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Purpose: Impaired activity of the peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) isomerase might contribute to link disturbed glucose metabolism and risk of glucose related neurotoxicity, neurodegeneration and cognitive decline. The isomerase modulates also pathways of peripheral insulin sensitivity and secretion. Methods: We enrolled 145 adolescents (age 12–17.8 years); 67 lean controls (46.2%) and 78 (53.8%) with overweight or obesity (males n= 62, 46%). We estimated glucose and insulin in fasting condition and after a standard oral glucose tolerance test; fasting serum levels of PIN1, amyloid β-protein 42 (Aβ42), presenilin 1 (PSEN1), glucagon-like peptide 1 (GLP1) and Non Esterified Fatty Acids (NEFA). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), the β cell function (HOMA-β) and the Adipo-IR. Results: There was no difference in PIN1 serum levels between normal weight individuals and patients with obesity. However, there was an inverse correlation between serum fasting PIN1 and glucose (r− 0.183 and p= 0.027). We confirmed levels of Aβ42 and PSEN1 were higher in teens with obesity than in lean controls and their correlation with the body mass index (Aβ42: r= 0.302, p= 0.0001, PSEN1 r= 0.231, p= 0.005) and the HOMA-IR (Aβ42: r= 0.219, p= 0.009, r= 0.170, p< 0.042). Conclusions: There was no significant rise of circulating PIN1 levels in young individuals with obesity. Increased levels reported in the literature in adult patients are likely to occur late in the natural history of the disease with the onset of an overt impairment of glucose homeostasis. Graphical abstract:

NA is a 51 years old dyslipidemic man without previous cardiovascular history. It’s been for 2 years that occasionally transient palpitations appear but nothing has been made. He came to ED for palpitations after vomiting: the ECG showed sinus rhythm with transient NSVT then sinus rhythm again and SVT with ST alteration. Metoprolol 2.5mg ev and MRA ev were administered because of mild hypokalemia with benefit. Echocardiogram and chest X–ray were normal without drugs intake. During hospitalization we started bisoprolol 2.5mg po and anti–dyslipidemic therapy but we observed very frequently PVC and PSVC and symptomatic wide QRS complex sustained tachycardia paroxysms at 180 bpm without loss of consciousness, hypotension or electrolytic abnormalities and SVT 170 bpm unresponsive to BB and amiodarone. The stress test without BB evidenced early wide QRS complex sustained tachycardia at 220 bpm well hemodynamically tolerated: metoprolol 10mg ev administration showed a brief sinus rhythm and then a narrow QRS complex sustained tachycardia at 160 bpm with significantly ST underleveled so flecainide 150mg ev was given with cardioversion to sinus rhythm and slowly ST abnormality regression. Subsequent coronary angiography and cardiac magnetic resonance resulted normal. The electrophysiological study demonstrated AVRT with a left lateral pathway retroconduction with and without LBBB and subsequent short AF paroxysms: the left lateral pathway was ablated without complications but the high atrial electrical vulnerability with reproducible SVT and triggered AF paroxysms lead to ILR implantation. The patient was discharged without antiarrhythmic and anticoagulant therapy: during the follow up there’s no arrhythmic relapses evidence and the patient is asymptomatic. Never give up to looking for solutions about palpitations: accessory pathway happens when you least expect it.

Digital health technologies may increase access to asthma self-management resources across diverse groups of patients. Limited evidence is available around the impact of these technologies on healthcare utilization.

•The engagement of Italian RTTs in clinical research is not homogeneous.•An active integration of RTTs in research pipelines may enhance RT research quality.•Italian RTTs are willing to be integrated into multidisciplinary research projects.

Los problemas relacionados con los medicamentos pueden ser ocasionados por la prescripción potencialmente inapropiada de medicamentos (PPIM). Una herramienta recomendada para su identificación son los criterios STOPP (Older Persons’ potentially inappropriate Prescriptions) - START (Screening Tool to Alert doctors to Right Treatment). El objetivo del estudio es determinar PPIM en adultos mayores que reciben atención farmacéutica en la Unidad de Optimización de la Farmacoterapia (UOF)-Rosario.

