| 1. |
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| 2. |
- Dahlgren, David, et al.
(author)
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Fasted and fed state human duodenal fluids : Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability
- 2021
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 163, s. 240-251
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Journal article (peer-reviewed)abstract
- Accurate in vivo predictions of intestinal absorption of low solubility drugs require knowing their solubility in physiologically relevant dissolution media. Aspirated human intestinal fluids (HIF) are the gold standard, followed by simulated intestinal HIF in the fasted and fed state (FaSSIF/FeSSIF). However, current HIF characterization data vary, and there is also some controversy regarding the accuracy of FaSSIF and FeSSIF for predicting drug solubility in HIF. This study aimed at characterizing fasted and fed state duodenal HIF from 16 human volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well as protein, phospholipid, and bile salt content. The fasted and fed state HIF samples were further used to investigate the equilibrium solubility of 17 representative low-solubility small-molecule drugs, six of which were confidential industry compounds and 11 were known and characterized regarding chemical diversity. These solubility values were then compared to reported solubility values in fasted and fed state HIF, FaSSIF and FeSSIF, as well as with their human bioavailability for both states. The HIF compositions corresponded well to previously reported values and current FaSSIF and FeSSIF compositions. The drug solubility values in HIF (both fasted and fed states) were also well in line with reported solubility data for HIF, as well as simulated FaSSIF and FeSSIF. This indicates that the in vivo conditions in the proximal small intestine are well represented by simulated intestinal fluids in both composition and drug equilibrium solubility. However, increased drug solubility in the fed vs. fasted states in HIF did not correlate with the human bioavailability changes of the same drugs following oral administration in either state.
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| 3. |
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| 4. |
- Notarnicola, A., et al.
(author)
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Autoantibodies against a subunit of mitochondrial respiratory chain complex I in inclusion body myositis
- 2023
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82, s. 574-574
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Journal article (peer-reviewed)abstract
- Background Autoantibodies are found in up to 80% of patients with idiopathic inflammatory myopathies (IIM) and are associated with distinct clinical phenotypes [1]. Autoantibodies targeting cytosolic 5´-nucleotidase 1A (anti-cN1A) are currently the only known serum biomarker for the subgroup inclusion body myositis (IBM) (2), although detected even in other autoimmune diseases.Objectives To identify new autoimmune targets in IIM by antigen bead array assay.Methods In a first cross-sectional exploratory study, 357 antigens representing 268 proteins were incubated with plasma samples from 219 IIM (108 Polymyositis (PM), 80 Dermatomyositis (DM) and 31 IBM) patients, 349 Systemic Lupus Erythematosus (SLE) patients and 306 population controls for screening of IgG reactivity by antigen bead array. All samples were identified in the local biobank of the Rheumatology clinic, Karolinska University Hospital. Interesting results obtained for the IBM subgroup were then validated in an independent larger cohort of 287 patients with IBM followed at nine European rheumatological or neurological centers. IBM serum samples were explored by antigen bead array and results validated by western blot. As controls, serum samples from 30 patients with PM and 30 with DM, HLA-matched with the IBM Swedish cohort, were included. Demographics, laboratory, clinical, and muscle biopsy data of the IBM cohort was retrieved.Results In the exploratory study IgG reactivity towards NADH dehydrogenase 1 α subcomplex 11 (NDUFA11), a subunit of the membrane-bound mitochondrial respiratory chain complex I, was discovered with higher frequency in the IBM (9,7%) than PM (2,8%) and DM samples (2,5%), although the difference was not statistically significant. Anti-NDUFA11 IgG was also found in 2,3% of SLE and 2,6% of population control samples. In the validation study anti-NDUFA11 autoantibodies were detected in 11/287 IBM patients (3,8%), 0/30 PM and 0/30 DM patients. Reactivity against NDUFA11 could be confirmed by western blot (Table 1, Figure 1). The eleven anti-NDUFA11 positive patients showed a trend of lower frequency of wheelchair/walker ever use and higher creatine kinase levels at time of IBM diagnosis compared to the anti-NDUFA11 negative group. Ragged red fibers were significantly more prevalent in anti-NDUFA11 positive than negative patients (p=0.04). Anti-cN1A autoantibodies were detected in 98/287 (34,1%) of IBM, 3/30 (10%) DM and 9/29 (31%) PM patients, p=0.03. Coexistence of anti NDUFA11 and anti-cN1A antibodies was observed in 3 IBM patients.Conclusion Our results reveal a new autoimmune target in the mitochondrial respiratory chain complex I that might be specifically associated with IBM. This is of particular interest as mitochondrial abnormalities are known histological findings in muscle biopsies of IBM patients.References [1]Galindo-Feria AS, Wang G, Lundberg IE. Autoantibodies: Pathogenic or epiphenomenon. Best Pract Res Clin Rheumatol. 2022;36(2):101767.[2]Herbert MK,et al. Disease specificity of autoantibodies to cytosolic 5’-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases. Ann Rheum Dis. 2016;75(4):696-701.
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| 5. |
- Pease, Jessica E., et al.
