| 1. |
- Munthe, Christian, 1962
(författare)
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Etiska aspekter på regenerativ medicin : Ethical aspects on regenerative medicine
- 2003
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Ingår i: SNIB-konferensen 2003, Chalmers tekniska högskola, Göteborg, 16-18 maj 2003.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Inom den regenerativa medicinen strävar man efter att ersätta skadat eller sjukligt biologiskt mänskligt material (celler, organ, kroppsdelar) med nya biologiska komponenter. Området aktualiserar en rad etiska frågeställningar vad gäller (1) produktionen av ersättningsmaterialet (t.ex. embryonala stamceller eller införskaffande av transplantationsvävnad från donatorer), (2) risker i samband med försök på människa (genmodifierat material, material från djur), samt (3) gränserna för hur långt man bör gå i denna slags försök att förlänga människans livsspann. Föredraget ger en kort översikt över dessa frågeställningar, ståndpunkter och argument i debatten kring dem.
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| 2. |
- Brennan, Donal J., et al.
(författare)
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Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer
- 2010
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10, s. 125-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.
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| 3. |
- Marcisauskas, Simonas, 1988, et al.
(författare)
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Univariate and classification analysis reveals potential diagnostic biomarkers for early stage ovarian cancer Type 1 and Type 2
- 2019
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 196, s. 57-68
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers for early detection of ovarian tumors are urgently needed. Tumors of the ovary grow within cysts and most are benign. Surgical sampling is the only way to ensure accurate diagnosis, but often leads to morbidity and loss of female hormones. The present study explored the deep proteome in well-defined sets of ovarian tumors, FIGO stage I, Type 1 (low-grade serous, mucinous, endometrioid; n = 9), Type 2 (high-grade serous; n = 9), and benign serous (n = 9) using TMT–LC–MS/MS. Data are available via ProteomeXchange with identifier PXD010939. We evaluated new bioinformatics tools in the discovery phase. This innovative selection process involved different normalizations, a combination of univariate statistics, and logistic model tree and naive Bayes tree classifiers. We identified 142 proteins by this combined approach. One biomarker panel and nine individual proteins were verified in cyst fluid and serum: transaldolase-1, fructose-bisphosphate aldolase A (ALDOA), transketolase, ceruloplasmin, mesothelin, clusterin, tenascin-XB, laminin subunit gamma-1, and mucin-16. Six of the proteins were found significant (p <.05) in cyst fluid while ALDOA was the only protein significant in serum. The biomarker panel achieved ROC AUC 0.96 and 0.57 respectively. We conclude that classification algorithms complement traditional statistical methods by selecting combinations that may be missed by standard univariate tests. Significance: In the discovery phase, we performed deep proteome analyses of well-defined histology subgroups of ovarian tumor cyst fluids, highly specified for stage and type (histology and grade). We present an original approach to selecting candidate biomarkers combining several normalization strategies, univariate statistics, and machine learning algorithms. The results from validation of selected proteins strengthen our prior proteomic and genomic data suggesting that cyst fluids are better than sera in early stage ovarian cancer diagnostics.
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| 4. |
- Bråbäck, Lennart, et al.
(författare)
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Confounding with familial determinants affects the association between mode of delivery and childhood asthma medication : a national cohort study
- 2013
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Ingår i: Allergy, Asthma & Clinical Immunology. - : BioMed Central. - 1710-1484 .- 1710-1492. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mode of delivery may affect the risk of asthma but the findings have not been consistent and factors shared by siblings may confound the associations in previous studies. METHODS: The association between mode of delivery and dispensed inhaled corticosteroid (ICS) (a marker of asthma) was examined in a register based national cohort (n=199 837). A cohort analysis of all first born children aged 2-5 and 6-9 years was performed. An age-matched sibling-pair analysis was also performed to account for shared genetic and environmental risk factors. RESULTS: Analyses of first-borns demonstrated that elective caesarean section was associated with an increased risk of dispensed ICS in both 2-5 (adjusted odds ratio (aOR)=1.19, 95% confidence interval (CI) 1.09-1.29) and 6-9 (aOR=1.21, 1.09-1.34) age groups. In the sibling-pair analysis, the increased risk associated with elective caesarean section was confirmed in 2-5 year olds (aOR=1.22, 1.05-1.43) but not in 6-9 year olds (aOR=1.06, 0.78-1.44). Emergency caesarean section and vacuum extraction had some association with dispensed ICS in the analyses of first-borns but these associations were not confirmed in the sibling-pair analyses. CONCLUSIONS: Confounding by familial factors affects the association between mode of delivery and dispensed ICS. Despite this confounding, there was some evidence that elective caesarean section contributed to a modestly increased risk of dispensed ICS but only up to five years of age.
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| 5. |
- Gustin, Klara, et al.
