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This paper contributes to the debate on the re-appraisal of monetization mechanism as a possible tool for dealing with macroeconomic imbalances due to close economic shocks (e.g. the Covid pandemic, the Russia-Ukraine conflict and the escalation in Israel-Hamas crisis). We analyze and empirically discuss the well-known Quantity Theory of Money (QTM), by applying the SVAR methodology to a heterogeneous panel including several Countries (Australia, China, India, Japan, United Kingdom and the United States) plus the block of Euro Zone (EZ) over the period 1992–2022. We investigate the dynamics and the impacts of the variables included in the theoretical model (inflation, GDP growth, money growth and the change in the velocity of money) through the analysis of the macro economic datasets retrieved from the OECD and Trading Economics databases. We find that money growth does not exert the decisive spillover effect on the path of inflation (i.e. common shock) throughout our sample. Moreover, our results indicate that the idiosyncratic component does not show a predominant and determining role of monetary growth in inflationary dynamics.

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Rising healthcare costs have been a major concern of business leaders for decades, and rapidly escalating premiums have reduced employers' ability to continue to pay for the healthcare of their [...]

Epigenetic-sensitive mechanisms, mainly DNA methylation, mirror the relationship between environmental and genetic risk factors able to affect the sensitiveness to development of obesity and its comorbidities. Bariatric and metabolic surgery may reduce obesity-related cardiovascular risk through tissue-specific DNA methylation changes. Among the most robust results, differential promoter methylation of ACACA, CETP, CTGF, S100A8, and S100A9genes correlated significantly with the levels of mRNA before and after gastric bypass surgery (RYGB) in obese women. Additionally, promoter hypermethylation of NFKB1gene was significantly associated with reduced blood pressure in obese patients after RYGB suggesting useful non-invasive biomarkers. Of note, sperm-related DNA methylation signatures of genes regulating the central control of appetite, such as MC4R, BDNF, NPY, and CR1, and other genes including FTO, CHST8, and SH2B1were different in obese patients as compared to non-obese subjects and patients who lost weight after RYGB surgery. Importantly, transgenerational studies provided relevant evidence of the potential effect of bariatric and metabolic surgery on DNA methylation. For example, peripheral blood biospecimens isolated from siblings born from obese mothers before bariatric surgery showed different methylation signatures in the insulin receptor and leptin signaling axis as compared to siblings born from post-obese mothers who underwent surgery. This evidence suggests that bariatric and metabolic surgery of mothers may affect the epigenetic profiles of the offspring with potential implication for primary prevention of severe obesity. We update on tissue-specific epigenetic signatures as potential mechanisms underlying the restoration of metabolic health after surgery suggesting useful predictive biomarkers.

Q: Should insurers give mental- and physical-health services parity of coverage? Yes: It would benefit American workers and save society from the hidden costs of mental illness. Consider Lisa Cohen. [...]

It is hard to believe, but fewer than a hundred years ago, European combat soldiers who developed tremors and nightmares were executed as traitors or branded as weaklings. Thankfully, we […]

In this work, we report the presence of surface-densified phases (β-Ni5O8, γ-Ni3O4, and δ-Ni7O8) in LiNiO2(LNO)- and LiNi0.8Al0.2O2(LNA)-layered compounds by combined atomic level scanning transmission electron microscopy (STEM) and electron energy loss spectroscopy (EELS). These surface phases form upon electrochemical aging at high state of charge corresponding to a fully delithiated state. A unique feature of these phases is the periodic occupancy by Ni2+in the Li layer. This periodic Ni occupancy gives rise to extra diffraction reflections, which are qualitatively similar to those of the LiNi2O4spinel structure, but these surface phases have a lower Ni valence state and cation content than spinel. These experimental results confirm the presence of thermodynamically stable surface phases and provide new insights into the phenomena of surface phase formation in Ni-rich layered structures.

