| 2721. |
- Rodríguez, M, et al.
(författare)
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Reduction of atherosclerotic nanoplaque formation and size by Ginkgo biloba (EGb 761) in cardiovascular high-risk patients
- 2007
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 192:2, s. 438-444
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Tidskriftsartikel (refereegranskat)abstract
- Coating a silica surface with the isolated lipoprotein receptor proteoheparan sulfate (HS-PG) from arterial endothelium and vascular matrices and adding both the atherogenic VLDL/IDL/LDL lipid fraction in its native composition and Ca2+ ions, we could observe in vitro the earliest stages of atherosclerotic plaque development by ellipsometric techniques (patent EP 0 946 876). This so-called nanoplaque formation is represented by the ternary aggregational complex of the HS-PG receptor, lipoprotein particles and calcium ions. The model was validated in several clinical studies on statins in cardiovascular high-risk patients. In eight patients who had undergone an aortocoronary bypass operation, the reduction of atherosclerotic nanoplaque formation amounted to 11.9±2.5% (p<0.0078) and of nanoplaque size to 24.4±8.1% (p<0.0234), respectively, after a 2-month therapy with Ginkgo biloba extract (2× 120mg daily, EGb 761). Additionally, superoxide dismutase (SOD) activity was upregulated by 15.7±7.0% (p<0.0391), the quotient oxLDL/LDL lowered by 17.0±5.5% (p<0.0234) and lipoprotein(a) concentration decreased by 23.4±7.9% (p<0.0234) in the patients’ blood. The concentration of the vasodilating substances cAMP and cGMP was augmented by 37.5±9.1% (p<0.0078) and 27.7±8.3% (p<0.0156), respectively. A multiple regression analysis between the patients’ VLDL/IDL/LDL lipoprotein fraction applied in the ellipsometry measurements as well as the further risk factors oxLDL/LDL and Lp(a) on the one hand and changes in nanoplaque formation on the other hand reveals a basis for a mechanistic explanation of nanoplaque reduction under ginkgo treatment. The atherosclerosis inhibiting effect is possibly due to an upregulation in the body's own radical scavenging enzymes and an attenuation of the risk factors oxLDL/LDL and Lp(a).
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| 2722. |
- Rodríguez, M., et al.
(författare)
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Towards biosensing of arteriosclerotic nanoplaque formation using femtosecond spectroscopy.
- 2007
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Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861 .- 1096-0384. ; 460:1, s. 92-99
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Tidskriftsartikel (refereegranskat)abstract
- The ultrafast dynamics of proteoheparan sulfate (HS-PG) in Krebs blood substitute solution was measured using femtosecond transient absorption spectroscopy after UV excitation. Interacting with blood lipoproteins and Ca2+ ions, the proteoglycan HS-PG is the key component of the so-called nanoplaque, the earliest stage in atherogenesis. Since tryptophan (Trp) residues are the main optically active parts of HS-PG, analogous measurements were performed on bare Trp in Krebs solution. The comparison reveals distinct differences to main characteristics of the HS-PG broadband absorption spectra. Analyzing the Trp spectra, we show that the results from transient absorption spectroscopy resemble the time constants of the chromophore ultrafast solvation dynamics that have been found by another group using fluorescence up-conversion techniques. Yet, the broadband transient absorption provides more details about the molecular dynamics, including stimulated emission, excited state absorption and resonant energy transfer. Furthermore, the absorption long time dynamics upon adding Ca2+ to the HS-PG probe were investigated by transient absorption spectroscopy and by surface force and ellipsometry investigations. Notably, a Ca2+-induced conformational change responsible for arteriosclerotic nanoplaque formation was detected. Slight differences, which are only visible as broad spectral features in the sub-picosecond time scale, provide a first insight into the molecular formation of nanoplaques in blood vessels, which may yield a better understanding of the genesis of arteriosclerosis.
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| 2723. |
- Rogers, Simon N., et al.
(författare)
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Variations in concerns reported on the patient concerns inventory in patients with head and neck cancer from different health settings across the world
- 2020
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Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 42:3, s. 498-512
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim was to collate and contrast patient concerns from a range of different head and neck cancer follow-up clinics around the world. Also, we sought to explore the relationship, if any, between responses to the patient concerns inventory (PCI) and overall quality of life (QOL). Methods Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias. Results There were 2136 patients with a median total number of PCI items selected of 5 (2-10). "Fear of the cancer returning" (39%) and "dry mouth" (37%) were most common. Twenty-five percent (524) reported less than good QOL. Conclusion There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case-mix variables. There was a strong progressive association between the number of PCI items and QOL.
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| 2724. |
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| 2725. |
- Rueda, B., et al.
(författare)
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The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:11, s. 2071-2077
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.
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| 2726. |
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| 2727. |
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| 2728. |
- Runkel, N., et al.
(författare)
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Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: Steps towards an international consensus
- 2011
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Ingår i: Injury. - 1879-0267. ; 42:Suppl. 1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Negative pressure wound therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this paper the results of the study of evidence in traumatic wounds (including soft tissue defects, open fractures and burns) and reconstructive procedures (including flaps and grafts) are reported. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel, followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% approval. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Twelve recommendations were developed in total; 4 for soft tissue trauma and open fracture injuries, 1 for burn injuries, 3 for flaps and 4 for skin grafts. The present evidence base is strongest for the use of NPWT on skin grafts and weakest as a primary treatment for burns. In the consultative process, 11/12 of the proposed recommendations reached the 80% agreement threshold. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone. (C) 2011 Elsevier Ltd. All rights reserved.
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| 2729. |
- Sacchet, Matthew D., et al.
(författare)
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Large-scale hypoconnectivity between resting-state functional networks in unmedicated adolescent major depressive disorder
- 2016
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Ingår i: Neuropsychopharmacology. - London : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 41:12, s. 2951-2960
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.
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| 2730. |
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