| 1. |
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| 2. |
- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 7. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 8. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 9. |
- Escala-Garcia, M, et al.
(författare)
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Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19787-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
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| 10. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 11. |
- Park, J, et al.
(författare)
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Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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| 12. |
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| 13. |
- Hagleitner, M M, et al.
(författare)
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Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).
- 2008
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Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244. ; 45:2, s. 93-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients. OBJECTIVE: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients. METHODS: Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors. Results and CONCLUSIONS: 45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.
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| 14. |
- Hagg, S, et al.
(författare)
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Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
- 2017
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:4, s. e1100-
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Tidskriftsartikel (refereegranskat)abstract
- The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=−0.053; 95% CI: −0.087, −0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10−5), whereas carriers performed better in STROOP (β=−0.074; 95% CI: −0.140, −0.009; P=0.03). Causal associations were found for STROOP only (β=−0.598 per s.d.-increase of TL; 95% CI: −1.125, −0.072; P=0.026), with a larger effect in ɛ4-carriers (β=−0.699; 95% CI: −1.330, −0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.
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| 15. |
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| 18. |
- Mavaddat, N, et al.
(författare)
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Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
- 2020
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 22:1, s. 8-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.MethodsA multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.ResultsThere was no association between RRSO and breast cancer forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR forBRCA2mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.ConclusionWe found no evidence that RRSO reduces breast cancer risk forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
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| 19. |
- Bocquier, Philipe, et al.
(författare)
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Ubiquitous burden : The contribution of migration to AIDS and tuberculosis mortality in rural South Africa
- 2014
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Ingår i: African Population Studies. - : Stellenbosch University. - 0850-5780 .- 2308-7854. ; 28:1, s. 691-701
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Tidskriftsartikel (refereegranskat)abstract
- The paper aims to estimate the extent to which migrants are contributing to AIDS or tuberculosis (TB) mortality among rural sub-district populations. The Agincourt (South Africa) health and socio-demographic surveillance system provided comprehensive data on vital and migration events between 1994 and 2006. AIDS and TB cause-deleted life expectancy, and crude death rates by gender, migration status and period were computed. The annualised crude death rate almost tripled from 5∙39 [95% CI 5∙13-5∙65] to 15∙10 [95% CI 14∙62-15∙59] per 1000 over the years 1994-2006. The contribution of AIDS and TB in returned migrants to the increase in crude death rate was 78∙7% [95% CI 77∙4-80∙1] for males and 44∙4% [95% CI 43∙2-46∙1] for females. So, in a typical South African setting dependent on labour migration for rural livelihoods, the contribution of returned migrants, many infected with AIDS and TB, to the burden of disease is high.
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| 24. |
- Stuiver, M., et al.
(författare)
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The Governance of Multi-Use Platforms at Sea for Energy Production and Aquaculture: Challenges for Policy Makers in European Seas
- 2016
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- European seas are encountering an upsurge in competing marine activities and infrastructures. Traditional exploitation such as fisheries, tourism, transportation, and oil production are accompanied by new sustainable economic activities such as offshore windfarms, aquaculture, and tidal and wave energy. One proposed solution to overcome possible competing claims at sea lies in combining these economic activities as part of Multi-Use Platforms at Sea (MUPS). MUPS can be understood as areas at sea, designated for a combination of activities, either completely integrated in a platform or in shared marine space. MUPS can potentially benefit from each other in terms of infrastructure, maintenance, etc. Developing MUPS in the marine environment demands adequate governance. In this article, we investigate four European sites to find out how governance arrangements may facilitate or complicate MUPs. In particular, we apply a framework specifying policy, economic, social, technical, environmental, and legal (PESTEL) factors to explore governance arrangements in four case study sites in different sea basins around Europe ( the Mediterranean Sea, the Atlantic Ocean, the North Sea, and the Baltic Sea). The article concludes with policy recommendations on a governance regime for facilitating the development of MUPS in the future.
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| 25. |
- Agardh, Carl-David, et al.
(författare)
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The influence of plasma insulin concentrations on tissue insulin levels in rodents: a study of the diabetic Chinese hamster and the ob/ob mouse
- 1986
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 35:3, s. 244-249
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Tidskriftsartikel (refereegranskat)abstract
- Immunoreactive insulin was measured in acid-ethanol extracts of kidney, brain, liver, and heart from genetically diabetic Chinese hamsters and their nondiabetic controls and from obese (ob/ob) mice and their thin littermates. Selected samples were filtered on Sephadex G-50 columns and the insulin concentration determined. There was a good correlation between the insulin level measured in the acid-ethanol extracts of tissues and the insulin level after gel filtration, suggesting that the concentration measured in the whole extract is representative of the true insulin content. The present data demonstrate that different extrapancreatic organs contain characteristic amounts of insulin that are often (sometimes several-fold) higher than the insulin level of plasma. The tissue insulin concentrations also exhibit a wide range of values, with occasional high values. The data also show a direct correlation between plasma and kidney insulins but no relationship between plasma and brain insulins and a mixed correlation among plasma and liver and heart insulins.
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| 32. |
- Gerritsen, Annette, et al.