(author)
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Comparison of triploid and diploid rainbow trout (Oncorhynchus mykiss) fine-scale movement, migration and catchability in lowland lakes of western Washington
- 2023
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In: Movement Ecology. - 2051-3933. ; 11:1
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Journal article (peer-reviewed)abstract
- Fisheries managers stock triploid (i.e., infertile, artificially produced) rainbow trout Oncorhynchus mykiss in North American lakes to support sport fisheries while minimizing the risk of genetic introgression between hatchery and wild trout. In Washington State, the Washington Department of Fish and Wildlife (WDFW) allocates approximately US $3 million annually to stock hatchery-origin rainbow trout in > 600 lakes, yet only about 10% of them are triploids. Many lakes in Washington State drain into waters that support wild anadromous steelhead O. mykiss that are listed as threatened under the U.S. Endangered Species Act. As a result, there is a strong interest in understanding the costs and benefits associated with stocking sterile, triploid rainbow trout as an alternative to traditional diploids. The objectives of this study were to compare triploid and diploid rainbow trout in terms of: (1) contribution to the sport fishery catch, (2) fine-scale movements within the study lakes, (3) rate of emigration from the lake, and (4) natural mortality. Our results demonstrated that triploid and diploid trout had similar day-night distribution patterns, but triploid trout exhibited a lower emigration rate from the lake and lower catch rates in some lakes. Overall, triploid rainbow trout represent a viable alternative to stocking of diploids, especially in lakes draining to rivers, because they are sterile, have comparable home ranges, and less often migrate.
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| 6. |
- Tataranno, M. L., et al.
(author)
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Morphine affects brain activity and volumes in preterms: An observational multi-center study
- 2020
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In: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 144
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Journal article (peer-reviewed)abstract
- Objective: We hypothesized that morphine has a depressing effect on early brain activity, assessed using quantitative aEEG/EEG parameter and depressed activity will be associated with brain volumes at term in extremely preterm infants. Study design: 174 preterm infants were enrolled in 3 European tertiary NICUs (mean GA:26 +/- 1wks) and monitored during the first 72 h after birth with continuous 2 channel aEEG. Six epochs of aEEG recordings were selected and minimum amplitude of aEEG (min aEEG), percentage of time amplitude< 5 mu V (% of time < 5 mu V), spontaneous activity transients (SATrate) and interSAT interval (ISI) were calculated. For infants receiving morphine, the cumulative morphine dosage was calculated. In a subgroup of 58 infants, good quality MRI at term equivalent age (TEA) and the cumulative morphine dose until TEA were available. The effects of morphine administration and cumulative dose on aEEG/EEG measures and on brain volumes were investigated. Results: Morphine administration had a significant effect on all quantitative aEEG/EEG measures, causing depression of early brain activity [longer ISI (beta 2.900), reduced SAT rate (beta -1.386), decreased min aEEG (beta -0.782), and increased % of time < 5 mu V (beta 14.802)] in all epochs. A significant effect of GA and postnatal age on aEEG/EEG measures was observed. Cumulative morphine dose until TEA had a significant negative effect on total brain volume (TBV) (beta -8.066) and cerebellar volume (beta -1.080). Conclusions: Administration of sedative drugs should be considered when interpreting aEEG/EEG together with the negative dose dependent morphine impact on brain development.
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| 7. |
- Tsiartas, P., et al.
(author)
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Seven days ex vivo perfusion of whole ewe ovaries with follicular maturation and oocyte retrieval: towards the development of an alternative fertility preservation method
- 2022
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In: Reproduction Fertility and Development. - : CSIRO Publishing. - 1031-3613 .- 1448-5990. ; 34:3, s. 331-342
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Journal article (peer-reviewed)abstract
- Fertility preservation methods for prepubertal women about to undergo gonadotoxic chemo and/or radiation therapy are limited. Therefore, the aim of this study was to investigate the feasibility to develop an alternative fertility preservation method based on an ex vivo perfusion platform for whole ewe ovaries. Thirteen ewe ovaries were divided into two groups (group 1 and 2) that were perfused in a bioreactor for up to 7 days. Group 1 (n = 3) were stimulated with human menopausal gonadotropin (hMG) administered in single daily dose, while group 2 (n = 10) were stimulated continuously for 24 h. The perfused ovaries in group 1 showed no significant differences in follicular density, sub-follicular morphology and oocyte quality after ischaemia and after ex vivo perfusion compared with non-perfused control ovaries. The perfused ovaries in group 2 showed a significant decrease in the follicular reserve and oocyte quality compared with the control group. In total, 16 GV-MI oocytes were retrieved from both groups. This study describes for the first time the ex vivo maintenance of viable follicles of ewe ovaries with oocyte integrity and the retrieval of oocytes after ex vivo hormonal perfusion with two different protocols for up to 7 days.
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| 8. |
- Ungaro, Ryan C., et al.
(author)
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Deep Remission at 1 Year Prevents Progression of Early Crohn's Disease
- 2020
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In: Gastroenterology. - : W. B. Saunders Company. - 0016-5085 .- 1528-0012. ; 159:1, s. 139-147
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD).METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period.RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome.CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.
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| 9. |
- Zeidan, AM, et al.
