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- Amann, F., et al.
(författare)
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A search for murarregamma at the level of 10-13
- 1991
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Ingår i: Proceedings of the 25th International Conference on High Energy Physics. - 9810024347 ; , s. 1070-1071
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Konferensbidrag (refereegranskat)abstract
- The MEGA experiment, which is a search for the decay murarregamma with a branching ratio sensitivity of about 10-13, employs highly modular, fast detectors, state-of-the-art electronics, and a staged trigger with on-line filters. The detectors are contained in a 1.5-T solenoidal field produced by a superconducting magnet. Positrons are confined to the central region and are measured by a set of thin MWPCs. Photons are measured by one of four layers of pair spectrometers in the outer region. Most aspects of the design have been validated in engineering runs; data taking will begin in 1990 with much of the electron arm and one pair spectrometer layer installed.
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- Szymanski, J. J., et al.
(författare)
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A study of the decay mu –> e gamma by the MEGA experiment
- 1996
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Ingår i: Proceedings, 9th Meeting, DPF'96, Minneapolis, USA, August 11-15, 1996. Vol. 1, 2.. ; , s. 1450-1452
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Konferensbidrag (refereegranskat)
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10. |
- Ahmed, M., et al.
(författare)
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Search for the lepton-family-number nonconserving decay μ +→e +γ
- 2002
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Ingår i: Physical Review D. - : American Physical Society. - 1550-7998 .- 1550-2368. ; 65:11
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Tidskriftsartikel (refereegranskat)abstract
- The MEGA experiment, which searched for the muon- and electron-number violating decay μ +→e + γ, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio, B(μ + →e + γ)<1.2×10 -11 with 90% confidence, is derived from a likelihood analysis.
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11. |
- Szymanski, J. J., et al.
(författare)
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MEGA : A search for the decay mu –> e gamma
- 1994
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Ingår i: Intersections between particle and nuclear physics. Proceedings, 5th Conference, St. Petersburg, USA, May 31-June 6, 1994. ; , s. 789-792
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Konferensbidrag (refereegranskat)
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12. |
- Palafox, B., et al.
(författare)
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Does greater individual social capital improve the management of hypertension? Cross-national analysis of 61 229 individuals in 21 countries
- 2017
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Ingår i: Bmj Global Health. - : BMJ. - 2059-7908. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Social capital, characterised by trust, reciprocity and cooperation, is positively associated with a number of health outcomes. We test the hypothesis that among hypertensive individuals, those with greater social capital are more likely to have their hypertension detected, treated and controlled. Methods Cross-sectional data from 21 countries in the Prospective Urban and Rural Epidemiology study were collected covering 61 229 hypertensive individuals aged 35-70 years, their households and the 656 communities in which they live. Outcomes include whether hypertensive participants have their condition detected, treated and/or controlled. Multivariate statistical models adjusting for community fixed effects were used to assess the associations of three social capital measures: (1) membership of any social organisation, (2) trust in other people and (3) trust in organisations, stratified into high-income and low-income country samples. Results In low-income countries, membership of any social organisation was associated with a 3% greater likelihood of having one's hypertension detected and controlled, while greater trust in organisations significantly increased the likelihood of detection by 4%. These associations were not observed among participants in high-income countries. Conclusion Although the observed associations are modest, some aspects of social capital are associated with better management of hypertension in low-income countries where health systems are often weak. Given that hypertension affects millions in these countries, even modest gains at all points along the treatment pathway could improve management for many, and translate into the prevention of thousands of cardiovascular events each year.
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- Teo, Kevin, et al.
(författare)
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rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis.
- 2021
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Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 74:1, s. 20-30
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Tidskriftsartikel (refereegranskat)abstract
- A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.
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14. |
- Ginsburg, A., et al.
(författare)
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Dense gas in the Galactic central molecular zone is warm and heated by turbulence
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 586, s. Art nr A50-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Galactic center is the closest region where we can study star formation under extreme physical conditions like those in high-redshift galaxies. Aims. We measure the temperature of the dense gas in the central molecular zone (CMZ) and examine what drives it. Methods. We mapped the inner 300 pc of the CMZ in the temperature-sensitive J = 3-2 para-formaldehyde (p-H2CO) transitions. We used the 3(2,1)-2(2,0)/3(0,3)-2(0,2) line ratio to determine the gas temperature in n similar to 10(4) - 10(5) cm(-3) gas. We have produced temperature maps and cubes with 30 0 0 and 1 km s(-1) resolution and published all data in FITS form. Results. Dense gas temperatures in the Galactic center range from similar to 60 K to > 100 K in selected regions. The highest gas temperatures T-G > 100 K are observed around the Sgr B2 cores, in the extended Sgr B2 cloud, the 20 km s(-1) and 50 km s(-1) clouds, and in "The Brick" (G0.253 + 0.016). We infer an upper limit on the cosmic ray ionization rate zeta(CR)
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15. |
- Swami, Viren, et al.