(författare)
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Mediation by Thyroid Hormone in the Relationships Between Gestational Exposure to Methylmercury and Birth Size
- 2024
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Ingår i: Exposure and Health. - : Springer. - 2451-9685 .- 2451-9766. ; 16:2, s. 357-368
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Tidskriftsartikel (refereegranskat)abstract
- Our previous studies have linked gestational methylmercury exposure, originating from seafood, to changes in maternal thyroid hormones and infant birth size in a Swedish birth cohort. Herein we aimed to determine associations between maternal thyroid hormones and infant birth size and elucidate if maternal hormones could mediate the relationship between methylmercury and lower birth size. In 515 women, without known thyroid disease, we assessed metal exposure by erythrocyte mercury concentrations (mainly methylmercury, reflecting exposure over the past months) in early third trimester measured with inductively coupled plasma-mass spectrometry. Plasma concentrations of total and free thyroxine (tT4 and fT4) and triiodothyronine (tT3 and fT3), and thyroid-stimulating hormone (TSH) were measured at an accredited clinical laboratory. In multivariable-adjusted linear regression models, maternal tT3 (per 1 nmol/L increase) was positively associated with birth weight (B: 125 g; 95% CI 36, 214) and length (B: 0.59 cm; 95% CI 0.21, 0.97). Maternal fT4 was inversely associated with birth weight (B: − 33 g; 95% CI − 57, − 9.5), driven by obese women (n = 76). Causal mediation analyses suggested that a doubling of erythrocyte mercury (> 1 µg/kg; n = 374) was associated with a mean tT3-mediated decrease in birth weight of 11 g (95% CI − 25, − 1.6) and in birth length of 0.1 cm (95% CI − 0.12, − 0.01), both equivalent to about 12% of the total effect. To conclude, tT3 was positively associated with infant birth size. Reduced tT3 levels appeared to mediate a minor part of the inverse association between methylmercury exposure and birth size.
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| 6. |
- Risberg, Anitha, et al.
(författare)
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Water balance during parturition and early puerperium : a prospective open trial
- 2015
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:13-14, s. 837-842
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo investigate how water balance is regulated during labour and 27 h postpartum. Design and methods A prospective open trial with 49 women giving birth vaginally. Ringer-acetate was infused intravenously and combined with epidural analgesia in seven women (fluid group). Intravenous infusions of oxytocin in 5% glucose were given to 12 women (oxytocin group). Thirty women delivered their babies without infusion (nofluid group). Blood and urine samples were collected at arrival, at early stage 1, at early stage 2, and at aftercare, and 9-, 15-, and 27-h postpartum. Plasma osmolality, sodium, cystatin C, vasopressin, oxytocin, urine flow, urine osmolality and urine sodium were measued.ResultsThe oxytocin group had significantly lower plasma osmolality than the nofluid group before parturition, and they had lower plasma sodium concentration at early stage one and two. Plasma vasopressin concentration was low and did not differ between groups or before and after parturition. Water diuresis developed postpartum in all groups. The cystatin C concentration decreased significantly after parturition in the oxytocin and nofluid groups.ConclusionsThe vasopressin levels were suppressed during parturition irrespective of the P-osmolality and the nongravid regulation of water balance had not returned within 27 h postpartum.
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| 7. |
- Adolfsson, Margareta, 1950-, et al.
(författare)
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Pain management for children with cerebral palsy in school settings in two cultures: action and reaction approaches
- 2018
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 40:18, s. 2152-2162
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Forskningsöversikt (refereegranskat)abstract
- © 2017 Informa UK Limited, trading as Taylor & Francis Group Background: Children with cerebral palsy (CP) face particular challenges, e.g. daily pain that threaten their participation in school activities. This study focuses on how teachers, personal assistants, and clinicians in two countries with different cultural prerequisites, Sweden and South Africa, manage the pain of children in school settings. Method: Participants’ statements collected in focus groups were analysed using a directed qualitative content analysis framed by a Frequency of attendance-Intensity of involvement model, which was modified into a Knowing-Doing model. Results: Findings indicated that pain management focused more on children’s attendance in the classroom than on their involvement, and a difference between countries in terms of action-versus-reaction approaches. Swedish participants reported action strategies to prevent pain whereas South African participants primarily discussed interventions when observing a child in pain. Conclusion: Differences might be due to school- and healthcare systems. To provide effective support when children with CP are in pain in school settings, an action-and-reaction approach would be optimal and the use of alternative and augmentative communication strategies would help to communicate children’s pain. As prevention of pain is desired, structured surveillance and treatment programs are recommended along with trustful collaboration with parents and access to “hands-on” pain management when needed.Implications for rehabilitation•When providing support, hands-on interventions should be supplemented by structured preventive programs and routines for parent collaboration (action-and-reaction approach).•When regulating support, Sweden and South Africa can learn from each other;○In Sweden, the implementation of a prevention program has been successful.○In South Africa, the possibilities giving support directly when pain in children is observed have been beneficial.
