475 research outputs found
BioPhotonics workstation: A versatile setup for simultaneous optical manipulation, heat stress, and intracellular pH measurements of a live yeast cell
Changes in characteristics of hospitalized heart failure patients in ten years: a single-center study
SummaryBackgroundProgress in therapy and the ageing patients hospitalized with heart failure may have impacted the characteristics of this patients.AimsWe compared epidemiological data of patients admitted with heart failure during two periods separated by a 10 year interval.MethodsCharacteristics of 353 heart failure patients recruited between 2002 and 2004 with those of 304 heart failure patients recruited between 1992 and 1994 were compared retrospectively.ResultsThere is now a majority of male patients (56.4%) not found ten years ago. The average age is unchanged (75.1±11 then 76.4±11 years) even though the proportion of patients aged over 70 years has increased (75% versus 70%). Hospital length of stay has fallen from 14±9 to 10±7 days. Hospital mortality (8%) are identical. The two main etiologies remain coronary and hypertensive heart disease at 29 and 24% respectively but these proportions are lower than ten years ago (42 and 28% respectively). The ejection fraction is more often preserved (56%) than before (44%). Increased prescription of inhibitors of the renin-angiotensin system and beta-blockers is confirmed. Post-hospital and total mortality has fallen by 50 and 30% from 30 to 16% and 35 to 24% respectively at the expense of a 25% increase in the frequency of hospital readmissions from 29 to 38%.ConclusionEven if mortality has declined, heart failure remains a major public health burden with a significant number of hospital readmissions. Other approaches such as therapeutic education must therefore be developed
Lumbar and ventricular CSF concentrations of extracellular matrix proteins before and after shunt surgery in idiopathic normal pressure hydrocephalus
Background: Idiopathic normal pressure hydrocephalus (iNPH) is a reversible CNS disease characterized by disturbed cerebrospinal fluid (CSF) dynamics. Changes in the extracellular matrix (ECM) composition might be involved in the pathophysiology of iNPH. The aim of this study was to explore possible differences between lumbar and ventricular CSF concentrations of the ECM markers brevican and neurocan, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and their relation to clinical symptoms in iNPH patients before and after shunt surgery. Methods: Paired lumbar and ventricular CSF was collected from 31 iNPH patients, before and four months after shunt surgery. CSF was analysed for concentrations of tryptic peptides originating from brevican and neurocan using a mass spectrometry-based panel, and for MMP-1, -2, -9, -10 and TIMP-1 using fluorescent or electrochemiluminescent immunoassays. Results: Brevican and neurocan peptide levels were not influenced by CSF origin, but MMP-1, -2, -10 and TIMP-1 were increased (p ≤ 0.0005), and MMP-9 decreased (p ≤ 0.0003) in lumbar CSF compared with ventricular CSF. There was a general trend of ECM proteins to increase following shunt surgery. Ventricular TIMP-1 was inversely correlated with overall symptoms (rho = − 0.62, p < 0.0001). CSF concentrations of the majority of brevican and neurocan peptides were increased in iNPH patients with a history of cardiovascular disease (p ≤ 0.001, AUC = 0.84–0.94) compared with those without. Conclusion: Levels of the CNS-specific proteins brevican and neurocan did not differ between the lumbar and ventricular CSF, whereas the increase of several CNS-unspecific MMPs and TIMP-1 in lumbar CSF suggests contribution from peripheral tissues. The increase of ECM proteins in CSF following shunt surgery could indicate disturbed ECM dynamics in iNPH that are restored by restitution of CSF dynamics
How clusters create shared value in rural areas: An examination of six case studies
The main aim of this paper is to demonstrate that clusters can support the sustainable development of rural areas through the creation of shared value. This is done via the close examination of six different cases of rural clusters in Greece, Italy, Germany, Poland, Denmark, and Sweden. Qualitative as well as quantitative data were taken from the clusters, which demonstrated that their main business approaches naturally coincided with the creation of economic, social, and environmental benefits for the local communities in which they operated. The case clusters were created in a top-down manner, aimed at boosting regional R&D activities and making the local economy more competitive and more sustainable. However, private initiative took over and al-lowed these clusters to flourish because meeting the regions’ economic, social, and environmental needs successfully coincided with the target of the clusters’ own development and profitability. The results show that clusters, with their potential for shared value creation, can constitute a powerful engine for the revitalisation and development of rural areas, addressing the significant challenges which they are currently facing
Tantalum sound velocity under shock compression
We used several variations of the shock compression method to measure the longitudinal sound velocity of shocked tantalum over the pressure range 37–363 GPa with a typical uncertainty of 1.0%%. These data are consistent with Ta remaining in the bcc phase along the principal Hugoniot from ambient pressure to ≈300 GPa, at which pressure melting occurs. These data also do not support the putative melting phenomena reported below 100 GPa in some static compression experiments
Tantalum sound velocity under shock compression
We used several variations of the shock compression method to measure the longitudinal sound velocity of shocked tantalum over the pressure range 37–363 GPa with a typical uncertainty of 1.0%%. These data are consistent with Ta remaining in the bcc phase along the principal Hugoniot from ambient pressure to ≈300 GPa, at which pressure melting occurs. These data also do not support the putative melting phenomena reported below 100 GPa in some static compression experiments
