified residential address history and estimated 1-year average road traffic noise at baseline. Using national patient and mortality registers, we identified 7777 stroke cases with a median follow-up of 20.2 years. Analyses were conducted using Cox proportional hazards models adjusting for individual and area-level potential confounders. Results Exposure to occupational noise at baseline was not associated with overall stroke in the fully adjusted models. For ischaemic stroke, occupational noise was associated with HRs (95% CI) of 1.08 (0.98 to 1.20), 1.09 (0.97 to 1.24) and 1.06 (0.92 to 1.21) in the 75-79, 80-84 and >= 85 dB(A) exposure groups, compared with <70 dB(A), respectively. In subanalyses using time-varying occupational noise exposure, we observed an indication of higher stroke risk among the most exposed (>= 85 dB(A)), particularly when restricting analyses to people exposed to occupational noise within the last year (HR: 1.27; 95% CI: 0.99 to 1.63). Conclusions We found no association between occupational noise and risk of overall stroke after adjustment for confounders. However, the non-significantly increased risk of ischaemic stroke warrants further investigation.
|
|
| 633. |
|
|
| 634. |
- Tierney, Jessica E., et al.
(författare)
-
Past climates inform our future
- 2020
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6517
-
Forskningsöversikt (refereegranskat)abstract
- As the world warms, there is a profound need to improve projections of climate change. Although the latest Earth system models offer an unprecedented number of features, fundamental uncertainties continue to cloud our view of the future. Past climates provide the only opportunity to observe how the Earth system responds to high carbon dioxide, underlining a fundamental role for paleoclimatology in constraining future climate change. Here, we review the relevancy of paleoclimate information for climate prediction and discuss the prospects for emerging methodologies to further insights gained from past climates. Advances in proxy methods and interpretations pave the way for the use of past climates for model evaluation—a practice that we argue should be widely adopted.
|
|
| 635. |
- Tiselius, Peter, 1958, et al.
(författare)
-
Functional response of Oikopleura dioica to house clogging due to exposure to algae of different sizes
- 2003
-
Ingår i: Marine Biology. - 0025-3162. ; 142:2, s. 253-261
-
Tidskriftsartikel (refereegranskat)abstract
- The functional response of the appendicularian Oikopleura dioica was investigated with a unialgal diet (Isochrysis galbana, 0-1,600 mug Cl-1) and with additions of specific concentrations of algae either smaller than the incurrent filter mesh size (Rhodomonas baltica, 90 mug Cl-1; Thalassiosira weissflogii, 60 mug Cl-1) or larger algae (Ceratium lineatum, 8 mug Cl-1; C. tripos, 52 mug C l(-1)). Clearance ranged from 0.13 to 3.3 ml mug C-1 h(-1) and followed a Michaelis-Menten curve corresponding to a maximum filtration rate (particles collected by both animal and house), FRmax = 164 ng C mug C-1 h(-1) and K-m = 64 mug C l(-1). Maximum pellet production was 9 pellets ind(-1) h(-1) and occurred at 100 mugC (-1). Pellet production was proportional to filtration rate below this level, but declined at higher concentrations. House production ranged from 0.5 to 5.5 houses ind(-1) day(-1) and the corresponding curve fit resulted in H-max = 4.6 houses ind(-1) day(-1) and K-m house = 32 mug Cl-1. Addition of edible small algae caused increased internal clogging of the houses, evidenced by significantly higher pigment concentrations in abandoned houses than in houses produced with I.. galbana as a single food. House production was not affected. In contrast, larger algae caused a significantly higher house production, but the algae were not collected on the houses. Increased levels of edible algae will not have negative effects on O. dioica at ecologically realistic concentrations. Ambient bloom concentrations of larger algae may, however, have a negative effect on the growth of O. dioica populations, owing to the compensatory increased house production.
|
|
| 636. |
- Vargas, C. A., et al.
(författare)
-
Importance of copepods versus appendicularians in vertical carbon fluxes in a Swedish fjord
- 2002
-
Ingår i: Marine Ecology-Progress Series. - 0171-8630. ; 241, s. 125-138
-
Tidskriftsartikel (refereegranskat)abstract
- We examined and quantified the contributions of copepods and appendicularians to the vertical flux of carbon during autumn and spring in Gullmar Fjord (west coast of Sweden). Faecal pellet-production rate was determined for major copepod and appendicularian species. In addition, house-production rates were estimated for the appendicularian Oikopleura dioica. Vertical flux of pigments, faecal carbon and appendicularian houses were measured using short-term (24 h) deployments of sediment traps at 2 depths (15 and 30 m). Copepods dominated the community biomass in both spring and autumn and their pellets dominated the faecal carbon flux. O. dioica houses with attached detritus were an important component of the biogenic carbon flux in October (15.3 mg C m(-2) d(-1)), equalling the contribution from copepods at 15 m and 50% of the flux at 30 m. At that time, we observed a loss rate of 70% d(-1) of the houses produced in the water column. In the spring, although Fritillaria borealis dominated the appendicularians, its houses did not appear to contribute to the biogenic flux. Our results suggest that oikopleurids and fritillariids may not operate equivalently in biogeochemical cycles. Because of the significant contribution of appendicularians to carbon fluxes, they should be incorporated in future flow models of coastal oceans.
|
|
| 637. |
- Viborg Lindskrog, Sia, et al.
(författare)
-
An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.
|
|
| 638. |
- Zamora, Juan Carlos, et al.
(författare)
-
Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
-
Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
-
Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
|
|
| 639. |
- Albinana, C, et al.
(författare)
-
Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots
- 2023
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 852-
-
Tidskriftsartikel (refereegranskat)abstract
- The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes.
|
|
| 640. |
|
|