(author)
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Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes
- 2023
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:17, s. 2047-2061
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Journal article (peer-reviewed)abstract
- Myelodysplastic syndromes/neoplasms (MDS) are associated with variable clinical presentations and outcomes. The initial response criteria developed by the International Working Group (IWG) in 2000 have been used in clinical practice, clinical trials, regulatory reviews, and drug labels. While the IWG criteria were revised in 2006 and 2018 (the latter focusing on lower-risk disease), limitations persist in their application to higher-risk MDS and in their ability to fully capture clinical benefits of novel investigational drugs or to serve as valid surrogates for longer-term clinical endpoints (e.g., overall survival). Further, issues related to ambiguity and practicality of some criteria lead to variability in interpretation and inter-observer inconsistency in reporting results from the same sets of data. Thus, we convened an international panel of 36 MDS experts and used an established modified Delphi process to develop consensus recommendations for updated response criteria that would be more reflective of patient-centered and clinically relevant outcomes in higher-risk MDS. Among others, the IWG 2023 criteria include changes in the hemoglobin threshold for complete remission (CR), the introduction of CR with limited count recovery (CRL) and CR with partial hematologic recovery (CRh) as provisional response criteria, elimination of marrow CR, and specific recommendations for standardization of time-to-event endpoints and the derivation and reporting of responses. The updated criteria should lead to better correlation between patient-centered outcomes and clinical trial results in an era of multiple emerging new agents with novel mechanisms of action.
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| 10. |
- Andreasson, Anna, et al.
(author)
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An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years : A Prospective Population-Based Study in Sweden
- 2021
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 116:1, s. 210-213
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Journal article (peer-reviewed)abstract
- INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing.METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21–79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22–80 years, rr = 87%), 1995 (n = 1,139, 20–85 years, rr = 76%), and 2011 (n = 1,175, 20–93 years, rr = 63%).RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60–4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42–1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50–2.73).DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.
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| 11. |
- Brönmark, Christer, et al.
(author)
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Ponds as experimental arenas for studying animal movement : current research and future prospects
- 2023
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In: Movement Ecology. - 2051-3933. ; 11
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Research review (peer-reviewed)abstract
- Animal movement is a multifaceted process that occurs for multiple reasons with powerful consequences for food web and ecosystem dynamics. New paradigms and technical innovations have recently pervaded the field, providing increasingly powerful means to deliver fine-scale movement data, attracting renewed interest. Specifically in the aquatic environment, tracking with acoustic telemetry now provides integral spatiotemporal information to follow individual movements in the wild. Yet, this technology also holds great promise for experimental studies, enhancing our ability to truly establish cause-and-effect relationships. Here, we argue that ponds with well-defined borders (i.e. “islands in a sea of land”) are particularly well suited for this purpose. To support our argument, we also discuss recent experiences from studies conducted in an innovative experimental infrastructure, composed of replicated ponds equipped with modern aquatic telemetry systems that allow for unparalleled insights into the movement patterns of individual animals.
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| 12. |
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| 13. |
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| 14. |
- Challis, Pontus, et al.
(author)
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Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)
- 2024
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In: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109, s. 87-93
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Journal article (peer-reviewed)abstract
- Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage >= II) were validated against hospital records.Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.Main outcome measures NEC incidence.Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.
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| 15. |
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| 16. |
- Ekerstad, Niklas, et al.
(author)
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Clinical Frailty Scale classes are independently associated with 6-month mortality for patients after acute myocardial infarction
- 2022
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In: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 11:2, s. 89-98
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Journal article (peer-reviewed)abstract
- Aims: Data on the prognostic value of frailty to guide clinical decision-making for patients with myocardial infarction (MI) are scarce. To analyse the association between frailty classification, treatment patterns, in-hospital outcomes, and 6-month mortality in a large population of patients with MI.Methods and results: An observational, multicentre study with a retrospective analysis of prospectively collected data using the SWEDEHEART registry. In total, 3381 MI patients with a level of frailty assessed using the Clinical Frailty Scale (CFS-9) were included. Of these patients, 2509 (74.2%) were classified as non-vulnerable non-frail (CFS 1–3), 446 (13.2%) were vulnerable non-frail (CFS 4), and 426 (12.6%) were frail (CFS 5–9). Frailty and non-frail vulnerability were associated with worse in-hospital outcomes compared with non-frailty, i.e. higher rates of mortality (13.4% vs. 4.0% vs. 1.8%), cardiogenic shock (4.7% vs. 2.5% vs. 1.9%), and major bleeding (4.5% vs. 2.7% vs. 1.1%) (allP < 0.001), and less frequent use of evidence-based therapies. In Cox regression analyses, frailty was strongly and independently associated with 6-month mortality compared with non-frailty, after adjustment for age, sex, the GRACE risk score components, and other potential risk factors [hazard ratio (HR) 3.32, 95% confidence interval (CI) 2.30–4.79]. A similar pattern was seen for vulnerable non-frail patients (fully adjusted HR 2.07, 95% CI1.41–3.02).Conclusion: Frailty assessed with the CFS was independently and strongly associated with all-cause 6-month mortality, also after comprehensive adjustment for baseline differences in other risk factors. Similarly, non-frail vulnerability was independently associated with higher mortality compared with those with preserved functional ability.
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| 17. |
- Fu, Z. J., et al.
