Assessing Nephrological Competence among Geriatricians: A Proof of Concept Internet Survey

Chronic kidney disease (CKD) is highly prevalent in the elderly and negatively impacts survival and health status. Thus, nephrological competence is mandatory for a skilled geriatrician. The present study aimed to assess nephrological competence in a sample of geriatricians recruited through a web survey. To this aim, a 12-items questionnaire was produced by an expert panel of nephrologists and geriatricians and was available online for members of the Italian Society of Gerontology and Geriatrics (SIGG). Two-hundred-eighty-seven geriatricians volunteered to fill in the questionnaire. The majority of them indirectly estimated the glomerular filtration rate (GFR) using mainly the Cockroft-Gault (C-G) formula. Selected nephrological exams, such as urinary Na and serum D-vitamin measurements, did not qualify as routine exams although the majority of geriatricians supplemented their patients with fat-soluble secosteroids. Ten percent of geriatricians asked for nephrological consultation only for stage 5 CKD patients and 30,9% only for stage 4 or 5. Erythropoietin supplementation was common practice for the majority of geriatricians, while only one third of them systematically used a procedure intended to prevent the contrast induced nephropathy (CIN). Finally, an alleged 50% adherence to the international guidelines for the management of CKD patients emerged from the questionnaire. Overall, results from this survey strongly recommend promoting nephrological education among geriatricians. Didactic standards for in training geriatricians need to be updated and the cooperation between geriatrics and nephrological societies promoted.     

Quantitative HIV-1 proviral DNA detection: a multicentre analysis

Despite the widespread use of molecular biology techniques, standardized methods for the measurement of HIV-1 proviral DNA are currently lacking and several discordant results are still present in different studies. To assess the clinical meaning of the proviral DNA load, a study group comprising seven different laboratories was set up to standardize a HIV-1 proviral DNA quantification method able to assess the DNA proviral load of the most relevant circulating HIV-1 subtypes. Reference samples (24 cellular samples infected with HIV-1 clade B, and 40 samples of peripheral blood mononuclear cells containing different concentrations of plasmids expressing different HIV-1 clades) were distributed and tested blindly. All laboratories employed hTERT gene as housekeeping gene and primers within the gag gene to quantify different HIV-1 clades. Inter-laboratory results did not differ statistically but showed only minor variations concerning HIV-1 DNA amounts and different HIV clades, with a good agreement among the laboratories participating in the study. Since test standardization represents a key step for future application in clinical practice, further studies of the patients' samples are in progress to establish the real meaning and utility of the proviral DNA load for clinical management of HIV-1 infected patients.     

Morphological plasticity of Parrotia persica leaves in eastern Hyrcanian forests (Iran) is related to altitude

Variation in leaf characters of Parrotia persica in relation to their position in the canopy along an altitudinal gradient were studied. Genetic and phenotypic characters make P. persica one of the most noteworthy plants in the five floristic regions of Iran. It is an endemic species of the Hyrcanian forests, and occurs naturally from sea level to over 900 m a.s.l. on the north side of the Mountain Ranges of Alborz, northern Iran. There was a significant effect of altitude only on few leaf features [width of lamina, base angle (internal angle of lamina), number of pair vein (number of principal veins of lamina) of leaf, top and end of leaf figure]. Among different geographical sides of the crown, there was no significant difference in the plasticity of leaf features, but leaf figure (both top of leaf figure and end of leaf figure) showed the lowest plasticity among the different leaf characters. Of all characters measured, the lowest plasticity among the three populations was found for base angle and number of vein pairs. A PCA analysis showed that leaf petiole and maximum width of lamina in 0.9 of its length, together with leaf figure and width of lamina, accounted for the greatest variation in difference of populations.     