Hydrogeological field studies rely often on a single conceptual representation of the subsurface. This is problematic since the impact of a poorly chosen conceptual model on predictions might be significantly larger than the one caused by parameter uncertainty. Furthermore, conceptual models often need to incorporate geological concepts and patterns in order to provide meaningful uncertainty quantification and predictions. Consequently, several geologically realistic conceptual models should ideally be considered and evaluated in terms of their relative merits. Here, we propose a full Bayesian methodology based on Markov chain Monte Carlo to enable model selection among 2‐D conceptual models that are sampled using training images and concepts from multiple‐point statistics. More precisely, power posteriors for the different conceptual subsurface models are sampled using sequential geostatistical resampling and Graph Cuts. To demonstrate the methodology, we compare and rank five alternative conceptual geological models that have been proposed in the literature to describe aquifer heterogeneity at the MAcroDispersion Experiment site in Mississippi, USA. We consider a small‐scale tracer test for which the spatial distribution of hydraulic conductivity impacts multilevel solute concentration data observed along a 2‐D transect. The thermodynamic integration and the stepping‐stone sampling methods were used to compute the evidence and associated Bayes factors using the computed power posteriors. We find that both methods are compatible with multiple‐point statistics‐based inversions and provide a consistent ranking of the competing conceptual models considered. A full Bayesian method is proposed for model selection among geologically realistic conceptual modelsThermodynamic integration and stepping‐stone sampling provide consistent ranking of conceptual modelsThe method is applied to solute concentration data collected during a tracer test at the MADE site

We present velocity anomalies for the upper mantle beneath the Pantanal, Paraná, and Chaco‐Paraná basins, using teleseismic P‐wave tomography. Three hundred thirty‐nine stations were used to record 4,989 events for Pand PKIKP phases, during the years 1992‐2017. A new temporary deployment with 34 stations improved the coverage in that region. A high‐velocity anomaly beneath the Paraná Basin was interpreted as a cratonic basement. Its northern portion is consistent with the cratonic block presented by Cordani et al. (1984), and the southern portion is consistent with that presented by Mantovani et al. (2005, https://doi.org/10.1016/s1342‐937x(05)71137‐0). Low velocities are consistent with the limits of the Rio de la Plata craton, proposed by Rapela et al. (2011, https://doi.org/10.1016/j.gr.2011.05.001). A low‐velocity anomaly under the Pantanal Basin correlates with the seismicity, suggesting lithospheric thinning. This result is not consistent with an extension of the Rio Apa Block beneath the Pantanal Basin. We observed high velocities separating the Pantanal and South‐Paraguay seismic zones. The Western Paraná Suture (as proposed by Dragone et al., 2017, https://doi.org/10.1016/j.precamres.2017.01.029) shows no correlation with the seismic tomography anomalies. The thick lithosphere in the central part of the Paraná Basin is consistent with deviation of mantle flow, as suggested by SKS fast polarization (Melo & Assumpção, 2018, https://doi.org/10.1093/gji/ggy288). Synthetic tests show low resolution of the model for structures smaller than 200 x 200 km in the southwest portion of the study area but good resolution for large structures. The limits of the Paranapanema lithospheric block were definedThe upper mantle flow is deviated around the Paranapanema block

High-precision motion industrial systems must satisfy tight performance requirements. Both positioning accuracy and throughput demands are typically achieved through improvements in hardware, thereby raising the bill of materials. A cost saving alternative could be to strive for a reduction in the hardware components needed, in combination with advanced motion control, to still meet the desired specifications. Particularly, in this paper, the possibility is analyzed to allow for resource sharing among several actuators. This results in a switched system, for which we develop a real-time MPC algorithm for optimization of both the input and the switching signals. This implementation applies to a fairly general class of nonlinear systems and uses a novel offset-free formulation in velocity form for LTV prediction models, to realize good tracking performance under the resource sharing constraints. We provide a proof of concept for this MPC solution on a high fidelity model of an industrial SCARA robot, where it is proposed to use a single amplifier to serve two actuators. The MPC solution is compared to heuristically switched LTI controllers, and the potential of the proposed approach is shown in simulations.