(author)
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Omega-3/Omega-6 Long-Chain Fatty Acid Imbalance in Phase I Retinopathy of Prematurity
- 2022
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 14:7
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Journal article (peer-reviewed)abstract
- There is a gap in understanding the effect of the essential omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA) on Phase I retinopathy of prematurity (ROP), which precipitates proliferative ROP. Postnatal hyperglycemia contributes to Phase I ROP by delaying retinal vascularization. In mouse neonates with hyperglycemia-associated Phase I retinopathy, dietary omega-3 (vs. omega-6 LCPUFA) supplementation promoted retinal vessel development. However, omega-6 (vs. omega-3 LCPUFA) was also developmentally essential, promoting neuronal growth and metabolism as suggested by a strong metabolic shift in almost all types of retinal neuronal and glial cells identified with single-cell transcriptomics. Loss of adiponectin (APN) in mice (mimicking the low APN levels in Phase I ROP) decreased LCPUFA levels (including omega-3 and omega-6) in retinas under normoglycemic and hyperglycemic conditions. omega-3 (vs. omega-6) LCPUFA activated the APN pathway by increasing the circulating APN levels and inducing expression of the retinal APN receptor. Our findings suggested that both omega-3 and omega-6 LCPUFA are crucial in protecting against retinal neurovascular dysfunction in a Phase I ROP model; adequate omega-6 LCPUFA levels must be maintained in addition to omega-3 supplementation to prevent retinopathy. Activation of the APN pathway may further enhance the omega-3 and omega-6 LCPUFA's protection against ROP.
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| 18. |
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| 19. |
- Hedberg, P. A. Mikael, et al.
(author)
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Measurements and Simulations of the Flow Distribution in a Down-Scaled Multiple Outlet Spillway with Complex Channel
- 2024
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In: Water. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2073-4441. ; 16:6
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Journal article (peer-reviewed)abstract
- Measurements of mass flow through a three-outlet spillway modeled after a scaled-down spillway were conducted. The inlet and channel leading up to the outlets were placed to lead the water toward the outlet at an angle. With this, measurements of the water level at three locations were recorded by magnetostrictive sensors. The volumetric flow rates for each individual outlet were recorded separately to study the differences between them. Additionally, Acoustic Doppler Velocimetry was used to measure water velocities close to the outlets. The conditions changed were the inlet volume flow rate and the flow distribution was measured at 90, 100, 110, and 200 L per second. Differences between the outlets were mostly within the error margin of the instruments used in the experiments with larger differences shown for the 200 L test. The results produced together with a CAD model of the setup can be used for verification of CFD methods. A simulation with the k-epsilon turbulence model is included and compared to earlier experiments and the new experimental results. Larger differences are seen in the new experiments. Differing inlet conditions are assumed as the principal cause for the differences seen.
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| 20. |
- Hedberg, P. A. Mikael, 1989-, et al.
(author)
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Numerical modelling of flow in parallel spillways
- 2020
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In: Proceedings of the 8th IAHR International Symposium on Hydraulic Structures ISHS2020. - : The University of Queensland.
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Conference paper (peer-reviewed)abstract
- Mathematical modelling of single spillways is well documented in literature. For parallel spillways however, there is a lack of documented, verified, and validated cases. Here, in this article, ANSYS-CFX is used to simulate the flow over three parallel ogee-crested spillways. For mesh size verification, a grid convergence study is performed by Richardson extrapolation. The turbulence model chosen for this simulation is the k-ε model and the volume of fluid method is used to simulate the water-air interface. This article details the models ability to accurately predict flow distribution at the spillways, and the water levels. The mesh is kept relatively coarse at the channel inlet with increased mesh density at the spillways. The results are validated against experimental data from Vattenfall AB, R&Ds laboratories. The geometry and boundary conditions of the experiment are tailored for CFD. The flow rate of each spillway is measured separately with high accuracy, and for several different inlet volumetric flows. The simulation results lie within the error estimates of the measuring tools used in the experiments, within ±1%. The volume flow rate differences between the three outlets is very small, within ±1%.
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| 23. |
- Nitzsche, Anja, 1985-, et al.
(author)
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Paladin is a phosphoinositide phosphatase regulating endosomal VEGFR2 signalling and angiogenesis
- 2021
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In: EMBO Reports. - : EMBO Press. - 1469-221X .- 1469-3178. ; 22:2
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Journal article (peer-reviewed)abstract
- Cell signalling governs cellular behaviour and is therefore subject to tight spatiotemporal regulation. Signalling output is modulated by specialized cell membranes and vesicles which contain unique combinations of lipids and proteins. The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2), an important component of the plasma membrane as well as other subcellular membranes, is involved in multiple processes, including signalling. However, which enzymes control the turnover of non-plasma membrane PI(4,5)P-2, and their impact on cell signalling and function at the organismal level are unknown. Here, we identify Paladin as a vascular PI(4,5)P-2 phosphatase regulating VEGFR2 endosomal signalling and angiogenesis. Paladin is localized to endosomal and Golgi compartments and interacts with vascular endothelial growth factor receptor 2 (VEGFR2) in vitro and in vivo. Loss of Paladin results in increased internalization of VEGFR2, over-activation of extracellular regulated kinase 1/2, and hypersprouting of endothelial cells in the developing retina of mice. These findings suggest that inhibition of Paladin, or other endosomal PI(4,5)P-2 phosphatases, could be exploited to modulate VEGFR2 signalling and angiogenesis, when direct and full inhibition of the receptor is undesirable.
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| 24. |
- Preger, C., et al.