In this article, we present a new data collection that combines information about earthquake damage with seismic shaking. Starting from the Da.D.O. database, which provides information on the damage of individual buildings subjected to sequences of past earthquakes in Italy, we have generated ShakeMaps for all the events with magnitude greater than 5.0 that have contributed to these sequences. The sequences under examination are those of Irpinia 1980, Umbria Marche 1997, Pollino 1998, Molise 2002, L’Aquila 2009 and Emilia 2012. In this way, we were able to combine, for a total of the 117,695 buildings, the engineering parameters included in Da.D.O., but revised and reprocessed in this application, and the ground shaking data for six different variables (namely, intensity in MCS scale, PGA, PGV, SA at 0.3s, 1.0s and 3.0s). The potential applications of this data collection are innumerable: from recalibrating fragility curves to training machine learning models to quantifying earthquake damage. This data collection will be made available within Da.D.O., a platform of the Italian Department of Civil Protection, developed by EUCENTRE.

ABSTRACTThe inappropriate use of antibiotics in man is driving to insurgence of pathogenic bacteria resistant to multiple drugs (MDR) representing a challenge in critical illness. The interaction of MDR bacteria with host cells can guide molecular perturbations of host transcriptional programmes involving epigenetic-sensitive mechanisms, mainly DNA methylation, histone modifications, and non-coding RNAs leading to pathogen survival. Clinical evidence of epigenetic manipulation from MDR bacteria mainly arises from Mycobacterium tuberculosisas well as Helicobacter pylori, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Legionella pneumophilainfection suggesting possible biomarkers of disease. For example, DNA hypermethylation of E-cadherin (CDH1), upstream transcription factor 1/2 (USF1/2), WW domain containing oxidoreductase (WWOX), and mutL homolog 1 (MLH1) genes in gastric mucosa is correlated with malignancy suggesting useful biomarkers of early disease state. Moreover, upregulated circulating miR-361-5p, miR-889, miR-576-3p may be useful biomarkers to discriminate tuberculosis patients. Moreover, Listeria monocytogenescan indirectly induce H3 hyperacetylation leading to inflammation in human endothelial cells whereas Pseudomonas aeruginosaexcretes QS 2-AA to directly induce H3 deacetylation leading to bacterial persistence in human monocytes. Remarkably, epigenetic-sensitive drugs may aid to counteract MDR in clinical setting. Trichostatin A, a histone deacetyltransferase inhibitor (HDACi), leads to AMP β-defensin 2 (HBD2) gene up-regulation in human epithelial cells suggesting a useful ‘epi-therapy’ for Escherichia coli-induced intestinal diseases. We update on the most current clinical studies focusing on epigenetic changes involved in bacterial-host interactions and their putative role as biomarkers or drug targets to improve precision medicine and personalized therapy in critical illness and transplantation setting.

Side reactions involving surface reduction play a critical role in the failure of LiNi0.8Co0.15Al0.05O2to reach its theoretical capacity as a cathode material for Li-ion batteries. While macroscopic consequences are known, the underlying nanoscopic mechanisms are not fully elucidated. By coupling X-ray spectroscopy with several X-ray microscopy modalities, we have spatially resolved the extent of Ni oxidation at several states of charge and uncovered heterogeneity that is hidden when considering ensemble measurements alone. The use of morphologically controlled particles enabled high-resolution imaging of these materials, uncovering gradients of Ni oxidation states within individual primary particles. At high states of charge, these gradients revealed regions of possible oxygen deficiency extending deeper into the particle than previously observed. Surface-sensitive X-ray coupled scanning tunneling microscopy allows oxidation states to be measured at the material’s surface, showing predominantly NiIIin the first atomic layer and mixtures of NiIIwith NiIII/NiIValready appearing 1.5 nm into the particle. These results reveal the subtle interplay between irreversible surface transformations and the bulk reactions that ultimately define function, which will refine strategies of surface passivation that are key to overcoming current performance limitations.

Resonant inelastic X-ray scattering (RIXS) at the O K-edge is considered a prime technique to identify bulk oxidized oxygen formation, but its fundamental interpretation is not straightforward. In this study, we intentionally induce RIXS signatures of oxidized oxygen upon beam exposure in LiAlO2polymorphs that are easily distinguished because of their wide band gaps. After careful consideration of beam exposure effects on Li[Li0.144Ni0.136Mn0.544Co0.136]O2(LR-NMC), we conclude that oxidized oxygen features are inherent at high states of charge and are lost upon aggressive beam exposure. The extracted oxidized oxygen line shapes from our X-ray irradiation studies for both LiAlO2(induced) and LR-NMC (inherent) are found to have an additional oxidized oxygen RIXS feature not observed in O2gas studies. This study highlights the unique insight of O K-edge RIXS into determining the nature and stability of oxidized oxygen states.