The collapse of a mine tailings dam and subsequent flood in SE Brazil on 5 November 2015 was preceded by a small‐magnitude seismic sequence. In this report, we explore the spatiotemporal associations between the seismic events and the accident and discuss their possible connection. We also analyze the signals generated by the turbulent mudflow, as recorded by the Brazilian Seismographic Network (RSBR). In light of our observations, we propose as possible contributing factor for the dam collapse either ground shaking and/or soil liquefaction triggered by the earthquakes. The possibility of such a small‐magnitude earthquake contributing to the collapse of a tailings dam raises important concerns regarding safety and related legislation of dams in Brazil and the world. We detected and characterized a small‐magnitude earthquake sequence preceding the collapse of a tailings dam in Southeast BrazilSeismic signals from the mudflow were recorded at regional stations for 25 min and confirmed by their polarizationThe tight spatiotemporal relation between quakes and accident makes the contribution of ground shaking to the dam rupture highly probable

Lo studio intende mostrare come la presenza di una Classe II scheletrica, combinata con un overbite e ipertono muscolare, sia un cofattore per lo sviluppo di una cisti radicolare infiammatoria.

This paper describes the research done in order to valorise the biomass ash and evaluate its use as supplementary cementitious material (SCM) in the cement industry. The biomass ash samples used in this study were collected from three different power plants. The characterisation of the ashes as SCMs was performed after two different valorisation processes: (i) a vitrification process in order to obtain a new material with high hydraulicity and (ii) an easy de-alkalisation process in order to reduce the alkali content. The results of this work show that biomass ash derived from the combustion of woodchips and straw, properly treated, is characterised by pozzolanic activity and latent hydraulicity that could be exploited for the manufacture of low embodied energy concrete. The ultimate strength of mortars prepared using vitrified biomass ash becomes higher than that of the parent Portland cement after 28 days.

Key distribution and renewing in wireless local area networks is a crucial issue to guarantee that unauthorized users are prevented from accessing the network. In this paper, we propose a technique for allowing an automatic bootstrap and periodic renewing of the network key by exploiting physical layer security principles, that is, the inherent differences among transmission channels. The proposed technique is based on scrambling of groups of consecutive packets and does not need the use of an initial authentication nor automatic repeat request protocols. We present a modification of the scrambling circuits included in the IEEE 802.11g standard which allows for a suitable error propagation at the unauthorized receiver, thus achieving physical layer security.

Frontotemporal Lobar Degeneration (FTLD) is a genetically and pathologically heterogeneous disorder characterized by behavioral change, executive dysfunction and language impairment associated with frontal and temporal lobe degeneration. Three major clinical subtypes have been identified so far, namely behaviour variant Frontotemporal dementia (bvFTD), Semantic Dementia (SD) and Progressive Non-Fluent Aphasia (PNFA). FTLD might also overlap with atypical parkinsonisms or motor neuron disease. Several pathogenetic mutations have been associated with specific pathological and clinical correlates. FTLD associated with either Microtuble Associated Protein Tau (MAPT) or Progranulin (PGRN) mutations is recognised as the most common form of autosomal dominant inherited disorder. However, monogenic mutations account for only about one third of all FTLD cases. Several studies have evaluated the contribution of genetic background in non-monogenic forms of FTLD, with the attempt to establish its role in increasing disease risk and in modulating clinical phenotypes. Specific MAPT and PGRN polymorphisms have been demonstrated to affect disease onset, clinical features and prognosis of FTLD, and genetic variations within other genes appear to play a role in influencing disease risk and clinical expression of FTLD. The aim of the present review is to discuss the impact and the role of genetic background in non-monogenic forms of FTLD, to highlight new potential pathogenetic and therapeutic targets.

