Comparative high-resolution chemostratigraphy of the Bonarelli Level from the reference Bottaccione section (Umbria-Marche Apennines) and from an equivalent section in NW Sicily: Consistent and contrasting responses to the OAE2.

The Bonarelli Level (BL) from the upper Cenomanian portion of the reference Bottaccione section (central Italy) is characterized by the presence of black shales containing high TOC concentrations (up to 17%) and amounts of CaCO3 near to zero. In the absence of carbonate and, consequently, of relative carbon- and oxygen- isotopic data, the elemental geochemistry revealed to be a very useful tool to obtain information about the palaeoclimatic and palaeoceanographic evolution of the Tethys Ocean during the OAE2. Based on several geochemical proxies (Rb, V, Ni, Cr, Si, Ba), the BL is interpreted as a high-productivity event driven by increasingly warm and humid climatic conditions promoting an accelerated hydrological cycle. The enrichment factors of peculiar trace metals (Zn, Cd, Pb, Sb, Mo, U) provide further insight about the H2S activity at the seafloor during the organic-rich sediment deposition and permitted us to evaluate the use of Ba as palaeoproductivity tracer in conditions of high rate of sulphate reduction. By comparing geochemical records from the reference Bottaccione section (central Italy) with those previously obtained for the coeval Calabianca section (northwestern Sicily), different degrees of oceanic anoxia were delineated and ascribed to different abundance and type (degradable or refractory) of organic matter, which are limiting factors in the bacterial sulphate reduction reactions and in subsequent euxinic conditions at seafloor in the Tethys realm. Based on a ciclostratigraphic approach, consistent fluctuations at 100 kyr scale in the chemostratigraphic signals from the two sections are inferred to be expression of a strong orbital-climatic forcing driving changes in the oceanic environment during the BL deposition

Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes

The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV-1 compound in all cellular systems. All effective integrase inhibitors exhibited a potent antiviral activity against both X4 and R5 HIV-1 strains. In general, raltegravir, MK-2048, L870,810 and IN5 showed anti HIV activity similar or slightly higher in macrophages compared to PBMC and C8166 T cells: for MK-2048, the EC(50) was 0.4, 0.9, 11.5nM in macrophages, in PBMCs and T cells, respectively; for L870,810, the EC(50) was 1.5, 14.3, and 10.6nM, respectively; for IN5 the EC(50) was 0.5, 13.7, and 5.7nM, respectively

Use of dipicolinate-based complexes for producing ion-imprinted polystyrene resins for the extraction of yttrium-90 and heavy lanthanide cations

Highly selective separation of yttrium (and lanthanides) is of interest for the design of radiopharmaceuticals, and an efficient method based on the ion-imprinting concept is proposed here. The synthesis and structural, thermodynamic and photophysical characterization of complexes of trivalent yttrium and lanthanides with two new vinyl derivatives of dipicolinic acid, HL1 and L2, are described. The feasibility of using ion-imprinted resins for yttrium and lanthanide separation is demonstrated. The resins were obtained by copolymerization with styrene and divinylbenzene and subsequent acid treatment to remove the metal ion. High-resolution Eu luminescence experiments revealed that the geometry of the complexation sites is well preserved in the imprinted polymers. The ion-imprinted polymer based on HL1 proved to be particularly well adapted for yttrium extraction, having a sizeable capacity (8.9 +- 0.2 g/mg resin) and a fast rate of extraction (t1/2 = 1.7 min). In addition, lighter and heavier lanthanide ions are separated. Finally, the resin displays high selectivity for yttrium and lanthanide cations against alkali and alkaline earth metals. For instance, in a typical experiment, 10 mg of yttrium was extracted from 5 g of milk ash sample by 2 g of the resin. The good separation properties displayed by the resin based on HL1 open interesting perspectives for the production of highly pure 90Y and radiolanthanides for medical applications, and for trace analysis of these radiochemicals in food and in the environment

Effects of long-term lercanidipine or hydrochlorothiazide administration on hypertension-related vascular structural changes.

Vascular remodelling and hypertrophy represent early therapeutic targets of antihypertensive treatment. The present study was aimed at assessing the effects of 1-year administration of the highly vasoselective calcium-channel blocker lercanidipine (10 mg/day) or the diuretic compound hydrochlorothiazide (25 mg/day) on hypertension-related vascular alterations. The study was also aimed at assessing whether and to what extent: (i) pharmacological regression of vascular hypertrophy is related only to the blood pressure (BP) reduction "per se" or also to the specific ancillary properties of a given drug and (ii) treatment provides restoration of vascular function indicative of normal vascular structure.In 26 untreated patients with mild-to-moderate essential hypertension sphygmomanometric and finger BP, heart rate, forearm and calf blood flow (venous occlusion plethysmography) and corresponding vascular resistance (forearm and calf vascular resistance: FVR and CVR) were assessed before and following 6 and 12 months of either lercanidipine or hydrochlorothiazide administration. Vascular resistance was also evaluated following a local ischaemic stimulus (FVR(min) and CVR(min)) in order to assess the effects of treatment on arteriolar structural alterations.For superimposable BP reductions, lercanidipine caused FVR and CVR to decrease significantly more than hydrochlorothiazide. Similarly, the FVR(min) and CVR(min) reductions induced by lercanidipine were markedly and significantly greater than those caused by hydrochlorothiazide (-46.1% and -40.9% vs -22.5% and -19.9%, p0.01 for both). FVR(min), and CVR(min), however, remained higher than those found in 10 age-matched normotensive individuals.These data provide evidence that, compared to hydrochlorothiazide, lercanidipine favours a greater regression of the vascular structural changes associated with hypertension, probably through its "ancillary" properties. Lercanidipine, however, does not allow restoration of a "normal" vascular structure, thereby suggesting that vascular hypertrophy is only in part a reversible phenomenon

