42,768 research outputs found

    [Cognitive deficiency in internal medicine]

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    Although patients admitted to Internal Medicine Departments are often older than 65 years, the "new geriatric culture" comes into conflict with the traditional goals of Medicine (diagnosis-therapy-recovery). Multidimensional assessment permits global evaluation of the needs and problems of the elderly patient and consequently guarantees an adequate and complete therapeutic plan. This approach is particularly valid if applied in a Medical Division because acute illnesses can compromise a functional state that is already in precarious equilibrium due to frequent multiple pathologies. Moreover, thanks to an accurate evaluation of this type, it is possible to recognize patients with cognitive deficits and diagnose dementia early. In the present study, we utilized a geriatric multidimensional assessment in our Department of Internal Medicine to search for cognitive impairment. Dementia was found in 20% of the geriatric patients: 29% were affected by Alzheimer's disease and 44% had vascular dementia. We evaluated the physical health, functional ability, psychological and socio-economical status together with behavioral syndromes

    Optimization of D-amino acid oxidase for low substrate concentrations--towards a cancer enzyme therapy.

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    d-Amino acid oxidase (DAAO) has recently become of interest as a biocatalyst for industrial applications and for therapeutic treatments. It has been used in gene-directed enzyme prodrug therapies, in which its production of H(2)O(2) in tumor cells can be regulated by administration of substrate. This approach is limited by the locally low O(2) concentration and the high K(m) for this substrate. Using the directed evolution approach, one DAAO mutant was identified that has increased activity at low O(2) and d-Ala concentrations and a 10-fold lower K(m) for O(2). We report on the mechanism of this DAAO variant and on its cytotoxicity towards various mammalian cancer cell lines. The higher activity observed at low O(2) and d-Ala concentrations results from a combination of modifications of specific kinetic steps, each being of small magnitude. These results highlight the potential in vivo applicability of this evolved mutant DAAO for tumor therapy

    On the reaction of D-amino acid oxidase with dioxygen: O2 diffusion pathways and enhancement of reactivity.

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    Evidence is accumulating that oxygen access in proteins is guided and controlled. We also have recently described channels that might allow access of oxygen to pockets at the active site of the flavoprotein D-amino acid oxidase (DAAO) that have a high affinity for dioxygen and are in close proximity to the flavin. With the goal of enhancing the reactivity of DAAO with oxygen, we have performed site-saturation mutagenesis at three positions that flank the putative oxygen channels and high-affinity sites. The most interesting variants at positions 50, 201 and 225 were identified by a screening procedure at low oxygen concentration. The biochemical properties of these variants have been studied and compared with those of wild-type DAAO, with emphasis on the reactivity of the reduced enzyme species with dioxygen. The substitutions at positions 50 and 225 do not enhance this reaction, but mainly affect the protein conformation and stability. However, the T201L variant shows an up to a threefold increase in the rate constant for reaction of O(2) with reduced flavin, together with a fivefold decrease in the K(m) for dioxygen. This effect was not observed when a valine is located at position 201, and is thus attributed to a specific alteration in the micro-environment of one high-affinity site for dioxygen (site B) close to the flavin that plays an important role in the storage of oxygen. The increase in O(2) reactivity observed for T201L DAAO is of great interest for designing new flavoenzymes for biotechnological applications

    Measurement of the ratio of branching fractions B(B0→K∗0γ )/B(B0s→φγ ) and the directCP asymmetry inB 0→K∗0γ

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    The ratio of branching fractions of the radiative B decays B0→K⁎0γ and B0s→ϕγ has been measured using an integrated luminosity of 1.0 fb−1 of pp collision data collected by the LHCb experiment at a centre-of-mass energy of s√=7TeV. The value obtained is B(B0→K⁎0γ)B(B0s→ϕγ)=1.23±0.06(stat.)±0.04(syst.)±0.10(fs/fd), where the first uncertainty is statistical, the second is the experimental systematic uncertainty and the third is associated with the ratio of fragmentation fractions fs/fd. Using the world average value for B(B0→K⁎0γ), the branching fraction B(B0s→ϕγ) is measured to be (3.5±0.4)×10−5. The direct CP asymmetry in B0→K⁎0γ decays has also been measured with the same data and found to be ACP(B0→K⁎0γ)=(0.8±1.7(stat.)±0.9(syst.))%. Both measurements are the most precise to date and are in agreement with the previous experimental results and theoretical expectations