Objective:Aim of the study was to investigate caffeine use in different types of eating disorders (ED) patients either using a categorical approach [Diagnostic and Statistical Manual of Mental Disorders — Fourth Edition — Text Revision (DSM-IV-TR) diagnostic criteria] or a dimensional perspective. Method:Fifty-eight ED female patients [anorexia nervosa (AN), restricting and binge-eating/purging type, N=15; bulimia nervosa (BN) purging type/nonpurging type, N=26; binge eating disorder (BED), N=17] referred to an Eating Disorder Unit and 15 non-clinical controls were administered the Eating Disorder Inventory-2 (EDI-2), the Clinical Global Impression (CGI) and the Caffeine Use Test, an interview specifically developed to investigate caffeine intake. Statistical analyses were then repeated clustering patients according to the presence/absence of purging behaviors (purgers, N=22; non-purgers, N=19; BED, N=17). Results:Current and lifetime caffeine use, measured as mg/day, were similar comparing controls and ED patients as a whole. BN patients showed a significantly higher maximum lifetime caffeine intake (817.4±528,9 vs 325.0±294.6 mg/die, F=3.246, p<0.05); the same for purgers vs controls (p<0.05). Caffeine abuse was significantly more represented among patients vs controls (p<0.01), but similar among different patients’ groups. As for diagnoses according to DSM-IV-TR Substance Use modified for caffeine, no significant difference was found among the different groups, for either Dependence, Intoxication or Withdrawal. Most of patients and controls reported pleasure as the main motivation for caffeine use, followed by increased vigilance and attention and appetite suppression in AN and BN patients. Note that a shift in diagnosis in the course of the ED from non-purging to purging type was associated with an increase in caffeine current, lifetime and maximum lifetime intake (F=1.667 p<0.05), except for BED patients. Severity of the ED measured as CGI score or comorbidity did not affect caffeine intake in patients as a whole, but in the purging subgroup current caffeine use was increased in presence of an anxiety disorder (p<0.05), and decreased in presence of a mood disorder (p<0.01). Conclusions:Data from the present study are in agreement with previous evidence in literature that a high percentage of ED patients ordinarily use caffeine with an average intake similar to that of the general population, however with a kind of binge attitude. Among heavy drinkers, daily caffeine intake and alcohol/cigarettes use are associated supporting the link with the dimension of impulse disregulation. The substantial number of subjects from our sample satisfying research criteria for Dependence, together with increasing reports of caffeine intoxication, suggests the growing relevance of these issues that deserve further investigation.

We report on a 9.5‐year‐old Italian boy affected by creatine transporter deficit (CT1), due to a de novo mutation in SLC6A8 gene. The patient was investigated by means of a comprehensive neuropsychological protocol and presented with an unusual alteration of speech and expressive‐language function, associated with mental retardation, that differed from CT1 patients described to date. In particular, he exhibited a developmental apraxia of speech (DAS) with motor planning and execution deficit, while receptive language was consistent with his mental age. © 2007 Wiley‐Liss, Inc.

The aim of this study was to evaluate plasma and synovial fluid concentrations of the non-steroidal anti-inflammatory drug nimesulide and its major metabolite (hydroxynimesulide, M1), after a single 100 mg dose of nimesulide and a repeated (14 day) administration, 100 mg twice a day, in patients with osteoarthritis of the knee and joint effusion. Nimesulide was rapidly absorbed in plasma and distributed in synovial fluid. On day 1, effective concentrations were present 30 min after the first dose and on day 14, the synovial fluid concentration of nimesulide was significantly higher than that measured on day 1; no accumulation was observed in plasma. After 14 days of treatment, both the plasma and synovial fluid concentrations of M1 were significantly higher than those measured on day 1. These data may help to explain the rapid onset of the analgesic effect of nimesulide demonstrated in several clinical conditions, including painful osteoarthritis.

We report here that chlorpromazine, a first generation antipsychotic drug, inhibits anionic amino acid transport mediated by system X−AG(EAAT transporters) in cultured human fibroblasts. With 30 µM chlorpromazine, transport inhibition is detectable after 3 h of treatment, maximal after 48 h (>60%), and referable to a decrease in Vmax. Chlorpromazine effect is not dependent upon changes of membrane potential and is selective for system X−AGsince transport systems A and y+are not affected. Among antipsychotic drugs, the inhibitory effect of chlorpromazine is shared by two dibenzodiazepines, clozapine and olanzapine, while other compounds, such as risperidon, zuclopentixol, sertindol and haloperidol, are not effective. Transport inhibition by clozapine and olanzapine, but not by chlorpromazine, is reversible, suggesting that the mechanisms involved are distinct. These results indicate that a subset of antipsychotic drugs inhibits EAAT transporters in non-nervous tissues and prompt further investigation on possible alterations of glutamate transport in peripheral tissues of schizophrenic patients.We report here that chlorpromazine, a first generation antipsychotic drug, inhibits anionic amino acid transport mediated by system X−AG(EAAT transporters) in cultured human fibroblasts. With 30 µM chlorpromazine, transport inhibition is detectable after 3 h of treatment, maximal after 48 h (>60%), and referable to a decrease in Vmax. Chlorpromazine effect is not dependent upon changes of membrane potential and is selective for system X−AGsince transport systems A and y+are not affected. Among antipsychotic drugs, the inhibitory effect of chlorpromazine is shared by two dibenzodiazepines, clozapine and olanzapine, while other compounds, such as risperidon, zuclopentixol, sertindol and haloperidol, are not effective. Transport inhibition by clozapine and olanzapine, but not by chlorpromazine, is reversible, suggesting that the mechanisms involved are distinct. These results indicate that a subset of antipsychotic drugs inhibits EAAT transporters in non-nervous tissues and prompt further investigation on possible alterations of glutamate transport in peripheral tissues of schizophrenic patients.