Phosphoinositide-specific phospholipases C (PI-PLCs) are involved in signaling pathways related to critical cellular functions, such as cell cycle regulation, cell differentiation, and gene expression. Nuclear PI-PLCs have been studied as key enzymes, molecular targets, and clinical prognostic/diagnostic factors in many physiopathologic processes. Here, we summarize the main studies about nuclear PI-PLCs, specifically, the imbalance of isozymes such as PI-PLCβ1 and PI-PLCζ, in cerebral, hematologic, neuromuscular, and fertility disorders. PI-PLCβ1 and PI-PLCɣ1 affect epilepsy, depression, and bipolar disorder. In the brain, PI-PLCβ1 is involved in endocannabinoid neuronal excitability and is a potentially novel signature gene for subtypes of high-grade glioma. An altered quality or quantity of PI-PLCζ contributes to sperm defects that result in infertility, and PI-PLCβ1 aberrant inositide signaling contributes to both hematologic and degenerative muscle diseases. Understanding the mechanisms behind PI-PLC involvement in human pathologies may help identify new strategies for personalized therapies of these conditions.

Oxygen participation, arising from increased transition metal–oxygen covalency during delithiation, is considered essential for the description of charge compensation in conventional layered oxides. The advent of high-resolution mapping of the O K-edge resonant inelastic X-ray scattering (RIXS) provides an opportunity to revisit the onset and extent of oxygen participation. Combining RIXS with an array of structural and electronic probes for the family of Ni-rich LiNi0.8Co0.2−yAlyO2cathodes, we identify common charge compensation regimes that are assigned to formal transition metal redox (<4.25 V) and oxygen participation through covalency (>4.25 V). From O K-edge RIXS maps, we find the emergence of a sharp RIXS feature in these systems when approaching full delithiation, which has previously been associated with lattice oxidized oxygen in alkali-rich systems. The lack of transition metal redox signatures and strong covalency at these high degrees of delithiation suggest this RIXS feature is similarly attributed to lattice oxygen charge compensation as in the alkali-rich systems. The RIXS feature's evolution with state of charge in conventional layered oxides is evidence that this feature reflects the depopulation of occupied O 2p states associated with oxygen participation.

This paper reports new insights into structural and chemical evolution of surface phases of LiNi0.8Co0.15Al0.05O2(NCA) held at constant high voltages (up to 4.75 V) as well as high temperatures (60 °C) by correlating crystal structure using high angle annular dark field scanning transmission electron microscopy (HAADF-STEM) imaging with chemistry using electron energy loss spectroscopy (EELS). We also followed the Al distribution within individual NCA particles by X-ray energy dispersive spectroscopy (EDS). The progression of these phases as a function of distance from the edge shows simultaneous evolution of crystal structures and chemistry from rocksalt to layered, forming a complete solid solution. We have also observed an extended disordered phase with rocksalt (Fm3̅m) symmetry in which quantitative electron energy loss spectroscopy reveals it to be an oxygen deficient cation disordered phase with chemical characteristics, as determined by EELS, similar to spinel. The formation of these disordered phases with cation and oxygen vacancies has been driven by surface oxygen loss caused by reactions with the electrolyte followed by cation migration from the octahedral 3a M (M = Ni, Co, Al) layer to the octahedral 3b Li layer. These surface rocksalt phases are not fully dense as they contain Al and Li as well as a high concentration of cation and oxygen vacancies. After discharge, Li is detected within these phases indicative that Li transport has occurred through these rocksalt phases. At 60 °C and 4.75 V a very large impedance rise is observed leading to complete cell irreversibility which is caused by significant metal dissolution from the cathode and formation of surface porosity. In the near surface region of some particles, a phase transformation from R3̅m (O3) to P3̅m1 (O1) is also observed which has become thermodynamically stable from complete delithiation as well as from local Al surface depletion.

