| 1. |
|
|
| 2. |
|
|
| 3. |
- Schiller, D, et al.
(författare)
-
The Human Affectome
- 2024
-
Ingår i: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
|
|
| 5. |
- van Leeuwen, S. J. M., et al.
(författare)
-
Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation
- 2021
-
Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365.
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1x/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3x/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (>= 2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.
|
|
| 6. |
- Bulthuis, Marjolein S., et al.
(författare)
-
Subjective Oral Dryness following Hematopoietic Cell Transplantation: A Report from the Orastem Study
- 2024
-
Ingår i: TRANSPLANTATION AND CELLULAR THERAPY. - 2666-6375 .- 2666-6367. ; 30:4
-
Tidskriftsartikel (refereegranskat)abstract
- Xerostomia, or subjective oral dryness, is a serious complaint after hematopoietic cell transplantation (HCT). Xerostomia is rated as one of the most bothersome symptoms by HCT recipients, negatively affecting quality of life. This substudy of the Orastem study, prospective longitudinal, international, observational, multicenter study, aimed to describe the prevalence and severity of xerostomia following HCT. Furthermore, the effect of the conditioning regimen, type of transplantation, and oral mucosal changes related to chronic graft -versus -host disease (cGVHD) in the development of xerostomia were studied. All HCT recipients rated xerostomia on a scale of 0 to 10 before the conditioning regimen, several times early post-HCT, and at 3 months post-HCT, and only allogeneic HCT recipients also rated xerostomia at 6 and 12 months post-HCT. In addition, stimulated whole mouth saliva was collected several times. Linear regression models and longitudinal mixed-effects models were created to investigate the influence of indicators on xerostomia. A total of 99 autologous and 163 allogeneic HCT recipients were included from 6 study sites in Sweden, Canada, the Netherlands, and the United States. The prevalence of xerostomia was 40% before the conditioning regimen, 87% early post-HCT, and 64% at 3 months post-HCT. Complaints after autologous HCT were transient in nature, while the severity of xerostomia in allogeneic HCT recipients remained elevated at 12 months post-HCT. Compared to autologous HCT recipients, allogeneic HCT recipients experienced 1.0 point more xerostomia (95% confidence interval [CI], .1 to 2.0) early post-HCT and 1.7 points more (95% CI, .4 to 3.0) months post-HCT. Allogeneic HCT recipients receiving a high-intensity conditioning regimen experienced more xerostomia compared to those receiving a nonmyeloablative or reduced-intensity conditioning regimen. The difference was 2.0 points (95% CI, 1.1 to 2.9) early post-HCT, 1.8 points (95% CI, .3 to 3.3) after 3 months, and points (95% CI, .0 to 3.3) after 12 months. Total body irradiation as part of the conditioning regimen and oral mucosal changes related to cGVHD did not significantly influence the severity of xerostomia. Conditioning regimen intensity was a significant risk indicator in the development of xerostomia, whereas total body irradiation was not. Allogeneic HCT recipients experienced more xerostomia than autologous HCT recipients, a difference that cannot be explained by a reduction in stimulated salivary flow rate or the development of oral mucosal changes related to cGVHD.
|
|
| 7. |
- Laheij, Amga, et al.
(författare)
-
Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.
|
|
| 8. |
- Bulthuis, M. S., et al.