In susceptible individuals, stressors can increase the risk of onset of depression and recent brain imaging studies have shown morphometric alterations in the limbic system of patients affected by depression. The volume loss observed in the hippocampus of depressed individuals suggests a possible involvement of structural neuronal plasticity in the pathogenesis of depression. Stressful conditions in animals can result in impaired structural neuronal plasticity in the hippocampus, characterised by retraction of apical dendrites and decreased neurogenesis. The intrinsic dynamic instability of the cytoskeletal microtubular system is essential for neuronal remodelling and plasticity. We have recently shown that both acute and chronic stress decrease microtubular dynamics in the rat hippocampus. Other authors have demonstrated that proteins functionally involved in the regulation of microtubule dynamics can be altered by stress in the rodent hippocampus. Furthermore, the existence of a link between stress-induced microtubular changes and depression is further strengthened by evidence showing that both acute and chronic treatment with antidepressant drugs can affect the expression of microtubular proteins. The present review will introduce a growing body of evidence suggesting that stress-induced alterations in neuronal plasticity might be considered the final result of activation and/or inhibition of molecular cascades regulating the dynamics of the microtubular system. In addition, the prospect of targeting microtubules as a pharmacotherapeutic approach to treat mood disorders will be discussed.

Background: Retrievable inferior vena cava (IVC) filters offer the attractive possibility to be definitive or to be removed when they become unnecessary. Objective: The purpose of this study was to evaluate the efficacy and the likelihood to remove the retrievable IVC filter ALN. Methods: A total of 30 patients (13 males and 17 females, mean age 57 ± 15 years) underwent placement of ALN filters. Indications for implantation were acute venous thromboembolism (VTE) with a contraindication to anticoagulation in 26 cases (86%), primary prophylaxis after major trauma in two cases (7%) or before surgery in two patients with very high thromboembolic risk (7%). Results: The filter was successfully placed in all patients. After a median follow‐up of 18.2 months, there were three cases (10%) of trapped emboli within the filter, one case (3%) of asymptomatic migration of the filter toward the heart and two patients (7%) had deep vein thrombosis (DVT) recurrences. ALN retrieval was attempted through transjugular approach in 18 patients (60%) and the maneuver was successful in 14 of them (78%); when the decision of removal was taken more than 3 months after the implantation, the retrieval was possible only in four of eight patients (50%). The median implantation period was 123 days (range: 30–345). Conclusions: The present study shows the efficacy of ALN filter; it also demonstrates the feasibility and safety of retrieval after a medium‐term period of placement. Removal after 3 months after implantation can be unsuccessful and maximum implantation time requires further studies.

In this lecture I review recent work done in collaboration with Beisert et al. [1-3] (For a concise summary see [4].). After a notational flash on the AdS/CFT correspondence, I will discuss higher spin (HS) symmetry enhancement at small radius and how this is holographically captured by free N = 4 SYM theory. I will then derive the spectrum of perturbative superstring excitations on AdS in this particular limit and successfully compare it with the spectrum of single-trace operators in free  = 4 SYM at large N, obtained by means of Polya(kov)'s counting. Decomposing the spectrum into HS multiplets allows one to precisely identify the 'massless' HS doubleton and the lower spin Goldstone multiplets which participate in the pantagruelic Higgs mechanism, termed “La Grande Bouffe”. After recalling some basic features of Vasiliev's formulation of HS gauge theories, I will eventually sketch how to describe mass generation in the AdS bulk à la Sückelberg and its holographic implications such as the emergence of anomalous dimensions in the boundary  = 4 SYM theory.

