| 96301. |
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| 96302. |
- Bergholtz, Helga, et al.
(author)
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Comparable cancer-relevant mutation profiles in synchronous ductal carcinoma in situ and invasive breast cancer
- 2020
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In: Cancer Reports. - : WILEY. - 2573-8348. ; 3:3
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Journal article (peer-reviewed)abstract
- Background: Ductal carcinoma in situ (DCIS) comprises a diverse group of preinvasive lesions in the breast and poses a considerable clinical challenge due to lack of markers of progression. Genomic alterations are to a large extent similar in DCIS and invasive carcinomas, although differences in copy number aberrations, gene expression patterns, and mutations exist. In mixed tumors with synchronous invasive breast cancer (IBC) and DCIS, it is still unclear to what extent invasive tumor cells are directly derived from the DCIS cells.Aim: Our aim was to compare cancer-relevant mutation profiles of different cellular compartments in mixed DCIS/IBC and pure DCIS tumors.Methods and results: We performed targeted sequencing of 50 oncogenes in microdissected tissue from three different epithelial cell compartments (in situ, invasive, and normal adjacent epithelium) from 26 mixed breast carcinomas. In total, 44 tissue samples (19 invasive, 16 in situ, 9 normal) were subjected to sequencing using the Ion Torrent platform and the AmpliSeq Cancer Hotspot Panel v2. For comparison, 10 additional, pure DCIS lesions were sequenced. Across all mixed samples, we detected 23 variants previously described in cancer. The most commonly affected genes were TP53, PIK3CA, and ERBB2. The PIK3CA:p.H1047R variant was found in nine samples from six patients. Most variants detected in invasive compartments were also found in the corresponding in situ cell compartment indicating a clonal relationship between the tumor stages. A lower frequency of variants were observed in pure DCIS lesions.Conclusion: Similar mutation profiles between in situ and invasive cell compartments indicate a similar origin of the two tumor stages in mixed breast tumors. The lower number of potential driver variants found in pure DCIS compared with the in situ cell compartments of mixed tumors may imply that pure DCIS is captured earlier in the path of progression to invasive disease.
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| 96303. |
- Bergholtz, Helga, et al.
(author)
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Contrasting DCIS and invasive breast cancer by subtype suggests basal-like DCIS as distinct lesions
- 2020
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In: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1
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Journal article (peer-reviewed)abstract
- Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer with highly variable potential of becoming invasive and affecting mortality. Currently, many patients with DCIS are overtreated due to the lack of specific biomarkers that distinguish low risk lesions from those with a higher risk of progression. In this study, we analyzed 57 pure DCIS and 313 invasive breast cancers (IBC) from different patients. Three levels of genomic data were obtained; gene expression, DNA methylation, and DNA copy number. We performed subtype stratified analyses and identified key differences between DCIS and IBC that suggest subtype specific progression. Prominent differences were found in tumors of the basal-like subtype: Basal-like DCIS were less proliferative and showed a higher degree of differentiation than basal-like IBC. Also, core basal tumors (characterized by high correlation to the basal-like centroid) were not identified amongst DCIS as opposed to IBC. At the copy number level, basal-like DCIS exhibited fewer copy number aberrations compared with basal-like IBC. An intriguing finding through analysis of the methylome was hypermethylation of multiple protocadherin genes in basal-like IBC compared with basal-like DCIS and normal tissue, possibly caused by long range epigenetic silencing. This points to silencing of cell adhesion-related genes specifically in IBC of the basal-like subtype. Our work confirms that subtype stratification is essential when studying progression from DCIS to IBC, and we provide evidence that basal-like DCIS show less aggressive characteristics and question the assumption that basal-like DCIS is a direct precursor of basal-like invasive breast cancer.
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| 96304. |
- Berghäll, Elisabeth, et al.