(författare)
-
Caries Progression after Haematopoietic Stem Cell Transplantation and the Role of Hyposalivation
- 2022
-
Ingår i: Caries Research. - : S. Karger AG. - 0008-6568 .- 1421-976X. ; 56:3, s. 187-196
-
Tidskriftsartikel (refereegranskat)abstract
- Haematopoietic stem cell transplantation (HSCT) preceded by a conditioning regimen is an established treatment option for many haematological diseases. Decreased salivary flow rates after HSCT may increase caries risk. We aim to estimate the extent to which caries lesions develop or progress in adult HSCT recipients and assess its association with salivary flow rates. A multi-centre prospective observational study was conducted in which patients receiving HSCT were followed up for 18 months. We included 116 patients (median age 56 years, 43% female) from two medical centres in the Netherlands. Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected, and full caries charts were made before HSCT and 3, 6, 12, and 18 months post-HSCT. Caries was scored according to the ICDAS criteria by trained dentist-examiners. New dentine lesions or lesion progression into dentine (ICDAS >= 4 or cavitated root lesions) occurred in 32% of patients over 18 months. The median number of affected surfaces was 2 (range: 1-12) per patient with caries progression. The influence of hyposalivation of unstimulated saliva (<0.2 mL/min) and stimulated saliva (<0.7 mL/min) at baseline and after 3 months on caries progression was determined with a negative binomial regression model. Hyposalivation of SWS 3 months after HSCT was a significant risk indicator for caries progression (incidence rate ratio: 5.30, 95% CI: 2.09-13.4, p < 0.001), while hyposalivation of SWS at baseline and hyposalivation of UWS were not. We conclude that caries progression is a common oral complication in patients after HSCT, and stimulated hyposalivation shortly after treatment is a significant risk indicator for caries progression.
|
|
| 9. |
- Bulthuis, M. S., et al.
(författare)
-
The effect of conditioning regimen and prescribed medications on hyposalivation in haematopoietic cell transplantation (HCT) patients: an 18-month prospective longitudinal study
- 2023
-
Ingår i: Clinical Oral Investigations. - 1432-6981. ; 27, s. 7369-7381
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Haematopoietic cell transplantation (HCT) preceded by a conditioning regimen is an established treatment option for (non)malignant haematologic disorders. We aim to describe the development of hyposalivation over time in HCT recipients, and determine risk indicators.Materials and methods A multi-centre prospective longitudinal observational study was conducted. Unstimulated (UWS) and stimulated (SWS) whole saliva was collected before HCT, early post-HCT, and after 3, 6, 12, and 18 months. The effect of type of transplantation (allogeneic vs autologous) and intensity (full vs reduced) of the conditioning regimen on hyposalivation (UWS < 0.2 mL/min; SWS < 0.7 mL/min) was explored.Results A total of 125 HCT recipients were included. More than half of the patients had hyposalivation early post-HCT; a quarter still had hyposalivation after 12 months. The conditioning intensity was a risk indicator in the development of hyposalivation of both UWS (OR: 3.9, 95% CI: 1.6-10.6) and SWS (OR: 8.2, 95% CI: 2.9-24.6). After 3 and 12 months, this effect was not statistically significant anymore.Conclusions Hyposalivation affects the majority of patients early post-HCT. The conditioning intensity and the type of transplantation were significant risk indicators in the development of hyposalivation. The number of prescribed medications, total body irradiation as part of the conditioning regimen and oral mucosal graft-versus-host disease did not influence hyposalivation significantly.
|
|
| 10. |
- Laheij, Amga, et al.
(författare)
-
Long-Term Analysis of Resilience of the Oral Microbiome in Allogeneic Stem Cell Transplant Recipients
- 2022
-
Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Stem cell transplantation (SCT) is associated with oral microbial dysbiosis. However, long-term longitudinal data are lacking. Therefore, this study aimed to longitudinally assess the oral microbiome in SCT patients and to determine if changes are associated with oral mucositis and oral chronic graft-versus-host disease. Fifty allogeneic SCT recipients treated in two Dutch university hospitals were prospectively followed, starting at pre-SCT, weekly during hospitalization, and at 3, 6, 12, and 18 months after SCT. Oral rinsing samples were taken, and oral mucositis (WHO score) and oral chronic graft-versus-host disease (NIH score) were assessed. The oral microbiome diversity (Shannon index) and composition significantly changed after SCT and returned to pre-treatment levels from 3 months after SCT. Oral mucositis was associated with a more pronounced decrease in microbial diversity and with several disease-associated genera, such as Mycobacterium, Staphylococcus, and Enterococcus. On the other hand, microbiome diversity and composition were not associated with oral chronic graft-versus-host disease. To conclude, dysbiosis of the oral microbiome occurred directly after SCT but recovered after 3 months. Diversity and composition were related to oral mucositis but not to oral chronic graft-versus-host disease.
|
|
| 11. |
- van Leeuwen, S. J. M., et al.