Double-stranded oligodeoxynucleotides (ODN) containing the consensus binding sequence of a transcription factor are valuable tools for the manipulation of gene expression at the transcriptional level by means of the decoy strategy. The approach involves flooding the cells with enough ODN decoy to compete for binding of the transcription factor with its consensus sequence in target genes. The technique has been proven effective in vitro and in vivo, suggesting its use in therapy. Therefore, great attention has been recently focused on chemical modifications enhancing biostability of the oligonucleotides so as to improve their pharmacological properties. Unfortunately, benefits in terms of nuclease resistance have been often negated by a decrease in the affinity and / or specificity of transcription factor binding. To circumvent these problems, circular dumbbell and chimeric decoy oligonucleotides, the latter comprising a central stretch of transcription factor recruiting deoxynucleotides flanked by modified nucleotides, have been introduced. Nevertheless, these approaches have the limitation of leaving the ODNs still sensitive to endonuclease cleavage. To address these concerns, we have recently investigated the use of a new class of nucleotide analogs termed locked nucleic acids (LNA) in the designing of decoy molecules for the transcription factor κB (NF-κB). In this article, we review the advantages of LNA in the design of ODN decoys pointing to the feasibility of introducing modifications in the transcription factor binding sequence in order to obtain molecules with increased stability compared to end-capped ODNs, while remaining efficiently recognized by NF-κB.

The paper presents an overview about the outcome of two hands-on courses on environmental reference material production organised by the European Commission’s Environment Institute within the context of its PHARE-AQUACON activities. Two plant reference materials, i.e. TP-28 (black tea) and TP-29 (mallow) were prepared and characterised by the course participants. Data on homogeneity and information values about the contents of inorganic and organic pollutants are presented. Furthermore, information about the AQUACON-Project are given, too.

This paper describes a collaborative interlaboratory exercise for freshwater analysis held in the framework of the “Analytical Quality Control and Assessment Studies in the Mediterranean Basin Project” (AQUACON). Two sample types were prepared and distributed: the first for the analysis of pH, conductivity and major ions (calcium, magnesium, sodium, potassium, chloride, sulphate, bicarbonate) and the second for algal nutrients (ammonium, nitrate, phosphate, total phosphorus and total nitrogen, silicate). Two solutions with different concentration levels were prepared for each of the samples; homogeneity throughout bottles and stability of samples in time were tested from the two organising laboratories. Results were obtained from 155 laboratories from 30 countries around the world. A detailed examination of results obtained by ion chromatography showed that an important source of error was the neglect of the non-linearity of calibration curves. Repeatability and reproducibility tests were performed in a selected number of experienced laboratories in accordance with the ISO standard 5725 for anion and cation ion chromatography determination. The best obtainable repeatability and reproducibility limits of IC methods of water analysis are about 5 and 10%, respectively.

Abstract Opioid switching is often used to improve the opioid response in cancer patients experiencing poor analgesia or adverse effects. However, no data are available on plasmatic changes of opioids and their metabolites during these phases, and whether there exists a relationship with the clinical events. In a prospective study of 10 consecutive cancer patients on oral morphine but with uncontrolled pain (greater >4 on a numerical scale of 0 to 10) and/or moderate to severe opioid adverse effects (on a level of 2 and 3 of a verbal scale) and not responsive to adjuvant medications, switching to oral methadone was performed using a fixed ratio of 5:1, leaving extra-doses of 1/5 of the daily dose of methadone calculated as needed. Blood samples were obtained at the same hour for four days, before the switching, and then on day 1, 2, and 3. The intensity of pain and the adverse effects were assessed daily to calculate the switching score before and after switching. Completed blood samples were obtained in 9 patients. One patient was separately considered, because of his renal impairment. Significant improvements in pain intensity as well as adverse effects within an average period of 1-2 days were observed. Morphine, morphine-6-glucuronide, and morphine-3-glucuronide were progressively cleared from plasma to almost disappear within three days. Methadone rapidly achieved a stable concentration in 1-2 days. The doses of methadone were changed, but not significantly, and tended to decrease in the following days, according to the clinical situation. The results of this study confirm the need to stop rapidly morphine, and to use a priming dose of methadone, rather than using progressive decrements and increments of morphine and methadone, respectively, during opioid switching. This method allows for a rapid clearance of morphine and its metabolites are rapidly cleared, except in patients with renal failure. Opioid plasma changes substantially overlap the clinical changes observed in these patients, in terms of benefit between analgesia and adverse effects.