Behavior of a forest of NiFe nanowires in KOH and NaCl solution for water electrolysis

The present work investigates the behavior of nanostructured electrodes consisting of an array of nanowires of NiFe alloy in KOH + 0.5 M NaCl solution. The aim is to explore the possibility of using these electrodes for hydrogen production by seawater electrolysis. Seawater splitting requires a highly selective electrode on the anode side, where the evolution of molecular chlorine or the formation of other active chlorine compounds can compete with the oxygen evolution reaction. Nanostructured electrodes, obtained by template electrosynthesis, were tested at room temperature in KOH + 0.5 M NaCl solution, and the results were compared with those obtained in pure KOH. The results showed that the presence of NaCl does not affect the electrocatalytic behavior of the nanostructured NiFe alloy. Furthermore, the chemical–physical characterizations carried out after the long-term galvanostatic tests, have shown that the nanostructured electrodes are also stable in terms of morphology and composition. In addition, the solution used to perform the long-term galvanostatic tests was analyzed to investigate the possible formation of chlorine compounds. The absence of these compounds, together with the measured potential value measured for the oxygen evolution reaction, which was always lower than the thermodynamic redox potential for the hypochlorite formation reaction, leads us to conclude that these electrodes are potentially suitable for seawater electrolysis

Mitochondrial enzyme GLUD2 plays a critical role in glioblastoma progression

Background: Glioblastoma (GBM) is the most frequent and malignant primary brain tumor in adults and despite the progress in surgical procedures and therapy options, the overall survival remains very poor. Glutamate and α-KG are fundamental elements necessary to support the growth and proliferation of GBM cells. Glutamate oxidative deamination, catalyzed by GLUD2, is the predominant pathway for the production of α-KG. Methods: GLUD2 emerged from the RNA-seq analysis of 13 GBM patients, performed in our laboratory and a microarray analysis of 77 high-grade gliomas available on the Geo database. Thereafter, we investigated GLUD2 relevance in cancer cell behavior by GLUD2 overexpression and silencing in two different human GBM cell lines. Finally, we overexpressed GLUD2 in-vivo by using zebrafish embryos and monitored the developing central nervous system. Findings: GLUD2 expression was found associated to the histopathological classification, prognosis and survival of GBM patients. Moreover, through in-vitro functional studies, we showed that differences in GLUD2 expression level affected cell proliferation, migration, invasion, colony formation abilities, cell cycle phases, mitochondrial function and ROS production. In support of these findings, we also demonstrated, with in-vivo studies, that GLUD2 overexpression affects glial cell proliferation without affecting neuronal development in zebrafish embryos. Interpretation: We concluded that GLUD2 overexpression inhibited GBM cell growth suggesting a novel potential drug target for control of GBM progression. The possibility to enhance GLUD2 activity in GBM could result in a blocked/reduced proliferation of GBM cells without affecting the survival of the surrounding neurons

The Videofluorographic Swallowing Study in Rheumatologic Diseases: A Comprehensive Review

Autoimmune connective tissue diseases are a heterogeneous group of pathologies that affect about 10% of world population with chronic evolution in 20%-80%. Inflammation in autoimmune diseases may lead to serious damage to other organs including the gastrointestinal tract. Gastrointestinal tract involvement in these patients may also due to both a direct action of antibodies against organs and pharmacological therapies. Dysphagia is one of the most important symptom, and it is caused by failure of the swallowing function and may lead to aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The videofluorographic swallowing study is a key diagnostic tool in the detection of swallowing disorders, allowing to make an early diagnosis and to reduce the risk of gastrointestinal and pulmonary complications. This technique helps to identify both functional and structural anomalies of the anatomic chain involved in swallowing function. The aim of this review is to systematically analyze the basis of the pathological involvement of the swallowing function for each rheumatological disease and to show the main features of the videofluorographic study that may be encountered in these patients

Swallowing evaluation with videofluoroscopy in the paediatric population

Paediatric swallowing disorders can have several causes, from prematurity and congenital anomalies to gastro-oesophageal reflux and infective or inflammatory pathologies of the upper digestive tract. In neonates, the swallowing process is reflexive and involuntary. Later in infancy, the oral phase comes under voluntary control, while the pharyngeal phase and oesophageal phases remain involuntary. Swallowing difficulties can severely compromise pulmonary health and nutritional intake of paediatric patients. Videofluoroscopic Swallow Study (VFSS) is a radiographic procedure that provides a dynamic view of the swallowing process and is frequently considered to be definitive evaluation for objective assessment of dysphagia in paediatric patients. This review focuses on the different possible aetiologies of paediatric swallowing disorders and related videofluoroscopic swallowing study procedures and appearances