(författare)
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The Attractive Female Body Weight and Female Body Dissatisfaction in 26 Countries Across 10 World Regions : Results of the International Body Project I
- 2010
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Ingår i: Personality and Social Psychology Bulletin. - : Sage Publications. - 0146-1672 .- 1552-7433. ; 36:3, s. 309-325
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Tidskriftsartikel (refereegranskat)abstract
- This study reports results from the first International Body Project (IBP-I), which surveyed 7,434 individuals in 10 major world regions about body weight ideals and body dissatisfaction. Participants completed the female Contour Drawing Figure Rating Scale (CDFRS) and self-reported their exposure to Western and local media. Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across high-socioeconomic-status (SES) sites. Within cultures, heavier bodies were preferred in low-SES sites compared to high-SES sites in Malaysia and South Africa (ds = 1.94-2.49) but not in Austria. Participant age, body mass index (BMI), and Western media exposure predicted body weight ideals. BMI and Western media exposure predicted body dissatisfaction among women. Our results show that body dissatisfaction and desire for thinness is commonplace in high-SES settings across world regions, highlighting the need for international attention to this problem.
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16. |
- Frosi, Y, et al.
(författare)
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Engineering an autonomous VH domain to modulate intracellular pathways and to interrogate the eIF4F complex
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4854-
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Tidskriftsartikel (refereegranskat)abstract
- An attractive approach to target intracellular macromolecular interfaces and to model putative drug interactions is to design small high-affinity proteins. Variable domains of the immunoglobulin heavy chain (VH domains) are ideal miniproteins, but their development has been restricted by poor intracellular stability and expression. Here we show that an autonomous and disufhide-free VH domain is suitable for intracellular studies and use it to construct a high-diversity phage display library. Using this library and affinity maturation techniques we identify VH domains with picomolar affinity against eIF4E, a protein commonly hyper-activated in cancer. We demonstrate that these molecules interact with eIF4E at the eIF4G binding site via a distinct structural pose. Intracellular overexpression of these miniproteins reduce cellular proliferation and expression of malignancy-related proteins in cancer cell lines. The linkage of high-diversity in vitro libraries with an intracellularly expressible miniprotein scaffold will facilitate the discovery of VH domains suitable for intracellular applications.
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- Kennedy, S. A., et al.
(författare)
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Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
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- Premeaux, Thomas A, et al.
(författare)
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Elevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals.
- 2019
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Ingår i: Journal of neurovirology. - : Springer Science and Business Media LLC. - 1538-2443 .- 1355-0284. ; 25:2, s. 150-161
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that galectin-9 (Gal-9), a soluble lectin with immunomodulatory properties, is elevated in plasma during HIV infection and induces HIV transcription. The link between Gal-9 and compromised neuronal function is becoming increasingly evident; however, the association with neuroHIV remains unknown. We measured Gal-9 levels by ELISA in cerebrospinal fluid (CSF) and plasma of 70 HIV-infected (HIV+) adults stratified by age (older >40years and younger <40years) either ART suppressed or with detectable CSF HIV RNA, including a subgroup with cognitive assessments, and 18 HIV uninfected (HIV-) controls. Gal-9 tissue expression was compared in necropsy brain specimens from HIV- and HIV+ donors using gene datasets and immunohistochemistry. Among older HIV+ adults, CSF Gal-9 was elevated in the ART suppressed and CSF viremic groups compared to controls, whereas in the younger group, Gal-9 levels were elevated only in the CSF viremic group (p<0.05). CSF Gal-9 positively correlated with age in all groups (p<0.05). CSF Gal-9 tracked with CSF HIV RNA irrespective of age (β=0.33; p<0.05). Higher CSF Gal-9 in the older viremic HIV+ group correlated with worse neuropsychological test performance scores independently of age and CSF HIV RNA (p<0.05). Furthermore, CSF Gal-9 directly correlated with myeloid activation (CSF-soluble CD163 and neopterin) in both HIV+ older groups (p<0.05). Among HIV+ necropsy specimens, Gal-9 expression was increased in select brain regions compared to controls (p<0.05). Gal-9 may serve as a novel neuroimmuno-modulatory protein that is involved in driving cognitive deficits in those aging with HIV and may be valuable in tracking cognitive abnormalities.
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- Gross, Sean M., et al.
(author)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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In: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Journal article (peer-reviewed)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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- Kuemmerli, Christoph, et al.
(author)
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Impact of enhanced recovery protocols after pancreatoduodenectomy : meta-analysis
- 2022
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In: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 256-266
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Journal article (peer-reviewed)abstract
- BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.
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- Kumar, Nallani Vijay, et al.
(author)
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Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8.
- 2016
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In: Molecular and cellular biology. - 1098-5549. ; 36:6, s. 913-22
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Journal article (peer-reviewed)abstract
- The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeast Saccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)] in vitro and in vivo and that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation.