The wild population of rusa deer (Cervus timorensis russa) in New Caledonia (South Pacific) is nearly as large as the cattle population. The cattle tick is widespread and occurs all year round. Opinions are divided on the role of deer in the biological cycle of the tick: i) Do they maintain a sustainable tick population that is secondarily available for cattle ii) Do they decrease the infestation of the environment by collecting larvae on the pasture, but preventing their development to the engorged female stage or iii) Do they contribute to both situations An experiment was conducted in three groups of pastures, each seeded with 450 000 larvaeha and allowed to be grazed only by cattle, only by deer, and by a mixed herd of deer and cattle (deer representing 30 of the biomass), at approximately the same stocking rate (470-510 kgha). After 15 months of exposure, the tick burden per weight unit of host was 42 tickskg for the steers-only herd and 0.01kg for the deer-only herd. The steers in the "mixed group" harbored 7 times fewer ticks (6.2kg) than the cattle-only group, and the deer in the "mixed group," 130 times more (1.3kg) than the deer-only group. Five emergency acaricide treatments had to be applied in the cattle-only group, but none in the other groups. The long-term sustainability of a viable tick population on deer as well as the potential benefit resulting from the association of deer and susceptible cattle in the tick control of cattle are highlighted.

Abstract: Cisplatin (c-DDP) is a widely used antineoplastic drug whose main side effect is nephrotoxicity. Selenium, administered intravenously or intraperitoneally, has been shown to provided protection against c-DDP-induced nephrotoxicity in rats. In the present study, the protective effect of orally administered sodium selenite on c-DDP toxicity was further examined. Animals treated with c-DDP alone showed increased urinary volume, decreased creatinine clearance (GFR), and a rise in urinary N-acetyl-(β-d-glucosaminidase) (NAG) isoenzyme B activity. When sodium selenite was given prior to c-DDP, rats showed less GFR decline, delayed urinary volume increases, and no urinary NAG isoenzyme B activity increment. It is suggested that a single oral dose of sodium selenite given prior to c-DDP administration, although not preventing deterioration of renal function, partially protects rats from early proximal tubular injury.

The pacemaker current I(f) of the sinoatrial node (SAN) is a major determinant of cardiac diastolic depolarization and plays a key role in controlling heart rate and its modulation by neurotransmitters. Substantial expression of two different mRNAs (HCN4, HCN1) of the family of pacemaker channels (HCN) is found in rabbit SAN, suggesting that the native channels may be formed by different isoforms. Here we report the cloning and heterologous expression of HCN1 from rabbit SAN and its specific localization in pacemaker myocytes. rbHCN1 is an 822-amino acid protein that, in human embryonic kidney 293 cells, displayed electrophysiological properties similar to those of I(f), suggesting that HCN1 can form a pacemaker channel. The presence of HCN1 in the SAN myocytes but not in nearby heart regions, and the electrophysiological properties of the channels formed by it, suggest that HCN1 plays a central and specific role in the formation of SAN pacemaker currents.

In this paper, we consider some well-known equilibrium problems and their duals in a topological Hausdorff vector space Xfor a bifunction Fdefined on Kx K,where Kis a convex subset of X. Some necessary conditions are investigated, proving different results depending on the behaviour of Fon the diagonal set. The concept of proper quasimonotonicity for bifunctions is defined, and the relationship with generalized monotonicity is investigated. The main result proves that the condition of proper quasimonotonicity is sharp in order to solve the dual equilibrium problem on every convex set.

High mobility group 2 protein (Hmgb2) is a member of the HMGB protein family, which includes the ubiquitous Hmgb1 and the embryo-specific Hmgb3. The three proteins are more than 80% identical at the amino acid level and their biochemical properties are indistinguishable. Hmgb1 is an abundant component of all mammalian nuclei and acts as an architectural factor that bends DNA and promotes protein assembly on specific DNA targets. Cells that lack Hmgb1 can survive, although mutant mice die shortly after birth. As Hmgb2 is present in all cultured cells and is abundant in thymus, the preferred source for HMGB proteins, it was considered a ubiquitous variant of Hmgb1. We show that in adult mice Hmgb2 is restricted mainly to lymphoid organs and testes, although it is widely expressed during embryogenesis. Mice that lack Hmgb2 are viable. However, male Hmgb2(-/-) mice have reduced fertility, that correlates with Sertoli and germ cell degeneration in seminiferous tubules and immotile spermatozoa. Significantly, Hmgb2 is expressed at very high levels in primary spermatocytes, while it is barely detectable in spermatogonia and elongated spermatids. This peculiar pattern of expression and the phenotype of mutants indicate that Hmgb2 has a specialised role in germ cell differentiation.