(author)
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Abundant autoantibody isotypes in idiopathic inflammatory myopathies
- 2022
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:Suppl 1, s. 242.2-243
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Journal article (other academic/artistic)abstract
- Anti-synthetase syndrome (ASSD), a sub-group of idiopathic inflammatory myopathies (IIM) is characterized by the presence of autoantibodies targeting aminoacyl tRNA synthetases (aaRS) and specific clinical manifestations such as myositis and interstitial lung disease (ILD) [1]. Some of the most common anti-aaRS autoantibodies in ASSD are anti-Jo1, -PL7, -PL12 and-EJ. In addition, many anti-aaRS positive patients are also positive for anti-Ro52. Having the combination of anti-Jo1 and anti-Ro52 increases the risk of developing ILD [2]. The presence of autoantibodies is an important part of the classification of ASSD, however only autoantibodies of IgG isotype are usually analyzed in the clinical setting. In rheumatoid arthritis there is evidence that anti-citrullinated protein/peptide antibodies (ACPA) can be found as IgG, IgA and IgM, and importantly, specific isotypes might correlate with disease activity [3, 4].ObjectivesTo verify if other autoantibody isotypes, besides IgG, might be present in sera of patients with IIM/ASSD and to compare with the corresponding frequencies in population controls (PC).MethodsStored sera collected from consecutive 366 IIM patients and 156 age/gender matched PC at Karolinska University Hospital were retrospectively selected. The serum samples were screened for the presence of autoantibodies of isotypes IgG, IgA and IgM, against a panel of 20 antigens representing Jo1 (HisRS), PL7 (ThrRS), PL12 (AlaRS), EJ (GlyRS), and Ro52 (TRIM21) using a multiplex bead array assay.ResultsWe identified IIM patients with autoantibodies of different isotypes, and a low frequency in PC (Figure 1). For anti-Jo1 autoantibodies we could detect IIM patients with only IgG (n=13), only IgM (n=8) and only IgA (n=4), but the majority had a combination of two (n=32) or three isotypes (n=16). For the other anti-aaRS autoantibodies the distribution was more equal to each of the three isotypes with anti-PL12 and anti-PL7 being represented by a slightly higher frequency of IgG and only a few patients had antibodies of more than one isotype targeting PL12, PL7 or EJ. The majority of anti-Ro52 positive IIM patients (n=52) only harbored IgG isotype. The combination of anti-Ro52 and anti-aaRS autoantibodies was identified in 28 patients (anti-Jo1 (n=19), -PL12 (n=2), -PL7 (n=3), and -EJ (n=4)). Most patients with such combination had anti-Ro52 IgG together with anti-aaRS IgG or IgG in combination with IgA and/or IgM. The exception was observed for three anti-Jo1 positive patients who had the combination anti-Ro52 IgG with only anti-Jo1 IgM and one anti-PL7 positive patient who had anti-Ro52 IgA together with anti-PL7 IgA and IgG.Figure 1.Venn diagrams showing reactivity in idiopathic inflammatory myopathies (IIM) (top) and population controls (PC) (bottom) for the three autoantibody isotypes IgG, IgA and IgM against five myositis antigens: Jo1 (HisRS), PL12 (AlaRS), ThrRS (PL7), EJ (GlyRS) and Ro52 (TRIM21).ConclusionThe frequency of the different autoantibody isotypes seems to be autoantigen dependent. Our results suggest that for anti-aaRS autoantibodies it could be important to investigate additional autoantibody isotypes, as some patients only harbor autoantibodies of IgM or IgA isotypes but not IgG. The clinical relevance of the different antibody isotypes still needs to be determined.References[1]Mahler, M., et al., Rev, 2014. 13(4-5): p. 367-71.[2]Huang, H.L., et al., J Clin Neurosci, 2020.[3]Arlestig, L., et al., Ann Rheum Dis, 2012. 71(6): p. 825-9.[4]Roos Ljungberg, K., et al., Arthritis Res Ther, 2020. 22(1): p. 274.Table 1.Total number of individuals and percentage (n (%)) in each group for each of the isotypes and antigens.anti-Jo1anti-PL12anti-PL7anti-EJanti-Ro52IIMPCIIMPCIIMPCIIMPCIIMPCIgG61 (16.7)1 (0.6)7 (1.9)0 (0.0)7 (1.9)0 (0.0)3 (0.8)0 (0.0)54 (14.8)5 (3.2)IgA20 (5.5)0 (0.0)2 (1.2)1 (0.6)3 (0.8)2 (1.3)1 (0.3)1 (0.6)3 (0.8)1 (0.6)IgM56 (15.3)1 (0.6)1 (0.3)2 (1.3)7 (1.9)0 (0.0)1 (0.3)0 (0.0)3 (0.8)2 (1.3)AcknowledgementsSciLifeLab facilities Autoimmunity and Serology Profiling and Human Antibody Therapeutics (Drug Discovery and Development). IMI project EUbOPEN, This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875510. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Ontario Institute for Cancer Research, Royal Institution for the Advancement of Learning McGill University, Kungliga Tekniska Hoegskolan, Diamond Light Source Limited.Disclosure of InterestsCharlotta Preger Grant/research support from: IMI project EUbOPEN, Grant no 875510, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren Grant/research support from: IMI project EUbOPEN, Grant no 875510, Ingrid E. Lundberg Shareholder of: Roche and Novartis, Consultant of: Corbus Pharmaceuticals Inc, Astra Zeneca, Bristol Myer´s Squibb, Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, and Janssen, Grant/research support from: Astra Zeneca, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Consultant of: UCB, Grant/research support from: Gesynta Pharma, Helena Persson Employee of: Affibody AB, Susanne Gräslund Grant/research support from: IMI project EUbOPEN, Grant no 875510
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| 25. |
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| 26. |
- Preger, C., et al.