(författare)
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Health and demographic surveillance systems : contributing to an understanding of the dynamics in migration and health
- 2013
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 6, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Migration is difficult to measure because it is highly repeatable. Health and Demographic Surveillance Systems (HDSSs) provide a unique opportunity to study migration as multiple episodes of migration are captured over time. A conceptual framework is needed to show the public health implications of migration.Objective/design: Research conducted in seven HDSS centres [International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) Network], published in a peer-reviewed volume in 2009, is summarised focussing on the age-sex profile of migrants, the relation between migration and livelihoods, and the impact of migration on health. This illustrates the conceptual structure of the implications of migration. The next phase is described, the Multi-centre Analysis of the Dynamics In Migration And Health (MADIMAH) project, consisting of workshops focussed on preparing data and conducting the analyses for comparative studies amongst HDSS centres in Africa and Asia. The focus here is on the (standardisation of) determinants of migration and the impact of migration on adult mortality.Results: The findings in the volume showed a relatively regular age structure for migration among all HDSS centres. Furthermore, migration generally contributes to improved living conditions at the place of origin. However, there are potential negative consequences of migration on health. It was concluded that there is a need to compare results from multiple centres using uniform covariate definitions as well as longitudinal analysis techniques. This was the starting point for the on-going MADIMAH initiative, which has increased capacity at the participating HDSS centres to produce the required datasets and conduct the analyses.Conclusions: HDSS centres brought together within INDEPTH Network have already provided strong evidence of the potential negative consequences of migration on health, which contrast with the beneficial impacts of migration on livelihoods. Future comparative evidence using standardised tools will help design policies for mitigating the negative effects, and enhancing the positive effects, of migration on health.
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| 33. |
- Gerritsen, Lotte, et al.
(författare)
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Influence of Negative Life Events and Widowhood on Risk for Dementia
- 2017
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Ingår i: The American journal of geriatric psychiatry. - : Elsevier BV. - 1064-7481 .- 1545-7214. ; 25:7, s. 766-778
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the current study was to examine the effect of negative life events and widowhood on the incidence of dementia. Methods: Data were from four Swedish longitudinal cohort studies with a total of nearly 2,000 participants and 8-25 years of follow-up. Seven stressful events were examined for which data were available in all cohorts. Clinical dementia diagnoses were made through medical and psychological examinations. Cox proportional hazards models were used to estimate the association between life events and dementia, adjusting for lifestyle and cardiovascular risk factors. Results: The experience of one stressful life event was not associated with dementia incidence, but two or more negative life events at baseline predicted higher risk for dementia (pooled HR:2.00). This was most apparent for the incidence of vascular dementia (pooled HR: 3.60) but not for Alzheimer disease (pooled HR: 1.29). Moreover, persons who were widowed and had experienced one or more negative life events were found to have a threefold risk for dementia. Conclusion: Widowhood augments the effect of negative life events on dementia incidence and negative life events specifically increase the risk for vascular dementia.
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| 34. |
- Gerritsen, L., et al.
(författare)
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The influence of negative life events on hippocampal and amygdala volumes in old age : a life-course perspective
- 2014
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Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 45:6, s. 1219-1228
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults.METHOD: In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning.RESULTS: Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women.CONCLUSIONS: These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.
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| 35. |
- Nilsson, R. Jonas A., et al.
(författare)
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Blood platelets contain tumor-derived RNA biomarkers
- 2011
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Ingår i: Blood. - New York : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:13, s. 3680-3683
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Tidskriftsartikel (refereegranskat)abstract
- Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer.
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| 36. |
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| 37. |
- Oprea-Lager, Daniela E, et al.
(författare)
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Dual-Phase PET-CT to Differentiate [(18)F]Fluoromethylcholine Uptake in Reactive and Malignant Lymph Nodes in Patients with Prostate Cancer
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e48430-
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate whether time-trends of enhanced [(18)F]Fluoromethylcholine ([(18)F]FCH) in lymph nodes (LN) of prostate cancer (PCa) patients can help to discriminate reactive from malignant ones, and whether single time point standardized uptake value (SUV) measurements also suffice.PROCEDURES: 25 PCa patients with inguinal (presumed benign) and enlarged pelvic LN (presumed malignant) showing enhanced [(18)F]FCH uptake at dual-phase PET-CT were analyzed. Associations between LN status (benign versus malignant) and SUV(max) and SUV(meanA50), determined at 2 min (early) and 30 min (late) post injection, were assessed. We considered two time-trends of [(18)F]FCH uptake: type A (SUV early > SUV late) and type B (SUV late ≥ SUV early). Histopathology and/or follow-up were used to confirm the assumption that LN with type A pattern are benign, and LN with type B pattern malignant.RESULTS: Analysis of 54 nodes showed that LN status, time-trends, and 'late' (30 min p.i.) SUV(max) and SUV(meanA50) parameters were strongly associated (P<0.0001). SUV(max) relative difference was the best LN status predictor. All but one inguinal LN showed a decreasing [(18)F]FCH uptake over time (pattern A), while 95% of the pelvic nodes presented a stable or increasing uptake (pattern B) type.CONCLUSIONS: Time-trends of enhanced [(18)F]FCH uptake can help to characterize lymph nodes in prostate cancer patients. Single time-point SUV measurements, 30 min p.i., may be a reasonable alternative for predicting benign versus malignant status of lymph nodes, but this remains to be validated in non-enlarged pelvic lymph nodes.
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| 38. |
- Persborn, Mats, et al.
(författare)
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The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis
- 2013
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 38:7, s. 772-783
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Tidskriftsartikel (refereegranskat)abstract
- Background less thanbrgreater than less thanbrgreater thanA total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. less thanbrgreater than less thanbrgreater thanAim less thanbrgreater than less thanbrgreater thanTo examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. less thanbrgreater than less thanbrgreater thanMethods less thanbrgreater than less thanbrgreater thanSixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and Cr-51-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanPouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P andlt; 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P andlt; 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. less thanbrgreater than less thanbrgreater thanConclusions less thanbrgreater than less thanbrgreater thanProbiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.
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| 39. |
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| 40. |
- Yurtman, Erinç, et al.
(författare)
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Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication
- 2021
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.
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