(author)
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The Evolution of Blood Cell Phenotypes, Intracellular and Plasma Cytokines and Morphological Changes in Critically Ill COVID-19 Patients
- 2022
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In: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:5
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Journal article (peer-reviewed)abstract
- Background: Severe coronavirus disease 2019 (COVID-19) causes a strong inflammatory response. To obtain an overview of inflammatory mediators and effector cells, we studied 25 intensive-care-unit patients during the timeframe after off-label chloroquine treatment and before an introduction of immunomodulatory drugs.Material and methods: Blood samples were weekly examined with flow cytometry (FCM) for surface and intracytoplasmic markers, cytokine assays were analyzed for circulating interleukins (ILs), and blood smears were evaluated for morphological changes. Samples from healthy volunteers were used for comparison. Organ function data and 30-day mortality were obtained from medical records.Results: Compared to that of the healthy control group, the expression levels of leukocyte surface markers, i.e., the cluster of differentiation (CD) markers CD2, CD4, CD8, CD158d, CD25, CD127, and CD19, were lower (p < 0.001), while those of leukocytes expressing CD33 were increased (p < 0.05). An aberrant expression of CD158d on granulocytes was found on parts of the granulocyte population. The expression levels of intracellular tumor necrosis factor alpha (TNF alpha) and IL-1 receptor type 2 in leukocytes were higher (p < 0.001) as well as plasma levels of TNF alpha, IL-2, IL-6, IL-8, IL-10 (p < 0.001), interferon gamma (IFN gamma) (p < 0.01), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.05). The expression levels of CD33+ leukocytes and circulating IL-6 were higher (p < 0.05) among patients with arterial oxygen partial pressure-to-fractional inspired oxygen (PaO2/FiO(2)) ratios below 13.3 kPa compared to in the remaining patients. The expression levels of TNF alpha, IL-2, IL-4, IL-6, IL-8, and IL-10 were higher in patients treated with continuous renal replacement therapy (CRRT) (p < 0.05), and the levels of the maximum plasma creatinine and TNF alpha Spearman's rank-order correlation coefficient (rho = 0.51, p < 0.05) and IL-8 (rho = 0.44, p < 0.05) correlated. Blood smears revealed neutrophil dysplasia with pseudo-Pelger forms being most common.Conclusion: These findings suggest that patients with severe COVID-19, in addition to augmented ILs, lymphopenia, and increased granulocytes, also had effects on the bone marrow.
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| 96305. |
- Bergia, Robert E., et al.
(author)
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Differential Glycemic Effects of Low-versus High-Glycemic Index Mediterranean-Style Eating Patterns in Adults at Risk for Type 2 Diabetes: The MEDGI-Carb Randomized Controlled Trial
- 2022
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In: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 14:3
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Journal article (peer-reviewed)abstract
- A Mediterranean-style healthy eating pattern (MED-HEP) supports metabolic health, but the utility of including low-glycemic index (GI) foods to minimize postprandial glucose excursions remain unclear. Therefore, we investigated the relative contribution of GI towards improvements in postprandial glycemia and glycemic variability after adopting a MED-HEP. We conducted a randomized, controlled dietary intervention, comparing high-versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of adults at risk for type 2 diabetes. For 12 weeks, participants consumed either a low-GI or high-GI MED-HEP. We assessed postprandial plasma glucose and insulin responses to high-or low-GI meals, and daily glycemic variability via continuous glucose monitoring at baseline and post-intervention. One hundred sixty adults (86 females, 74 males; aged 55 ± 11 y, BMI 31 ± 3 kg/m2, mean ± SD) with ≥two metabolic syndrome traits completed the intervention. Postprandial insulin concentrations were greater after the high-GI versus the low-GI test meals at baseline (p = 0.004), but not post-intervention (p = 0.17). Postprandial glucose after the high-GI test meal increased post-intervention, being significantly higher than that after the low-GI test meal (35%, p < 0.001). Average daily glucose concentrations decreased in both groups post-intervention. Indices of 24-h glycemic variability were reduced in the low-GI group as compared to baseline and the high-GI intervention group. These findings suggest that low-GI foods may be an important feature within a MED-HEP.