Practical utilization of energy densities near the theoretical limit for R3̅mlayered oxide positive electrode materials is dependent on the stability of the electrochemical performance of these materials at or near full delithiation. To develop new chemistries and novel approaches toward the improvement of the electrochemical performance of these materials at such high states of charge, a robust understanding of the failure mechanisms limiting current materials is necessary. Thorough analysis of LixCo1–yAlyO2and LixNi1–yAlyO2as well as LixNi0.8Co0.2O2and LixNi0.8Co0.15Al0.05O2(1 ≥ x≥ 0 and 0.2 ≥ y≥ 0) enabled the identification of key relationships between the transition metal chemistry of the electrode, its structural stability, and cycling characteristics at or near complete delithiation (4.75 V). Extensive characterization of these materials was achieved by a multitude of physical and electrochemical techniques to investigate the relative importance of surface vs bulk phenomena. The resulting insights derived from these analyses highlight the importance of the intrinsic structural and mechanical stability of the electrode when highly delithiated and establish guidelines for identifying positive electrode materials with improved high state of charge performance. Particularly important is the contrasting electrochemical impact of Al substitution into LiCoO2- and LiNiO2-based materials, which is shown to likely arise from the enhanced propensity for Al ions to migrate to the tetrahedral site in Co-rich compounds at high states of delithiation.

For layered oxide cathodes, aluminum doping has widely been shown to improve performance, particularly at high degrees of delithiation. While this has led to increased interest in Al-doped systems, including LiNi0.8Co0.15Al0.05O2 (NCA), the aluminum surface environment has not been thoroughly investigated. Using hard x-ray photoelectron spectroscopy measurements of the Al 1s core region for NCA electrodes, we examined the evolution of the surface aluminum environment under electrochemical and thermal stress. By correlating the aluminum environment to transition metal reduction and electrolyte decomposition, we provide further insight into the cathode-electrolyte interface layer. A remarkable finding is that Al-O coatings in LiPF6 electrolyte mimic the evolution observed for the aluminum surface environment in doped layered oxides.

Post-reperfusion syndrome during orthotopic liver transplantation, which definition best predicts postoperative graft failure and recipient mortality?

In this paper we explore the feasibility of formulating the hazard assessment procedure to include the information of past earthquakes into the probabilistic seismic hazard analysis, together with the use of an ensemble modeling technique. This strategy allows, on the one hand, to enlarge the information used in the evaluation of the hazard, from alternative models for the earthquake generation process to past shaking and, on the other hand, to explicitly account for the uncertainties. The Bayesian scheme we propose is applied to evaluate the seismic hazard of Naples. The framework in which we have embedded the tools is flexible to include all types of uncertainties. Here we focus on a sensitive study of the earthquake occurrence by implementing models that span from random to cluster-type temporal behavior and models that include quasiperiodic occurrence of earthquakes on faults. We implement five different spatiotemporal models to parameterize the occurrence of earthquakes potentially dangerous for Naples. Subsequently, we combine these hazard curves with ShakeMaps of past earthquakes that have been felt in Naples since 1200 A.D. The results are posterior ensemble hazard curves for three exposure times, e.g., 5, 10, and 50 years, in a dense grid that covers the municipality of Naples, considering rocky soil and including the site amplification. Our results show the importance to include the data from past shaking since the difference between the prior and the posterior is about 8–15% for the different exposure times. Statistical modeling of the spatiotemporal earthquake occurrence: ETAS, Poisson, and Brownian Passage TimeQuantification of the seismotectonic potential for NaplesBayesian hazard maps including the soil amplification effects

Surface impurity species, most notably Li2CO3, that develop on layered oxide positive electrode materials with atmospheric aging have been reported to be highly detrimental to the subsequent electrochemical performance. LiNi0.8Co0.15Al0.05O2 (NCA) was used as a model layered oxide compound to evaluate the growth and subsequent electrochemical impact of H2O, LiHCO3, LiOH and Li2CO3. Methodical high temperature annealing enabled the systematic removal of each impurity specie, thus permitting the determination of each specie's individual effect on the host material's electrochemical performance. Extensive cycling of exposed and annealed materials emphasized the cycle life degradation and capacity loss induced by each impurity, while rate capability measurements correlated the electrode impedance to the impurity species present. Based on these characterization results, this work attempts to clarify decades of ambiguity over the growth mechanisms and the electrochemical impact of the specific surface impurity species formed during powder storage in various environments.