Dynamics of cerebrospinal fluid levels of matrix metalloproteinases in human traumatic brain injury
Matrix metalloproteinases (MMPs) are extracellular enzymes involved in the degradation of extracellular matrix (ECM) proteins. Increased expression of MMPs have been described in traumatic brain injury (TBI) and may contribute to additional tissue injury and blood–brain barrier damage. The objectives of this study were to determine longitudinal changes in cerebrospinal fluid (CSF) concentrations of MMPs after acute TBI and in relation to clinical outcomes, with patients with idiopathic normal pressure hydrocephalus (iNPH) serving as a contrast group. The study included 33 TBI patients with ventricular CSF serially sampled, and 38 iNPH patients in the contrast group. Magnetic bead-based immunoassays were utilized to measure the concentrations of eight MMPs in ventricular human CSF. CSF concentrations of MMP-1, MMP-3 and MMP-10 were increased in TBI patients (at baseline) compared with the iNPH group (p < 0.001), while MMP-2, MMP-9 and MMP-12 did not differ between the groups. MMP-1, MMP-3 and MMP-10 concentrations decreased with time after trauma (p = 0.001–0.04). Increased concentrations of MMP-2 and MMP-10 in CSF at baseline were associated with an unfavourable TBI outcome (p = 0.002–0.02). Observed variable pattern of changes in MMP concentrations indicates that specific MMPs serve different roles in the pathophysiology following TBI, and are in turn associated with clinical outcomes
Imaging Mitochondrial Calcium Fluxes with Fluorescent Probes and Single- or Two-Photon Confocal Microscopy
The concentration of calcium ions in the mitochondria has been shown to affect its function, modulating respiratory activity at low levels and causing lethal damage at high concentrations. The rhodamine series of dyes can be used to measure mitochondrial calcium concentration, but the reliability of measurements depends upon correct partitioning of the dye within to the mitochondria. Methods are described to aid verification and quantification of the mitochondrial calcium concentration using single- or two-photon confocal microscopy. The method of linear unmixing to separate fluorescent signals based on either differing excitation or emission spectra is outlined and for the purposes of illustration is applied to the separation of rhod-2 signals originating from the dye within the mitochondria and nucleoli
Development of fluorescent probes for bioimaging applications
Fluorescent probes, which allow visualization of cations such as Ca2+, Zn2+ etc., small biomolecules such as nitric oxide (NO) or enzyme activities in living cells by means of fluorescence microscopy, have become indispensable tools for clarifying functions in biological systems. This review deals with the general principles for the design of bioimaging fluorescent probes by modulating the fluorescence properties of fluorophores, employing mechanisms such as acceptor-excited Photoinduced electron Transfer (a-PeT), donor-excited Photoinduced electron Transfer (d-PeT), and spirocyclization, which have been established by our group. The a-PeT and d-PeT mechanisms are widely applicable for the design of bioimaging probes based on many fluorophores and the spirocyclization process is also expected to be useful as a fluorescence off/on switching mechanism. Fluorescence modulation mechanisms are essential for the rational design of novel fluorescence probes for target molecules. Based on these mechanisms, we have developed more than fifty bioimaging probes, of which fourteen are commercially available. The review also describes some applications of the probes developed by our group to in vitro and in vivo systems
Risk-Stratified Screening for Colorectal Cancer Using Genetic and Environmental Risk Factors:A Cost-Effectiveness Analysis Based on Real-World Data
Background & Aims: Previous studies on the cost-effectiveness of personalized colorectal cancer (CRC) screening were based on hypothetical performance of CRC risk prediction and did not consider the association with competing causes of death. In this study, we estimated the cost-effectiveness of risk-stratified screening using real-world data for CRC risk and competing causes of death. Methods: Risk predictions for CRC and competing causes of death from a large community-based cohort were used to stratify individuals into risk groups. A microsimulation model was used to optimize colonoscopy screening for each risk group by varying the start age (40–60 years), end age (70–85 years), and screening interval (5–15 years). The outcomes included personalized screening ages and intervals and cost-effectiveness compared with uniform colonoscopy screening (ages 45–75, every 10 years). Key assumptions were varied in sensitivity analyses. Results: Risk-stratified screening resulted in substantially different screening recommendations, ranging from a one-time colonoscopy at age 60 for low-risk individuals to a colonoscopy every 5 years from ages 40 to 85 for high-risk individuals. Nevertheless, on a population level, risk-stratified screening would increase net quality-adjusted life years gained (QALYG) by only 0.7% at equal costs to uniform screening or reduce average costs by 1.2% for equal QALYG. The benefit of risk-stratified screening improved when it was assumed to increase participation or costs less per genetic test. Conclusions: Personalized screening for CRC, accounting for competing causes of death risk, could result in highly tailored individual screening programs. However, average improvements across the population in QALYG and cost-effectiveness compared with uniform screening are small.</p
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