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| 96306. |
- Berginström, Nils, 1984-, et al.
(author)
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White matter hyperintensities increases with traumatic brain injury severity : associations to neuropsychological performance and fatigue
- 2020
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In: Brain Injury. - : Taylor & Francis. - 0269-9052 .- 1362-301X. ; 34:3, s. 415-420
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Journal article (peer-reviewed)abstract
- Objective: To examine the prevalence of white matter hyperintensities (WMHs) in patients with traumatic brain injury (TBI) as compared to healthy controls, and to investigate whether there is an association between WMH lesion burden and performance on neuropsychological tests in patients with TBI.Methods: A total of 59 patients with TBI and 27 age- and gender-matched healthy controls underwent thorough neuropsychological testing and magnetic resonance imaging. The quantification of WMH lesions was performed using the fully automated Lesion Segmentation Tool.Results: WMH lesions were more common in patients with TBI than in healthy controls (p = .032), and increased with higher TBI severity (p = .025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > .05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = - 0.33, p = .026).Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. These lesions could not explain decreased cognitive functioning in patients with TBI but did relate to decreased self-assessment of fatigue after TBI.
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| 96307. |
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| 96308. |
- Bergkvist, Göran, et al.
(author)
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Bone Density at Implant Sites and Its Relationship to Assessment of Bone Quality and Treatment Outcome
- 2010
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In: INTERNATIONAL JOURNAL OF ORAL and MAXILLOFACIAL IMPLANTS. - : Quintessence Publishing Co, Inc. - 0882-2786 .- 1942-4434. ; 25:2, s. 321-328
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Journal article (peer-reviewed)abstract
- Purpose: To investigate the relationship between bone mineral density (BMD) before implant placement, implant stability measures at implant placement, and marginal bone loss of immediately loaded implants after 1 year in situ. Materials and Methods: Consecutively recruited patients received Straumann SLActive implants loaded with fixed provisional prostheses within 24 hours. BMD was measured from computed tomographic images before implant placement. Alveolar bone quality was assessed during surgery. Implant stability-both rotational and as measured with resonance frequency analysis- and marginal bone height were assessed at implant placement and after 1 year. The Pearson correlation coefficient was used to calculate correlations, and significance was considered when P andlt; .05. Results: Twenty-one patients received 137 implants (87 in maxillae and 50 in mandibles). BMD was significantly correlated with bone quality classification in both arches (P andlt; .001). Mean BMD was also significantly correlated with stability values (P andlt; .001). Mean marginal bone loss at implant surfaces differed, but not significantly, at the 1-year follow-up, regardless of BMD values (P = .086) and measured stability (rotational stability P = .34, resonance frequency analysis P = .43) at implant placement. Conclusion: Within the limits of this study, it can be concluded that computed tomographic examination can be used as a preoperative method to assess jawbone density before implant placement, since density values correlate with prevailing methods of measuring implant stability. However, in the short time perspective of 1 year, there were no differences in survival rates or changes in marginal bone level between implants placed in bone tissue of different density.
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| 96309. |
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| 96310. |
- Bergkvist, Max, et al.
(author)
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Assessment of oxygenation with polarized light spectroscopy enables new means for detecting vascular events in the skin
- 2020
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In: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 130
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Journal article (peer-reviewed)abstract
- Introduction: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals. Materials and methods: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (C-RBC,(TiVi)), oxygenation (Delta C-OH,(TiVi)) and deoxygenation (Delta C-DOH,(TiVi)) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS). Results: During arterial occlusion, C-RBC,(TiVi) remained unchanged while Delta C-OH,(TiVi) decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, C-RBC,C-TiVi increased to 39.2 (18.8) AU (p < 0.001), Delta C-OH,C-TiVi increased to 38.5. During venous occlusion, C-RBC,C-TiVi increased to 28.9 (11.2) AU (p < 0.001), Delta C-OH,C-TiVi decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively. Conclusion: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.
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