A reliable method for purifying envelope-stripped nuclei from immortalized murine embryonic fibroblasts (iMEFs) was established. Quantitative profiling of the glycerophospholipids (GPLs) in envelope-free iMEF nuclei yields several conclusions. First, we find the endonuclear glycerophospholipidome differs from that of bulk membranes, and phosphatidylcholine (PtdCho) and phosphatidylethanolamine species are the most abundant endonuclear GPLs by mass. By contrast, phosphatidylinositol (PtdIns) represents a minor species. We also find only a slight enrichment of saturated versus unsaturated GPL species in iMEF endonuclear fractions. Moreover, much lower values for GPL mass were measured in the iMEF nuclear matrix than those reported for envelope-stripped IMF-32 nuclei. The collective results indicate that the nuclear matrix in these cells is a GPL-poor environment where GPL occupies only approximately 0.1% of the total nuclear matrix volume. This value suggests GPL accommodation in this compartment can be satisfied by binding to resident proteins. Finally, we find no significant role for the PtdIns/PtdCho-transfer protein, PITPα, in shuttling PtdIns into the iMEF nuclear matrix.

Photoacoustic (PA) imaging is an emerging hybrid optical-ultrasound based imaging technique that can be used to visualize optical absorbers in deep tissue. Free organic dyes can be used as PA contrast agents to concurrently provide additional physiological and molecular information during imaging, but their use in vivo is generally limited by rapid renal clearance for soluble dyes and by the difficulty of delivery for hydrophobic dyes. We here report the use of the block copolymer directed self-assembly process, Flash NanoPrecipitation (FNP), to form series of highly hydrophobic optical dyes into stable, biocompatible, and water-dispersible nanoparticles (NPs) with sizes from 38 to 88 nm and with polyethylene glycol (PEG) surface coatings suitable for in vivo use. The incorporation of dyes with absorption profiles within the infrared range, that is optimal for PA imaging, produces the PA activity of the particles. The hydrophobicity of the dyes allows their sequestration in the NP cores, so that they do not interfere with targeting, and high loadings of >75 wt % dye are achieved. The optical extinction coefficients (ε (mL mg–1cm–1)) were essentially invariant to the loading of the dye in NP core. Co-encapsulation of dye with vitamin E or polystyrene demonstrates the ability to simultaneously image and deliver a second agent. The PEG chains on the NP surface were functionalized with folate to demonstrate folate-dependent targeting. The spectral separation of different dyes among different sets of particles enables multiplexed imaging, such as the simultaneous imaging of two sets of particles within the same animal. We provide the first demonstration of this capability with PA imaging, by simultaneously imaging nontargeted and folate-targeted nanoparticles within the same animal. These results highlight Flash NanoPrecipitation as a platform to develop photoacoustic tools with new diagnostic capabilities.

In a single‐center prospective cohort study to assess the risk factors for infection with carbapenem‐resistant Klebsiella pneumoniaeafter liver transplantation, the authors analyze the significance of carbapenem‐resistant K. pneumoniaerectal carriage before and after liver transplantation, and develop a risk score that effectively discriminates patients at low versus higher risk for infection.

To assess the safety and tolerability of high-dose weekly (10 mgkg) liposomal amphotericin B (LamB) for antifungal prophylaxis in liver transplantation (LT) recipients with predefined risk factors for invasive fungal infection (IFI), a prospective phase II noncomparative trial was performed at our center over a 4-year period.

Medicaid faces new threats that would undoubtedly harm millions of people with mental disorders and other chronic illnesses. This program comprises more than half of all state and local mental [...]

NO The National Mental Health Association is against the use and expansion of involuntary outpatient treatment. Mandating psychiatric care for people with serious mental illness is an overly simplistic solution [...]

A new coated anionic exchange resin for blood purification specifically designed to remove phosphates was experimentally employed in animals. 3 pigs, in which uremia had been surgically induced, underwent 6 extracorporeal hemoperfuslon sessions (2 per pig) with a cartridge containing 100 gr of resin.The phosphate clearance proved satisfactory, values being 120 ml/min after 10' and around 80 ml/min after 2 hours. The biocompat ibility of the resin and of the coating membrane was satisfactory. The negligible variation in pH and plasma bicarbonate during all sessions confirmed the low absorption by the tested resin of other blood anions competing with phosphate.