(författare)
-
The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach
- 2023
-
Ingår i: Bmc Oral Health. - 1472-6831. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundOral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score & GE; 2) or not (NON-OM).MethodsIn the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler.ResultsA different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis.ConclusionsThe salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively.
|
|
| 12. |
- Skallsjö, Kristina, 1976, et al.
(författare)
-
Oral health in patients scheduled for hematopoietic stem cell transplantation in the Orastem study
- 2023
-
Ingår i: Plos One. - 1932-6203. ; 18:5
-
Tidskriftsartikel (refereegranskat)abstract
- Despite advances in transplant medicine, prevalence of complications after hematopoietic stem cell transplantation (HSCT) remains high. The impact of pre-HSCT oral health factors on the incidence and severity of complications post-HSCT is poorly understood. The aim of this prospective, observational study was to analyze oral health in patients planned for HSCT. Patients >= 18 years requiring HSCT were included from five sites between 2011-2018. General health, oral findings and patient-reported symptoms were registered in 272 patients. Oral symptoms around disease onset were reported by 43 patients (15.9%) and 153 patients (58.8%) reported oral complications during previous chemotherapy. One third of patients experienced oral symptoms at the oral examination before conditioning regimen and HSCT. In total, 124 (46.1%) patients had dental caries, 63 (29.0%) had >= one tooth with deep periodontal pockets, 147 (75.0%) had >= one tooth with bleeding on probing. Apical periodontitis was observed in almost 1/4 and partially impacted teeth in 17 (6.3%) patients. Oral mucosal lesions were observed in 84 patients (30.9%). A total of 45 (17.4%) of 259 patients had at least one acute issue to be managed prior to HSCT. In conclusion, oral symptoms and manifestations of oral disease were prevalent in patients planned for HSCT. The extent of oral and acute dental diseases calls for general oral screening of patients pre-HSCT.
|
|
| 13. |
- Brennan, M. T., et al.
(författare)
-
Impact of Oral Side Effects from Conditioning Therapy Before Hematopoietic Stem Cell Transplantation: Protocol for a Multicenter Study
- 2018
-
Ingår i: Jmir Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 7:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The oral cavity is a common site of complications related to the cytotoxic effect of high-dose chemotherapy and radiation therapy. Considering our limited understanding of the burden of illness in the oral cavity from various cytotoxic therapies, it is difficult to produce evidence-based, preventive and management protocols. A prospective multicenter study is necessary to collect data on the burden of illness from various cytotoxic regimens. Objective: The objectives of this prospective international observational multicenter study in hematopoietic stem cell transplant (HSCT) patients are to establish the nature, incidence and temporal relationship of oral complications related to conditioning regimens (chemotherapy with or without total body irradiation), stem cell transplantation and the immunologic reactions (mainly graft-vs-host-disease) that may follow, and to determine what subjective and objective oral complications related to treatment can predict negative clinical and economic outcomes and reduced quality of life. Methods: Adult patients at six study sites receiving full intensity conditioning, reduced intensity conditioning or nonmyeloablative conditioning, followed by autologous or allogeneic hematopoietic stem cell infusion, are included. A pre-treatment assessment includes medical conditions, planned chemo- and radiation therapy regimen, medications, allergies, social history, patient report of oral problems, dental history, subjective oral complaints, objective measures of oral conditions, current laboratory values, dental treatment recommended and untreated dental disease. Starting 1-3 days after hematopoietic stem cell infusion, a bedside assessment is completed 3 days per week until resolution of neutropenia. A patient questionnaire is also completed during hospitalization. Beyond this time, patients with continued oral mucositis or