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| 8. |
- Hartvigsson, Olle, 1991, et al.
(författare)
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Associations of the placental metabolome with immune maturation up to one year of age in the Swedish NICE-cohort
- 2024
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Ingår i: Metabolomics. - : Springer Nature. - 1573-3882 .- 1573-3890. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Allergies and other immune-mediated diseases are thought to result from incomplete maturation of the immune system early in life. We previously showed that infants’ metabolites at birth were associated with immune cell subtypes during infancy. The placenta supplies the fetus with nutrients, but may also provide immune maturation signals. Objectives: To examine the relationship between metabolites in placental villous tissue and immune maturation during the first year of life and infant and maternal characteristics (gestational length, birth weight, sex, parity, maternal age, and BMI). Methods: Untargeted metabolomics was measured using Liquid Chromatography-Mass Spectrometry. Subpopulations of T and B cells were measured using flow cytometry at birth, 48 h, one, four, and 12 months. Random forest analysis was used to link the metabolomics data with the T and B cell sub populations as well as infant and maternal characteristics. Results: Modest associations (Q2 = 0.2–0.3) were found between the placental metabolome and kappa-deleting recombination excision circles (KREC) at birth and naïve B cells and memory T cells at 12 months. Weak associations were observed between the placental metabolome and sex and parity. Still, most metabolite features of interest were of low intensity compared to associations previously found in cord blood, suggesting that underlying metabolites were not of placental origin. Conclusion: Our results indicate that metabolomic measurements of the placenta may not effectively recognize metabolites important for immune maturation.
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| 9. |
- Danielsson, H., et al.
(författare)
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Blood protein profiles related to preterm birth and retinopathy of prematurity
- 2022
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 91:4, s. 937-946
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Tidskriftsartikel (refereegranskat)abstract
- Background Nearly one in ten children is born preterm. The degree of immaturity is a determinant of the infant's health. Extremely preterm infants have higher morbidity and mortality than term infants. One disease affecting extremely preterm infants is retinopathy of prematurity (ROP), a multifactorial neurovascular disease that can lead to retinal detachment and blindness. The advances in omics technology have opened up possibilities to study protein expressions thoroughly with clinical accuracy, here used to increase the understanding of protein expression in relation to immaturity and ROP. Methods Longitudinal serum protein profiles the first months after birth in 14 extremely preterm infants were integrated with perinatal and ROP data. In total, 448 unique protein targets were analyzed using Proximity Extension Assays. Results We found 20 serum proteins associated with gestational age and/or ROP functioning within mainly angiogenesis, hematopoiesis, bone regulation, immune function, and lipid metabolism. Infants with severe ROP had persistent lower levels of several identified proteins during the first postnatal months. Conclusions The study contributes to the understanding of the relationship between longitudinal serum protein levels and immaturity and abnormal retinal neurovascular development. This is essential for understanding pathophysiological mechanisms and to optimize diagnosis, treatment and prevention for ROP. Impact Longitudinal protein profiles of 14 extremely preterm infants were analyzed using a novel multiplex protein analysis platform combined with perinatal data. Proteins associated with gestational age at birth and the neurovascular disease ROP were identified. Among infants with ROP, longitudinal levels of the identified proteins remained largely unchanged during the first postnatal months. The main functions of the proteins identified were angiogenesis, hematopoiesis, immune function, bone regulation, lipid metabolism, and central nervous system development. The study contributes to the understanding of longitudinal serum protein patterns related to gestational age and their association with abnormal retinal neuro-vascular development.
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| 10. |
- Dobilas, Arturas, et al.
(författare)
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Preoperative ctDNA Levels Are Associated With Poor Overall Survival in Patients With Ovarian Cancer
- 2023
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Ingår i: Cancer Genomics & Proteomics. - 1790-6245. ; 20:6 suppl, s. 763-770
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Circulating tumor DNA (ctDNA), which is shed from cancer cells into the bloodstream, offers a potential minimally invasive approach for cancer diagnosis and monitoring. This research aimed to assess the preoperative ctDNA levels in ovarian tumors patients' plasma and establish correlations with clinicopathological parameters and patient prognosis.PATIENTS AND METHODS: Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/ml and variant allele frequency.RESULTS: Somatic mutations were found in 24 tumor samples, 17 of which were from ovarian cancer patients. The most frequently mutated gene was TP53. Preoperative plasma ctDNA levels were detected in 14 of the 24 patients. With higher stage, plasma ctDNA mutant concentration increased (p for trend <0.001). The overall survival of cancer patients with more than 10 ctDNA mutant copies/ml in plasma was significantly worse (p=0.008).CONCLUSION: Pre-operative ctDNA measurement in ovarian cancer patients' plasma holds promise as a predictive biomarker for tumor staging and prognosis.
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