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23. |
- Mariz, FC, et al.
(author)
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Peak neutralizing and cross-neutralizing antibody levels to human papillomavirus types 6/16/18/31/33/45/52/58 induced by bivalent and quadrivalent HPV vaccines
- 2020
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In: NPJ vaccines. - : Springer Science and Business Media LLC. - 2059-0105. ; 5:1, s. 14-
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Journal article (peer-reviewed)abstract
- We performed an independent comparison of neutralizing and cross-neutralizing antibody (ab) levels seven months after initiation of three-dose, six-month vaccination schedules with the bivalent and quadrivalent human papillomavirus (HPV) vaccines in adolescent Finnish and Indian females, respectively. We used a semi-automated Pseudovirion-Based Neutralization Assay and observed significantly higher HPV16/18 peak ab-levels in bivalent as compared to quadrivalent vaccine recipients. Bivalent vaccine induced cross-neutralizing HPV31/33/45/52/58 antibodies significantly more frequently and to higher levels than the quadrivalent vaccine. The correlation of bivalent vaccine-induced HPV45 ab-levels with HPV16/18 ab-levels was stronger than that of corresponding quadrivalent vaccine-induced ab-levels, suggesting a qualitatively different cross-reactive response. Our findings on the comparison of the immunogenicity of two HPV vaccine tested in two different populations indicate that further head-to-head studies are warranted.
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- Olsson, M E, et al.
(author)
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Antioxidants, low molecular weight carbohydrates, and total antioxidant capacity in strawberries (Fragaria x ananassa): Effects of cultivar, ripening, and storage
- 2004
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In: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 52:9, s. 2490-2498
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Journal article (peer-reviewed)abstract
- Four cultivars of strawberries (Senga Sengana, BFr77111, Elsanta, and Honeoye) were studied for their content of antioxidants, total antioxidant capacity, and low molecular weight carbohydrates in relation to harvest year, ripening stage, and cold storage. For ascorbic acid, chlorogenic acid, ellagic acid, and total antioxidative capacity, measured in both water-soluble and water-insoluble extracts, there was a 2-5-fold variation among cultivars. Unripe berries contained lower concentrations of chlorogenic acid and p-coumaric acid and also quercetin and kaempferol compared with riper berries. During cold storage for up to 3 days, relatively few changes in the concentration of the different antioxidants occurred. The concentrations of several investigated parameters were interrelated, for example, for ascorbic acid and water-soluble antioxidant capacity and for ellagic acid and water-insoluble antioxidant capacity. The dominating sugars in strawberries were fructose and glucose, but considerable amounts of sucrose were also present, and their contents varied among cultivars, giving a predicted glycemic index of similar to81. Verbascose, raffinose, and stachyose were found in only minor amounts. The study shows that the concentration of a number of bioactive compounds in strawberries varied according to cultivar, ripening stage, and storage. This information should make it possible to select strawberries with an optimal content of bioactive compounds.
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26. |
- Pillai, Rajath S, et al.
(author)
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Assessment of Somatosensory and Psychosocial Function of Patients With Trigeminal Nerve Damage
- 2020
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In: Clinical Journal of Pain. - : Lippincott Williams & Wilkins. - 1536-5409 .- 0749-8047. ; 36:5, s. 321-335
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The present study assessed somatosensory changes related to trigeminal nerve damage using extensive evaluation tools and assessed the effect of such damage on the patients' psychosocial status and quality of life compared with healthy participants.METHODS: In 37 patients with intraorally or extraorally presenting trigeminal nerve damage diagnosed as painful or nonpainful posttraumatic trigeminal neuropathy, psychophysical tests like quantitative sensory testing (QST) and qualitative sensory testing and the electrophysiological "nociceptive-specific" blink reflex were performed. The patients and 20 healthy participants completed a set of questionnaires assessing their psychosocial status and quality of life.RESULTS: A loss or gain of somatosensory function was seen in at least 1 QST parameter in >88.9% of the patients. Patients in whom extraoral QST was performed showed an overall loss of somatosensory function, whereas intraoral QST showed a general gain of somatosensory function. Qualitative sensory testing identified a side-to-side difference in the tactile and pinprick stimulation in >77% of the patients. An abnormal "nociceptive-specific" blink reflex response was seen in 42.1% to 71.4% of patients dependent on the trigeminal branch stimulated, though comparisons with healthy reference values showed ambiguous results. Compared with the healthy participants, patients showed higher scores for pain catastrophizing, symptoms of depression and anxiety, limited jaw function, more somatic symptoms, and significantly impaired oral health-related quality of life (all P<0.038).DISCUSSION: The results from the present study showed presence of varied somatosensory abnormalities when assessed using psychophysical and electrophysiological investigations and a significantly impaired psychosocial status.
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