Migration, Money and Masculinity in Kerala

This article examines migration, styles of masculinity and male trajectories through the life-cycle in Kerala, South India, in a region with a long history of high migration, most lately to the Persian Gulf states. Ethnography suggests that migration may be integrated into wider identity projects and form part of local subjectivities. The article considers four important local categories: the gulfan migrant, typically an immature unmarried male; the kallan , a self-interested maximizer or individualistic anti-social man; the pavam , an innocent good-guy, generous to the point of self-destruction; mature householder status, a successful, social, mature man holding substantial personal wealth, supporting many dependents and clients. Another theme to emerge is the relationship between masculinity and cash: migration appears as particularly relevant to masculinity in its enhanced relationship with money, an externalizable (detachable) form of masculine potency: maturity means being able to use such resources wisely.     

Dissecting drug and vehicle metabolic effects in rats by a metabonomic approach

A combined application of high resolution (1)H NMR spectroscopy and multivariate statistical techniques focused on establishing a consistent statistical approach to metabonomic studies was tested. The data reduction, which is preliminary to the application of multivariate analysis to NMR spectra, was carried out by means of two complementary methods: pure Pattern Recognition (PR) and Assigned Signal Analysis (ASA). The simultaneous use of both approaches allowed us to obtain additional information in the analysis of metabonomic data, compared to the use of PR alone. This additional information consists in the possibility of a biochemical interpretation of the effects induced by treatment with xenobiotics, such as drugs or drug vehicles, on the metabolic networks of the systems under investigation. This approach allowed us to ascertain that a single-dose treatment with ST1959 vehicled by Sesame oil affects the production of hepatic glucose associated to an increment of the amino acid ketogenic process.     

Determination of the optimal therapeutic protocols in cancer immunotherapy

Cancer immunotherapy aims at eliciting an immune system response against the tumor. However, it is often characterized by toxic side-effects. Limiting the tumor growth and, concurrently, avoiding the toxicity of a drug, is the problem of protocol design. We formulate this question as an optimization problem and derive an algorithm for its solution. Unlike the standard optimal control approach, the algorithm simulates impulse-like drug administrations. It relies on an exact computation of the gradient of the cost function with respect to any protocol by means of the variational equations, that can be solved in parallel with the system. In comparison with previous versions of this method [F. Castiglione, B. Piccoli, Optimal control in a model of dendritic cell transfection cancer immunotherapy, Bull. Math. Biol. 68 (2006) 255-274; B. Piccoli, F. Castiglione, Optimal vaccine scheduling in cancer immunotherapy, Physica A. 370 (2) (2007) 672-680], we optimize both the timing and the dosage of each administration and introduce a penalty term to avoid clustering of subsequent injections, a requirement consistent with the clinical practice. In addition, we implement the optimization scheme to simulate the case of multi-therapies. The procedure works for any ODE system describing the pharmacokinetics and pharmacodynamics of an arbitrary number of therapeutic agents. In this work, it was tested for a well known model of the tumor-immune system interaction [D. Kirschner, J.C. Panetta, Modeling immunotherapy of tumor-immune interaction, J. Math. Biol. 37 (1998) 235-252]. Exploring three immunotherapeutic scenarios (CTL therapy, IL-2 therapy and combined therapy), we display the stability and efficacy of the optimization method, obtaining protocols that are successful compromises between various clinical requirements.     

Photosynthesis responses to ozone in young trees of three species with different sensitivities, in a 2-year open-top chamber experiment (Curno, Italy)

This paper reports the findings of an open-top chamber experiment carried out in northern Italy (Forest nursery at Curno), during the 2004 and 2005 growth seasons, on Fagus sylvatica and Quercus robur seedlings and on Populus nigra cuttings, in order to test their photosynthesis response to ambient ozone. The experimental protocols were non-filtered air (NF), charcoal-filtered air (CF) and open air (OA). Tests performed included morphological features of leaves; development of foliar symptoms; chlorophyll content, determined by non-destructive means; chlorophyll fluorescence (direct fluorescence and JIP test) and gas exchanges and net photosynthesis (P_N). Main findings were as follows: (1) symptoms occurred early and were extensive in P. nigra , and they occurred later in F. sylvatica , whereas early degeneration of chlorophyll occurred in late summer in Q. robur ; (2) in conditions of ozone exposure, the three species all presented a decline in photosynthesis efficiency and a decrease in P_N, regardless of the symptomatology they displayed; (3) leaf traits are predictors of species-specific sensitivity to ozone—the high density of Q. robur foliar tissues prevents this species from developing visible symptoms and reduces the extent of physiological responses and (4) physiological responses varied from year to year in the same species—responses were lower in the second year of the experiment, when plants had become better acclimatized to plot conditions.     

