Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion: a double-blind, randomized, active-controlled trial

Abstract Background Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent μ-opioid agonist, reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia. Methods Sixty-four patients, undergoing remifentanil infusion during general anaesthesia and major lung surgery, were randomly assigned to receive either buprenorphine i.v. infusion (25 μg h −1 for 24 h) or morphine (equianalgesic dose) perioperatively. The presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative pain scores, opioid consumption and postoperative neuropathic pain assessed one and three months postoperatively. Results A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the buprenorphine-treated group than in the morphine-treated group: 18 vs 9 min ( P =0.002). At 30 min postoperatively, patients receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine ( P =0.009). At three months, no differences between groups were noted. Conclusions Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical incision but shows no long-term efficacy at three months follow-up

PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases

Paleoambientes de la Cuenca Media del río Luján (Buenos Aires, Argentina) durante el último Período Glacial (EIO 4-2)

El objetivo de este trabajo es definir unidades depositacionales y realizar inferencias paleoambientales a partir del análisis de facies y del contenido paleobiológico (moluscos, fitolitos y diatomeas) de depósitos acotados cronológicamente entre ca. <70.000 años y 11.000 años AP., Estadios Isotópicos de Oxígeno (EIO) 4 a 2, para la cuenca media del río Luján. Se seleccionaron tres secciones en las cuales se realizaron un total de siete perfiles estratigráficos de detalle y donde se extrajeron las muestras para los análisis sedimentológico, del contenido paleobiológico y para dataciones. Los depósitos estudiados fueron agrupados en cinco facies sedimentarias (F1, F2, F3, F4 y F5), ubicados cronológicamente y correlacionados con unidades semejantes descriptas por otros autores. Se reconocieron varias discontinuidades erosivas y de estabilidad para el lapso Pleistoceno tardío-Holoceno, las que permitieron definir cinco unidades depositacionales (UD). La presencia en el río Luján de una barranca, donde se exponen depósitos de edad Pleistoceno tardío-Holoceno, está estrechamente asociada a la incisión de los depósitos de relleno de antiguas depresiones interconectadas, ocurrida durante el Holoceno. Esto permitió inferir que la paleotopografía de esta área ha ejercido un control determinante en la existencia de barrancas con afloramientos del Pleistoceno tardío–Holoceno. Aún cuando las sucesiones son incompletas y las dataciones no permiten ajustar el inicio y la finalización de las UD para el lapso EIO 4 a 2, el análisis facial sugiere la existencia de una marcada variabilidad ambiental durante ese lapso, para el noreste de la provincia de Buenos Aires. En función del análisis facial se interpretó que el ambiente de depositación correspondió a sistemas fluvio-lacustres efímeros y eólicos, con sedimentación para el lapso ca. <70.000 años - <11.000 14C años AP, bajo condiciones áridas, principalmente climas seco-subhúmedo y semiárido. Durante al menos una parte del EIO4 y durante el EIO2 habría ocurrido depositación eólica predominante, durante intervalos climáticos sub-húmedos secos. En tanto durante el EIO3 habrían tenido lugar eventos aluvionales episódicos bajo condiciones climáticas subhúmedas a subhúmedas secas o fuertemente estacionales y con alternancia de fases sub-húmedas-húmedas. Esto indicaría que las acumulaciones habrían tenido lugar mayormente en ambientes depositacionales con déficit hídrico aunque de variado grado. Las características geomorfológicas y las evidencias sedimentológicas y paleobiológicas permitieron inferir que el clima fue el forzante principal en el desarrollo de la sucesión sedimentaria.Facultad de Ciencias Naturales y Museo (FCNM

Paleoambientes de la Cuenca Media del río Luján (Buenos Aires, Argentina) durante el último Período Glacial (EIO 4-2)