other oral problems are followed 1 day per week in an inpatient or outpatient setting. Additional visits for urgent care for acute oral problems after hospitalization are documented. Autologous transplant patients are being followed up at 100 days (SD 30 days) and at 1 year (SD 30 days) post-transplantation to identify any long-term side effects. Patients treated with allogeneic transplantation are being followed at 100 days (SD 30 days), 6 months (SD 30 days), and 12 months (SD 30 days). The follow-up assessments include cancer response to therapy, current medical conditions, medications, subjective and objective oral findings, quality of life measures and laboratory values. The targeted enrollment is 254 patients who have received HSCT. Results: A total of 260 participants have been enrolled, with 233 (91%) who have received HSCT. We anticipate enrollment of 20-30 additional participants to obtain the sample size of 254 enrolled participants who have received HSCT. Conclusions: The results of the ongoing prospective study will provide a unique dataset to understand the impact of oral complications on patients undergoing HSCT and provide needed evidence for guidelines regarding the management of this patient cohort.
|
|
| 14. |
- Singer, S., et al.
(författare)
-
Methodological approach for determining the Minimal Important Difference and Minimal Important Change scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-HN43) exemplified by the Swallowing scale
- 2022
-
Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 31, s. 841-853
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. Methods In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. Results From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14. Conclusions For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Ericson, D, et al.
(författare)
-
Clinical evaluation of efficacy and safety of a new method for chemo-mechanical removal of caries. A multi-centre study
- 1999
-
Ingår i: Caries research. - : S. Karger AG. - 0008-6568 .- 1421-976X. ; 33:3, s. 171-177
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate the clinical efficacy and safety of a new method (Carisolv™) for chemo–mechanical removal of caries. At four centres, 137 consecutive patients (64 females and 73 males aged 3–85 years, mean 35) entered a prospective, controlled, randomised open study. One primary caries lesion with distinct dentine involvement was selected per patient. A total of 116 lesions in permanent and 21 in deciduous teeth were selected. Caries was removed with traditional drilling or the new method. Gel was applied onto the carious dentine and the softened caries gently removed with specially designed hand instruments. New gel was applied and the procedure was repeated until no more debris could be removed and the surface was hard as judged by clinical criteria (probing and visual inspection). An independent examiner judged the cavity being caries–free or not, using clinical criteria. One hundred and thirteen patients were randomised for gel treatment and 24 for drilling. Three patients selected for drilling did not complete the treatment. Total caries removal was achieved in 106 cases with gel and in 19 with drilling. The reasons for incomplete caries removal were step–by–step excavation in 5 cases, unsuccessful caries removal in 1 case for each treatment, while 2 cases refused inspection. Mean (± SD) time for caries removal was 10.4 (±6.1) min with the gel method and 4.4 (±2.2) min with drilling. Mean volume of gel used was 0.4 (±0.2) ml. Eighty–two of 107 patients perceived that the new method caused less discomfort compared to drilling. Dentine caries was effectively removed using the Carisolv method without any adverse reactions.
|
|
| 18. |
- Giannisis,, Andreas, et al.
(författare)
-
Brain integrity is altered by hepatic APOEε4 in humanized-liver mice
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer’s disease (AD) risk and AD biomarker levels. Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 liver phenotype promotes brain injury and neurodegeneration is unknown. Here we investigated the brains of Fah-/-, Rag2-/-, Il2rg-/- mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation, and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEε4-associated risk neurodegenerative diseases.
|
|
| 19. |
- Giannisis, Andreas, et al.
(författare)
-
Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice
- 2022
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 27:8, s. 3533-3543
-
Tidskriftsartikel (refereegranskat)abstract
- Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer’s disease (AD) risk and AD biomarker levels. Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 liver phenotype promotes neurodegeneration is unknown. Here we investigated the brains of Fah−/−, Rag2−/−, Il2rg−/− mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEε4-associated risk of neurodegenerative disease.
|
|
| 20. |
- Haraldsson, M Katarina, et al.
(författare)
-
The lupus-related Lmb3 locus contains a disease-suppressing Coronin-1A gene mutation.
- 2008
-
Ingår i: Immunity. - : Elsevier BV. - 1074-7613 .- 1097-4180. ; 28:1, s. 40-51
-
Tidskriftsartikel (refereegranskat)abstract
- Here, we show that a lupus-suppressing locus is caused by a nonsense mutation of the filamentous actin-inhibiting Coronin-1A gene. This mutation was associated with developmental and functional alterations in T cells including reduced migration, survival, activation, and Ca2+ flux. T-dependent humoral responses were impaired, but no intrinsic B cell defects were detected. By transfer of T cells, it was shown that suppression of autoimmunity could be accounted for by the presence of the Coro1a(Lmb3) mutation in T cells. Our results demonstrate that Coronin-1A is required for the development of systemic lupus and identify actin-cytoskeleton regulatory proteins as potential targets for modulating autoimmune diseases.
|
|
| 21. |
|
|
| 22. |
- Kessler, Kat, et al.
(författare)
-
Behavioral and cognitive performance of humanized APOEε3/ε3 liver mice in relation to plasma apolipoprotein E levels
- 2023
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Plasma apolipoprotein E levels were previously associated with the risk of developing Alzheimer’s disease (AD), levels of cerebrospinal fluid AD biomarkers, cognition and imaging brain measures. Outside the brain, the liver is the primary source of apoE and liver transplantation studies have demonstrated that liver-derived apoE does not cross the blood–brain-barrier. How hepatic apoE may be implicated in behavioral and cognitive performance is not clear. In the current study, we behaviorally tested FRGN mice with humanized liver harboring the ε3/ε3 genotype (E3-human liver (HL)) and compared their behavioral and cognitive performance with that of age-matched ε3/ε3 targeted replacement (E3-TR) mice, the latter produces human apoE3 throughout the body whereas the E3-HL mice endogenously produce human apoE3 only in the liver. We also compared the liver weights and plasma apoE levels, and assessed whether plasma apoE levels were correlated with behavioral or cognitive measures in both models. E3-HL were more active but performed cognitively worse than E3-TR mice. E3-HL mice moved more in the open field containing objects, showed higher activity levels in the Y maze, showed higher activity levels during the baseline period in the fear conditioning test than E3-TR mice, and swam faster than E3-TR mice during training to locate the visible platform in the water maze. However, E3-HL mice showed reduced spatial memory retention in the water maze and reduced fear learning and contextual and cued fear memory than E3-TR mice. Liver weights were greater in E3-HL than E3-TR mice and sex-dependent only in the latter model. Plasma apoE3 levels were similar to those found in humans and comparable in female and male E3-TR mice but higher in female E3-HL mice. Finally, we found correlations between plasma apoE levels and behavioral and cognitive measures which were predominantly model-dependent. Our study demonstrates mouse-model dependent associations between plasma apoE levels, behavior and cognition in an ‘AD-neutral’ setting and suggests that a humanized liver might be sufficient to induce mouse behavioral and cognitive phenotypes.
|
|
| 23. |
- Piper, Brian J., et al.
(författare)
-
Non-replication of an association of Apolipoprotein E2 with sinistrality
- 2013
-
Ingår i: Laterality. - 1357-650X .- 1464-0678. ; 18:2, s. 251-261
-
Tidskriftsartikel (refereegranskat)abstract
- A recent report found that left-handed adolescents were more than three times more likely to have an Apolipoprotein (APOE) E2 allele. This study was unable to replicate this association in young adults (N=166). A meta-analysis of nine other datasets (N=360 to 7559, Power > 0.999) including that of National Alzheimer's Coordinating Center also failed to find an over-representation of E2 among left-handers indicating that this earlier outcome was most likely a statistical artefact.
|
|
| 24. |
- Raber-Durlacher, J. E., et al.
(författare)
-
Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients
- 2013
-
Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 21:1, s. 343-355
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible. Sixty-four clinical studies across 11 interventions were evaluated. A recommendation was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60 mu g/kg per day for 3 days prior to conditioning treatment and for 3 days post-transplant for prevention of oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by autologous stem cell transplantation for hematological malignancies. A suggestion was made against using granulocyte macrophage colony-stimulating factor mouthwash for the prevention of oral mucositis in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. No guideline was possible for any other cytokine or growth factor agents due to inconclusive evidence. Of the cytokine and growth factor agents studied for oral mucositis, the evidence only supports use of palifermin in the specific population listed above. Additional well-designed research is needed on other cytokine and growth factor interventions and in other cancer treatment settings.
|
|
| 25. |
- Singer, Susanne, et al.
(författare)
-
International validation of the revised European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43: Phase IV.
- 2019
-
Ingår i: Head & neck. - : Wiley. - 1097-0347 .- 1043-3074. ; 41:6, s. 1725-1737
-
Tidskriftsartikel (refereegranskat)abstract
- We validated the new European Organisation for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN43).We enrolled 812 patients with head and neck cancer from 18 countries. Group 1 completed the questionnaire before therapy, and 3 and 6 months later. In group 2 (survivors), we determined test-retest reliability using intraclass correlation coefficients (ICC). Internal consistency was assessed using Cronbach's Alpha, the scale structure with confirmatory factor analysis, and discriminant validity with known-group comparisons.Cronbach's alpha was >0.70 in 10 of the 12 multi-item scales. All standardized factor loadings exceeded 0.40. The ICC was >0.70 in all but two scales. Differences in scale scores between known-groups were >10 points in 17 of the 19 scales. Sensitivity to change was found to be sufficient in 18 scales.Evidence supports the reliability and validity of the EORTC QLQ-HN43 as a measure of quality of life.
|
|
| 26. |
- Walladbegi, Java, et al.
(författare)
-
Hemodynamics of the oral mucosa during cooling: A crossover clinical trial
- 2023
-
Ingår i: HELIYON. - 2405-8440. ; 9:10
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Oral cryotherapy is used to prevent the onset of oral mucositis, a common and debilitating adverse effect following cancer chemotherapy. A protective mechanism associated with oral cooling is thought to be mediated through reduced tissue microcirculation. The aim of the present study was to examine the underlying mechanism associated with oral mucosal cooling by measuring oral microcirculation and tissue oxygen saturation after cooling with ice chips (IC) and an intraoral cooling device (ICD).Study design: In a single-center randomized crossover study, 10 healthy volunteers were assigned (1:1) randomly to the order in which the two intraoral cooling procedures (IC/ICD) were to be commenced. On day 1, half of the study participants started with IC and then crossed over to intraoral cooling with the ICD on day 2, while the other half of the participants undertook the same two procedures in the reverse order. Total and functional capillary density (T/FCD) and tissue oxygen saturation (StO2) measurements were obtained at baseline and 30 min following oral cooling.Results: Following 30 min of oral cooling, a statistically significant difference was found for FCD between IC and ICD (percentage points; +2 vs. -13; p < 0.05). A statistically significant decrease in StO2 was observed with both IC and ICD (%; 13 vs. 10) after 30 min of cooling as compared to baseline (p < 0.05). As for the participants' preference the ICD was preferred over IC by 9 out of 10 participants (p = 0.021).Conclusions: Both microcirculation parameters and tissue oxygen saturation are altered in conjunction with oral cooling, indicating their potential mechanistic contribution towards cryoprevention of oral mucositis.
|
|
| 27. |
|
|