    Predictors of survival within 2 years of inpatient rehabilitation among older adults

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    Background Restoring functional independence in elderly people with disabilities is one of the main purposes of a geriatric rehabilitation unit. However, the rehabilitation period may also represent a useful circumstance to identify predictors of long-term health outcomes. The aim of this study was to evaluate a broad spectrum of characteristics in geriatric patients admitted to a rehabilitation unit in order to identify possible predictors of long-term survival. Methods This cross-sectional and prospective study was carried out in an Evaluation and Rehabilitation unit in Northern Italy. 243 persons aged 65 or older were enrolled over a period of 12 months (2007–8) and followed for 2 years. Possible predictors of survival were identified among a large spectrum of demographic, clinical (Charlson Index, lab data), nutritional (Mini-Nutritional Short-Form, bio-impedance analysis), and respiratory (spirometry) features. Logistic regression models were used to evaluate the association between patients' characteristics and survival. Results 189 (86.3%) participants were alive after 2 years of follow-up. Younger age, better functional status at discharge, a lower Charlson Index score, higher hemoglobin and albumin values at discharge, lower basal fasting glucose, creatinine, TNF-α levels, and extra-cellular water, as well as higher cholesterol, vital capacity (VC), and inspiratory capacity were significantly associated with survival. In the multivariate model, higher VC (OR = 6.2; 95%CI = 1.6–24.6) and albumin (OR = 3.7; 95%CI = 1.2–11.8) were associated with survival, whereas the Charlson Index and male gender showed an inverse correlation (OR = 0.77; 95%CI = 0.60–0.99 and OR = 0.23; 95%CI = 0.10–0.95, respectively). Conclusion VC was identified as one of the best predictors of survival along with higher albumin and lower Charlson Index score within 2 years of inpatient rehabilitation among older adults

    ∑_(l+m=k,l,m≥0) ((α+l-1)¦l) ((β+m-1)¦m)=((α+β+k-1)¦k) and its application to negative binomial distribution

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    We prove here the following equation: ∑_(l+m=k,l,m≥0) ((α+l-1)¦l) ((β+m-1)¦m)=((α+β+k-1)¦k) and give its application to prove the reproductive property of the negative binomial distribution. These finite sum equation involving binomial coefficients and proof of the reproductive property are not known as far as the author knows.論文(Article)departmental bulletin pape

    Characterization of cholesterol oxidase from Streptomyces hygroscopicus and Brevibacterium sterolicum

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    The FAD-containing enzyme cholesterol oxidase catalyzes the oxidation and isomerization of 3beta-hydroxysteroids having a trans double bond at delta5-delta6 of the steroid ring backbone to the corresponding delta4-3-ketosteroid. Two representative enzymes of this family, namely cholesterol oxidase from Streptomyces hygroscopicus (SCO) and the recombinant enzyme from Brevibacterium sterolicum (BCO) expressed in Escherichia coli, have been characterized herein in their chemical, physical, and biochemical properties. In the native form, both enzymes are monomeric (55 kDa), acidic (pI 4.4-5.1) and contain oxidized FAD (peaks in the 370-390-nm and 440-470-nm regions). Marked differences exist between the oxidized, reduced, and (red) anion semiquinone spectra of the two enzymes, suggesting substantial differences in the flavin microenvironment. Both enzymes form reversibly flavin N(5)-sulfite adducts via measurable k(on) and k(off) steps. BCO has a higher affinity for sulfite (Kd approximately 0.14 mM) compared to SCO (approximately 24 mM). This correlates well with the midpoint redox potentials of the bound flavin, which in the case of BCO are about 100 mV more positive than for SCO. Both enzymes show a high pKa (approximately 11.0) for the N(3) position of FAD. With both enzymes, the rearrangement of 5-cholesten-3-one to 4-cholesten-3-one is not rate limiting indicating that the rate-limiting step of the overall reaction is not the isomerization. The absence of the double bond in the steroid molecule does not significantly affect turnover and affinity for the substrate, whereas both these parameters are affected by a decreasing length of the substrate C17 chain
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