El objetivo de este trabajo es definir unidades depositacionales y realizar inferencias paleoambientales a partir del análisis de facies y del contenido paleobiológico (moluscos, fitolitos y diatomeas) de depósitos acotados cronológicamente entre ca. <70.000 años y 11.000 años AP., Estadios Isotópicos de Oxígeno (EIO) 4 a 2, para la cuenca media del río Luján. Se seleccionaron tres secciones en las cuales se realizaron un total de siete perfiles estratigráficos de detalle y donde se extrajeron las muestras para los análisis sedimentológico, del contenido paleobiológico y para dataciones. Los depósitos estudiados fueron agrupados en cinco facies sedimentarias (F1, F2, F3, F4 y F5), ubicados cronológicamente y correlacionados con unidades semejantes descriptas por otros autores. Se reconocieron varias discontinuidades erosivas y de estabilidad para el lapso Pleistoceno tardío-Holoceno, las que permitieron definir cinco unidades depositacionales (UD). La presencia en el río Luján de una barranca, donde se exponen depósitos de edad Pleistoceno tardío-Holoceno, está estrechamente asociada a la incisión de los depósitos de relleno de antiguas depresiones interconectadas, ocurrida durante el Holoceno. Esto permitió inferir que la paleotopografía de esta área ha ejercido un control determinante en la existencia de barrancas con afloramientos del Pleistoceno tardío–Holoceno. Aún cuando las sucesiones son incompletas y las dataciones no permiten ajustar el inicio y la finalización de las UD para el lapso EIO 4 a 2, el análisis facial sugiere la existencia de una marcada variabilidad ambiental durante ese lapso, para el noreste de la provincia de Buenos Aires. En función del análisis facial se interpretó que el ambiente de depositación correspondió a sistemas fluvio-lacustres efímeros y eólicos, con sedimentación para el lapso ca. <70.000 años - <11.000 14C años AP, bajo condiciones áridas, principalmente climas seco-subhúmedo y semiárido. Durante al menos una parte del EIO4 y durante el EIO2 habría ocurrido depositación eólica predominante, durante intervalos climáticos sub-húmedos secos. En tanto durante el EIO3 habrían tenido lugar eventos aluvionales episódicos bajo condiciones climáticas subhúmedas a subhúmedas secas o fuertemente estacionales y con alternancia de fases sub-húmedas-húmedas. Esto indicaría que las acumulaciones habrían tenido lugar mayormente en ambientes depositacionales con déficit hídrico aunque de variado grado. Las características geomorfológicas y las evidencias sedimentológicas y paleobiológicas permitieron inferir que el clima fue el forzante principal en el desarrollo de la sucesión sedimentaria.Facultad de Ciencias Naturales y Museo (FCNM

XIPE: the X-ray Imaging Polarimetry Explorer

X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017 but not selected. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus and two additional GPDs filled with pressurized Ar-DME facing the sun. The Minimum Detectable Polarization is 14 % at 1 mCrab in 10E5 s (2-10 keV) and 0.6 % for an X10 class flare. The Half Energy Width, measured at PANTER X-ray test facility (MPE, Germany) with JET-X optics is 24 arcsec. XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil).Comment: 49 pages, 14 figures, 6 tables. Paper published in Experimental Astronomy http://link.springer.com/journal/1068

Urokinase Plasminogen Activator Inhibits HIV Virion Release from Macrophage-Differentiated Chronically Infected Cells via Activation of RhoA and PKCε

HIV replication in mononuclear phagocytes is a multi-step process regulated by viral and cellular proteins with the peculiar feature of virion budding and accumulation in intra-cytoplasmic vesicles. Interaction of urokinase-type plasminogen activator (uPA) with its cell surface receptor (uPAR) has been shown to favor virion accumulation in such sub-cellular compartment in primary monocyte-derived macrophages and chronically infected promonocytic U1 cells differentiated into macrophage-like cells by stimulation with phorbol myristate acetate (PMA). By adopting this latter model system, we have here investigated which intracellular signaling pathways were triggered by uPA/uPAR interaction leading the redirection of virion accumulation in intra-cytoplasmic vesicles.uPA induced activation of RhoA, PKCδ and PKCε in PMA-differentiated U1 cells. In the same conditions, RhoA, PKCδ and PKCε modulated uPA-induced cell adhesion and polarization, whereas only RhoA and PKCε were also responsible for the redirection of virions in intracellular vesicles. Distribution of G and F actin revealed that uPA reorganized the cytoskeleton in both adherent and polarized cells. The role of G and F actin isoforms was unveiled by the use of cytochalasin D, a cell-permeable fungal toxin that prevents F actin polymerization. Receptor-independent cytoskeleton remodeling by Cytochalasin D resulted in cell adhesion, polarization and intracellular accumulation of HIV virions similar to the effects gained with uPA.These findings illustrate the potential contribution of the uPA/uPAR system in the generation and/or maintenance of intra-cytoplasmic vesicles that actively accumulate virions, thus sustaining the presence of HIV reservoirs of macrophage origin. In addition, our observations also provide evidences that pathways controlling cytoskeleton remodeling and activation of PKCε bear relevance for the design of new antiviral strategies aimed at interfering with the partitioning of virion budding between intra-cytoplasmic vesicles and plasma membrane in infected human macrophages

The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem

Predictors of Hospitalized Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease

Background and Aim Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs?particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients. Methods This was a retrospective population-based cohort study.We selected 900 patients with confirmed COPD aged 35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission.We observed exacerbation frequency over the previous year (2011) and following year (2012). We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1?4). We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year. Results Of the patients, 16.4%had 1 severe exacerbations, varying from 9.3%in mild GOLD grade 1 to 44%in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95%confidence interval [CI], 3.53?12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41?17.05). Older age and several comorbidities, such as heart failure and diabetes, were similarly associated. Conclusions Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening