| 531. |
- Ostrom, Quinn T., et al.
(författare)
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Age‐specific genome‐wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'‐like features associated with younger age
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 143:10, s. 2359-2366
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age‐at‐diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age‐at‐diagnosis has been explored, genome‐wide association studies (GWAS) have not previously been stratified by age. Potential age‐specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age‐stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta‐analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54–63 = 1.50x10−9, OR54–63 = 1.28, 95%CI54–63 = 1.18–1.39; p64+ = 2.14x10−11, OR64+ = 1.32, 95%CI64+ = 1.21–1.43] and rs11979158 [p54–63 = 6.13x10−8, OR54–63 = 1.35, 95%CI54–63 = 1.21–1.50; p64+ = 2.18x10−10, OR64+ = 1.42, 95%CI64+ = 1.27–1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p18–53 = 9.30 × 10−11, OR18–53 = 1.76, 95%CI18–53 = 1.49–2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of ‘LGG’‐like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p = 0.0005). Age‐specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with ‘secondary glioblastoma.’
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| 532. |
- Ostrom, Quinn T., et al.
(författare)
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Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
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| 533. |
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Ovisshetens tid. Den nationella SOM-undersökningen 2022
- 2023
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Vi befinner oss i en ovisshetens tid. Säkerhetsläget i omvärlden har försämrats. Det rasar ett krig i Europas östligaste delar. Oron för nationens säkerhet har fått svenska politiker att bryta en tvåhundraårig tradition av alliansfrihet. Parallellt har energi- och matpriser rusat, boräntor höjts och inflationen stigit till den högsta nivån på trettio år. Det har väckt osäkerhet om den svenska ekonomins styrka och oro för den egna plånboken. Nationellt slogs rekord i dödligt skjutvapenvåld, med allt yngre gärningspersoner. Samhällets insatser tycks ständigt ligga steget efter och det råder oenighet om vilka de rätta insatserna är. I samband med 2022 års valrörelser fick frågan om kärnkraftens bevarande ny energi. Efter valet deklarerade den nytillträdda regeringen en ny riktning för svensk migrationspolitik. Ovisshet föder osäkerhet och oro. Samtidigt kan ovissheten leda till beslutsamhet när gamla sanningar ses i ett nytt ljus. Ovissheten har många nyanser. Ovisshetens tid är SOM-institutets 82:a forskarantologi. Utifrån 2022 års nationella SOM-undersökning – nummer 37 i ordningen – analyserar forskare från olika discipliner vid svenska universitet och högskolor de senaste årens samhällsutveckling. Bokens innehåll berör på många sätt den ovisshet som präglar Sverige inom områden som rör (S)amhället, (O)pinion och (M)edier.
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| 534. |
- Padilla, Nelly, et al.
(författare)
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Breakdown of Whole-brain Dynamics in Preterm-born Children
- 2020
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:3, s. 1159-1170
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Tidskriftsartikel (refereegranskat)abstract
- The brain operates at a critical point that is balanced between order and disorder. Even during rest, unstable periods of random behavior are interspersed with stable periods of balanced activity patterns that support optimal information processing. Being born preterm may cause deviations from this normal pattern of development. We compared 33 extremely preterm (EPT) children born at < 27 weeks of gestation and 28 full-term controls. Two approaches were adopted in both groups, when they were 10 years of age, using structural and functional brain magnetic resonance imaging data. The first was using a novel intrinsic ignition analysis to study the ability of the areas of the brain to propagate neural activity. The second was a whole-brain Hopf model, to define the level of stability, desynchronization, or criticality of the brain. EPT-born children exhibited fewer intrinsic ignition events than controls; nodes were related to less sophisticated aspects of cognitive control, and there was a different hierarchy pattern in the propagation of information and suboptimal synchronicity and criticality. The largest differences were found in brain nodes belonging to the rich-club architecture. These results provide important insights into the neural substrates underlying brain reorganization and neurodevelopmental impairments related to prematurity.
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| 535. |
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| 536. |
- Parnetti, L, et al.
(författare)
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Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer's disease.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 124:2, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- Objectives - To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs). Materials and methods - Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1-year treatment. Results - Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment. Conclusions - AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.
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| 537. |
- Pekny, Tulen, et al.
(författare)
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Short general anaesthesia induces prolonged changes in gene expression in the mouse hippocampus
- 2014
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 58:9, s. 1127-1133
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe long-term molecular changes in the central nervous system constitute an important aspect of general anaesthesia, but little is known about to what extent these molecular changes are affected by anaesthesia duration. The aim of the present study was to evaluate the effects of short duration (20min) general anaesthesia with isoflurane or avertin on the expression of 20 selected genes in the mouse hippocampus at 1 and 4 days after anaesthesia. MethodsNine to eleven-weeks-old male mice received one of the following treatments: 20min of avertin-induced anaesthesia (n=11), 20min of isoflurane-induced anaesthesia (n=10) and no anaesthesia (n=5). One and four days after anaesthesia, gene expression in the hippocampus was determined with reverse transcription quantitative real-time polymerase chain reaction. ResultsWe found that anaesthesia led to the upregulation of six genes: Hspd1 (heat shock protein 1), Plat (tissue plasminogen activator) and Npr3 (natriuretic peptide receptor 3) were upregulated only 1 day after anaesthesia, whereas Thbs4 (thrombospondin 4) was upregulated only 4 days after anaesthesia. Syp (synaptophysin) and Mgst1 (microsomal glutathione S-transferase 1) were upregulated at both time points. Hspd1, Mgst1 and Syp expression was increased regardless of the anaesthetic used, Npr3 and Plat were increased only in mice exposed to avertin, and Thbs4 was upregulated only after isoflurane-induced anaesthesia. ConclusionsThis study shows that some of the effects of short general anaesthesia on gene expression in the mouse hippocampus persist for at least 4 days.
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| 538. |
- Pettersson, Stefan, 1972, et al.
(författare)
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A Hydrogel Drink With High Fructose Content Generates Higher Exogenous Carbohydrate Oxidation and Lower Dental Biofilm pH Compared to Two Other, Commercially Available, Carbohydrate Sports Drinks
- 2020
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Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the substrate oxidation of three commercially available, 14%-carbohydrate sports drinks with different compositions, osmolality, and pH for their impact on dental exposure to low pH. In a cross-over, randomized double-blinded design, 12 endurance athletes (age 31. 2 +/- 7.7 years, (V) over dotO(2max) 65.6 +/- 5.0 mL.kg(-1)) completed 180 min of cycling at 55% W-max. During the first 100 min of cycling, athletes consumed amylopectin starch (AP), maltodextrin+sucrose (MD+SUC), or maltodextrin+fructose hydrogel (MD+FRU) drinks providing 95 g carbohydrate.h(-1), followed by water intake only at 120 and 160 min. Fuel use was determined using indirect calorimetry and stable-isotope techniques. Additionally, dental biofilm pH was measured using the microtouch method in a subsample of participants (n= 6) during resting conditions before, and at different time intervals up to 45 min following a single bolus of drink. Exogenous carbohydrate oxidation (CHOEXO) during the 2nd hour of exercise was significantly (P< 0.05) different between all three drinks: MD+FRU (1.17 +/- 0.17 g.min(-1)), MD+SUC (1.01 +/- 0.13 g.min(-1)), and AP (0.84 +/- 0.11 g.min(-1)). At the end of exercise, CHO(EXO)and blood glucose concentrations (3.54 +/- 0.50, 4.07 +/- 0.67, and 4.28 +/- 0.47 mmol.L-1, respectively) were significantly lower post MD+FRU consumption than post MD+SUC and AP consumption (P< 0.05). Biofilm acidogenicity at rest demonstrated a less pronounced pH fall for MD+FRU compared to the acidulant-containing MD+SUC and AP (P< 0.05). In conclusion, while total intake of MD+FRU showed signs of completed uptake before end of monitoring, this was less so for MD+SUC, and not at all the case for AP. Thus, this study showed that despite carbohydrates being encapsulated in a hydrogel, a higher CHO(EXO)was observed following MD+FRU drink ingestion compared to AP and MD+SUC consumption upon exposure to the acidic environment of the stomach. This finding may be related to the higher fructose content of the MD+FRU drink compared with the MD+SUC and AP drinks. Furthermore, a carbohydrate solution without added acidulants, which are commonly included in commercial sport drinks, may have less deleterious effects on oral health.
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| 539. |
- Pilheden, Mattias, et al.
(författare)
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Duplex sequencing uncovers recurrent low-frequency cancer-associated mutations in infant and childhood KMT2A-rearranged acute leukemia
- 2022
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Ingår i: HemaSphere. - : Wolters Kluwer. - 2572-9241. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3D835H or NRASG13D/G12S mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.
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| 540. |
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