PeroxiBase: the peroxidase database

Peroxidases (EC 1.11.1.x), which are encoded by small or large multigenic families, are involved in several important physiological and developmental processes. Analyzing their evolution and their distribution among various phyla could certainly help to elucidate the mystery of their extremely widespread and diversified presence in almost all living organisms. PeroxiBase was originally created for the exhaustive collection of class III peroxidase sequences from plants (Bakalovic, N., Passardi, F., et al., 2006. PeroxiBase: a class III plant peroxidase database. Phytochemistry 67, 534-539). The extension of the class III peroxidase database to all proteins capable to reduce peroxide molecules appears as a necessity. Our database contains haem and non-haem peroxidase sequences originated from annotated or not correctly annotated sequences deposited in the main repositories such as GenBank or UniProt KnowledgeBase. This new database will allow obtaining a global overview of the evolution the protein families and superfamilies capable of peroxidase reaction. In this rapidly growing field, there is a need for continual updates and corrections of the peroxidase protein sequences. Following the lack of unified nomenclature, we also introduced a unique abbreviation for each different family of peroxidases. This paper thus aims to report the evolution of the PeroxiBase database, which is freely accessible through a web server (http://peroxibase.isb-sib.ch). In addition to new categories of peroxidases, new specific tools have been created to facilitate query, classification and submission of peroxidase sequences.     

Unexpected inhibition of peptidoglycan LD-transpeptidase from Enterococcus faecium by the beta-lactam imipenem

The beta-lactam antibiotics mimic the D-alanyl(4)-D-alanine(5) extremity of peptidoglycan precursors and act as "suicide" substrates of the DD-transpeptidases that catalyze the last cross-linking step of peptidoglycan synthesis. We have previously shown that bypass of the dd-transpeptidases by the LD-transpeptidase of Enterococcus faecium (Ldt(fm)) leads to high level resistance to ampicillin. Ldt(fm) is specific for the L-lysyl(3)-D-alanine(4) bond of peptidoglycan precursors containing a tetrapeptide stem lacking D-alanine(5). This specificity was proposed to account for resistance, because the substrate of Ldt(fm) does not mimic beta-lactams in contrast to the D-alanyl(4)-D-alanine(5) extremity of pentapeptide stems used by the DD-transpeptidases. Here, we unexpectedly show that imipenem, a beta-lactam of the carbapenem class, totally inhibited Ldt(fm) at a low drug concentration that was sufficient to inhibit growth of the bacteria. Peptidoglycan cross-linking was also inhibited, indicating that Ldt(fm) is the in vivo target of imipenem. Stoichiometric and covalent modification of Ldt(fm) by imipenem was detected by mass spectrometry. The modification was mapped into the trypsin fragment of Ldt(fm) containing the catalytic Cys residue, and the Cys to Ala substitution prevented imipenem binding. The mass increment matched the mass of imipenem, indicating that inactivation of Ldt(fm) is likely to involve rupture of the beta-lactam ring and acylation of the catalytic Cys residue. Thus, the spectrum of activity of beta-lactams is not restricted to transpeptidases of the DD-specificity, as previously thought. Combination therapy with imipenem and ampicillin could therefore be active against E. faecium strains having the dual capacity to manufacture peptidoglycan with transpeptidases of the LD- and DD-specificities.