(author)
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Characterization of anti-aminoacyl TRNA synthetase autoantibodies in patients with idiopathic inflammatory myopathies
- 2020
-
In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1084-1085
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Journal article (other academic/artistic)abstract
- Idiopathic inflammatory myopathies (IIM) are rare chronic inflammatory diseases associated with high mortality and morbidity [1]. One sub-group of IIM, anti-synthetase syndrome (ASS), is characterized by the presence of autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS), together with specific clinical manifestations such as myositis, interstitial lung disease (ILD), arthritis, mechanic’s hand, Raynaud’s syndrome and fever [2]. The most common anti-aaRS autoantibody, anti-Jo1 targeting histidyl tRNA synthetase (HisRS), is present in up to 20-30% of patients with IIM, and up to 90% of patients with myositis and ILD [3, 4]. Besides Jo1, there are today seven other identified autoantigens within the aaRS family.Objectives:A large part of patients with IIM, including individuals with clinical manifestations indicating ASS, test seronegative to all known myositis specific autoantibodies. However, these patients could potentially harbor autoantibodies against targets not tested for in clinic. In this study, we aimed at extending the detection of autoantibodies by including all cytoplasmic aaRS in the analysis of patients with IIM. We hypothesized the existence of new potential autoantigens within this protein family.Methods:The presence of anti-aaRS autoantibodies was determined using a multiplex suspension bead array assay on 242 IIM patients from the Karolinska University Hospital myositis cohort. A panel of 186 recombinant constructs, representing 57 proteins that included full-length or partial sequence overlaps between constructs of all cytoplasmic aaRS as well as other myositis related proteins, were coupled to magnetic color-coded beads and each plasma sample was tested against the complete antigen panel.Results:By the use of this multiplex method we identified patients with autoantibodies against many of the tested aaRS. Autoantibodies binding to HisRS have previously been shown to bind with higher reactivity to the WHEP domain of HisRS and this was also confirmed in this study. We confirmed reactivity against three of the other aaRS tested for in the clinic (PL-12, PL-7, and EJ). In addition, we identified patients positive for anti-Zo, -KS and -HA, autoantibodies usually not screened for in routine. Finally, our data indicates that there are autoantibodies binding to other aaRS than the previously known eight autoantigens, which will be presented.Conclusion:In this study, we could detect autoantibodies in plasma from patients with IIM, both against the most common aaRS autoantigens, but also against other aaRS that are usually not tested for in clinic. We conclude that it is important to continue the studies of anti-aaRS autoantibodies, and their correlation to clinical manifestations, and in the long run also include more aaRS autoantigens in clinical practice.References:[1]Dobloug, G.C., et al., Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Ann Rheum Dis, 2018. 77(1): p. 40-47.[2]Barsotti, S. and I.E. Lundberg, Myositis an evolving spectrum of disease. Immunol Med, 2018. 41(2): p. 46-54.[3]Vencovsky, J., H. Alexanderson, and I.E. Lundberg, Idiopathic Inflammatory Myopathies. Rheum Dis Clin North Am, 2019. 45(4): p. 569-581.[4]Richards, T.J., et al., Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum, 2009. 60(7): p. 2183-92.Disclosure of Interests:Charlotta Preger: None declared, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren: None declared, Catia Cerqueira: None declared, Peter Nilsson: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Helena Persson: None declared, Susanne Gräslund: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,
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| 27. |
- Ramos Santesmases, David, et al.
(author)
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Optical concentration in fully delineated mid-wave infrared T2SL detectors arrays
- 2023
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 123:18
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Journal article (peer-reviewed)abstract
- The dependence of quantum efficiency (QE) on fill factor and pixel pitch is studied theoretically and experimentally in fully delineated type-II superlattice (T2SL) detectors. Theoretically, a 2-dimensional simulation model is used to compute the absorption in the array geometry, which shows an insensitivity of the optical response to the fill factor. This is a result of the photodiode array (PDA) geometry concentrating the light in the pixel area. QE measurements on PDAs with varying pixel pitch (from 225 to 10 μm) and fill factors (from 98% to 64%) confirm this independence of the QE on the fill factor and results in a 50% increase in the photocurrent density in 10 μm pitch PDAs compared to 225 μm pitch PDAs. Furthermore, measurements of the dark current density vs pixel size revealed an absence of surface leakage in these PDAs, which, combined with the increased photocurrent density results in an improved signal-to-noise ratio when reducing the pitch in these T2SL detectors. Finally, this result resolves the QE-modulation transfer function trade-off, as the electrical isolation of the pixel is carried out without impacting the QE of the array.
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| 28. |
- Ramos Santesmases, David, et al.