Two isoforms of inositide-dependent phospholipase C β1 (PI-PLCβ1) are generated by alternative splicing (PLCβ1a and PLCβ1b). Both isoforms are present within the nucleus, but in contrast to PLCβ1a, the vast majority of PLCβ1b is nuclear. In mouse erythroid leukemia cells, PI-PLCβ1 is involved in the regulation of cell division and the balance between cell proliferation and differentiation. It has been demonstrated that nuclear localization is crucial for the enzymatic function of PI-PLCβ1, although the mechanism by which this nuclear import occurs has never been fully characterized. The aim of this study was to characterize both the mechanism of nuclear localization and the molecular function of nuclear PI-PLCβ1 by identifying its interactome in Friend's erythroleukemia isolated nuclei, utilizing a procedure that coupled immuno-affinity purification with tandem mass spectrometry analysis. Using this procedure, 160 proteins were demonstrated to be in association with PI-PLCβ1b, some of which have been previously characterized, such as the splicing factor SRp20 (Srsf3) and Lamin B (Lmnb1). Co-immunoprecipitation analysis of selected proteins confirmed the data obtained via mass spectrometry. Of particular interest was the identification of the nuclear import proteins Kpna2, Kpna4, Kpnb1, Ran, and Rangap1, as well as factors involved in hematological malignancies and several anti-apoptotic proteins. These data give new insight into possible mechanisms of nuclear trafficking and functioning of this critical signaling molecule.

Phospholipase C β1 (PLCβ1) is known to play an important role in cell proliferation. Previous studies reported an involvement of PLCβ1 in G0-G1/S transition and G2/M progression in Friend murine erythroleukemia cells (FELC). However, little has been found about its role in human models. Here, we used K562 cell line as human homologous of FELC in order to investigate the possible key regulatory role of PLCβ1 during cell proliferation of this human cell line. Our studies on the effects of the overexpression of both these isoforms showed a specific and positive connection between cyclin D3 and PLCβ1 in K562 cells, which led to a prolonged S phase of the cell cycle and a delay in cell proliferation. In order to shed light on this mechanism, we decided to study the possible involvement of protein kinases C (PKC), known to be direct targets of PLC signaling and important regulators of cell proliferation. Our data showed a peculiar decrease of PKCα levels in cells overexpressing PLCβ1. Moreover, when we silenced PKCα, by RNAi technique, in order to mimic the effects of PLCβ1, we caused the same upregulation of cyclin D3 levels and the same decrease of cell proliferation found in PLCβ1-overexpressing cells. The key features emerging from our studies in K562 cells is that PLCβ1 targets cyclin D3, likely through a PKCα-mediated-pathway, and that, as a downstream effect of its activity, K562 cells undergo an accumulation in the S phase of the cell cycle.

Among cellular second messengers inositides play key roles in signal transduction pathways. Indeed, nuclear phosphoinositide- specific phospholipase C (PI-PLC) 1 and Akt are involved in cell cycle progression and apoptosis. Nuclear lipid metabolism has raised interest in the last years, mainly because of its link with haematopoietic progenitor cells. Myelodysplastic syndromes (MDS) are stem-cell clonal diseases characterized by an impaired hempoiesis and a differentiation defect in one or more of the bone marrow lineages, often leading to progression to acute myeloid leukaemia (AML). The MDS evolution to AML is not completely understood but, at a molecular level, the nuclear inositide signalling pathways can play an important role in this process.