(author)
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Simulation and Characterization of the Modulation Transfer Function in Fully Delineated Type-II Superlattices Infrared Detectors
- 2024
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In: IEEE Transactions on Electron Devices. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9383 .- 1557-9646. ; 71:4, s. 2459-2464
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Journal article (peer-reviewed)abstract
- The modulation transfer function (MTF) in fully delineated 15 μ m pitch type-II superlattice (T2SL) mid-wave infrared (IR) detectors is studied theoretically and experimentally. Theoretically, a 2-D model to simulate the spot scan (SS) profile is presented and used to compute the MTF as a function of the wavelength and the array geometry (pitch size, trench width). The dependence of the detector trench on the MTF is also evaluated experimentally by the edge spread function (ESF) method according to the ISO12233 standard. The experimental results show an excellent agreement with the theoretical model, reporting an MTF of 0.61 and 0.60 at the Nyquist frequency for 1 and 2 μ m trench, respectively. With the simulation model, the effect of the increased optical crosstalk for smaller pixel pitch is discussed as a function of the trench width (0.5, 1, and 2 μ m) and incidence angle up to ± 30 ∘ . Simulation results show MTF values at the Nyquist frequency between 0.61–0.62, 0.58–0.60, and 0.55–0.57 with an average degradation of 1%, 2%, and 7% at an angle of ± 30 ∘ compared to normal incidence for the 10, 7.5, and 5 μ m pitch, respectively.
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| 29. |
- Ruiz-Caldas, Maria-Ximena, 1991-, et al.
(author)
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Citrated cellulose nanocrystals from post-consumer cotton textiles
- 2023
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In: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 11:13, s. 6854-6868
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Journal article (peer-reviewed)abstract
- We propose a new method for the extraction of cellulose nanocrystals (CNCs) from post-consumer cotton textiles through surface functionalization followed by mechanical treatment. Cotton-based textiles were esterified using an 85 wt% solution of citric acid at 100 °C, then further fibrillated in a microfluidizer. The final product, citrated cellulose nanocrystals (CitCNCs), was a dispersion of needle-like nanoparticles with high crystallinity. Up to 78 wt% of the cotton fabric was converted to CitCNCs that exhibited higher yields and a higher surface group content than CNCs extracted through H2SO4 hydrolysis, although CitCNCs showed a broader size distribution and decreased thermal stability. Experimental data supported by DFT calculations showed that the carboxyl groups on the CitCNC surface are bonded to cellulose by mono or diester linkages. An early-stage life cycle assessment (LCA) was performed to evaluate the environmental impact of using discarded textiles as a source of cellulose and analyze the environmental performance of the production of CitCNCs. Our work showed a significant reduction in the environmental burden of CNC extraction using post-consumer cotton instead of wood pulp, making clothing a good feedstock. The environmental impact of CitCNC production was mainly dominated by citric acid. As a proof of concept, around 58 wt% of the citric acid was recovered through evaporation and subsequent crystallization, which could reduce climate impact by 40%. With this work, we introduce a catalyst-free route to valorize textiles with the extraction of CitCNCs and how conducting LCA in laboratory-scale processes might guide future development and optimization.
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| 30. |
- Scarpellini, E., et al.
(author)
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International consensus on the diagnosis and management of dumping syndrome
- 2020
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In: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 16:8, s. 448-466
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Journal article (peer-reviewed)abstract
- Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose. Dumping syndrome is a frequent complication of oesophageal and gastric surgery, as well as bariatric surgery; however, guidance on how to manage patients with this condition is lacking. In this Evidence-based guideline, the authors use a Delphi consensus process to develop uniform guidance for the definition, diagnosis and management of dumping syndrome.
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| 31. |
- Shrestha, Sarita, 1991-, et al.
(author)
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The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
- 2020
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:4, s. 430-435
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Journal article (peer-reviewed)abstract
- Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.
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| 32. |
- Talley, Nicholas J., et al.
(author)
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Role of smoking in functional dyspepsia and irritable bowel syndrome : three random population-based studies
- 2021
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In: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 54:1, s. 32-42
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Journal article (peer-reviewed)abstract
- Background: It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients.Aim: To assess if smoking is an independent risk factor for FD and IBS.Methods: Three population-based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta-analysis using mixed effect logistic regression, adjusted for snuffing, age and sex.Results: Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD-PDS) (OR 10-19 cig/day = 1.42, 95% CI 1.04-1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38-3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS-diarrhoea (OR = 2.40, 95% CI 1.12-5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28-3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41-3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14-2.76, P = 0.012) than non-smokers. Smoking was not associated with IBS-constipation or IBS-mixed.Conclusion: Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS-diarrhoea, but not constipation, is also likely important.
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| 33. |
- Tran, Hang T. T., et al.
(author)
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Hypothermic treatment for neonatal asphyxia in low-resource settings using phase-changing material : An easy to use and low-cost method
- 2021
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In: Acta Paediatrica. - : CSIRO Publishing. - 0803-5253 .- 1651-2227. ; 110:1, s. 85-93
-
Journal article (peer-reviewed)abstract
- Aim: To evaluate whether phase-changing material can be used for therapeutic hypothermia of asphyxiated newborns in low-resource settings.Methods: Prospective interventional study of asphyxiated term infants fulfilling criteria for hypothermia treatment at Vietnam National Children's Hospital from September 2014 to September 2016. Hypothermia was induced within 6 hours after birth and maintained for 72 hours by a phase-changing material mattress with melting point of 32 degrees C. Rectal temperature was continuously measured, and deviations from target temperature range 33.5-34.5 degrees C were recorded.Results: In total 52 infants (mean gestational age 39.3 1.1 weeks) included and cooled, the median temperature at initiation of cooling was 35.3 (IQR 34.5-35.9)degrees C. The median time to reach target temperature was 2.5 (IQR 2-3) hours. The mean temperature during the cooling phase was 33.95 +/- 0.2 degrees C. Throughout the cooling phase, the target temperature range (33.5-34.5 degrees C) was maintained more than 80% of the time. Rate of rewarming was 0.5 +/- 0.14 degrees C/hour.Conclusion: Phase-changing material can be used as an effective cooling method. Though not a servo-controlled system, it is easy to induce hypothermia, maintain target temperature and rewarm infants in a slow and controlled manner without need for frequent changes and minimum risk of skin injury.