Recent data indicate that some PKC isoforms are translocated to the nucleus, in response to certain stimuli, where they play an important role in nuclear signaling events. To identify novel interacting proteins of conventional PKC (cPKC) at the nuclear level during myogenesis and to find new PKC isozyme-specific phosphosubstrates, we performed a proteomics analysis of immunoprecipitated nuclear samples from mouse myoblast C2C12 cells following insulin administration. Using a phospho(Ser)-PKC substrate antibody, specific interacting proteins were identified by LC-MS/MS spectrometry. A total of 16 proteins with the exact and complete motif recognized by the phospho-cPKC substrate antibody were identified; among these, particular interest was given to eukaryotic elongation factor 1α (eEF1A). Nuclear eEF1A was focalized in the nucleoli, and its expression was observed to increase following insulin treatment. Of the cPKC isoforms, only PKCβI was demonstrated to be expressed in the nucleus of C2C12 myocytes and to co-immunoprecipitate with eEF1A. In-depth analysis using site-directed mutagenesis revealed that PKCβI could phosphorylate Ser53of the eEF1A2 isoform and that the association between eEF1A2 and PKCβI was dependent on the phosphorylation status of eEF1A2.

Several letters to the editor are presented in response to articles in previous issues including "Great Expectations," by M.T. Schwartzman in the January/February 2008 issue, an article on "Celebrations At Sea" Cruise Roundup in the January/February 2008 issue and an article on the 2010 SOLAS (Safety Of Lite At Sea) international regulations by Theodore W. Scull in the November/December 2007 issue.

Analysis of intraoperative changes of metabolic, hemodynamic, and coagulative parameters is useful to detect early ischemia-reperfusion damage after intestinal transplant.

The use of the Model for End-Stage Liver Disease (MELD) score to prioritize patients on liver waiting lists must take the bias of different laboratories into account.

Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT, or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT. Three patients with no history of previous liver diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6–24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT. Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients.

Although the University of Wisconsin (U.W.) solution continues to be the most commonly used for intra-abdominal organs, a new solution, Celsior, already used for heart and lungs, has been proposed for kidney and liver preservation. The aim of this research was to assess the effect of Celsior as compared with U.W. on immediate graft function and a 2-year follow-up of kidney transplants.

Various studies have been performed concerning haemodynamics in the shock state. The aim of this study was to examine if a haemodynamic approach based on volumetric indices can offer a new method of evaluation. Volumetric measurements of ventricular filling and cardiac function were compared with classical haemodynamic variables during induced haemorrhagic shock in swine. Twelve hybrid swine were anaesthetized and underwent arteriectomy to induce haemorrhagic shock. Blood was collected in ACD treated bags and reinfused via the same vein after a shock period of 90 min. Haemodynamic and volume measurements were evaluated. Seven swine survived to complete the protocol and reached the final experimental time (90 min after reinfusion), while the remaining five died 1 h after reinfusion. Concerning the haemodynamics, afterload changes characterized the haemorrhagic shock period, while blood volume distribution dictated ventricular filling and ventricular kinetics during the post-reinfusion period. Systemic vascular resistance was different in the two groups. This study suggests that blood volumetric evaluations can offer better comparative data than pulmonary catheterisation for a precise assessment of cardiac output. Preload values have turned out to be of greater relevance than traditional pressure variables.

Using NIH 3T3 cells, we have investigated nuclear phosphoinositide metabolism in response to insulin, a molecule which acts as a proliferating factor for this cell line and which is known as a powerful activator of the mitogen‐activated protein (MAP) kinase pathway. Insulin stimulated inositol lipid metabolism in the nucleus, as demonstrated by measurement of the diacylglycerol mass produced in vivo and by in vitro nuclear phosphoinositide‐specific phospholipase C (PI‐PLC) activity assay. Despite the fact that nuclei of NIH 3T3 cells contained all of the four isozymes of the β family of PI‐PLC (i.e. β1, β2, β3, and β4), insulin only activated the β1 isoform. Insulin also induced nuclear translocation of MAP kinase, as demonstrated by Western blotting analysis, enzyme activity assays, and immunofluorescence staining, and this translocation was blocked by the specific MAP kinase kinase inhibitor PD98059. By means of both a monoclonal antibody recognizing phosphoserine and in vivo labeling with [32P]orthophosphate, we ascertained that nuclear PI‐PLC‐β1 (and in particular the b subtype) was phosphorylated on serine residues in response to insulin. Both phosphorylation and activation of nuclear PI‐PLC‐β1 were substantially reduced by PD98059. Our results conclusively demonstrate that activation of nuclear PI‐PLC‐β1 strictly depends on its phosphorylation which is mediated through the MAP kinase pathway.

Phosphoinositide signaling resides in the nucleus, and among the enzymes of the cycle, phospholipase C (PLC) appears as the key element both in Saccharomyces cerevisiaeand in mammalian cells. The yeast PLC pathway produces multiple inositol polyphosphates that modulate distinct nuclear processes. The mammalian PLCβ1, which localizes in the nucleus, is activated in insulin-like growth factor 1-mediated mitogenesis and undergoes down-regulation during murine erythroleukemia differentiation. PLCβ1exists as two polypeptides of 150 and 140 kDa generated from a single gene by alternative RNA splicing, both of them containing in the COOH-terminal tail a cluster of lysine residues responsible for nuclear localization. These clues prompted us to try to establish the critical nuclear target(s) of PLCβ1subtypes in the control of cell cycle progression. The results reveal that the two subtypes of PLCβ1that localize in the nucleus induce cell cycle progression in Friend erythroleukemia cells. In fact when they are overexpressed in the nucleus, cyclin D3, along with its kinase (cdk4) but not cyclin E is overexpressed even though cells are serum-starved. As a consequence of this enforced expression, retinoblastoma protein is phosphorylated and E2F-1 transcription factor is activated as well. On the whole the results reveal a direct effect of nuclear PLCβ1signaling in G1progression by means of a specific target, i.e.cyclin D3/cdk4.

Although interleukin 1 (IL-1) functions have been extensively characterized, the mechanisms by which IL-1 signals are transduced from the plasma membrane to the nucleus are less known. Recent evidence indicates that phosphatidylinositol 3-kinase (PI3-kinase) could be activated by a direct association with the activated IL-1 receptor. In this study we analyzed the effects of IL-1 on the intracellular distribution of PI3-kinase in wild-type Saos-2 human osteosarcoma cells, and in cell clones overexpressing type I IL-1 receptor (IL-1RI). PI3-kinase intracellular distribution displays two distinct patterns. In quiescent cells, PI3-kinase is distributed through the cytoplasm, although a portion is present in the nucleus; following stimulation with IL-1, PI3-kinase is redistributed, increasing in the nuclear compartment. Both immunoblotting and immunofluorescence data indicate that IL-1 causes a rapid and transient translocation of PI3-kinase from the cytoplasm to the nucleus. This phenomenon is prevented by PI3-kinase inhibitors, suggesting that the maintenance of PI3-kinase activity is essential for IL-1-induced translocation. Indeed, in cell clones stably transfected with Y479F receptor mutant, in which the binding of the enzyme to the activated receptor is blocked, IL-1-induced PI3-kinase translocation to the nucleus is completely prevented. These data suggest that PI3-kinase translocation to the nucleus upon IL-1R activation is an early event in IL-1 signaling mechanism, and may be involved in transcriptional activation.

Abstract: Ureteral obstruction with impaired urine flow is the most common urological complication following renal transplantation. From December 1976 to December 1997, 869 kidney grafts were performed by our kidney transplantation group, 96 from living related donors and 773 from cadaver donors (736 first grafts and 37 regrafts). A stricture of the ureter (SU) was observed in 27 cases with a follow-up ranging from 18 months to 18 years after the graft and 11 months to 11 years after the treatment of the SU. In six patients, SU was immediately apparent and limited to the anastomosis: they were obviously technical flaws. In all the other patients, there was a free interval ranging from 2 months to 11 years after surgery; the SU usually involved the entire ureter, suggesting multiple etiologies. Repeated urinary infections could be a cause but immunological problems might be more determinant. In our series, acute rejection was more common than chronic so that the correction of SU was followed in many cases by a good and long lasting result (up to 11 years). In our experience, SU was not a dangerous complication even in patients in whom for different reasons (mainly refusal of treatment) the therapy was delayed – even if anuria occurred, no case of graft loss or serious damage were observed. At the beginning of our experience, the diagnosis of SU was based on urography, and therapy has always been re-operation. For 15 years, the diagnosis of SU has been based on routine echographic surveillance, which was intensified after each rejection, and the first treatment of SU in the last 8 years was re-operation in early technical SU and interventional radiology (balloon dilatation with or without temporary stent) in other cases. When it failed or in case of recurrence, surgical correction was performed utilizing the native ipsilateral or contralateral ureter for a uretero-ureterostomy.