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| 34. |
- Tsiartas, Panos, et al.
(author)
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P–459 Ex vivo perfusion of whole ewe ovaries with follicular maturation for up to seven days: towards the development of an alternative fertility preservation method
- 2021
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In: Human Reproduction Vol 36 Issue Supplement 1. - : Oxford University Press (OUP). - 0268-1161.
-
Conference paper (other academic/artistic)abstract
- Abstract Study question To develop an alternative fertility preservation method for young female cancer patients based on an ex vivo perfusion of whole ovaries serving as a platform for future ovarian stimulation studies. Summary answer It is possible to maintain viable follicles and to retrieve oocytes after ex vivo perfusion of ewe ovaries for up to 7 days. What is known already Some progress has been made in terms of follicular growth and the isolation of mature oocytes in vitro. However, full development, from early follicular stages to a viable offspring, has only been described in rodent models. The complex events controlling follicular expansion and the long time required for folliculogenesis and oocyte maturity in large mammalian species creating challenges and limitations for in vitro studies. Ex vivo perfusion of a whole ovary could potentially be a solution by exploiting the intact ovarian architecture to support folliculogenesis and oocyte maturation. Study design, size, duration Thirty-one ewe ovaries were divided into 4 groups and ex vivo perfused in a bioreactor. Group 1 (n=14) perfusion for 48hours with no hormone supplementation; Group 2 (n=4) perfusion 96–101hours with follicle stimulating hormone (FSH); Group 3 (n=3) perfusion 120–168hours with human menopausal gonadotropin (hMG); Group 4 (n=10) perfusion 72–144hours with hMG. Participants/materials, setting, methods Ewe ovaries from sexually mature ewes were ex vivo perfused in a bioreactor under normothermic conditions for up to 7 days (max total 168hours). Histomorphological, immunohistochemical, hormonal and biochemical analyses were performed to assess ovarian structure and viability after cold ischemia and after perfusion which was subsequently compared to control ovaries. Main results and the role of chance The perfused ovaries in group 2 and 3 showed no significant differences in follicular density, viability and oocyte quality after ischemia and perfusion compared to control ovaries. Estradiol and progesterone levels did not increase during the perfusion. The perfused ovaries in group 1 and 4 showed a significant decrease in the ovarian reserve and oocyte quality. In total, 16 GV-MI oocytes were retrieved from groups 3 and 4. Limitations, reasons for caution 1. Ovaries were retrieved from ewes of unknown cycle and reproductive history. 2. The perfusion medium was changed after 24hours from perfusion start to remove detrimental metabolites and this could affect the measured concentrations of hormones and metabolites in the perfusion medium. Wider implications of the findings: These results pave the way to propose ex vivo perfusion as a good platform for fertility preservation studies on whole mammalian and human ovaries to retrieve fully mature oocytes. Trial registration number Not applicable
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| 35. |
- Vanhatalo, Sampsa, et al.
(author)
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Why monitor the neonatal brain-that is the important question
- 2023
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In: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. ; 93:1, s. 19-21
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Journal article (other academic/artistic)abstract
- A key goal of neonatal neurocritical care is improved outcomes, and brain monitoring plays an essential role. The recent NEST trial(1) reported no outcome benefits using aEEG monitoring compared to clinical seizure identification among neonates treated for seizures. However, the study failed to prove the effects of monitoring on seizure treatment in the first place.
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| 36. |
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| 37. |
- Zhong, Wen, et al.
(author)
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Dramatic changes in blood protein levels during the first week of life in extremely preterm infants
- 2021
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 89, s. 604-612
-
Journal article (peer-reviewed)abstract
- Background Preterm birth and its complications are the primary cause of death among children under the age of 5. Among the survivors, morbidity both perinatally and later in life is common. The dawn of novel technical platforms for comprehensive and sensitive analysis of protein profiles in blood has opened up new possibilities to study both health and disease with significant clinical accuracy, here used to study the preterm infant and the physiological changes of the transition from intrauterine to extrauterine life. Methods We have performed in-depth analysis of the protein profiles of 14 extremely preterm infants using longitudinal sampling. Medical variables were integrated with extensive profiling of 448 unique protein targets. Results The preterm infants have a distinct unified protein profile in blood directly at birth regardless of clinical background; however, the pattern changed profoundly postnatally, expressing more diverse profiles only 1 week later and further on up to term-equivalent age. Clusters of proteins depending on temporal trend were identified. Conclusion The protein profiles and the temporal trends here described will contribute to the understanding of the physiological changes in the intrauterine-extrauterine transition, which is essential to adjust early-in-life interventions to prone a normal development in the vulnerable preterm infants. Impact We have performed longitudinal and in-depth analysis of the protein profiles of 14 extremely preterm infants using a novel multiplex protein analysis platform. The preterm infants had a distinct unified protein profile in blood directly at birth regardless of clinical background. The pattern changed dramatically postnatally, expressing more diverse profiles only 1 week later and further on up to term-equivalent age. Certain clusters of proteins were identified depending on their temporal trend, including several liver and immune proteins. The study contributes to the understanding of the physiological changes in the intrauterine-extrauterine transition.
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